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Biomedical subjects

B J Collins

Publications and source records attributed to B J Collins.

At least 37 records · Page 2Linked to original sources
PubMed1996

Non-rapid eye movement sleep is suppressed in transgenic mice with a deficiency in the somatotropic system.

Sleep-wake activity was studied in a transgenic mouse model (TH-hGH) with a deficiency in the somatotropic axis (growth hormone (GH)-releasing hormone (GHRH)-GH-insulin-like growth factor-I (IGF-I)). This dwarf transgenic mouse strain expresses a human GH (hGH) reporter gene linked to 4.8 kb of the rat tyrosine hydroxylase flanking sequence, targeting the production of hGH to sites of tyrosine hydroxylase synthesis in the brain. Endogenous GH and IGF-I are suppressed in these mice, as well as GHRH. Sleep-wake activity (EEG and EMG) was recorded for 2 to 3 days in nine transgenic mice and nine wild-type littermates. Non-rapid eye movement sleep (NREMS) was significantly suppressed during both the light and the dark period in the transgenic mice; rapid eye movement sleep (REMS) was not altered. The results provide evidence that the somatotropic axis contributes to normal sleep regulation.

Animals↗
PubMed1996

Carcinogenicity of 2',3'-dideoxycytidine in mice.

2',3'-dideoxycytidine (ddC) is a synthetic pyrimidine nucleoside analogue approved for treatment of HIV-positive patients. Previous studies indicated that ddC has the potential to cause thymic lymphoma in C57BL/6 x C3H F1 (hereafter called B6C3F1) mice. In this study, we evaluated the carcinogenic potential of ddC in two different mouse models. B6C3F1 hybrid mice carry ecotropic endogenous proviral sequences that may be activated to cause lymphoma, whereas NIH Swiss mice lack proviral sequences that can be expressed. The mice were treated with ddC by gavage at 500 and 1000 mg/kg/day for up to 6 months (human dose, 2.25 mg/day) and evaluated for toxicity, plasma levels of ddC, and pathological changes. Lymphocyte cell markers from the thymic lymphomas were assessed by immunophenotyping. Expression of p53 protein was evaluated using immunohistochemical staining. Treatment-related thymic lymphomas were present in both mouse models with a higher incidence in NIH Swiss than in B6C3F1 mice. The lymphomas were more prevalent in females than in males of both mouse models. Most mice with thymic lymphoma died during the course of the study. In addition to the thymus, lymphoma was often present in lymph nodes, spleen, and other organs. Lymphomas arose more frequently in mice that lack endogenous ecotropic retroviral sequences and thus were not due to activation of endogenous provirus. During the third month of the study, a few NIH Swiss mice that died had granulosa cell tumors of the ovary. Treatment-related but reversible thymic atrophy was observed in both mouse models. There was a very high correlation between the internal dose of ddC and the incidence of thymic lymphoma in both mouse models. Most of the lymphocytes from control thymuses and ddC-induced lymphomas were positive for Thy-1.2 (pan-T), heat stable antigen, and CD4 and CD8 markers, with no marked differences in the lymphocyte markers of the tumors between sexes or dose groups. p53 protein was detected in only 20% (23/115) of the ddC-induced lymphomas with mostly minimal expression in scattered cells. Because ddC induced lymphomas in two different mouse models, the potential carcinogenic risk should be considered in long-term treatment of HIV-positive patients, especially children and adolescent patients treated with ddC.

Anemia↗
PubMed1996

Alterations in individual molecular species of human platelet phospholipids during thrombin stimulation: electrospray ionization mass spectrometry-facilitated identification of the boundary conditions for the magnitude and selectivity of thrombin-induced platelet phospholipid hydrolysis.

