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PubMed2001

HIV-infected American Indians/Alaska natives in the Western United States.

OBJECTIVE: We sought to describe HIV-infected American Indians/Alaska Natives (AI/ AN) in the western United States. DESIGN: One hundred fifty-one Al/AN and 11,344 non-AI/AN HIV-infected patients in Seattle, Denver, and Los Angeles were followed by medical record review from January 1989 through June 1998 for the Adult/Adolescent Spectrum of HIV-related Diseases study. METHODS: Bivariate and multivariate statistical analyses comparing HIV-infected Al/AN and non-AI/AN were performed. RESULTS: There were 103 (68%) male and 48 (32%) female Al/AN patients, while non-Al/AN patients were 86% male and 14% female (P<.001). The median age among AI/ AN was 32 years vs. 34 years among non-AI/AN (P = .05). Male Al/AN were more likely than male non-AI/AN to report the dual risks of having sex with men and injection drug use (32% vs. 14%; P<.001) compared with other HIV risks. Median CD4 cell counts were higher in Al/AN than in non-AI/AN (P< or =.001). AI/AN were more likely to be diagnosed with an acute sexually transmitted disease (STD) than were non-AI/AN (11% vs. 4%, P<.001). Five (6%) of AI/AN with AIDS had active pulmonary tuberculosis (TB) compared with 132 (2%) of non-AI/AN with AIDS (P = .02). While 52% of Al/AN and 44% of non-AI/AN had a psychiatric illness (P = .04), and 13% of AI/AN, and 6% of non-AI/ AN had suicidal ideation (P<.001), these associations became non-significant in analyses stratified by alcohol and drug use (P>.05). In adjusted models, survival and progression to opportunistic infection or CD4 cell count less than 200/mm3 did not significantly differ between Al/AN and non-AI/AN. CONCLUSIONS: HIV-infected AI/AN were younger than non-AI/AN, and a greater proportion of Al/AN were women relative to non-AI/AN. AI/AN were more likely to be diagnosed with STDs and TB. In adjusted models, their risks of death and developing AIDS did not significantly differ from those of non-AI/AN.

Adolescent↗

PubMed2006

Potential of imidacloprid to control four species of psocids (Psocoptera: Liposcelididae) infesting stored grain.

The effectiveness of the neonicotinoid insecticide imidacloprid was evaluated against four psocid pests of stored grain. This research was undertaken because of the growing importance of psocids in stored grain and the need to identify methods for their control. The mortality and reproduction of adults of Liposcelis bostrychophila Badonnel, L. entomophila (Enderlein), L. decolor (Pearman) and L. paeta Pearman in wheat treated with imidacloprid were determined. There were five application rates (0.5, 1, 2, 5 and 10 mg AI kg(-1) grain) and an untreated control. There were significant effects of application rate on both adult mortality and reproduction for all four species, but the effect of imidacloprid was sometimes more pronounced on reproduction. Imidacloprid was most effective against L. bostrychophila, with 100% adult mortality after 7 d at 5 mg AI kg(-1), 14 d at 2 mg AI kg(-1) and 28 d at 0.5 and 1 mg AI kg(-1). No live progeny were produced at 2 mg AI kg(-1). For L. decolor, there was 100% adult mortality after 28 d at 10 mg AI kg(-1) and no live progeny were produced at 2 mg AI kg(-1). For L. entomophila, there was 100% adult mortality after 14 d at 10 mg AI kg(-1) and 28 d at 2 and 5 mg AI kg(-1). No live progeny were produced at 10 mg AI kg(-1). At 10 mg AI kg(-1) there was 100% mortality of L. paeta adults after 28 d exposure and no live progeny developed. Because reproduction at some application rates occurred only in the first 14 d of exposure, it is concluded that the application rate leading to population extinction was 1 mg AI kg(-1) for L. bostrychophila, 2 mg AI kg(-1) for L. decolor and L. entomophila and 5 mg AI kg(-1) for L. paeta. This study shows that imidacloprid has potential as a grain protectant to control all four Liposcelis species in stored grain.

Animals↗

PubMed2002

Evaluation of the clinical course of acute attacks in patients with ulcerative colitis through the use of an activity index.

