Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 703 records · Page 39Linked to original sources

PubMed1999

Gonadotropin stimulation of pituitary adenylate cyclase-activating polypeptide (PACAP) messenger ribonucleic acid in the rat ovary and the role of PACAP as a follicle survival factor.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a novel neuropeptide with considerable homology to vasoactive intestinal peptide and GH-releasing hormone, exists in two biologically active forms, PACAP-38 and -27. The presence of PACAP in the ovary has been demonstrated, where it stimulates steroidogenesis and cAMP accumulation in cultured granulosa cells. In the present study, gonadotropin regulation of PACAP gene expression was examined in PMSG/human (h)CG-treated immature rat ovaries and cultured preovulatory follicles. Northern blot analysis of ovaries obtained from PMSG/hCG-treated immature animals revealed the transient induction of PACAP transcripts by hCG, reaching a maximum at 6 h. The major cell types expressing PACAP messenger RNA were granulosa cells of preovulatory follicles and some theca/interstitial cells. In preovulatory follicles cultured in serum-free medium, PACAP transcripts were transiently induced by LH and FSH, reaching a maximum 6-9 h after stimulation in granulosa cells but not in theca cells. Treatment with cycloheximide or alpha-amanitin abolished LH-induced PACAP transcripts, indicating that new protein synthesis and transcription are necessary. Treatment with MDL-12,330A, an inhibitor of adenylate cyclase, inhibited LH-induced PACAP messenger RNA, and forskolin mimicked the LH action, implying the role of adenylate cyclase activation. In contrast, treatment with chelerythrine, an inhibitor of protein kinase C, and 2-O-tetradecanol-phorbol-13-acetate had no effect. We further tested the role of PACAP in follicle apoptosis using apoptotic DNA fragmentation analysis. Treatment with PACAP-38 suppressed follicle apoptosis in a dose-dependent manner. Moreover, the LH suppression of follicle apoptosis was partially blocked by cotreatment with PACAP-38 antagonist, indicating mediation by endogenous PACAP-38. These results suggest that PACAP, transiently induced by the gonadotropin surge, could be a local regulator of a number of events and may act as a follicle survival factor during the periovulatory period.

Adenylyl Cyclases↗

PubMed1999

Transgenic expression of epidermal growth factor and keratinocyte growth factor in beta-cells results in substantial morphological changes.

The upregulation of a limited number of growth factors in our interferon-gamma transgenic model for regeneration within the pancreas lead us to propose that these factors are important during pancreatic regeneration. In this study, we have assessed the influence of two growth factors within the pancreas, epidermal growth factor (EGF) and keratinocyte growth factor (KGF), by ectopically expressing these proteins under the control of the human insulin promoter in transgenic mice. This beta-cell-targeted expression of either EGF or KGF resulted in significant morphological changes, including cellular proliferation and disorganized islet growth. Intercrossing the individual Ins-EGF and Ins-KGF transgenic mice resulted in more profound changes in pancreatic morphology including proliferation of pancreatic cells and extensive intra-islet fibrosis. Insulin-producing beta-cells were found in some of the ducts of older Ins-EGF and Ins-EGFxKGF transgenic mice, and amylase-producing cells were observed within the islet structures of the double transgenic mice. These data suggest that both EGF and KGF are capable of affecting pancreatic differentiation and growth, and that co-expression of these molecules in islets has a more substantial impact on the pancreas than does expression of either growth factor alone.

Animals↗

PubMed1999

Identification and functional analysis of novel human melanocortin-4 receptor variants.