Although the rapid thrombin-induced release of arachidonic acid in human platelets has been known for over 20 years, the amount of arachidonic acid mass mobilized and the source of the released arachidonic acid has remained a subject of intense controversy. Herein, we exploit the analytic power and sensitivity of electrospray ionization mass spectrometry to identify plasmenylethanolamines as the largest source of arachidonic acid mass released during thrombin stimulation and to demonstrate the presence of multiple novel molecular species of plasmenylethanolamines in human platelets. Specifically, 90 s after thrombin stimulation a total of 60.1 nmol of arachidonic acid-containing phospholipids/10(9) platelets was hydrolyzed which included the loss of 31.8 nmol/10(9) platelets from ethanolamine glycerophospholipids (hydrolysis of plasmenylethanolamines represented 63% of the mass lost from the ethanolamine glycerophospholipid pool) but only 10.9 nmol/10(9) platelets from choline glycerophospholipids. Human platelet phosphatidylserine and phosphatidylinositol pools contained similar amounts of arachidonic acid mass in resting platelets (approximately equal to 20 nmol/10(9) platelets), and each pool contributed 8.7 nmol/10(9) platelets after thrombin stimulation. From these results, a lower boundary for the rate of thrombin-induced arachidonic acid mobilization in human platelets can be set at > 60 nmol/10(9) platelets, thereby identifying specific kinetic characteristics and substrate selectivities of the phospholipase(s) activated during platelet stimulation. Collectively, these results underscore the importance of plasmenylethanolamines as the major storage depot of arachidonic acid in resting platelets and as the major source of arachidonic acid mobilized after thrombin stimulation of human platelets.

Blood Platelets↗
PubMed1996

Presence of rabbit haemorrhagic disease virus antigen in rabbit tissues as revealed by a monoclonal antibody dependent capture ELISA.

The production of monoclonal antibodies (mAbs) to a common antigenic region on rabbit haemorrhagic disease virus (RHDV) has enabled the development of a capture ELISA for virus detection. The assay was shown to detect reliably the presence of viral antigen in crude homogenates of a range of rabbit tissues and has provided the first evidence for the presence of RHDV in blood, serum and heart tissue. A limited time course study of the progression of virus infection revealed viral antigen is first detected in the liver at between 18 and 24 h post-infection (p.i.) and in the spleen between 24 and 30 h p.i. The assay displayed a high level of specificity, clearly differentiating between groups of infected (lowest observed optical density (O.D.) 0.45) and uninfected (highest O.D. 0.06) rabbits. No viral antigen was detected in the urine or faeces collected from infected rabbits at post-mortem. Experiments employing the 'spiking' of pools of urine and faecal homogenates collected from uninfected rabbits, with a known amount of virus, indicated that RHDV may not be present in the faeces of infected animals and if present in urine, it appears to undergo substantial degradation.

Animals↗
PubMed1996

Differential desensitization response of the neonatal and adult rat somatotroph to growth hormone-releasing hormone and phorbol ester.

Elevated levels of circulating growth hormone (GH) in the perinatal animal may be caused in part by relative resistance to the desensitizing effects of GH secretagogues. We compared the effects of 4-day exposure of primary pituitary cell cultures from adult male and 2-day-old rats to GH-releasing hormone (GHRH; 10 nM) or 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 1 microM) on subsequent acute GH response to these secretagogues. Prolonged exposure to GHRH reduced subsequent GHRH-induced GH release from pituitary cells of both age groups, but the reduction in GH response was significantly less in neonates than adults. In addition, GH secretion from neonatal pituitaries rose progressively during each day of GHRH exposure, to reach levels almost 7 times basal; by contrast, GH secretion from adult pituitaries increased only transiently and then declined. Prolonged exposure to TPA reduced the subsequent GH response to TPA equally in neonates and adults, but differentially affected the GH response to GHRH; TPA exposure reduced the GH response to GHRH in neonates, but not in adults. These data suggest a fundamental difference between the GH regulatory processes of neonatal and adult pituitaries. The ability of the somatotroph to exhibit attenuated GH response on exposure to secretagogue is developmentally regulated, and relative resistance of the immature somatotroph to homologous desensitization by GHRH may contribute to elevated serum GH levels during the perinatal period.

Animals↗
PubMed1996

Ultrastructural evidence of intestinal mucosal macrophage activation after bone marrow transplantation.

Previous studies have demonstrated upregulation of intestinal mucosal macrophage CD16 (an Fc receptor for IgG) in bone marrow transplant (BMT) recipients with graft-versus-host disease (GVHD). We sought to determine whether there was ultrastructural evidence of mucosal macrophage activation in allogeneic BMT recipients and relate appearances to those seen in autologous BMT patients and to immunohistological findings. Sigmoid colonic mucosal biopsies from five allogeneic and three autologous BMT patients were taken prior to, 30 days after transplant and, in three of the allogeneic patients, 120 days after transplant. These were examined by immunohistochemistry and electron microscopy. Immunohistological analysis revealed upregulation of lamina propria macrophage CD16 after transplant in all patients except one autologous BMT recipient; there were no such changes in total macrophage numbers. Ultrastructural evidence of lamina propria macrophage activation was prominent after both allogeneic and autologous BMT. There was an increase in nuclear size accompanied by increased euchromatin and larger nucleoli. In the cytoplasm there were increased numbers of lysosomes, many of which were small and cylindrical, and cytoplasmic flaps were prominent. Phagosomes were less numerous after transplant. These data confirm that after BMT intestinal mucosal macrophages become activated. However changes in macrophage ultrastructure specific to patients at risk of developing clinical GVHD are lacking.

