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PubMed1999

Congenitally bicuspid aortic valves: a surgical pathology study of 542 cases (1991 through 1996) and a literature review of 2,715 additional cases.

OBJECTIVE: To describe a clinicopathologic study of a large group of congenitally bicuspid aortic valves surgically excised at a single institution. MATERIAL AND METHODS: The medical charts and bicuspid valves from patients undergoing aortic valve replacement at Mayo Clinic Rochester between 1991 and 1996 were retrospectively reviewed. RESULTS: The age of the 542 patients ranged from 1 to 86 years (mean, 61), and 372 (69%) were men. Among these, 409 (75%) had pure aortic stenosis (AS), 73 (13%) had pure aortic insufficiency (regurgitation) (AI), 53 (10%) had combined AS and AI, and 7 (1%) had normal function. The mean age was higher for those with AS than AI (65 versus 46 years; P < 0.001), whereas the male-to-female ratio was higher for AI than AS (17.3:1 versus 1.7:1; P < 0.001). The two cusps were not equal in size in 95%, and a raphe was present in 76% (67% typical, 9% atypical). Raphal position was described in 315 and was between the right and left cusps in 270 (86%). Raphal absence occurred more often in valves with equal-sized cusps than unequal (33% versus 14%; P = 0.005). Moderate to severe calcification affected valves with AS more frequently than AI (99% versus 41%; P < 0.001). In contrast, annular dilatation was associated with AI more than AS (48% versus 11%; P < 0.001). Acquired commissural fusion involved valves with combined AS and AI more often than the other functional states (31% versus 14%; P = 0.002). Sixteen patients (age range, 18 to 78 years; 13 men) had infective endocarditis (6 active, 10 healed), including 10 with AI (9 men), 3 with AS plus AI, 2 with AS, and 1 with normal function but embolization. CONCLUSION: Functionally, the most common fate of congenitally bicuspid aortic valves was calcific stenosis with or without regurgitation (85%). Because approximately 4 million US citizens have bicuspid valves and because valve replacement is currently the only treatment of symptomatic AS, this disorder will continue to affect health-care costs.

Adolescent↗

PubMed2004

Autoinducer-2-like activity associated with foods and its interaction with food additives.

The autoinducer-2 (AI-2) molecule produced by bacteria as part of quorum sensing is considered to be a universal inducer signal in bacteria because it reportedly influences gene expression in a variety of both gram-negative and gram-positive bacteria. The objective of this study was to determine whether selected fresh produce and processed foods have AI-2-like activity and whether specific food additives can act as AI-2 mimics and result in AI-2-like activity. The luminescence-based response of the reporter strain Vibrio harveyi BB170 was used as the basis for determining AI-2 activity in the selected foods and food ingredients. Maximum AI-2 activity was seen on the frozen fish sample (203-fold, compared with the negative control) followed by tomato, cantaloupe, carrots, tofu, and milk samples. Interestingly, some samples were capable of inhibiting AI-2 activity. Turkey patties showed the highest inhibition (99.8% compared with the positive control) followed by chicken breast (97.5%), homemade cheeses (93.7%), beef steak (90.6%), and beef patties (84.4%). AI-2 activity was almost totally inhibited by sodium propionate, whereas sodium benzoate caused 93.3% inhibition, compared with 75% inhibition by sodium acetate. Sodium nitrate did not have any appreciable effect, even at 200 ppm. Understanding the relationships that exist between AI-2 activity on foods and the ecology of pathogens and food spoilage bacteria on foods could yield clues about factors controlling food spoilage and pathogen virulence.

Food Additives↗

PubMed2000

Intramedullary apoptosis of hematopoietic cells in myelodysplastic syndrome patients can be massive: apoptotic cells recovered from high-density fraction of bone marrow aspirates.

