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Biomedical subjects

M Sidhu

Publications and source records attributed to M Sidhu.

34 records · Page 2Linked to original sources
PubMed1996

Detection of bovine polyomavirus contamination in fetal bovine sera and modified live viral vaccines using polymerase chain reaction.

A nested polymerase chain reaction (PCR) assay has been developed for the detection of bovine polyomavirus (BPyV) DNA. The assay has been used to screen commercial lots of fetal bovine serum and modified live veterinary vaccines for the presence of the agent. A PCR product of the expected size was detected after the first round of PCR for eight out of 20 serum lots, but in none of the 14 vaccines tested. The subsequent nested assay revealed that four more serum lots were positive for BPyV DNA, as well as two vaccine lots. When hybridized with a labelled probe, blots of the PCR products from vaccines revealed that in one of the two positive samples a specific product was present after the first PCR at a level not detectable in gel electrophoresis. Nested PCR appears to be a useful tool for the detection of low level contamination with BPyV DNA of products used in, and derived from cell culture.

Animals↗
PubMed1995

Characterization of a human adenovirus 5: rabies glycoprotein recombinant vaccine reisolated from orally vaccinated skunks.

An infectious recombinant human adenovirus which carries the rabies glycoprotein gene and accompanying SV40 control elements can be given orally to skunks to immunize them against rabies. We have looked for adenovirus in the feces and oral fluids of animals that have been given this recombinant and have obtained 111 virus positive samples from 16 test animals. DNA from these virus isolates was examined for possible mutations. One possible insertion mutation was detected by SmaI restriction endonuclease analysis of genomic DNA. Further analysis by HaeIII restriction and nucleotide sequencing of polymerase chain reaction products encompassing the whole SV40-rabies insert revealed that this isolate contained an insert of the 72 base pair sequence found in the SV40 promoter region. A second mutation, in which 54 base pairs were deleted from within the rabies glycoprotein gene, was also detected in two independent isolates from one skunk.

Adenoviruses, Human↗
PubMed1995

Nucleotide sequence of the thymidine kinase gene of raccoon poxvirus.

Using primers directed against the thymidine kinase gene of vaccinia virus, PCR products were generated from nucleic acids extracted from raccoon poxvirus-infected Vero cells. The PCR products were consistent in size with the expected products from vaccinia virus. Nucleotide sequence determination revealed that the raccoon pox thymidine kinase gene and flanking regions were 84.3% homologous to the corresponding sequences of vaccinia virus. At the amino acid level, an open reading frame coding for a polypeptide of 177 amino acids was found with 87% homology to thymidine kinase of vaccinia.

Amino Acid Sequence↗
PubMed1995

Insulin resistance syndrome in postmenopausal women with cardiological syndrome X.

OBJECTIVE: To determine whether postmenopausal women with cardiological syndrome X (chest pain and abnormal exercise electrocardiogram despite normal coronary angiography) exhibit disturbances in the full range of proposed components of the putative "insulin resistance syndrome". PATIENTS AND METHODS: 20 postmenopausal women with syndrome X and 20 healthy controls each underwent measurement of insulin resistance (by minimal model analysis of the intravenous glucose tolerance test), lipid, lipoprotein, and apolipoprotein concentrations, a range of haemostatic variables, serum uric acid concentration, and centrality of body fat distribution (by dual energy x ray absorptiometry). RESULTS: Women with syndrome X had higher fasting triglyceride concentrations than controls (median: 1.60 v 1.02 mmol/l, P < 0.05). Concentrations of high density lipoprotein cholesterol were lower (1.33 v 1.61 mmol/l, P < 0.05) as were those of the high density lipoprotein apolipoproteins AI and AII. Insulin and C peptide responses to the intravenous glucose tolerance test were higher (27.6 v 19.8 microU/ml/min, P < 0.01; 101 v 72 pmol/ml/min, P < 0.05, respectively), and insulin sensitivity was lower (1.89 v 3.09 min/microU/ml, P < 0.05). There were, however, no significant differences between other proposed components of the insulin resistance syndrome (blood pressure, glucose tolerance, proportion of central body fat, serum uric acid concentration, and plasminogen activator inhibitor-1 activity). Antithrombin III activity was higher in women with syndrome X (121 v 113%, P < 0.01). CONCLUSIONS: Women with syndrome X tend to be insulin resistant and have lipid and lipoprotein abnormalities, but do not exhibit all characteristics of the insulin resistance syndrome. Such variation in correlated risk factors is consistent with underlying heterogeneity in the insulin resistance syndrome and cardiological syndrome X.