BACKGROUND: Because it is not easy to make a clinical decision regarding surgical treatment in patients with acute attacks of ulcerative colitis, an objective, simple, criterion is needed to determine the optimum timing for colectomy. The aim of this study was to retrospectively examine to what extent an activity index (AI) can evaluate the clinical course in such acute attacks. METHODS: One hundred and twenty-seven patients with moderate or severe attacks of ulcerative colitis were examined. AI values and the decline in AI values were compared between surgical and nonsurgical groups after 1 week and 2 weeks of medical therapy. To evaluate the clinical course of acute attacks, cutoff AI values were set at every 10 points between values of 180 and 210. The positive predictive value for surgery was examined. RESULTS: AI values in the surgical group were significantly higher than those in nonsurgical group at pretreatment, and after 1 or 2 weeks of medical therapy. The decline of AI values in the nonsurgical group was significantly higher than that in the surgical group after 1 or 2 weeks of medical therapy. At pretreatment, the prediction of colectomy was less than 50% at any of the cutoff values. After 1 week of therapy, approximately 60% of patients with an AI value greater than any of the cutoff AI values required colectomy. After 2 weeks of therapy, 30 of 43 (70%), 28 of 38 (74%), 24 of 29 (83%), and 17 of 21 (81%) patients with AI values greater than 180, 190, 200, and 210, respectively, required colectomy. Overall accuracy was 86%, 87%, 88%, and 83% for cutoff AI values of 180, 190, 200, and 210, respectively. Because the overall accuracy and positive predictive value for colectomy at AI values of 200 were significantly higher than these parameters at other AI values after 2 weeks of therapy, an AI value of 200 was regarded as the cutoff value most able to predict colectomy. CONCLUSIONS: We concluded that patients with an AI value in excess of 200 after 2 weeks of medical therapy would require surgical treatment.

Acute Disease↗

PubMed1991

Effect of PG F2 alpha treatment on conception rates of dairy cows treated with a GnRH agonist 12 to 14 days after Artificial Insemination.

The effect of a GnRH agonist (10 ug Buserelin) on conception rate was determined when injected into dairy cows 12 to 14 days after Artificial Insemination (AI). The following factors were taken into account: previous treatment prior to AI with Prostaglandin F2 alpha, clinical history recorded prior to AI since last calving, parity and milk yield. A number of 118 cows, from one large dairy herd, were involved in this study. A total of 210 AI's were performed, followed by 140 GnRH treatments and 70 saline injections. Reproductive events were then recorded. The rank of AI was equally distributed among the two groups. 153 AI's were preceded by a Prostaglandin F2 alpha (Dinoprost - 25 mg) treatment among which 103 were subsequently GnRH-treated and 50 were controls. Plasma progesterone concentrations were determined daily for 34 days after AI in 13 treated and 13 control cows. An Early Pregnoncy Diagnosis (EPD) from milk progesterone concentration was performed on Day 21 after AI in all cases. Post-AI GnRH agonist treatment resulted in a significant enhancement of the conception rate: 60% vs 44%; p < 0.01, respectively for treated and control animals. PG F2 alpha treatment prior to GnRH injection had a major influence on the conception rate (62% vs 40%; p < 0.01). No effect was seen (54 % vs 55 %) in non-PG F2 alpha treated females which were subsequently injected respectively with GnRH or saline after AI. Previous clinical reproductive disorders, parity and milk yield had no significant effect. In non-pregnant treated animals, GnRH agonist treatment resulted in an increased rate of heat detection on days 20 - 25 after AI (91 % vs 74 %) and a higher fertility rate on the following AI was seen (59 % vs 44 %; p < 0.05). In conclusion, GnRH agonist treatment 12 to 14 days after AI only enhanced the conception rate of females which had previously been treated with PG F2 alpha. In non-pregnant cows, this treatment had also a benficial effect on heat detection and improved the conception rate at the subsequent AI.

Journal Article↗

PubMed2004

Factors affecting conception rate after artificial insemination and pregnancy loss in lactating dairy cows.