A higher percentage of apoptotic cells (apoptotic index or AI) is consistently found in bone marrow (BM) biopsies compared to BM aspirates of patients with myelodysplastic syndrome (MDS). Most studies have only investigated the low-density fraction (LDF) mononuclear cells from BM aspirates following density separation for AI determination. In the present study, both LDF and high-density fraction (HDF) cells for AI were examined by electron microscopy (EM) in 10 MDS patients and 4 healthy donors. Matched BM biopsies were subjected to AI detection by in situ end labeling (ISEL) of fragmented DNA. The results indicate that in LDF and HDF cells, AI is consistently higher in MDS patients (8.5% vs 1.5%, respectively; P =.039) compared to healthy donors (27% vs 4%, respectively; P =. 004). The BM biopsy AI was also higher in MDS patients than in healthy donors (3+ vs 0+, respectively; P =.036). In addition, in MDS patients, more apoptotic cells were found in HDF cells than in LDF cells (27% vs 8.5%, respectively;P =.0001). All stages of maturation, ranging from blasts to terminally mature cells belonging to all 3 lineages, were represented in the dying cells in both compartments. Using EM, typical Pelger-Huett-type cells appeared to be apoptotic granulocytes. Both LDF and HDF cells should be examined for an accurate estimation of apoptotic cells because AI would be underestimated if only the LDF cells were studied. Ultrastructural studies consistently show a higher AI in BM biopsies compared to BM aspirates despite the correction factor of HDF cells provided by AI. This may represent the actual extant state, which could conceivably be due to a higher concentration of proapoptotic signals in the biopsies. (Blood. 2000;96:1388-1392)

Apoptosis↗

PubMed2000

Evidence for neuronal dysfunction in migraine: concurrence between specific qEEG findings and clinical drug response--a retrospective analysis-.

OBJECTIVE: The aim of this analysis was to verify objective correlates of the clinical improvement of migraine in patients by means of quantitative topographical EEG (qEEG). METHODS: Overall 40 migraine-outpatients participated in this retrospective analysis of prophylactic migraine treatment over 3-8 months with 1600 to 2000 mg cyclandelate daily. In all patients qEEG was recorded and analysed using the Fast Fourier Transformation and the determination of the Abberation Index (AI = the statistical probability of belonging to a qEEG reference group of healthy people, n = 500). RESULTS: A clinical response (> 50% reduction of migraine attack frequency and duration) was observed in 77.5% (n = 31). The number and duration of migraine attacks per month (median values) were reduced in a highly significant manner. In this observation 75% of all patients investigated showed a pathological positive Aberration Index at a single electrode or a cluster of neighbouring brain sites. This consisted in a power increase in theta, alpha and/or beta1 activity, and 73.3% of them had also a corresponding negative AI-focus (power decrease). In 15 patients EEG aberrations (positive AI clusters) within one frequency band were found, whereas 15 patients showed aberrations in more than one frequency. Positive AI s were mainly found in fronto-temporal and occipital brain areas with one single topographical difference between the patients with and without aura. CONCLUSIONS: Positive AI values were the main electrophysiological findings in these migraine patients. This was supported by the highly significant decrease of the median amount of the positive AI after clinically successful treatment with cyclandelate. Twenty four out of thirty patients with positive AI foci showed concurrence between qEEG-changes and clinical response. Patients with positive AI foci involving the lower or middle frequencies (theta and/or alpha 1) seemed to show a better clinical response (84.6%) than those with AI foci with participation of only faster frequencies (alpha 2 and/or beta 1; 54.5%). A controlled study is needed to confirm these observations.

Adolescent↗

PubMed2001

Terminal uridine nick end labelling and mitosis in breast carcinoma. Correlation with tumor grade and p53 overexpression.