Aged↗
PubMed1995

Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion.

Neural reflex pathways activated in response to mucosal stroking were investigated in segments of distal colon from guinea pigs. Stroking the mucosal surface of whole thickness or muscle-stripped segments with a brush at 1/s evoked an increase in short-circuit current (Isc) whose duration and amplitude were dependent on the number of strokes. The increase in Isc induced by mucosal stroking was virtually abolished by inhibitors of chloride secretion and by tetrodotoxin. The response was reduced by atropine, renzapride, and N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide but not by mecamylamine, ketanserin, tropisetron, or SDZ-205-557. Mucosal application of 5-hydroxytryptamine and 5-hydroxyindalpine increased Isc, which was attenuated by tetrodotoxin and renzapride. The results suggest that mucosal stroking evokes chloride secretion by activating neural reflex pathways utilizing serotoninergic receptors, of the 5-HT1P class, as well as muscarinic receptors within the submucosal plexus.

Acetylcholine↗
PubMed1995

In vitro assessments of the genetic stability of a live recombinant human adenovirus vaccine against rabies.

The genetic stability of a live human adenovirus 5: rabies glycoprotein recombinant vaccine has been assessed upon 20 serial passages in a permissive cell line of human origin. Restriction endonuclease analysis and the polymerase chain reaction were used to examine the integrity of the expression cassette for the rabies glycoprotein and the viral vector at the site of insertion of the cassette. It was found that the restriction endonuclease profile was identical for each sample assayed. A more detailed analysis of the expression cassette following amplification by the polymerase chain reaction revealed no changes in the size and number of fragments originating from the coding sequence for the glycoprotein nor the signals controlling the expression of the protein product. The amplified product obtained from the 10th and 20th passages was subjected to nucleotide sequencing. Additionally, 20 plaques isolated from the 20th passage of the virus expressed the rabies glycoprotein as demonstrated by fluorescent antibody staining with glycoprotein specific monoclonal antibodies. These results suggest that the recombinant vaccine maintains the integrity of the heterologous sequences upon passage in tissue culture.

Adenoviruses, Human↗
PubMed1995

Hypertensive lower esophageal sphincter pressures and gastroesophageal reflux: an apparent paradox that is not unusual.

UNLABELLED: The association of a hypertensive lower esophageal sphincter pressure (LESP) with significant gastroesophageal reflux (GER) has always seemed paradoxical because of the original association of a hypotensive sphincter with reflux. OBJECTIVES AND METHODS: In this study, the manometric and ambulatory pH studies of a group of consecutive patients evaluated over a 3-yr period were reviewed to identify and characterize patients with a hypertensive LESP and abnormal GER as defined by increased acid exposure in the distal esophagus as measured on ambulatory pH monitoring. RESULTS: Eighteen such patients were identified, which represented 5.2% of all patients with abnormal GER and 23.4% of all patients with a hypertensive LESP. Heartburn (nine patients) and chest pain (nine patients) represented the dominant symptoms. LESP ranged from 47 to 73 mm Hg. Incomplete LES relaxation in response to swallow was found in nine out of 18 patients. Intact peristalsis was found in all patients, and seven patients had a nutcracker esophagus. Patients showed a wide range of abnormal distal esophageal acid exposure times with only slightly abnormal recumbent or upright reflux times to greater than 25% pH less than 4 total (although most patients had mild reflux with 17 out of 18 patients having total distal esophageal acid exposure less than 10%). There was no correlation between LESP and total % pH less than 4 (r = 0.11). Of 16 patients, 12 responded to antireflux treatment, including the three patients who required fundoplication. The four patients who did not respond to treatment had poor correlation of reflux episodes to symptoms on pH monitoring, had markedly elevated LESPs, and did not present with heartburn. CONCLUSIONS: The association of a hypertensive LESP and abnormal GER is not uncommon. When abnormal GER does occur in these patients, it tends to be mild but can be clinically important and respond to antireflux treatments. We recommend that patients with a hypertensive LESP and/or nutcracker esophagus who present with heartburn or chest pain should undergo ambulatory pH monitoring to evaluate the possibility of GER disease.

Adult↗
PubMed1994

Bone density and endometriosis.