Inactivation of the melanocortin-4 receptor (MC4-R) by gene-targeting results in mice that develop maturity-onset obesity, hyperinsulinemia, and hyperglycemia. These phenotypes resemble common forms of human obesity, which are late-onset and frequently accompanied by NIDDM. It is not clear whether sequence variation of the MC4-R gene contributes to obesity in humans. Therefore, we examined the human MC4-R gene polymorphism in 190 individuals ascertained on obesity status. Three allelic variants were identified, including two novel ones, Thr112Met and Ile137Thr. To analyze possible functional alterations, the variants were cloned and expressed in vitro and compared with the wild-type receptor. One of the novel variants, Ile137Thr, identified in an extremely obese proband (BMI 57), was found to be severely impaired in ligand binding and signaling, raising the possibility that it may contribute to development of obesity. Furthermore, our results also suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a common cause of obesity in the population studied, given the low frequency of functionally significant mutations.

Adolescent↗

PubMed1999

Metabolic effects of amylin in lactating goats.

The objective of this study was to investigate the role of amylin (a pancreatic hormone) in regulating metabolism in support of lactation. Rat amylin was infused (320 pmol.kg LW(-1).h(-1)) for 6 h via an external pudic (mammary) artery into six lactating goats. This dose of amylin led to a sixfold increase in plasma concentrations of amylin relative to baseline. Amylin infusion increased plasma concentrations (jugular) of glucose and NEFA up to 16 and 168%, respectively, relative to saline infusion. In contrast, plasma concentrations of Ca and PO4 during amylin infusion were reduced by 18 and 30%, respectively, relative to saline infusion. Plasma concentrations of IGF-I, insulin, and Mg were not different between the two treatments, although IGF-I concentrations in the amylin-infused group, 1 and 6 h postinfusion, were significantly higher than those in the saline-infused group. Similarly, amylin infusion failed to affect milk yield and major constituents of milk except protein; milk protein content decreased progressively until the end of amylin infusion and remained low thereafter. Amylin also had no effect on minerals in milk (Ca, PO4, Mg, Fe, Sr, S, K, or Na) except Zn, which was significantly decreased from 56.8+/-5.8 micromol/L at 0 h to 44.5+/-2.4 micromol/L at 6 h postinfusion. Mammary blood flow (measured with a transit-time blood flow probe) increased up to 26% during amylin infusion, although this effect lasted only for the first 3 h. In conclusion, amylin increased plasma concentrations of glucose and NEFA, and mammary blood flow, while decreasing plasma concentrations of Ca and PO4. Despite these metabolic changes, amylin infusion did not increase milk yield of lactating goats.

Amyloid↗

PubMed1999

Significance of amount and form of dietary selenium on blood, milk, and casein selenium concentrations in grazing cows.

Organic selenized yeast enriched with selenoamino acids or inorganic sodium selenate (Na2SeO4) was administered per os three times weekly as a drench for 133 d to previously unsupplemented cows that were grazing low Se pastures. Treatment groups received the equivalent of 2 or 4 mg of Se/d of either supplement form. Control cows did not receive a drench. Samples of blood and milk were collected regularly throughout the trial. Selenium concentrations in blood, milk, casein, and liver and glutathione peroxidase activity in blood and liver are reported as responses per milligram of Se intake. Mean blood Se concentrations in treated cows increased steadily and, by d 133, were 4.7 to 8.8 times that in controls. Selenized yeast was 2 to 3 times more effective than was Na2SeO4, and low Se intakes were 27% more efficient per milligram of Se administered than were high Se intakes at increasing milk Se concentration. Casein Se content mirrored that of milk; among all treated and control cows and throughout the trial, the molar ratio of Se in casein as a percentage of the Se in whole milk was constant at 71 +/- 1.2%. The Se concentration in liver biopsies taken on d 133 was indicative of total Se intake during the trial and ranged from 920 to 3920 nmol of Se/kg of fresh weight. These results demonstrate the differing efficacy of organic and inorganic Se dietary supplements to increase dairy cow Se status and to enhance Se content of milk and casein.

Animals↗

PubMed1999

Surgical treatment of subretinal neovascular membrane.

