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Biomedical subjects

M Ahmed

Publications and source records attributed to M Ahmed.

At least 163 records · Page 9Linked to original sources

Gastrin effects on growth and exocrine secretion in the neonatal rat pancreas.

In adult rats, cholecystokinin (CCK) binds to pancreatic CCK-A receptors and stimulates exocrine secretion and pancreatic growth. In newborn rats there is very little mature intestinal CCK and few pancreatic CCK-A receptors. However, there is an abundant source of the related peptide gastrin, and in addition, there are pancreatic CCK-B/gastrin receptors. In this study, we have explored the hypothesis that gastrin may "deputise" for CCK in the neonate and cause pancreatic exocrine secretion, growth, and maturation. Newborn rats were injected intraperitoneally with the gastrin antagonist, C1-988, or placebo for 5 days and sacrificed on day 6. Body weight (CI-988, 8.25 +/- 0.48 g; placebo, 10.17 +/- 0.93 g) and pancreatic weight (19.41 +/- 1.5 vs. 21.58 +/- 1.72 mg) were the same. Protein (1,202 +/- 78 vs. 1,254 +/- 56 micrograms), amylase (22.3 +/- 0.9 vs. 19.2 +/- 1.00 U), RNA (117 +/- 7 vs. 126 +/- 5 micrograms), and DNA (95 +/- 8 vs. 100 +/- 7 micrograms) contents of the pancreas were similar in the two groups. The weight of the stomach was reduced (p = 0.04) in the treated group (50.8 +/- 2.5 mg) compared to the placebo group (59.8 +/- 3.7 mg). In both neonates and adults, CCK-8 was approximately 1,000 times more potent than gastrin-17 in stimulating amylase release from isolated pancreatic acini. This suggests that enzyme release is probably mediated by the same receptors in both adults and neonates, and in adults previous work has shown this to be the CCK-A receptor. In conclusion, these data show that gastrin has very weak effects on neonatal pancreatic exocrine secretion, and furthermore, gastrin is not essential for growth and maturation of the neonatal pancreas. The role of gastrin and CCK-B/gastrin receptors in the neonatal pancreas remains speculative.

Amylases↗

Computer-facilitated therapy for inpatients with schizophrenia.

The authors present three case vignettes in which inpatients with schizophrenia participated in psychotherapy sessions that included three phases: traditional verbal psychotherapy, computer-facilitated therapy, and recapitulation of the session. In the computer-facilitated phase, the therapist typed the conversation between the patient and therapist, and the patient was able to look at the computer screen to review what was said. Clinical observation was used to determine patients' frequency of delusional symptoms during the first two phases. For all three patients, the frequency of delusional symptoms decreased from the first to the second phase. The computer, by visually representing words, may facilitate communication by compensating for deficits in auditory processing, information processing, attention, and memory often found among patients with schizophrenia.

Adult↗

Nephrotic syndrome, renal failure, and renal malignancy: an unusual tumor-associated glomerulonephritis.

The association between malignancy and glomerular disease has been appreciated for over three decades. Although the relationship between membranous glomerulonephritis or minimal-change nephrotic syndrome and carcinoma or lymphoma, respectively, are the most widely known, several other glomerular lesions have been described in patients with malignancy. In this article, a patient who presented with nephrotic syndrome, volume overload, and renal failure, who was subsequently found to have a renal mass, is described. Resection of the mass, which proved to be a renal cell carcinoma, led to resolution of proteinuria and improvement of renal function. Pathology on the noninvolved portion of the kidney revealed a membranoproliferative glomerular lesion, a lesion usually associated with lymphomas and not previously described with renal carcinoma. Although a role of tumor antigens and anti-tumor antibodies in producing glomerular immune deposits has been speculated upon, the evidence for this assertion was spotty. However, reports of remission of proteinuria after tumor treatment or removal support a role of tumor products in pathogenesis. Although the association between proteinuria and malignancy is rare, it should be kept in mind, particularly in older patients with membranous glomerulonephritis where the possibility of malignancy needs to be further evaluated.

Acute Kidney Injury↗

Preliminary studies on the antiinflammatory, analgesic and diuretic activity of stagninol, a sesquiterpene isolated from Persicaria stagnina.