OBJECTIVE: To study the relationship of cell death and proliferation to histologic grade and p53 expression in invasive carcinoma of the breast. STUDY DESIGN: A total of 31 cases of infiltrating duct carcinoma of the breast were randomly selected. The terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) reaction and p53 immunostaining were performed on representative paraffin-embedded tissue sections. Mitotic and apoptotic indices (MI and AI) were also measured on hematoxylin-eosin-stained sections. Histologic grade of infiltrating duct carcinoma was performed with the help of the Nottingham modification of the Bloom-Richardson system. Tumor grade and p53 overexpression were correlated with MI, AI and AI detected by TUNEL. RESULTS: There were a total of 31 infiltrating duct carcinomas of the breast, of which 13 cases were grade 1 and nine cases each were grade 2 and 3. Cells with positive TUNEL showed a strong brown nuclear positivity. TUNEL showed positivity from the periphery of the nuclear margin to the central portion. AI detected by TUNEL did not correlate with tumor grade (ANOVA, P > .05). MI was significant only in grade 1 versus grade 3 and 2 versus grade 3 carcinomas (ANOVA, P < .01). The morphologic apoptotic index was significant only in grade 1 versus grade 3 carcinomas. Nine cases showed p53 overexpression, and the rest of the cases were negative for p53 immunostaining. MI, AI and TUNEL were not significantly different in p53-negative and -positive groups. Pearson's correlation coefficient showed that AI and MI were significantly related, but there was no significant relation between AI detected by TUNEL and MI. CONCLUSION: MI is still more useful than AI or AI detected by TUNEL in differentiating various grades of carcinoma of the breast.

Analysis of Variance↗

PubMed1998

[Clinical and experimental study on treatment of acute cerebral infarction with Acanthopanax Injection].

OBJECTIVE: To evaluate the effect of Radix Acanthopanacis Senticosi in treating acute cerebral infarction and its mechanism. METHODS: Clinical study using single-blind, control trial, in which 60-80 ml of Acanthopanax Injection (AI) added to 500 ml of 0.9% normal saline was given by intravenous drip once a day for 14 days in the AI group(34 patients), while 500 ml of dextra-40 was given by the same way in the control group(26 patients). In experimental study, rabbit model of acute incomplete cerebral ischemia was made by ligation of bilateral common carotid artery. 10 ml of AI were given once daily intravenously for 7 days to the AI group and 10 ml of normal saline was given to the control group in the same way. Clinical effects (in clinical study) and effect of AI on cerebral oxygen free radicals (OFR), superoxide dismutase (SOD), and serum concentration of ACTH and cortisone were observed (in experimental study). RESULTS: Clinical study showed that the total effective rate of AI group (86%) was higher than that of the control group (50%) while nervous functional deficit score was lower in AI group (9.96 +/- 4.66) than that in the control group (13.56 +/- 1.84) significantly. Experimental study showed that the cerebral level of OFR decreased while SOD increased and serum concentration of ACTH and cortisone decreased after treatment in AI group. CONCLUSIONS: AI was effective in treating acute cerebral infarction, the mechanism is probably by ameliorating peroxidation in brain and improving hypothalamic-pituitary-adrenocortical axis function.

Adrenocorticotropic Hormone↗

PubMed2002

Apoptosis in breast cancer: Nigerian vs. Finnish material.

OBJECTIVE: To evaluate apoptotic activity in breast cancer from Nigerian (n = 300) and Finnish (n=285) women. STUDY DESIGN: Apoptotic bodies were expressed as square millimeters of neoplastic tissue (apoptotic index [AI]). The standardized mitotic index (SMI) and mitotic activity index (MAI) estimated proliferation. RESULTS: The mean (+/- SD) AI was higher in Nigeria (9.6+/-14.8/mm2) than in Finland (5.2+/-6.1/ mm2). In both populations, AI values were higher in premenopausal than postmenopausal women, in lymph node positive than lymph node negative tumors and in larger than smaller tumors. However, the differences were not statistically significant. Increasing histologic grade was associated with increasing AI values (Nigeria, P =.012; Finland, P= .0001). AI in infiltrating ductal carcinomas were higher than in special types of breast cancer (Nigeria, P = .0700; Finland, P = .0168). As a continuous variable, AI was a significant prognosticator (Nigeria, P = .0125, Finland, P = .0466). Increasing AI appeared to be associated with tumor progression and dedifferentiation. The higher SMI/AI in Nigeria (9.2) than in Finland (4.5) reflects higher proliferative activity in the Nigerian material. In multivariate analysis of AI, SMI, MAI and tumor size, the proliferative indices (SMI and MAI) and tumor size only were significant independent prognosticators. CONCLUSION: In Nigerian and Finnish material, AI has limited prognostic value as a tool in grading breast cancer. The higher mean SMI/AI in Nigerian cancer suggests a shift in the proliferation/cell death balance, which may be associated with a later phase of the cancer progression cascade.