Objectives were to determine factors associated with conception rate (CR) and pregnancy loss (PL) in high producing lactating Holstein cows. In Study 1, CR was evaluated in 7633 artificial inseminations (AI) of 3161 dairy cows in two dairy farms. Pregnancy diagnosis was performed by palpation per rectum 39+/-3 days after AI. Environmental temperature was recorded at different intervals prior to and after AI. In Study 2, 1465 pregnancies from 1393 cows diagnosed at 31+/-3 days after AI by ultrasonography on three dairy farms were re-examined 14 days later to determine PL. Temperature > or =29 degrees C was considered to be heat stress (HS). Exposure to HS was defined as following: NH, no heat stress; HS1, exposure to at least 1 day of maximum temperature > or =29 degrees C and average daily maximum temperature (ADMT) <29 degrees C; and HS2, exposure to ADMT > or =29 degrees C. In Study 1, exposure of cows to HS1 and HS2 from 50 to 20 prior to AI was associated with reduced CR compared to cows not exposed to HS (28.8, 23.0, and 31.3%, respectively). Post-AI HS was not associated with CR. Cows inseminated following estrus detection or timed AI had similar CR. As the number of AI increased, CR decreased. Multiparous cows had lower CR than primiparous cows, and occurrence of milk fever and retained placenta was associated with decreased CR. In Study 2, PL was not associated with exposure to HS either prior to or after AI. Cows diagnosed with clinical mastitis experienced increased PL, but parity, number of AI, AI protocol, milk production, and days postpartum at AI were not associated with PL. In conclusion, CR was affected by HS prior to AI, parity, number of AI, and postparturient diseases, whereas PL was affected by clinical mastitis.

Abortion, Veterinary↗

PubMed2006

Prospective endometrial assessment of breast cancer patients treated with third generation aromatase inhibitors.

OBJECTIVE: A prospective evaluation of the effects on endometrium of third generation aromatase inhibitors (AIs), administered as adjuvant up-front therapy or switched therapy in menopausal patients suffering from breast cancer. METHODS: Forty-five patients suffering from estrogen-receptor positive breast cancer were treated with AIs as adjuvant endocrine therapy; 27 patients switched from tamoxifen to AIs (group 1) due to adverse medical events related to tamoxifen intake (22 patients) or to an extended endocrine treatment after 60 months of tamoxifen therapy (5 patients); whereas 18 patients received AIs as up-front adjuvant therapy (group 2). All patients underwent endometrial investigation before the start of AIs therapy and, thereafter, at 12 month intervals. Endometrial assessment was based on Transvaginal Ultrasonography (TU), followed by hysteroscopy and endometrial biopsy when a double layered endometrial stripe above 4 mm was measured on the longitudinal plane of uterine scanning. Six patients, showing endometrial hyperplasia before the start of AIs therapy, underwent hysteroscopy on a yearly basis, disregarding the endometrial thickness measured by TU. Histopathologic results on endometrial biopsies represented the reference test in order to estimate the prevalence of endometrial morbidity. RESULTS: Demographic and clinical variables evaluated (age, parity, age at menarche and menopause, Body Mass Index, previous chemotherapy and radiotherapy) did not differ in groups 1 and 2. The average period of endometrial surveillance after the start of AIs therapy was 24.8 +/-10.8 months for group 1 and 21.4 +/- 11.5 months for group 2. A progressive decrease of endometrial thickness, from 8.2 +/- 5.0 to 3.0 +/- 1.2 in group 1 and from 4.7 +/- 4.3 to 1.9 +/- 0.3 in group 2, was found before the start and after 36-48 months of AIs therapy. The second line endometrial investigations' rate dropped from 70.3% to 12.5% in group 1 and from 27.7% to 0.0% in group 2, at baseline and after 36-48 months of AIs therapy, respectively. We found baseline endometrial abnormalities in 25.9% and in 22.2% of patients in groups 1 and 2 (P = 0.4), respectively. During AIs administration, an endometrial pathology was found in 1 patient of group 1 and in 3 patients of group 2. In 3 patients, the abnormality consisted of simple hyperplasias and in all these patients an abnormal endometrium (1 complex atypical hyperplasia and 2 simple hyperplasias) was already detected at baseline assessment. Only in 1 patient (2.2%) of group 2 did we find an emerging pathology, consisting of adenosarcoma harbored within an endometrial polyp, detected after 12 months of therapy with letrozole. In 3 out of 5 patients showing simple hyperplasia and in 1 patient showing atypical hyperplasia before the start of AIs therapy, we observed a reversal to normal endometrium and to simple hyperplasia, respectively, after 12 months of therapy with anastrozole. CONCLUSIONS: AIs delivered as up-front therapy for breast cancer have no effects on unspecific endometrial thickening. When administered as switched therapy after tamoxifen withdrawal, AIs may reverse tamoxifen-associated endometrial thickening. As a consequence, we reduced unnecessary second-line endometrial investigations. A low rate of emerging endometrial pathology was found during AIs therapy.