Stagninol, a sesquiterpene, isolated from Persicaria stagnina Linn showed significant antiinflammatory and analgesic activity (P < 0.001) in animals. A sedative action of stagninol was revealed by a marked potentiation of pentobarbital induced sedation with significant effect on both onset (P < 0.001) and duration (P < 0.01) of sleep. Measurement of urine volume after administration of stagninol indicated its significant diuretic action. Biochemical investigations revealed that both crude extract and stagninol showed dose dependent reduction of blood uric acid and blood urea nitrogen (BUN). There was an increase in serum glutamic pyruvic transaminase (SGPT) and serum alkaline phosphatase (SAP) level with the crude extract but stagninol showed no significant changes of serum glutamic oxaloacetic transaminase (SGOT), SGPT and SAP level.

Analgesics, Non-Narcotic↗

Computer-assisted learning; experience at the Bristol Urological Institute in the teaching of urology.

OBJECTIVE: To report the use of a computer-assisted learning (CAL) program in the teaching of urology to medical students. SUBJECTS AND METHODS: Four CAL tutorials were developed, covering the examination of the urological patient, prostate cancer, impotence and lower urinary tract symptoms, for an initial evaluation of the use of CAL. Twenty-six third-year medical students seconded to the department for one week of urology teaching were randomized to two equal groups. One group used the CAL programs in addition to daily formal teaching, while the other group only received daily teaching. Teaching was of a standardized format, covering all aspects of urology, including the four areas covered by the CAL tutorials. Students were assessed using standardized multiple-choice questions (MCQ) at the start and end of the week's teaching. Incorrect responses were marked negatively. The content and ease of use of the CAL programs were also evaluated by a questionnaire. RESULTS: There was no difference between the groups in MCQ scores at the start of the week. The mean (SD) change in score over the week for those using the CAL tutorials was 6.0 (7.0), and for the control group was 0.9 (6.0), a significant difference (P < 0.005). Students reported the tutorials to be easy to use and of satisfactory content. CONCLUSION: The results of this study suggest that CAL programs are of benefit to students learning urology.

Adult↗

Neuropeptides in heterotopic bone induced by bone matrix in immunosuppressed rats.

The effects of cyclosporin A on the occurrence of neuroendocrine peptides in bone induced by demineralized allogeneic and xenogeneic bone matrix were studied in rats. Cyclosporin A enhanced bone induction in demineralized allogeneic bone matrix implants by 40% to 50% at 4 weeks, whereas there was no difference to the control group at 8 weeks. In demineralized xenogeneic bone matrix implants there was virtually no cartilage or bone formation at 4 weeks, but some bone and cartilage formation was seen at 8 weeks. In both cyclosporin A treated groups the net bone formation in demineralized xenogeneic bone matrix implants was increased four to five times at 4 weeks. Cyclosporin A treatment did not alter the temporal occurrence or distribution of neuropeptide containing nerve fibers in the bone induced by allogeneic bone matrix. Fibers containing substance P, calcitonin gene related peptide, neuropeptide Y, vasoactive intestinal peptide, and tyrosine hydroxylase were detected in the ossicles of cyclosporin A treated and control rats. In the xenogeneic bone matrix of the control group, no immunoreactive nerve fibers could be detected at 4 weeks, but at 8 weeks all five neuropeptides were detected. However, after cyclosporin A treatment immunoreactive nerve fibers could be seen at 4 weeks in the demineralized xenogeneic bone matrix implants. Thus, immunologic properties of the inductive matrix affect the yield of mineralized bone and the degree of innervation. Cyclosporin A decreases the immune response and enhances the formation of bone and the number of transmitter identified nerves in demineralized xenogeneic bone matrix induced ossicles.

Animals↗

Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis.