Adult↗

PubMed2003

Distinct amplification of an untranslated regulatory sequence in the egfr gene contributes to early steps in breast cancer development.

Overexpression of the epidermal growth factor receptor (egfr) gene is a common feature in breast cancer. We demonstrated recently that the expression of EGFR in breast cancer strongly correlates with the length of a CA simple sequence repeat within the first 2000 bases in intron 1 of the egfr gene [CA simple sequence repeat (CA-SSR) I; H. Buerger et al., Cancer Res., 60: 854-857, 2000]. Using a standardized semiautomated method of microsatellite analysis for loss of heterozygosity detection, we identified an allelic imbalance (AI) at the egfr locus in 55 of 163 primary breast cancer cases. Fine mapping of the chromosomal region at 7p12-15 around the egfr gene using 10 CA-SSR markers showed that mutations of egfr in breast cancer are frequently restricted to the first intron of egfr. Thereby, the simple sequence repeat CA-SSR I in intron 1 was affected in 84% of the patients with AI. Reverse transcription-PCR analysis of 23 breast cancer tissues with AI excluded the presence of in-frame deletions between exon 2 and exon 7. For additional characterization of the underlying phenomenon leading to the detection of an AI in microsatellite analysis, a quantitative 5'-nuclease assay for the first CA-SSR I in intron 1 was established. In breast cancer cases with AI the presence of amplifications of this sequence was shown. Kaplan-Meier analysis revealed a statistically significant worse prognosis for patients with AI in the cancer tissue at the egfr locus compared with patients without AI. Interestingly, 75% of the patients bearing AI of CA-SSR I in the tumor also showed AI at normal, nontumorous breast tissue. Our data strongly support the assumption that distinct amplifications in intronic sequences of the egfr gene, which enhance the basic transcription activity of the gene, represent one of the first steps in breast carcinogenesis. Furthermore, they point to the presence of prognosis-associated markers for breast cancer already in morphological normal breast tissue.

Adult↗

PubMed2003

A contribution to examination of propidium iodide and annexin V plasma cells indices in multiple myeloma.