Aged↗

PubMed1996

Artificial insemination, hybridization and pregnancy detection in sika deer (Cervus nippon ).

Artificial insemination (AI) was performed on sika hinds (Cervus nippon ) receiving various dosages of pregnant mare serum gonadotropin (PMSG; Year 1: 0, 50 and 100 IU; Year 2: 100 and 150 IU) and using semen collected from elk and 1 2 elk x 1 2 sika stags. The time from synchronization device removal (CIDR vs norgestomet) to estrus was determined through observations of mounting activity. Methods for pregnancy detection, serum progesterone (P4), estrone sulfate (E1S), pregnancy-specific protein B (PSPB) and ultrasonography, following AI (Year 1: AI, Days 28 and 48 after AI; Year 2: AI, Days 42, 53 and 100 after AI) and a 90-d natural breeding season were investigated. From available production data, body weights were compared among sika and 1 4 elk x 3 4 sika hybrids relative to age. Pregnancy rates tended (P < 0.10) to differ relative to PMSG treatment and sire; administration of 0 IU PMSG resulted in fewer hinds becoming pregnant to AI than 50 or 100 IU of PMSG. Hinds receiving 100 IU of PMSG had higher (P < 0.05) pregnancy rates than hinds receiving 150 IU PMSG. Time to standing estrus did not differ (P > 0.10) between the CIDR and norgestomet groups. Pregnancy rates 50 d after a 90-d breeding season were similar (P > 0.10) between ultrasound (70.9%) and PSPB (61.6%). Serum P4 after 90 d in breeding groups and 50 d after stag removal were higher (P < 0.05) for pregnant than open hinds. Pregnancy rates (Year 1) 48 d after AI were similar (P > 0.10) between ultrasound (49.0%) and PSPB (37.3%). Serum P4 28 and 48 d after AI were higher (P < 0.05) for pregnant than open hinds. Serum E1S was higher (P < 0.01) for pregnant than open hinds 48 d after AI. Pregnancy rates (Year 2) 100 d after AI did not differ (P > 0.10) between ultrasound and PSPB (66.7%). Serum P4 was higher (P < 0.03) in pregnant than open hinds at 42, 53 and 100 d after AI. At 100 d after AI, pregnant hinds had higher (P < 0.002) serum E1S than open hinds. At 6 to 8 and 11 to 13 mo of age, 1 4 elk x 3 4 sika males tended (P < 0.08) to be heavier than sika males, while 1 4 elk x 3 4 sika females were heavier (P < 0.05) than sika females at all ages. In summary, this study documents the use of AI and methods for pregnancy detection in sika hinds as well as preliminary information regarding the production of elk-x-sika hybrids.

Journal Article↗

PubMed1974

Role of extrapulmonary conversion in mediating the systemic pressor activity of angiotensin I.

The effect of antibodies against angiotensin II (AII) on systemic pressor responses to intravenously injected AII and angiotensin I (AI) was studied in a group of bioassay rats. AII antibody was only 29% as effective in neutralizing AI given intravenously as it was in neutralizing AII injected by the same route. Control plasma caused no change in the relative potencies of AI and AII. In a further series of experiments, AII antibody was significantly less effective in blocking intra-arterial AI than in blocking intravenous AI. The potency of intra-arterial AI, initially less than that of intravenous AI, became nearly twice that of intravenous AI after antibody administration, a result which could not occur if AI were inactive before lung transit. Thus, AI can elicit systemic pressor activity independently of pulmonary conversion to AII. However, since the intra-arterial AI responses were abolished by an inhibitor of angiotensin-converting enzyme, the activity would appear to be mediated by peripheral conversion to AII rather than by an intrinsic action of the decapeptide. Both series of experiments suggest that the efficacy of AII antibody in abolishing the systemic pressor activity of AI is highly dependent on the site of conversion of the AI to AII. The occurrence of localized intramural conversion of AI to AII near arteriolar receptors in vivo may so minimize exposure of the liberated AII to circulating antibody as to render AII immunization an inefficient means of blocking endogenous pressor activity of the renin-angiotensin system.

Angiotensin II↗

PubMed2006

Generalized osteopenia in adolescent idiopathic scoliosis--association with abnormal pubertal growth, bone turnover, and calcium intake?