Adult↗
PubMed1996

Long-term follow-up of gastric histology after Helicobacter pylori eradication.

Helicobacter pylori causes chronic active gastritis and is thought to be associated with the development of gastric atrophy, intestinal metaplasia and carcinoma. As the effect of H. pylori eradication on this process is poorly understood, we sought to determine the long-term effects of H. pylori eradication on gastric histology. Fifty-four patients with duodenal ulceration associated with H. pylori infection received H. pylori eradication therapy in 1985/86 and either remained infected (n = 22) or had the infection eradicated (n = 32); patients were followed up by endoscopy with gastric antral biopsy for 7.1 years (mean). Histopathological analysis of gastric antral mucosa from patients rendered H. pylori-negative revealed a marked decrease in both inflammatory cells within the lamina propria and intraepithelial neutrophils and an increase in epithelial mucinogenesis. Gland atrophy remained unchanged in both H. pylori-positive and -negative patients. When examined for the presence and severity of intestinal metaplasia, there was neither a difference between the two patient groups nor a change with time. These data demonstrate that significant long-term improvements in gastric histology accompany H. pylori eradication when compared with histology in patients with persistent infection. Whether this confers a protective effect by reducing the risk of gastric carcinoma remains unknown.

Adult↗
PubMed1996

The application of microridge analysis in the diagnosis of gastro-oesophageal reflux disease.

BACKGROUND: The percentage of epithelial surface area covered by microridges (%MR) seen during scanning electron microscopy of oesophageal biopsy specimens has previously been shown to correlate with symptomatic reflux disease, a result < or = 35% being abnormal. The aim of this study was to compare %MR with endoscopy, light microscopy, and pH monitoring results. METHODS: Sixty-seven patients with heartburn were divided into oesophagitis or none on the basis of endoscopy and light microscopy findings and into those with and without abnormal acid reflux on the basis of pH monitoring. RESULTS: The endoscopic and light microscopic oesophagitis groups had significantly greater degrees of acid reflux than those without oesophagitis (p < 0.05), even though neither the specific %MR nor the number of patients below the 35% cutoff showed any difference between those with and without endoscopic oesophagitis, light microscopic oesophagitis or those with normal and abnormal acid reflux on pH monitoring. CONCLUSION: Despite the significant relationship between endoscopic and light microscopic oesophagitis and abnormal pH monitoring microridge analysis did not correlate with any of these variables

Biopsy↗
PubMed1996

Order of rotation in third-year clerkships. Influence on academic performance.

OBJECTIVE: To determine if student performance during the third-year clerkship is influenced by the order of departmental rotation. STUDY DESIGN: In this retrospective, descriptive study, the National Board of Medical Examiners (NBME) scores, departmental examination grade (DE) and final block grade (FG) were stratified into six segments based on the order of block time in obstetrics-gynecology, pediatrics, psychiatry, internal medicine, surgery and family medicine. Consistency was validated by comparing these performance criteria from 1988 to 1992. RESULTS: When all six clerkships were assessed by year, there was no uniform trend of improved performance over time. In the obstetrics-gynecology block, however, NBME scores and FGs were highest for students assigned to the fifth and sixth rotation as compared to the first two groups (P < .02). No such trend was noted with the departmental written examination. In surgery, DE and FG were always lower in the first rotation (P = .0001). Psychiatry DE scores were significantly higher on the second or third blocks as compared to the fifth and sixth rotation positions (P < .001). Students had a higher FG in pediatrics when the sixth position was compared to the second block (P = .02), but the DE grades and NBME scores were not altered by rotational schema. In family medicine and internal medicine, no effect of rotation was noted. CONCLUSION: Third-year clerks tended to have higher NBME scores and FGs in obstetrics-gynecology if they selected this rotation later in the academic year. Surgery DEs and FGs were lowest if selected first in the academic year. There was no similar trend in other nonsurgical specialties. These data suggest that prior clinical rotations positively influence student performance in obstetrics-gynecology.