BACKGROUND: Orthotopic liver transplantation in patients positive for hepatitis B virus (HBV) DNA is associated with a high reinfection rate, even with hepatitis B immunoglobulin (HBIG) prophylaxis. Nucleoside analogues that inhibit hepatitis B replication in patients with chronic hepatitis B could prevent reinfection after transplantation. The aim of this study was to analyse the efficacy and safety of prophylaxis both before and after transplantation with the nucleoside analogue lamivudine, without HBIG, in patients undergoing liver transplantation. METHODS: 17 HBsAg-positive patients with decompensated cirrhosis and previous evidence of viral replication were enrolled. 12 were HBV-DNA-positive by a signal amplification assay. Patients were treated with oral lamivudine (100 mg daily) for at least 4 weeks before transplantation and followed up for 18-90 weeks after transplantation. FINDINGS: HBV DNA became undetectable in serum before transplantation in all HBV-DNA-positive patients. Four died before transplantation from complications of cirrhosis; one patient was withdrawn from the study because of a cerebrovascular accident. The remaining 12 patients underwent transplantation. Two patients died after transplantation (one at 3 days and one [suicide] at 20 weeks). HBV DNA reappeared in one patient with histological evidence of recurrent hepatitis (72 weeks). By week 24 the nine remaining patients had lost HBsAg and remained negative for HBV DNA. INTERPRETATION: Lamivudine treatment may prove useful in preventing recurrence of hepatitis B after liver transplantation. The effect on survival of patients after transplantation remains to be assessed.

DNA, Viral↗

Potency of wild-type and temperature-sensitive vesicular stomatitis virus matrix protein in the inhibition of host-directed gene expression.

The matrix (M) protein of vesicular stomatitis virus (VSV) functions in virus assembly and also appears to be involved in the inhibition of host gene expression that is a characteristic cytopathic effect of VSV infection. Previous studies have shown that expression of M protein inhibits host-directed transcription in the absence of other viral gene products and have suggested that only small amounts of M protein are required for the inhibition. In experiments described here, the potency of M protein in inhibition of host-directed gene expression was determined by cotransfecting different amounts of in vitro-transcribed M protein mRNA together with a target gene encoding chloramphenicol acetyl transferase (CAT) into BHK cells or PC12 cells that had been cultured in the presence or the absence of nerve growth factor. The results of these experiments showed that the potency of M protein was similar in the two cell types and was not affected by the extent of differentiation of PC12 cells. Inhibition of CAT gene expression by M protein was also independent of the nature of the promoter activating sequences of several different RNA polymerase II-dependent promoters. The amount of M protein needed to give 50% inhibition of CAT expression was estimated to be 6700-11,000 copies per cell. Earlier data that temperature-sensitive (ts) M gene mutants of VSV inhibit host transcription had been interpreted to indicate that M protein was not involved in the inhibition. When the amount of M protein expressed was taken into account, ts M protein was as effective as wild-type M protein in the inhibition of host-directed transcription at the nonpermissive temperature. Thus, inhibition of host transcription by ts M mutants of VSV is due to the potent activity of M protein, which is evident even at the low levels produced at the nonpermissive temperature.

Animals↗

Overexpression of the normal phosphoribosylpyrophosphate synthetase 1 isoform underlies catalytic superactivity of human phosphoribosylpyrophosphate synthetase.

To define the enzymatic and genetic basis of X-linked phosphoribosylpyrophosphate synthetase (PRS) catalytic superactivity, we measured concentrations of X-linked PRS1 and PRS2 isoforms in cultured fibroblasts and lymphoblasts by immunoblotting after separation by polyacrylamide-urea isoelectric focusing. PRS1 comprised >80% of measurable PRS isoforms in all fibroblast strains, but PRS1 concentrations in cells from six affected males exceeded those in normal cells by 2-6-fold. PRS absolute specific activities (activity per mg of PRS isoforms) were comparable in all fibroblast strains and in purified recombinant normal PRS1, confirming selectively increased levels of PRS1 isoform as the enzymatic basis of PRS catalytic superactivity. Cloning, sequencing, and expression of normal subject- and patient-derived PRS cDNAs predicted normal translated region sequences for both PRS isoforms and revealed no differences in catalytic properties of recombinant PRS1. Normal and patient PRPS1 transcribed but untranslated DNA sequences were also identical. Northern blot analysis showed selective increase in relative concentrations of PRS1 transcripts in patient fibroblasts. In PRS catalytic superactivity, overexpression of the normal PRS1 isoform thus appears to result from an altered pretranslational mechanism of PRPS1 expression. In lymphoblasts, however, expression of this alteration is attenuated, explaining the absence of phenotypic expression of PRS catalytic superactivity in these cells.