STUDY DESIGN: A cross-sectional study in girls with adolescent idiopathic scoliosis (AIS) and healthy counterparts of similar age. OBJECTIVES: To study the association of bone mass with anthropometric parameters, bone turnover, and calcium intake in 621 girls with AIS, aged 11-6-years, and compare the results with 300 healthy girls of similar age. SUMMARY OF BACKGROUND DATA: Generalized low bone mass has been documented in AIS, yet the cause of low bone mineral density in AIS is unknown. METHODS: Corrected height and arm span, bone mineral density and bone mineral content of proximal femur, lumbar spine, and distal tibia, and bone turnover markers (bone alkaline phosphatase [bALP] and deoxypyridinoline) were evaluated. RESULTS: From age 13 years and older, the AIS group had longer anthropometric parameters (P < 0.05), generalized lower bone mass (P < 0.035), and 38.6% higher in bALP (P < 0.004) when compared with controls. A stronger inverse correlation between bALP and bone mass was noted in the AIS group. The bALP was positively correlated with bone area of tibia (P = 0.013) in the AIS group only. Deoxypyridonine of the AIS group was not different from the controls until age 15 years. The mean calcium intake of the AIS group was very low (only 361 mg/day), and calcium intake was significantly associated with bone mass in the AIS group. Low bone mass in AIS could be explained by faster anthropometric bone growth, higher bone turnover, and lower calcium intake in multiple regression analysis. CONCLUSIONS: Results from the current study showed that an abnormally faster growth rate and higher bone turnover in the patient with AIS might lead to increased bone dimensions. Calcium intake in patients with AIS was very low and likely to be insufficient for normal bone mineralization. Therefore, low bone mass in AIS may result from abnormal bone mineralization qualitatively and quantitatively and, thus, fails to catch up with increased bone growth during the peripubertal period.

Adolescent↗

PubMed1996

Protective mechanism of the Mexican bean weevil against high levels of alpha-amylase inhibitor in the common bean.

Alpha-amylase inhibitor (alpha AI) protects seeds of the common bean (Phaseolus vulgaris) against predation by certain species of bruchids such as the cowpea weevil (Callosobruchus maculatus) and the azuki bean weevil (Callosobruchus chinensis), but not against predation by the bean weevil (Acanthoscelides obtectus) or the Mexican bean weevil (Zabrotes subfasciatus), insects that are common in the Americas. We characterized the interaction of alpha AI-1 present in seeds of the common bean, of a different isoform, alpha AI-2, present in seeds of wild common bean accessions, and of two homologs, alpha AI-Pa present in seeds of the tepary bean (Phaseolus acutifolius) and alpha AI-Pc in seeds of the scarlet runner bean (Phaseolus coccineus), with the midgut extracts of several bruchids. The extract of the Z. subfasciatus larvae rapidly digests and inactivates alpha AI-1 and alpha AI-Pc, but not alpha AI-2 or alpha AI-Pa. The digestion is caused by a serine protease. A single proteolytic cleavage in the beta subunit of alpha AI-1 occurs at the active site of the protein. When degradation is prevented, alpha AI-1 and alpha AI-Pc do not inhibit the alpha-amylase of Z. subfasciatus, although they are effective against the alpha-amylase of C. chinensis. Alpha AI-2 and alpha AI-Pa, on the other hand, do inhibit the alpha-amylase of Z. subfasciatus, suggesting that they are good candidates for genetic engineering to achieve resistance to Z. subfasciatus.

Amino Acid Sequence↗

PubMed2006

Use of IgG avidity ELISA to differentiate acute from persistent infection with Salmonella Dublin in cattle.