The visual results of laser photocoagulation for subfoveal choroidal neovascular membrane (CNVM) has not always been satisfactory. The surgical removal of the neovascular membrane may be another treatment option. To investigate the prognosis and risk factors of this surgery, we analyzed the results of surgical removal of subfoveal CNVM (23 eyes), subfoveal hemorrhage with CNVM (6 eyes), and subfoveal hemorrhage alone (6 eyes). The mean follow-up period was 17.7 months (range 2 to 47 months). The mean preoperative membrane size was 0.89 disc diameter and the mean postoperative retinal pigment epithelial (RPE) defect size was 1.33 disc diameter. Visual improvement was observed in 13 out of the 23 eyes (56.5%) with sufoveal CNVM, four out of the six eyes (66.6%) with subretinal hemorrhage and CNVM, and five out of the six eyes (83.3%) with subretinal hemorrhage only. The visual outcome of subfoveal CNVM surgery was related to the presence of a subfoveal RPE defect (p = 0.005) rather than to the size of the RPE defect. No recurrence of neovascular membrane was observed during the follow up period. In conclusion, surgical removal may be a good alternative treatment for subfoveal CNVM.

Choroidal Neovascularization↗

PubMed1999

Differentially-altered vascular guanylate cyclase isoforms in experimental hypertensive rats.

Pathophysiological implications of the vascular nitric oxide (NO)/cGMP pathway were investigated in various rat models of hypertension. The expression of brain and endothelial constitutive NO synthases (bNOS, ecNOS) was determined by Western blot analysis, and the biochemical activity of soluble and particulate guanylate cyclases (GC) was assessed by the amount of cGMP generated in the thoracic aortae of rats with deoxycorticosterone acetate (DOCA)-salt, two-kidney, one dip (2K1C), and spontaneous hypertension (SHR). Plasma nitrite/ nitrate levels were decreased in DOCA-salt and 2K1C hypertension, and increased in SHR. The vascular expression of bNOS as well as that of ecNOS was decreased along with tissue nitrite/nitrate contents in DOCA-salt and 2K1C hypertension. The expression of both bNOS and ecNOS was increased in SHR with concomitant changes of tissue nitrite/nitrate contents. The activity of soluble GC was decreased, and that of particulate GC was increased in DOCA-salt hypertension. The soluble GC activity was increased, while the particulate GC activity was not affected in 2K1C hypertension. The soluble GC activity was not significantly changed, but the particulate GC activity was decreased in SHR. These results indicate that the high blood pressure is associated with differentially-altered vascular NO/cGMP pathway in different models of hypertension.

Animals↗

PubMed1999

Augmented expression of cardiac atrial natriuretic peptide system in hypertensive rats.

The present study was aimed at investigating the regulation of atrial natriuretic peptide (ANP) system in association with either enhanced or attenuated activity of the renin-angiotensin system (RAS). The cardiac tissue mRNA and peptide levels of ANP were measured in rats with two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertension. Plasma renin concentration was increased in 2K1C hypertension along with increases of renin mRNA and protein contents in the clipped kidney. On the contrary, it was suppressed in DOCA-salt hypertension along with decreases of renin mRNA and protein contents in the remaining kidney. The plasma ANP concentration was similarly increased in both models of hypertension. The cardiac tissue ANP contents were not significantly changed, but the tissue ANP mRNA levels were upregulated in the hypertrophied heart in these two models of hypertension. It is suggested that the cardiac ANP system is transcriptionally enhanced by cardiac hypertrophy associated with hypertension, independent of the systemic RAS.

Animals↗

PubMed1999

Identification of IgE-reacting Clonorchis sinensis antigens.