To establish whether there is evidence of low bone density in women with endometriosis, we compared bone density between 48 women with laparoscopically proven endometriosis and 48 age-matched normal controls. Bone density of the lumbar spine (L2-4), proximal femur (femoral neck, Ward's triangle, and trochanteric region), and total body were measured by dual energy roentgenogram absorptiometry. After adjusting for physical and lifestyle differences, bone density was not significantly different between the groups in any site. Bone density measurements were not related to the severity of endometriosis. These results do not confirm evidence of low bone density in women with endometriosis.

Absorptiometry, Photon↗
PubMed1993

Effect of chronic cadmium exposure on glutathione S-transferase and glutathione peroxidase activities in rhesus monkey: the role of selenium.

The effect of cadmium (Cd) on the activity of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) which play an important role in the detoxification of xenobiotics, was studied in the liver, kidney, heart and lung of Rhesus monkeys. Furthermore, the role of selenium (Se) in the modulation of Cd toxicity with respect to GST and GSH-Px was also evaluated. Cadmium exposure (5 mg Cd/kg body wt./day as CdCl2 for 10 weeks) to monkeys resulted in decreased GSH-Px activity in all four organs present in the order liver > kidney > heart > lung. Cadmium administration also resulted in a significant decrease in total GST activity present in the order liver > heart > kidney > lung, whereas a significant increase in the pi class GST activity was observed greatest in the heart followed by lung, kidney and liver. Oral administration of Se (0.5 mg Se/kg body wt./day as Na2SeO3 for 10 weeks) caused a significant increase in GSH-Px activity in the order liver > heart > kidney > lung. Selenium administration caused an increase in total GST activity in liver and lung but a decrease in kidney and heart. Simultaneous administration of Cd and Se resulted in an increase in total GST activity (except in lung) including the pi class activity as well as GSH-Px activity in all four tissues under study. Thus, the mechanism by which selenium decreases Cd toxicity in Rhesus monkeys, seems to rely on the protection of the enzyme systems GST and GSH-Px in the four organs, possibly by forming non-toxic cadmium selenide.

Animals↗
PubMed1993

Nonsteroidal antiinflammatory drugs and lower gastrointestinal bleeding.

To define the association of the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA), and lower gastrointestinal bleeding (GIB) a retrospective, case-controlled study was undertaken of 188 patients admitted to three community hospitals in three cities with a diagnosis of lower GIB. Information was obtained about NSAID usage among these patients, and the data were compared with an age- and sex-matched control group of 185 patients admitted with a nongastrointestinal diagnosis, derived from a daily admission list. At the time of admission, in the New Jersey group, NSAID consumption was present in 26 of 90 (29%) patients with lower GIB compared with 16 of 90 (18%) of controls (P < 0.05, odds ratio 1.88, 95% CI 1.2-3.1) whereas, in the South Carolina group 34 of 98 (35%) were taking NSAID compared with 18 of 95 (19%) of controls (P < 0.01, odds ratio 2.27, 95% CI 1.2-4.4). These data indicate that there is a significantly increased rate of NSAID ingestion in patients admitted with lower GIB, implying that NSAID may unmask bleeding from a variety of lower gastrointestinal lesions.

Aged↗
PubMed1993

Effects of a low-estrogen, desogestrel-containing oral contraceptive on lipid and carbohydrate metabolism.

Fasting serum lipids, lipoproteins and apolipoproteins, and fasting plasma glucose, insulin and C-peptide were measured in 107 non-users and 83 users of an oral contraceptive containing the progestin desogestrel, combined with 20 micrograms ethinyl estradiol. Plasma glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT) were measured in a subgroup of 69 non-users and 39 users. Compared with non-users, users had higher concentrations of total, high density lipoprotein (HDL), HDL subfraction 3 and very low density lipoprotein (VLDL) cholesterol, total triglycerides, VLDL triglycerides, apolipoproteins AI and AII and fasting plasma insulin. There were no differences in HDL subfraction 2, low density lipoprotein cholesterol and apolipoprotein B. OGTT glucose was 60% higher in the users and OGTT insulin response 19% higher. The OGTT C-peptide response did not differ. The effects of 20 micrograms ethinyl estradiol combined with 150 micrograms desogestrel on lipid, lipoprotein, glucose and insulin metabolism are similar to those described previously with a 30 micrograms ethinyl estradiol combination containing the same dose of desogestrel. The relatively favourable metabolic profile associated with the higher estrogen dose desogestrel combination is maintained at the lower dose.