AIMS: To investigate whether an immunoglobulin (Ig)G avidity ELISA can be used to differentiate between acute and persistent infection with Salmonella (S.) Dublin in cattle. To determine whether the IgG isotype, IgG(1) and IgG(2) responses in acute and persistent infections differ. METHODS AND RESULTS: Animals were selected from two herds with long-term infection (years) and two herds recently infected (<3 months). Forty-seven animals were categorized into groups based on the persistence of their antibody level in milk. Based on titre from two serial dilutions the avidity index (AI) was calculated for IgG (IgG-AI), IgG(1) (IgG(1)-AI) and IgG(2) (IgG(2)-AI). The mean IgG-AI for suspected carrier animals with either persistently high (group 1) or persistently high to medium high (group 2) antibody levels was significantly (P = 0.003) higher (32.1% and 38.4%) than for acutely infected animals (21.7% and 22.3%). The probability of being a suspect carrier was associated with IgG-AI, antibody level in the sample and age. However, the effect of age could be the result of a biased sample selection. Specificities and sensitivities were calculated at a range of cut-off values for IgG-AI and IgG(1)-AI. Overall, IgG(2)-AI was high compared with IgG(1)-AI, and there was no difference in IgG(2)-AI between infection groups. There was no difference in the ratio IgG(2):IgG(1) for acute and persistent infection groups. CONCLUSIONS: Assuming that a persistently high antibody response is indicative of persistent infection with S. Dublin in cattle, it can be concluded that the IgG-AI can aid in differentiating between acute and long-term infection on herd level. However, for the test to be useful as an alternative tool to repeated sampling over time for detection of persistently infected carriers during control strategies in cattle herds, the test needs to be optimized and studied further in a larger sample of well-characterized infections in cattle. The affinity of IgG(2) is higher than IgG(1) early in the S. Dublin infection. There appears to be no difference in the IgG(2)-AI between the acute and chronic infection stages. SIGNIFICANCE AND IMPACT OF THE STUDY: For decades the strategies for detection of persistently infected cattle in S. Dublin infected herds have involved repeated bacteriological culture of faecal samples or repeated antibody measurements over several months. Both methods are time consuming and costly, leaving a new method for detection of carrier animals based on a single sampling highly desirable. This study illustrates a tool, IgG-AI, which may prove useful, although more validation of the method is required before it is used in practice.

Acute Disease↗

PubMed1993

Functional organization of auditory cortex in the mongolian gerbil (Meriones unguiculatus). I. Electrophysiological mapping of frequency representation and distinction of fields.

The frequency representation within the auditory cortex of the anaesthetized Mongolian gerbil (Meriones unguiculatus) was studied using standard microelectrode (essentially multiunit) mapping techniques. A large tonotopically organized primary auditory field (AI) was identified. High best frequencies (BFs) were represented rostrally and low BFs caudally along roughly dorsoventrally oriented isofrequency contours. Additional tonotopic representations were found adjacent to AI. Rostral to AI was a smaller field with a complete tonotopic gradient reversed with respect to that in AI (mirror image representation) and was termed the anterior auditory field (AAF). BFs in the range from 0.1 to 43 kHz, apparently covering the hearing range of the Mongolian gerbil, were found in AI and AAF. Units in these two core fields responded to narrow frequency ranges with short latencies. Ventral to the common high-frequency border to AAF and AI, a rapid transition to very low BFs suggested the presence of a ventral field (V). Caudal to AI two small tonotopically organized fields were identified, a dorsoposterior field (DP) and a ventroposterior field (VP). The VP showed a tonotopic organization mirror imaged to that of AI, i.e. low frequencies were represented rostrally near the caudal border of AI, and high frequencies caudally. The DP showed a concentric frequency organization with high BFs located in the centre. Units in DP and VP fired less strongly, with considerably longer latencies, and responded to a broader range of frequencies than units in AI and AAF. Dorsocaudal to AI a dorsal field (D) was identified, harbouring units that responded to very broad ranges of frequencies. A tonotopic organization of field D could not be discerned. In the border region of AI and D, low-frequency responses were similar to those found in parts of AI and AAF, but without a clear-cut tonotopic organization. This region was termed Ald. The two core fields AI and AAF appeared to be located within the koniocortex, while the remaining fields lay outside. Our data show that the organization of the gerbil auditory cortex is highly elaborate, with parcellation into fields as complex as in cat or primates.

Acoustic Stimulation↗

PubMed2000

IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells.