Clonorchis sinensis is a liver fluke and it is the most prevalent human parasite in Korea at present. The parasite infection induces immune responses, characteristically an increased production of parasite-specific IgE in the host. Major IgE-reacting C. sinensis antigens in infected humans have been protein bands with MWs of 15, 28, 37, 45, 51, 56, 62, 66, 74, 97 and 160 KD identified by immunoblot analysis. Individual variations of the IgE binding pattern to C. sinensis antigens have also been documented. Using immune BALB/c mouse sera, IgE-reacting protein bands have been visualized with MWs of 28, 74, 86, 160 and several > 200 KD. One of the most strongly reacted C. sinensis antigenic proteins with a molecular weight of 28 KD was purified by gel filtration and preparative electrophoresis. Using a monoclonal antibody produced against the antigenic protein, the protein was localized in the parasite's intestine, and also found to be contained in excretory-secretory antigens.

Animals↗

PubMed1999

Identification and purification of IgE-reactive proteins in German cockroach extract.

Cockroaches have been implicated as a cause of respiratory allergy in urban areas worldwide. IgE-reactive German cockroach proteins were identified with molecular weights (MWs) of 90, 66, 50, 43 and 36 KD by immunoblot analysis in both immune BALB/c mice and sensitized humans. Prominent IgE-reactive proteins were purified using FPLC by ion-exchange chromatography, gel filtration and hydrophobic chromatography. The N-terminal amino acid sequence of a purified protein with a MW of 66 KD on SDS-PAGE was Val-Thr-Leu-Lys-Lys(Val)-Met-Ile-Lys-Thr-Phe-Tyr. No homologous protein was found through a search of GenBank that indicated a novel IgE-reactive protein in German cockroach extract. Another purified protein with a MW of 36 KD reacted strongly with a monoclonal antibody against Bla g 2.

Amino Acid Sequence↗

PubMed1999

Adenosquamous carcinoma of the prostate.

An unusual adenosquamous carcinoma originating in the prostate of a 73-year-old man is described. The histological finding showed a well differentiated squamous cell carcinoma admixed in an adenocarcinomatous area. A transitional area of 2 carcinomatous elements was also noted. Seven months prior to the development of this lesion, a diagnosis of adenocarcinoma had been established by transurethral resection of the prostate and the patient had been treated with bilateral orchiectomy. This is the first case of adenosquamous carcinoma of the prostate reported in Korea. The pathogenesis and previous reports of this lesion will be discussed.

Aged↗

PubMed1999

A case with intrahepatic double cancer: hepatocellular carcinoma and cholangiocarcinoma associated with multiple von Meyenburg complexes.

Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) is sometimes found in resected livers, however, cases with double cancer of HCC and CC are very rare. As well, the rarity of CC arising in von Meyenburg complexes (VMCs) is appreciated. We report the case of a 74-year-old man found to have intrahepatic double cancer composed of well-differentiated HCC and CC which exhibited a histologic progression from VMCs to adenomatous lesions and CC. To our knowledge, this is the first case report published in the literature of a double HCC and CC associated with multiple VMCs. The pathogenesis and previous associated reports of these lesions are discussed.

Aged↗

PubMed1999

Immune dysfunction during alcohol consumption and murine AIDS: the protective role of dehydroepiandrosterone sulfate.

Acquired immune deficiency syndrome (AIDS) is a clinical disorder caused by the human immunodeficiency virus (HIV) after development of severe immunosuppressive changes. Chronic ethanol (EtOH) consumption accentuates the severity of murine AIDS (MAIDS). Because hormone production is often suppressed by chronic EtOH intake, as well as retrovirus infection, we investigated whether hormone supplementation during chronic EtOH consumption contributes to slowing immune dysfunction caused by LP-BM5 infection and/or EtOH use. Because dehydroepiandrosterone sulfate (DHEAS) was previously shown to have immune-enhancing properties during MAIDS, we determined whether DHEAS reduced cytokine dysregulation otherwise exacerbated by chronic EtOH intake during MAIDS. Adult female C57BL/6 mice were infected with LP-BM5 murine retrovirus. Some were fed 40% EtOH in drinking water and agar gel for 16 weeks postinfection. EtOH consumption further inhibited T- and B-cell proliferation beyond suppression due to retrovirus infection. Interleukin (IL)-2 release produced by concanavalin A-stimulated splenocytes was reduced by EtOH use by infected and uninfected mice. DHEAS overcame much of the effects induced by retrovirus infection and/or EtOH use. IL-4 secretion and IL-6 secretion were enhanced. Hepatic vitamin E levels were decreased by murine retrovirus infection, as well as by EtOH use in both uninfected and infected mice. In addition, DHEAS (0.01%) supplementation during MAIDS prevented the further dysregulation of cytokines and hepatic lipid peroxidation due to EtOH intake, partially restored T- and B-cell proliferation, and maintained hepatic vitamin E levels to near normal levels.