The aim of this study was a contemporaneous measurement and a mutual comparison of plasma cells proliferative activity and grade of apoptosis in patients with monoclonal gammopathy of undetermined significance (MGUS) and various phases of MM i.e. smoldering (SMM), stable/plateau and active (progression/relapse) forms of this disease. The analyzed group of 197 patients consisted of 30 MGUS, 21 SMM, 82 patients examined at the time of MM diagnosis and 64 patients analyzed during various phases of the disease after previous chemotherapy. Plasma cell proliferative activity was measured by means of a propidium iodide index (PC-PI) examined by flow cytometry using a DNA/CD138 double staining technique. For detection of plasma cells entering apoptosis (PC-AI) flow cytometry method with annexin V FITC and MoAb CD138 was used. The individuals with MGUS, SMM and stable/plateau form of MM had overall low levels of PC-PI (M-1.8, 1.7% and 2.1%) and relatively high levels of PC-AI (M-9.1, 10.8 and 9.0%). The correlation between PC-PI and PC-AI was in all the groups mutually highly statistically significant (p=0.000). Analysis of plasma cells proliferative activity (PC-PI) was statistically significant in comparison of MGUS or SMM and versus: patients examined at the time of MM diagnosis (p=0.018 or 0.016); patients evaluated during various phases of MM after previous chemotherapy (p=0.021 or 0.019); stable/plateau MM phase in the cohort of all patients (p=0.017 or 0.040); in the plateau phase after chemotherapy (p=0.008 or 0.024) but insignificant in comparison of MGUS and SMM and with the stable group examined at the time of MM diagnosis. Analysis of the apoptotic process revealed significant differences when comparing PC-AI of SMM but not MGUS group versus all cohort of stable/plateau MM patients (p=0.045); there were also insignificant differences in comparison of MGUS and SMM groupsand versus the stable form of MM measured at the time of MM diagnosis or plateau phase after chemotherapy. There was observed a statistically significant difference in the PC-AI in comparison of SMM group versus group of all patients examined at the time of MM diagnosis (p=0.001) or in various phases of this disease (p=0.015) and the group of MGUS patients compared with patients evaluated at the time of MM diagnosis (p=0.03). Very significant statistical differences of plasma cell proliferative (PC-PI) and apoptotic (PC-AI) activity were found when comparing the levels of both the indices of MGUS, SMM and stable/plateau MM group versus the active (progression/relapse) form of MM marked by a higher level of PC-PI (3.2%, p=0.000) and PC-AI (4.8%, p=0.000) in the whole cohort of MM patients, but also in comparison with both the active forms at the time of MM diagnosis or active forms evaluated during various phases of the disease after chemotherapy. Highly significant inverse relationship between PC-PI versus PC-AI was also revealed in the group of patients in the active (progression/relapse) phase of MM (p=0.000). These results revealed importance of measurement not only of proliferative but also of apoptotic plasma cells indices for a complex evaluation of the cells kinetics of plasma cells compartments in patients with MGUS or MM. This study confirmed the initial hypothesis of a common 'inverse relationship between the proliferative (PC-PI) and the apoptosis activity (PC-AI) in plasma cells compartments in patients with MGUS, smoldering, stable/plateau and active (progression/ relapse) forms of MM'.

Annexin A5↗

PubMed2003

Vaccines for List A poultry diseases: emphasis on avian influenza.

Various vaccine technologies have been shown experimentally to be effective for immunization against avian influenza (AI) virus and include conventional inactivated oil-based whole AI virus, vectored virus, subunit protein and DNA vaccines. Vaccine-induced protection is based upon antibodies produced against the surface glycoproteins, principally the haemagglutinin, but also the neuraminidase. This protection is specific only for individual subtypes of haemagglutinin (H1-15) and neuraminidase (N1-9) proteins. AI vaccines protect chickens and turkeys from clinical signs and death, and reduce respiratory and intestinal replication of a challenge virus containing homologous haemagglutinin protein. Many of the vaccines are effective if given as a single injection and provide protection for greater than 20 weeks. Protection has been demonstrated against both low and high doses of challenge virus. Furthermore, subtype H5 AI vaccine has been shown to provide protection against heterologous H5 strains with 89.4% or greater haemagglutinin deduced amino acid sequence similarity and isolated over 38 years. Currently, inactivated whole AI virus vaccines and a fowl pox-vectored vaccine with AI H5 haemagglutinin gene insert are used commercially in various countries of the world. These vaccines have some disadvantages associated with the labour requirements for parenteral administration. However, an experimental recombinant Newcastle disease virus vaccine with an AI haemagglutinin gene insert shows some promise as a low cost, mass administered aerosol vaccine. A critical issue for the use of vaccines in the field is the need to differentiate vaccinated birds from those infected with the field virus. Differentiation is necessary for outbreak surveillance and trade. The use of AI vaccines varies with individual countries and for different AI virus subtypes.

Animals↗

PubMed2003

[Application prospect of human-artificial intelligence system in future manned space flight].