The objectives of this study were to determine whether rat aortic smooth muscle cells (RASMC) express arginase and to elucidate the possible mechanisms involved in the regulation of arginase expression. The results show that RASMC contain basal arginase I (AI) activity, which is significantly enhanced by stimulating the cells with either interleukin (IL)-4 or IL-13, but arginase II (AII) expression was not detected under any condition studied here. We further investigated the signal transduction pathways responsible for AI induction. AI mRNA and protein levels were enhanced by addition of forskolin (1 microM) and inhibited by H-89 (30 microM), suggesting positive regulation of AI by a protein kinase A pathway. Genistein (10 microgramg/ml) and sodium orthovanadate (Na(3)VO(4); 10 microM) were used to investigate the role of tyrosine phosphorylation in the control of AI expression. Genistein inhibited, whereas Na(3)VO(4) enhanced the induction of AI by IL-4 or IL-13. Along with immunoprecipitation and immunoblot analyses, these data implicate the JAK/STAT6 pathway in AI regulation. Dexamethasone (Dex) and interferon (IFN)-gamma were investigated for their effects on AI induction. Dex (1 microM) and IFN-gamma (100 U/ml) alone had no effect on basal AI expression in RASMC, but both reduced AI induction by IL-4 and IL-13. In combination, Dex and IFN-gamma abolished AI induction by IL-4 and IL-13. Finally, both IL-4 and IL-13 significantly increased RASMC DNA synthesis as monitored by [(3)H]thymidine incorporation, demonstrating that upregulation of AI is correlated with an increase in cell proliferation. Blockade of AI induction by IFN-gamma, H-89, or genistein also blocked the increase in cell proliferation. These observations are consistent with the possibility that upregulation of AI might play an important role in the pathophysiology of vascular disorders characterized by excessive smooth muscle growth.

Animals↗

PubMed2001

Chickenpox and stroke in childhood: a study of frequency and causation.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether infection with varicella is causal for arterial ischemic stroke (AIS) in children. METHODS: First, a prospective cohort study was conducted in young children (aged 6 months to 10 years) with AIS at 2 institutions (cohort study). The presence of varicella infection <12 months before AIS was determined and compared with the published frequency of varicella infection in the healthy pediatric population. The clinical and radiographic features of AIS were compared between the varicella and nonvaricella study cohorts. Second, a literature search of varicella-associated AIS was conducted, and the clinical and radiographic features were compared with the study nonvaricella cohort. RESULTS: In the cohort study, 22 (31%) of 70 consecutive children with AIS had a varicella infection in the preceding year compared with 9% in the healthy population. Children in the varicella cohort were more likely to have basal ganglia infarcts (P<0.001), abnormal cerebral vascular imaging (P<0.05), and recurrent AIS or transient ischemic attacks (P<0.05) than those in the nonvaricella cohort. The pooled literature analysis of 51 cases of varicella-associated AIS showed similar findings to the varicella cohort. CONCLUSION: In young children with AIS, there is a 3-fold increase in preceding varicella infection compared with published population rates, and varicella-associated AIS accounts for nearly one third of childhood AIS. Varicella-associated AIS has characteristic features, including a 2-fold increase in recurrent AIS and transient ischemic attacks. Varicella is an important risk factor for childhood AIS.

Age Distribution↗

PubMed2024

Diverse phenotypes and fertility outcomes of patients with androgen insensitivity syndrome in a Chinese family harboring identical AR gene variant.

BACKGROUND: Androgen insensitivity syndrome (AIS) is a rare genetic disorder characterized by resistance to androgens, mainly due to mutations in the androgen receptor (AR) gene. It can manifest as complete AIS, partial AIS and mild AIS. While there have been studies linking specific AR gene mutations to AIS phenotypes, different clinical AIS phenotypes are also reported in patients with the same AR gene mutation. So far, the precise correlations between phenotypes and genotypes remain incompletely understood. METHODS: We conducted a thorough investigation involving four patients diagnosed with different types of AIS from a single Chinese family. Clinical manifestations, laboratory examinations, and fertility outcomes were well-documented. Furthermore, we performed genetic sequencing to detect possible pathogenetic variants. RESULTS: Whole exome sequencing identified a hemizygous missense variant (c.2263T > C; p.Phe755Leu) of AR gene in all four affected patients with different degrees of undermasculinisation and heterogeneous spermatogenesis. The proband, diagnosed with partial AIS, opted for treatment with donated sperm due to non-obstructive azoospermia, while their older sibling, diagnosed with complete AIS, was raised as a girl. His two maternal uncles were both diagnosed with mild AIS, the older uncle fathered two girls naturally, whereas the younger uncle utilized assisted reproductive technology to conceive a boy because of severe oligoasthenozoospermia. CONCLUSION: Our study first identified the same AR variant (c.2263T > C;p.Phe755Leu) in four affected patients displaying highly diverse phenotypes of AIS and fertility outcomes, thereby significantly expanding the phenotypic spectrum of AIS. Notably, we presented a clear insight into different fertility outcomes of AIS patients with identical AR (c.2263T > C;p.Phe755Leu) variant, which provided reliable evidence that males harboring this variant may obtain biological offspring naturally or in combination with assisted reproductive technology. Furthermore, our study underscored the potential role of androgen concentration in shaping the phenotypic diversity of AIS, warranting further investigation.