Adult↗

PubMed1999

Four amino acid changes are associated with the Aldh3a1 locus polymorphism in mice which may be responsible for corneal sensitivity to ultraviolet light.

We studied the phenotype and the nucleotide sequence for the cDNAs of the Aldh3a1a and Aldh3a1c allelic forms of the dioxin-inducible cytosolic aldehyde dehydrogenase (ALDH3A1) present in inbred mouse strains. This gene is constitutively expressed in cornea, stomach, skin, urinary bladder and lungs. The Aldh3a1a allele is found in most inbred mouse strains and codes for a 'high-activity' corneal enzyme compared to the 'low-activity' encoded by the Aldh3a1c allele in SWR/J strain. The 'low-activity' variant is associated with extensive corneal clouding after a single exposure to ultraviolet light. The ALDH3A1 phenotype was examined in tissues from inbred mouse strains carrying the Aldh3a1a allele including, SJL/J, C57BL/6 J/Ibg, DBA/2 J/Ibg, C3H/Ibg and the Aldh3a1c allele (SWR/J). Only trace levels of ALDH3A1 activity were found in all SWR/J tissues. All other strains had significant levels of ALDH3A1 activity in eye, stomach, skin, less in urinary bladder and lungs and only trace amounts in liver. However, no differences were found in corneal and stomach ALDH3A1 mRNA levels between the 'low-' and 'high-activity' variants. A 1556-bp ALDH3A1 cDNA fragment, containing the entire coding region plus 5' and 3' untranslated regions, was amplified by reverse transcriptase-polymerase chain reaction from SWR/J and DBA/2 J/Ibg mouse strains. Sequence analysis revealed 13 nucleotide changes in the Aldh3a1c allele. Four of these changes result in G88R, I154N, H305R and I352V substitutions, whereas nine changes are silent. The I154N disrupts a potential alpha helix, which belongs to the Rossmann fold. Replacement of Arg with the more ionizable His at position 305 of a beta strand might directly affect catalytic activity of the enzyme. It is likely that structural changes associated with these amino acid changes are responsible for the loss of ALDH3A1 enzymatic activity in SWR/J mice.

Aldehyde Dehydrogenase↗

PubMed1999

Report of eight cases of pulmonary actinomycosis and their treatment with imipenem-cilastatin.

Studies on the efficacy of antimicrobial agents against actinomycosis in vivo have been limited apart from those involving penicillin. A prospective ministudy on the efficacy of imipenem-cilastatin in the treatment of pulmonary actinomycosis was performed based on preliminary encouraging in vitro and in vivo data. Eight patients were diagnosed as having pulmonary actinomycosis using fibreoptic bronchoscopy (7) and percutaneous transthoracic needle biopsy (1) in the authors' unit between 1994 and 1996. Each patient received a 4-week course of imipenem-cilastatin that comprised 2 weeks of intravenously administered drug (500 mg at 8-hourly intervals) and 2 weeks of intramuscularly administered drug (500 mg at 12-hourly intervals). Seven patients showed a very good clinical and radiographic response as well as bronchoscopically-documented treatment success. Treatment failed in one patient. Amongst the former group, one patient was lost to follow-up, another relapsed 3 months after treatment cessation and the rest remained relapse-free when followed-up for 18-44 months (mean 30.2 months). Furthermore, all patients showed good clinical tolerance and no abnormal treatment-related laboratory findings. The favourable outcome for most patients in this mini-study suggest that a 4-week parenteral course of imipenem-cilastatin is an efficacious treatment for pulmonary actinomycosis. This antimicrobial regimen might be a promising alternative to the time-honoured long-course treatment with intravenous and oral penicillin.