Clinical Clerkship↗
PubMed1995

The reproductive and neural toxicities of acrylamide and three analogues in Swiss mice, evaluated using the continuous breeding protocol.

Acrylamide is a known genetic, reproductive, and neural toxicant, although it is not known if one effect is predominant. The toxicities of several structural analogues of acrylamide have been incompletely characterized, and the relative sensitivity of the second generation is not known. The present studies were designed to explore the relationship between neurotoxicity and reproductive toxicity, to further characterize the toxicities of three acrylamide analogues, and to evaluate the relative sensitivity of a second generation to these compounds. For the F0 generation, male and female Swiss CD-1 mice were provided drinking water containing acrylamide (ACR; 3, 10, 30 ppm), N,N'-methylenebisacrylamide (MBA; 10, 30, 60 ppm), N-(hydroxymethyl)acrylamide (HMA; 60, 180, 360 ppm), or methacrylamide (MACR; 24, 80, 240 ppm) during and after a 14-week cohabitation. The last litter was reared and dosed after weaning until mating at 74 +/- 10 days of age with the same level of compound given to the parents Neurotoxicity was assessed at several times in both generations by measuring forelimb and hindlimb grip strength. In the F0 generation, ACR caused an 11% decrease in pup number without measurable neurotoxicity; female fertility was not affected. Although both generations consumed the same amount of ACR, there were larger changes in the fertility-related endpoints in the F1 mice than in the F0's, with no concomitant change in organ weights or sperm parameters. In F0 mice, MBA reduced the number of live pups and their adjusted weight, with no neurotoxicity and no change in F0 female reproduction. MBA caused greater adverse effects in the second generation, concomitant with increased consumption. In the F0 generation, HMA caused the largest decrease in pup number during cohabitation (26%) together with a small effect on grip strength. Female reproduction was not affected. The second generation consumed more HMA and showed slightly greater toxic effects. In both generations, MACR was negative for both neurotoxicity and reproductive toxicity. Dominant-lethal studies showed that the fertility effects for ACR, MBA, and HMA could be explained by a male-mediated increase in postimplantation loss. These studies found that dominant lethality occurred without structural effects on the reproductive system in the presence of only minor effects on grip strength and without detectable neural histopathology. Female reproduction was not significantly affected by these compounds at the doses used. Thus, these data confirm the male as the affected gender and that the reproductive toxicity was greater than motoneuron toxicity when measured as grip strength.

Acrylamide↗
PubMed1995

The reproductive and developmental toxicity of indium in the Swiss mouse.

Indium is increasingly used in a variety of industries, and while there are few studies of its developmental toxicity, ther are no reports of its potential reproductive toxicity. These studies were undertaken to investigate the possible reproductive toxicity of indium and to determine the relative vulnerability of males and females. We used, initially, a 21-day combined developmental/reproductive toxicity protocol. Oral exposures to InCl3 ( < or = 250 mg/kg) were without effect on the male reproductive system or liver. A kidney effect was demonstrated in males by a decrease in urinary N-acetyl glucosaminidase. The ability of females to become pregnant was unaffected. However, fetal development was adversely affected, manifested as increased intrauterine deaths in the presence of reduced maternal weight gain. A developmental toxicity study identified no increase in fetal malformations, but verified the increased fetal deaths, in the absence of effects on adjusted maternal body weight. In vitro toxicity studies showed that the embryolethality was at least in part a result of direct toxicity to the conceptus, with effective doses in the low micromolar range. A limited disposition study showed that fetuses contained low micromolar concentrations of indium, more indium than maternal liver, and comparable to levels that were toxic in vitro. Although studies of greater exposure duration are required for risk assessment, these data indicate that fetal development is likely to be more affected by indium than female or male reproduction, with adverse effects occurring at low micromolar levels in vivo and at exposures that may or may not affect body weight.

Abnormalities, Drug-Induced↗
PubMed1995

Induction of thymic lymphoma in mice administered the dideoxynucleoside ddC.