OBJECTIVE: To make the manned space flight more efficient and safer, a concept of human-artificial (AI) system is proposed in the present paper. METHOD: The task of future manned space flight and the technique requirement with respect to the human-AI system development were analyzed. RESULT: The main points are as follows: 1)Astronaut and AI are complementary to each other functionally; 2) Both symbol AI and connectionist AI should be included in the human-AI system, but expert system and Soar-like system are used mainly inside the cabin, the COG-like robots are mainly assigned for EVA either in LEO flight or on the surface of Moon or Mars; 3) The human-AI system is hierarchical in nature with astronaut at the top level; 4) The complex interfaces between astronaut and AI are the key points for running the system reliably and efficiently. CONCLUSION: As the importance of human-AI system in future manned space flight and the complexity of related technology, it is suggested that the R/D should be planned as early as possible.

Artificial Intelligence↗

PubMed2004

Gestational trophoblastic neoplasia in American Indians.

OBJECTIVE: To analyze gestational trophoblastic neoplasia (GTN) trends among American Indians (AI) using population-based data. STUDY DESIGN: GTN incidence, by race and age, was calculated using data collected by the New Mexico Tumor Registry over 29 years (1973-2001). Live birth, pregnancy and women at risk were tabulated using data derived from the state's vital record annual reports and from the registry. Statistical methods included trends analysis and Poisson regression. There is no national registry in the United States for all GTN. Therefore, the Surveillance, Epidemiology and End Results (SEER) database was used to identify choriocarcinoma cases in American Indians between 1973 and 1999. RESULTS: Within New Mexico, 1,082 cases of GTN were identified among 752,374 live births and 904,831 pregnancies, with ratios of 1:695 and 1:836, respectively, affecting 234 AI, 355 non-Hispanic whites (NHW), 463 Hispanic whites (HW) and 30 other nonwhites. Ratios per live births (pregnancy), respectively, were significantly higher in AI (AI 1:439 [1:487], NHW 1:739 [1:949], HW 1:783 [1:903]), as was age-adjusted incidence per 100,000 woman-years (AI 10.62, NHW 3.53, HW 5.15; all P<.0001). Using Poisson models with live birth and woman-year denominators, AI were found to be at increased risk for all GTN histologic subsets (complete, partial and invasive hydatidiform mole and choriocarcinoma). Of 524 total gestational choriocarcinoma cases identified within SEER, 8 (1.8%) affected American Indians; of them, 7 were from New Mexico. CONCLUSION: In New Mexico, AI continue to be at higher risk of GTN than are other groups. Given the rarity of choriocarcinoma within SEER, especially among AI, the New Mexico dataset provides the best available estimate of trends in U.S. AI GTN risk.

Black or African American↗

PubMed2005

[Aromatase inhibitor letrozole induces sex inversion in the protogynous red spotted grouper (Epinephelus akaara).].

The objective of this study was to investigate the effects of the aromatase inhibitor (AI) letrozole on gonadal development, serum steroids and aromatase activities in 2-year-old female red spotted grouper (Epinephelus akaara) during reproductive season. Groupers were divided into two groups, one implanted with aromatase inhibitor (AI, 5 mg/kg body weight) and the other elastomer without AI into peritoneal cavity once every four weeks for 8 weeks. Spermiation was checked through gentle abdominal pressure every 2 weeks. Blood samples were obtained from 6 fish of each group every 4 weeks for later analysis of sex steroids. After blood samples were collected, forebrain, midbrain, hindbrain, and gonads were collected and stored at -70 degrees C for later aromatase activity measurement and gonadal histological study. Significantly lower gondadosomatic index (GSI) was observed in AI-implanted group. Fish implanted with AI once showed complete degradation of oocytes and sex inversion with developing testicular tissues in the 4th week. AI induced females to develop into functional males with authentic males testes similar in structure to those in normal males. Spermiating rate of AI-treated males were 14.3%, 35.3%, and 48.4%in the 4th, 6th, and 8th week, respectively, while all fish in the control group were still female with developing ovaries. Aromatase activities in gonads decreased significantly after implantation with aromatase inhibitor, but showed no significant difference between control and AI-implanted group. No difference in serum testosterone (T) levels was observed in control and AI-treated group, while serum levels of 17beta-estradiol (E(2)) decreased but 11-ketotestosterone (11-KT) concentration increased significantly. The present results suggest that the decrease in serum 17beta-estradiol (E(2)) and increase in 11-KT levels may be important for sex inversion induced by aromatase inhibitor in red spotted grouper.