Adult↗

PubMed2005

The psychosocial impact of developmental dental defects in people with hereditary amelogenesis imperfecta.

BACKGROUND: Amelogenesis imperfecta (AI) is a hereditary dental condition with poor esthetics and dental sensitivity that frequently requires extensive dental treatment. The authors hypothesized that AI is associated with a negative psychosocial outcome. METHODS: Family members with and without AI completed a questionnaire including demographic and dental history questions, as well as a number of psychometric scales. The authors investigated the effects of AI status (with versus without), sex and age on each of the psychosocial outcomes using a generalized linear model. RESULTS: Subjects with AI (n = 30) had higher levels of social avoidance and distress, as well as higher levels of dysfunction, discomfort and disability attributable to their oral condition compared with subjects without AI (n = 29). The relationship of AI status to fear of negative evaluation, mastery and self-esteem was age-dependent. Younger subjects with AI tended to have higher fear of negative evaluation scores, while older subjects without AI tended to have higher fear of negative evaluation scores. Additionally, subjects without AI showed a definite decrease in mastery and self-esteem scores with age, while subjects with AI tended to show an increase in mastery and self-esteem scores with age. CONCLUSIONS: These results indicate that having AI has a marked impact on the psychosocial health of affected people comparable with the impact of systemic health conditions, especially at younger ages. CLINICAL IMPLICATIONS: Dental coverage for AI traditionally is excluded by third-party payers as being solely for esthetic reasons. The authors' study shows that AI has marked psychosocial effects, which suggests that dental treatment could be medically necessary and has far-reaching implications for the affected person's overall health.

Adult↗

PubMed1994

Effect of sampling status and adjustment for heterogeneous variance on bias in bull evaluations.

Holstein bulls were assigned to sampling categories (AI stud, AI nonstud, or non-AI) based on bull code, controller number, and age at semen distribution. The AI stud bulls were sampled through traditional progeny-testing programs of 13 AI organizations; AI nonstud bulls had AI semen collection reported by another organization or by multiple organizations. The non-AI bulls had no reported AI semen collection. Actual daughter yield deviations for these three groups of bulls were compared with expected performance (parent average) to provide an indication of whether evaluations were free from bias for daughter yield deviations. Mean difference of daughter yield deviation from parent average was close to 0 kg for animal model evaluations of all 22,930 bulls but was positively biased by 46 kg of milk for AI nonstud bulls. Mean PTA and reliabilities for parents were highest for AI stud bulls and lowest for non-AI bulls. The AI stud bulls varied least and were intermediate for mean management, approximated as mean daughter yield minus bull PTA. Management was highest for AI nonstud bulls, which suggested that adjustment for heterogeneous variance might reduce bias. However, the effect of this adjustment on mean difference of daughter yield deviation from parent average was small.

Animals↗

PubMedDate not supplied

Enamel protein in smooth hypoplastic amelogenesis imperfecta.

Amelogenesis imperfecta (AI) remains a poorly understood group of hereditary enamel defects characterized by a wide array of clinical presentations. Although numerous reports have described the histological features of AI, knowledge concerning the biochemical composition of the affected enamel remains minimal. The purpose of this investigation was to examine the protein of smooth hypoplastic AI enamel. Exfoliated primary teeth were obtained from an individual with smooth hypoplastic AI together with exfoliated teeth from normal healthy individuals for controls. Enamel was dissected from the AI and control teeth to determine protein content and amino acid profile. The analyses showed that the hypoplastic AI teeth contained 2% protein, compared with 0.3% in normal primary enamel. The protein content of the hypoplastic AI enamel was similar to that reported for the late maturation stage of normal primary enamel. The amino acid profiles of both normal and AI enamel were similar although there appeared to be increased amounts of glycine in the AI enamel. Hypoplastic AI enamel showed an amino acid profile similar to normal mature primary enamel in contrast to hypomaturation AI that exhibits an amelogenin-like character. The amount of retained protein also was different from that reported for hypomaturation AI enamel which contains approximately 5% protein compared with the 2% seen in hypoplastic AI enamel. This study emphasizes the potential usefulness of protein characterization in delineating different AI types and illustrates how this information may lead to an understanding of the developmental defects responsible for producing abnormal enamel.

Amelogenesis Imperfecta↗