Groups of 10 male and 20 female B6C3F1 mice received 0, 500, or 1000 mg/kg/day 2'3'-dideoxycytidine (ddC) by gavage for 13 weeks. At the end of the 13-week exposure period all males and 10 females per group were necropsied while the remaining females were held for 1 month without further treatment. Thymic atrophy was present at the 13-week necropsy in male and female mice administered 1000 mg/kg/day and in females administered 500 mg/kg/day, but was not present in females following 1 month of recovery. Thymic lymphoma was present in 1 female that received 500 mg/kg/day and 1 female that received 1000 mg/kg/day. In a follow-up study groups of 70 female mice received 0, 500, or 1000 mg/kg/day for 13 weeks. At the end of the 13-week exposure period 20 mice per group were necropsied and the remaining animals held for 3 months without further treatment. Thymic atrophy was observed in ddC-exposed groups at the 13-week necropsy but not in mice allowed to recover for 13 weeks. Thymic lymphoma occurred in 3/50 mice that received 500 mg/kg/day and in 17/50 mice that received 1000 mg/kg/day but did not occur in mice from the vehicle control group.

Animals↗
PubMed1995

A competition ELISA for the detection of antibodies to rabbit haemorrhagic disease virus.

Monoclonal antibodies (mAbs) were raised to a preparation of rabbit haemorrhagic disease virus (RHDV) purified from the livers of experimentally infected rabbits. Rabbit antisera to RHDV significantly blocked the binding of two mAbs (2D3(3) and 2D4(5)) to RHDV-coated microplate wells in a competition ELISA. The virus-specific nature of these mAbs was confirmed by immunoperoxidase and immunofluorescence assays on formalin-fixed and fresh infected liver tissue. Utilization of one of these mAbs (2D3(3)) in a competition ELISA, resulted in an RHDV antibody assay which proved more specific than an indirect ELISA and more rapid and reliable than a haemagglutination inhibition assay for screening serum samples from wild and experimental rabbits.

Animals↗
PubMed1995

A prospective study of screening upper gastrointestinal (GI) endoscopy prior to and after bone marrow transplantation (BMT).

BACKGROUND: Upper gastrointestinal (GI) endoscopic abnormalities are common in symptomatic bone marrow transplant (BMT) recipients but the incidence of occult gastrointestinal disease in these patients is unknown. AIMS: To examine the role of screening upper GI endoscopy before and after BMT. METHODS: Endoscopy was performed routinely on allogeneic (n = 24) and autologous (n = 17) BMT patients before transplant and at 30 and 120 days after transplant. RESULTS: Twenty-one of 41 patients (51%) had an endoscopic abnormality on one or more occasions which necessitated a change in treatment. These abnormalities were present in ten of 41 (24%) pre-transplant endoscopies, ten of 32 (31%) endoscopies at day 30 after BMT, and in seven of 22 (32%) day 120 endoscopies. Abnormalities included mucosal erosions or ulcers n = 22 endoscopies), infections (n = 5) or previously undiagnosed GI graft-versus-host disease (n = 3). Mucosal erosions or ulcers were present in eight of 28 endoscopies despite regular anti ulcer drug therapy. CONCLUSIONS: Screening upper GI endoscopy before and after BMT is generally safe and detects a high yield of significant GI abnormalities. However, it remains to be demonstrated that treatment of these lesions will improve the clinical outcome in BMT recipients without GI symptoms.

Adult↗
PubMed1995

Twenty to 40 year follow up of infantile hiatal hernia.

The aim of this study was to assess clinical and radiological findings of gastro-oesophageal reflux in adults who were diagnosed as having a hiatal hernia in infancy or early childhood. One hundred and eighteen patients with a minimum age of 20 who were diagnosed as having a hiatal hernia in childhood were interviewed; barium meal examination was performed in 96 of these cases. Ninety four patients had not required surgery for their hernia. The hiatal hernia persisted in 53% of these patients and 46% experienced heartburn at least monthly but in only three was this severe. Heartburn was significantly more common in patients in whom reflux was seen on barium meal. The consumption of antacids was significantly lower (20% v 46%) in patients who responded well to treatment as children. Eighteen of 24 patients who underwent surgery as children experienced heart-burn monthly but in only one patient was this severe. Two patients underwent endoscopy at their request because of symptoms during this follow up. Both had Barrett's oesophagus. In conclusion, despite the persistence of the hiatal hernia in half of the non-surgically treated patients, few complained of significant symptoms. Effective treatment in childhood was associated with a significant reduction in antacid consumption for heartburn as adults. The finding of Barrett's oesophagus in two patients high-lights a possible role for endoscopic screening in this patient group.

Adult↗