English Abstract↗

PubMed2006

Geographic latitude and prevalence of adolescent idiopathic scoliosis.

Adolescent Idiopathic Scoliosis (AIS) prevalence has been reported to be different in various geographic latitudes and demonstrates higher values in northern countries. A study on epidemiological reports from the literature was conducted to record the prevalence of AIS among the general population of boys and girls, aged 10-16 years old, in different geographic latitudes, in order to test the hypothesis that the prevalence of AIS among boys and girls is different in various geographic latitudes and to examine if there is a possible association between them. Seventeen peer-reviewed published papers reporting AIS prevalence in the general population of boys and girls from most geographic areas of the northern hemisphere were retrieved from the literature. The geographic latitude of each centre where a particular study was originated was documented. The statistical analysis included a linear regression forward modeling procedure of the AIS prevalence by latitude, weighted by sample size. According to the modelling of the data, a significant positive association between prevalence of AIS and latitude was found for girls (p<0.001), following a rather curvilinear trend, but not a significant positive association was found for boys (p<0.111). A positive association between prevalence of AIS and geographic latitude is reported only for girls in the present study. Prevalence of AIS in boys is not associated significantly with geographic latitude. This differing significant association implicates the possible role of environmental factors in the pathogenesis of AIS that may act in a different way between boys and girls.

Adolescent↗

PubMed1989

Apolipoprotein assays: methodological considerations and studies in non-insulin-dependent diabetes treated by diet, glibenclamide and insulin.

The effect of sample pre-treatment as a source of variability of apolipoprotein (apo) AI, AII and B assays was demonstrated with lipid dissociating agents. The average mean percentage change ranged from -58 to +133% compared with untreated samples. The apolipoprotein method selected was validated by comparing their concentrations with their corresponding lipoprotein lipid or protein in normal controls and Type 2 (non-insulin-dependent) diabetic patients. The coefficient of variation was maintained below 3.5% for apo AI, AII, B and HDL2-apo AI. The apolipoprotein concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of non-obese (body-mass index less than or equal to 30) patients with Type 2 diabetes mellitus. Compared with normal subjects matched for sex, age, body-mass index, exercise, alcohol consumption and smoking. Type 2 patients at diagnosis showed reduced apo AI and HDL2-apo AI concentrations, lowered apo AI:B ratio and increased concentrations of apo B. Type 2 patients treated by diet alone (for 6-72 months) and diet plus glibenclamide (2.5-15 mg/day for 6-48 months) exhibited similar abnormalities of plasma apolipoprotein concentration to Type 2 patients at diagnosis. However, in Type 2 patients treated with insulin (25-65 U/day for 8-144 months) concentrations of apo AI and HDL2-apo AI, and the apo AI:B ratio were normal. Apo B concentrations were generally lower compared with all groups of non-insulin treated patients. These abnormalities of apolipoprotein metabolism, which are associated with premature coronary disease, are still evident in patients treated by diet and diet plus glibenclamide, but are not seen in Type 2 patients treated with insulin.

Adult↗

PubMed1983

Kallikrein potentiation of angiotensin I-induced contraction on isolated mesenteric artery.