Actinomycosis↗

PubMed1999

Is inhaled corticosteroid useful as adjunctive management in tuberculous pyrexia?

Systemic corticosteroid is currently the standard adjunctive therapy for tuberculous pyrexia. A preliminary prospective open study to examine the efficacy of inhaled budesonide at a dose of 2,400 micrograms daily in the management of this condition was performed. Out of nine non-HIV infected patients with tuberculous pyrexia studied, four patients succeeded to achieve defervescence at a mean of 3.25 days (range = 2 to 5 days), while the rest of the patients failed to do so within 7 days. None of the patients had unwanted side effects of systemic corticosteroid and patients' acceptance of such therapy was high. The potential usefulness of inhaled corticosteroid in some patients with tuberculous pyrexia might warrant further evaluation.

Administration, Inhalation↗

PubMed1999

A 12-Mb complete coverage BAC contig map in human chromosome 16p13.1-p11.2.

We have constructed a complete coverage BAC contig map that spans a 12-Mb genomic segment in the human chromosome 16p13.1-p11.2 region. The map consists of 68 previously mapped STSs and 289 BAC clones, 51 of which-corresponding to a total of 7.721 Mb of genomic DNA-have been sequenced, and provides a high resolution physical map of the region. Contigs were initially built based mainly on the analysis of STS contents and restriction fingerprint patterns of the clones. To close the gaps, probes derived from BAC clone ends were used to screen deeper BAC libraries. Clone end sequence data obtained from chromosome 16-specific BACs, as well as from public databases, were used for the identification of BACs that overlap with fully sequenced BACs by means of sequence match. This approach allowed precise alignment of clone overlaps in addition to restriction fingerprint comparison. A freehand contig drawing software tool was developed and used to manage the map data graphically and generate a real scale physical map. The map we present here is approximately 3.5 x deep and provides a minimal tiling path that covers the region in an array of contigous, overlapping BACs.

Base Sequence↗

PubMed1999

Lipid profiles in untreated patients with rheumatoid arthritis.

OBJECTIVE: To investigate lipid profiles in patients with untreated active rheumatoid arthritis (RA) and to assess the relationship of the inflammatory condition of RA with lipid profiles. METHODS: Forty-two patients with RA and 42 age and sex matched healthy controls were studied. Patients with RA had not been treated with corticosteroid or disease modifying antirheumatic drugs prior to the study. Total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apolipoprotein A1 (apo A1), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and C-reactive protein (CRP) were measured in both groups. RESULTS: The levels of apo A1 and HDL-cholesterol were significantly lower in patients than in controls (128.5 vs. 151.8 mg/dl, 41.2 vs. 54.9 mg/dl, respectively). The level of Lp(a) was significantly higher in patients than in controls (27.1 vs. 18.0 mg/dl). The ratios of apo B/apo A1, total cholesterol/HDL-cholesterol, and LDL-cholesterol/HDL-cholesterol were significantly higher in patients than in controls (0.82 vs. 0.67, 4.4 vs. 3.4, 2.8 vs. 1.9, respectively). CRP showed a significant correlation with apo A1 (r = -0.44, p<0.01) and HDL-cholesterol (r = -0.35, p<0.05). CONCLUSION: Our study suggests that patients with untreated active RA have altered lipoprotein and apolipoprotein patterns that may possibly expose them to higher risk of atherosclerosis. The inflammatory condition of RA may affect the metabolism of HDL-cholesterol and apo A1.

Adult↗