Apolipoprotein A-I↗
PubMed1993

Effects of tibolone on serum concentrations of lipoprotein(a) in postmenopausal women.

OBJECTIVE: To evaluate the effects of tibolone (Org OD14), a synthetic steroid used for the relief of postmenopausal symptoms, on serum concentrations of lipoprotein(a) (Lp(a)), an independent risk marker for coronary heart disease. DESIGN: Subset of women participating in a non-randomized prospective trial of tibolone therapy. Twenty-seven women requesting relief of menopausal symptoms were treated with tibolone 2.5 mg/day for six months; 27 women who did not request treatment acted as controls. RESULTS: Tibolone induced a substantial fall (p < 0.001) in serum Lp(a) levels (median change -48%, range -100% to +3%). CONCLUSIONS: In terms of cardiovascular risk, the ability of tibolone to lower serum concentrations of Lp(a) may be advantageous in view of the unwanted reduction in high density lipoprotein concentrations which has previously been demonstrated in users of this steroid.

Anabolic Agents↗
PubMed1992

Lipoprotein Lp(a) levels are reduced by danazol, an anabolic steroid.

Serum levels of lipids, lipoproteins and apolipoproteins were measured in 26 premenopausal women with endometriosis both before and after six months therapy with the anabolic steroid danazol (600 mg/day) and in 15 untreated women who acted as controls. No changes were seen in the control group over six months. In women treated with danazol, mean levels of low density lipoprotein (LDL) cholesterol increased by 36% while those of high density lipoprotein (HDL) cholesterol decreased by 46%, changes characteristic of androgenic steroids. In contrast to this potentially detrimental lipoprotein profile, lipoprotein(a) [Lp(a)] levels were reduced by 78.6% +/- 24.0% (mean +/- S.D.) in women taking danazol. These dramatic changes in Lp(a) levels correlated with baseline Lp(a) levels but not with changes in LDL or HDL. Anabolic steroids such as danazol appear to be powerful modulators of serum Lp(a) concentrations. This could be due to direct effects on Lp(a) metabolism, or secondary to the effects of these steroids on insulin metabolism or on the coagulation and fibrinolysis system.

Adolescent↗
PubMed1992

Inverse relationship between serum Lp(a) levels and first-phase insulin secretion.

Relationships between serum Lp(a) levels and insulin metabolism were investigated in 147 healthy nonobese men attending an executive health-screening program. Each subject received an IVGTT with measurement of plasma levels of glucose, insulin, and C-peptide. An inverse relationship was seen with the first-phase plasma insulin response when subjects were stratified into quartile ranges of the serum Lp(a) distribution. This relationship was supported by mathematical modeling analyses of these data, which revealed an inverse relationship between serum Lp(a) levels and first-phase pancreatic insulin secretion and plasma insulin responsiveness to glucose.

Blood Glucose↗
PubMedDate not supplied

Intraluminal contrast enhancement and MR visualization of the bowel wall: efficacy of PFOB.

Efforts to develop satisfactory intraluminal gastrointestinal contrast agents for magnetic resonance (MR) imaging have focused on depicting only the bowel lumen to exclude possible involvement by a pathologic process. To determine whether the bowel wall can be adequately imaged with use of the contrast agent and whether bowel wall visualization is a better index of the utility of the contrast agent for MR imaging, perfluoroocytlbromide (PFOB) was studied in human subjects. Twenty consecutive patients referred for abdominal or pelvic MR imaging were selected. All patients were given 400-1,000 mL of PFOB orally. MR imaging was performed at 0.38 and 1.5 T with T1- and T2-weighted spin-echo pulse sequences before and after administration of PFOB. The images were graded independently by three blinded readers. All readers reported significantly superior conspicuity of the bowel lumen and wall after PFOB than before PFOB administration (P less than .002). Among the post-PFOB studies, those with superior bowel wall visualization demonstrated superior overall image quality. In three patients, lesions were optimally demonstrated because the relationship of the process to the bowel wall, rather than just to the lumen, was identified. In two patients, masses arising within the bowel wall could be identified prospectively only when the bowel wall was adequately imaged. The authors conclude that while lumen identification is improved with PFOB, its greatest clinical utility may be in facilitating intestinal wall visualization.

Administration, Oral↗