The hypotheses that glandular kallikrein (KK) potentiate the conversion of angiotensin I (AI) to angiotensin II (AII) was tested on isolated mesenteric artery from rabbit. Cumulative additions of A1 in concentrations 10(-8), 5 X 10(-8) and 10(-7) M gave dose-related contractions of the artery. Due to tachyphylaxis second dose-response run was used for comparison. KK, 0.4 U/ml, potentiated these contractions. Addition of captopril (C, 10(-5) M) to inhibit angiotensin converting enzyme (ACE) reduced the AI responses markedly and tachyphylaxis almost completely. The responses of the KK induced potentiation of AI was the same regardless of the presence of captopril. KK, 0.01 U/ml or 0.4 U/ml, produced the same effects. Saralasin (S, 10(-5) M), an AII receptor antagonist, completely abolished the responses following C+KK+AI. Thus, these results indicate that the KK induced potentiation of the AI response is due to a conversion to AII. Bradykinin (BK, 10(-7), 10(-5) M) did not mimic the KK potentiation of AI. Three different kallikrein inhibitors, S-2441 (H-D-Pro-Phe-Arg-NH-heptyl X 2HCl), Trasylol and amiloride, reduced the KK potentiation of AI. Phentolamine, an alpha-adrenergic receptor antagonist added for inhibition of AII adrenergic facilitation, also reduced the KK induced potentiation of AI. In conclusion, these results indicate that KK potentiate the conversion of AI to AII and thereby induces vasopressor effects.

Angiotensin I↗

PubMed1983

An angiotensin I-protein complex isolated by SDS-polyacrylamide gel electrophoresis from rat serum incubated with angiotensin I.

Angiotensin I (AI) protein complex with Mr 25,000 and an angiotensin I immunoreactive protein with Mr 60,000 were isolated from rat serum. The proteins were separated from AI by sodiumdodecylsulphate polyacrylamide gel electrophoresis under denaturing and reducing conditions using SDS and 2-mercaptoethanol (SDS-PAGE). The Mr 60,000 protein was isolated from non-incubated serum. Special attention was given to the Mr 25,000 AI-protein complex, called AI-25,000, which was generated in rat serum incubated with both synthetic and native AI for 1-5 h at 24 degrees C and neutral pH. The AI-25,000 was determined in two radioimmunoassays using two anti-AI antisera and 125I-AI. The experiments showed that AI reacts with a serum protein and forms a stable complex with a high molecular mass.

Angiotensin I↗

PubMed1981

[Echocardiographic study of left ventricular motion in cases with acute left ventricular diastolic volume overload(author's transl)].

M-mode and two-dimensional echocardiography were performed to investigate the motion of the interventricular septum (IVS) and posterior wall (PW) in cases with pure mitral (MI) or aortic (AI) insufficiency. Subjects were classified into four groups; 15 cases with chorda rupture or floppy mitral valve (acute MI), four with AI of acute onset (acute AI), 17 with chronic MI including rheumatic MI, mitral valve prolapse syndrome, and 11 with chronic AI. There wee no differences of left ventricular dimension (LVDI), stroke volume (SV), ejection fraction (EF) and cardiac output (CI) between acute and chronic MI, and between acute and chronic AI, although LVDI and CI were increased in all groups. The ratio of the amplitude of IVS to PW excursion was significantly increased in cases with LV dilation due to acute MI or AI, compared with that in chronic MI or AI. This ratio had a linear relationship with LVDI in acute volume overload, but in chronic volume overload, it was constantly 1.0 or less. The mechanism of the increased septal motion in acute MI or AI is still unknown, but it appears to reflect the intact and contractile septum which adapts to volume overload more readily than the posterior wall. It is probably because the posterior wall is prevented from distension by the pericardium. On the other hand, in chronic MI or AI, vigorous septal motion would not be observed because of the occasional presence of relative tricuspid insufficiency, the effects of the long standing burden on the septal myocardium, and compensatory distension of the posterior wall and pericardium.

Adolescent↗