Base Sequence↗

The development of autonomic innervation in bone and joints of the rat.

The development of autonomic nerves in the hindlimb skeleton, was studied in rats from gestational day (G) 15 to postnatal day (P) 24 by immunoreactivity to neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). Control labelling with antisera to neurofilaments, protein gene-product 9.5 (PGP 9.5), and nerve terminals, synaptophysin (SYN), showed nerve fibres at G15 and nerve terminals at G19 in the perichondrial tissue. From P4, nerve fibres and terminals were observed within the bone organ. Noradrenergic sympathetic nerves, containing NPY, were first discerned at birth, G21, in the perichondrial tissue and within the bone organ at P4. Autonomic cholinergic nerve fibres, indicated by immunoreactivity to VIP, exhibited a similar temporal and regional occurrence. The diaphyseal parts were first supplied with autonomic nerves at P4. The nerve fibres extended into the metaphyses at P6-8 and finally into the epiphyses at P10, concomitant with the first signs of mineralization. Vascular as well as non-vascular nerve fibres were seen. The study shows that developing bone organ is supplied with autonomic nerves from birth, and the the growth of nerves parallels the mineralisation process. Previous studies have demonstrated that NPY potently inhibits parathyroid hormone (PTH) induced effects on osteoblastic bone cells and that VIP is a strong inductor of bone resorption. NPY and VIP also exert vasoregulatory effects. The combined findings suggest an autonomic influence on bone development.

Animals↗

Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine.

We describe mutations in the hepatitis B virus (HBV) polymerase gene in viruses which reactivated in two patients during therapy with -2'-deoxy-3'-thiacytidine, or lamivudine (3TC), and following orthotopic liver transplantation for chronic hepatitis B. Virus resistance to 3TC is associated with mutations which lead to amino acid substitutions in the highly conserved tyr-met-asp-asp (YMDD) motif, part of the active site of the polymerase, and which parallel those seen in resistant human immunodeficiency virus (HIV). Substitutions of valine and isoleucine for methionine were found in the two cases. The significance of single secondary mutations, which differ between viruses from the two patients, remains to be determined. Thus, viral resistance to lamivudine of hepatitis B virus mimics that of HIV and can occur in the setting of immunosuppression after liver transplantations.

Adult↗

Inactivation of hepatitis C virus cDNA transgene by hypermethylation in transgenic mice.

Transgenic mice were produced by microinjection of a partial hepatitis C virus (HCV) genome sequence including the structural protein region, under the control of the albumin promoter and enhancer into fertilized eggs of C57BL/6 and BDF1 mice. Three founders carrying at least five copies of the transgene but not expressing HCV-specific RNA were generated. Methylation analysis indicated that the transgene was extensively methylated. Mapping of methylated cytosine residues of the transgenic mouse DNA showed that all C residues of a particular part of the HCV genome but not all the CpG island like sequences were methylated. Transiently expressed HCV cDNA in COS7 cells and the active endogenous albumin gene were not methylated. Furthermore, 5-azacytidine, a potent demethylating agent, induced HCV gene expression in a line of these transgenic mice. These results suggest that methylation of HCV cDNA is a cause of its inactive expression in transgenic mice, and that this phenomenon may occur in other stable systems for expression of the HCV genome.

Animals↗

Malignant mesothelioma of the tunica vaginalis testis diagnosed by aspiration cytology--a case report with review of literature.

A case of malignant mesothelioma of the tunica vaginalis testis diagnosed by preoperative cytology of hydrocele fluid is reported. In our view this is only the second case diagnosed by preoperative cytology. The unique feature of this case, the characteristic ultrasound appearance, was recognized and confirmation by aspiration cytology led directly to radical orchiectomy, thus avoiding hydrocelectomy, hemiscrotectomy and possible local recurrence. Aetiopathogenesis and management options of this rare tumour are discussed, with a review of the literature.

Aged↗