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Biomedical subjects

R Shukla

Publications and source records attributed to R Shukla.

At least 127 records · Page 7Linked to original sources
PubMed1991

Ultrastructural morphology of ectoplacental cone trophoblasts of hamster embryos.

The invasiveness of trophoblast cells is well known, but it is not clear whether they achieve this property by being transformed to other cell types (like malignant ones) or remain benign. Trophoblasts, in culture, were studied ultrastructurally by examining the surface morphology of the cell vis-à-vis their cytoplasmic outgrowth, and the presence and/or absence of ruffling membranes, filopodia, microvilli, pinocytotic pits or bleb-like structures was observed. Results revealed formation of ruffling membranes only on the leading edge, a presence of slender filopodia and pinocytotic pits but an absence of microvilli and bleb-like structures, the characteristic features of a transformed cell. The study indicated that the trophoblast cells, in spite of being invasive, do not convert to any other cell type.

Animals↗
PubMed1991

Adjuvant activity of some nonpyrogenic hydrophobic analogues of muramyl dipeptide in enhancing the primary humoral and cell mediated immune responses in guinea pig model.

Five muramyl dipeptide analogues synthesized by derivatization of gamma-carboxyl of D-isoglutamine residue of MDP into alkyl amides or incorporation of lysine residue at the site via epsilon-NH2 function were evaluated for immuno-adjuvant activity. Derivatization of gamma-carboxyl of D-isoglutamine into butyl, octyl and dibutyl residues stimulated delayed type of hypersensitivity (DTH) response, the maximum stimulation being observed with octyl amide. Introduction of lauryl amide residue abolished DTH response. The antibody response was impaired with all the alkyl amide analogues except for the lysyl amide derivative with which the response was higher than MDP. Correlation was observed between DTH response and macrophage migration.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Influence of plasma and red cell factors on the rheologic properties of oxygenated sickle blood during clinical steady state.

Yield stress is a sensitive index of blood fluidity at low shear stress. Using a method that measured the stress required to cause motion of a thin sedimenting layer of red cells, we found significant elevations of yield stress in patients with homozygous sickle cell anemia during clinical steady state. Mixing studies of sickle cells in normal plasma and buffered saline and of normal red cells in sickle plasma showed (1) that the increased yield stress of sickle blood was not due to differences between sickle and normal plasma factors and (2) that yield stress of sickle cells was not increased in the absence of plasma proteins. Multivariate regression analysis was performed to determine the dependence of sickle blood yield stress on several red cell and plasma factors. The yield stress measurements were normalized for differences in plasma fibrinogen concentration. Other factors studied included cell density, fetal hemoglobin concentration, alpha globin genotype, cell deformability as measured by high shear viscosity, and fibronectin and von Willebrand factor concentrations. Cell density was the primary determinant of yield stress. Measurements of yield stress on density fractionated sickle cells confirmed that the increased yield stress of sickle blood was due to the dense sickle erythrocyte. We conclude that the increased yield stress of sickle blood during clinical steady state was due to an abnormal interaction between the dense sickle cell membrane and plasma protein(s).

Adolescent↗
PubMed1991

Lead exposure and growth in the early preschool child: a follow-up report from the Cincinnati Lead Study.

This report is a follow-up of an earlier study of the effects of low to moderate prenatal and postnatal lead exposure on children's growth in stature. Two hundred thirty-five subjects were assessed every 3 months for lead exposure (blood lead level) and stature (recumbent length) up to 33 months of age. Fetal lead exposure was indexed by maternal blood lead level during pregnancy. The adverse effects of lead on growth during the first year of life were reported previously. This analysis covers essentially the second and third years of life. The results indicate that mean blood lead level during this period was negatively associated with attained height at 33 months of age (P = .002). This association was, however, evidenced only among those children who had mean blood lead levels greater than the cohort median (greater than or equal to 10.77 micrograms/dL) during the 3- to 15-month interval. The results also suggest that the effect of lead exposure (both in utero as well as during the first year of life) are transient provided that subsequent exposure to lead is not excessive. It appears that maintaining an average blood lead level of 25 micrograms/dL or more during the second and third year of life was detrimental to the child's attained stature at 33 months of age. Approximately 15% of this cohort experienced these levels of lead exposure. Continued follow-up of this cohort will reveal whether these lead-related deficits persist and whether they continue to be dependent on the level of exposure in an earlier period.

Body Height↗
PubMed1991

Prevalence of hemodynamically significant stenosis of the carotid artery in an asymptomatic veteran population.

The results of previous studies have suggested that significant stenosis of the carotid artery occurs in less than 6 per cent of asymptomatic patients. However, some populations studied were not representative of those seen by most vascular surgeons. Accordingly, we examined two cohorts of patients at the Veterans Administration Medical Center using Duplex scanning. There were 153 volunteers in group 1, all more than 50 years of age, who were being treated at our outpatient department for nonvascular problems. There were 116 patients of similar age in group 2 but who were known to have significant arterial occlusive disease of the lower extremity. The majority of patients were men with a mean age of 64.4 years. Risk factors in the total population included hypertension, diabetes mellitus, coronary arterial disease, peripheral vascular disease and smoking. Over-all, significant (greater than 50 per cent diameter) stenosis of the carotid artery was discovered in 25 of 269 patients. The prevalence for those in group 1 was 6.5 per cent versus 12.9 per cent for those in group 2 (p = 0.058). The prevalence in patients with cardiac disease was 15.2 per cent compared with 6.8 per cent in those without cardiac disease (p = 0.032). Smoking was associated with a 10.6 per cent rate of significant disease compared with a 2.3 per cent rate in nonsmokers (p = 0.065). Hypertension and diabetes were not significant risk factors. Significant stenosis of the carotid artery was found in seven of 40 patients in whom coronary arterial disease, peripheral vascular disease and smoking were all present.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Preferential use of EPTFE for above-knee femoropopliteal bypass grafts.

We have used polytetrafluoroethylene preferentially for bypasses to the above-knee popliteal artery since 1979. Since this approach has recently been challenged, we reviewed our experience with 138 grafts in 128 patients. The majority (74%) of patients were male with a mean age of 63.2 years. Risk factors included: smoking (85%), hypertension (55%), diabetes mellitus (45%), and coronary artery disease (41%). The indications for operation were disabling claudication (18%), rest pain (42%), gangrene/tissue loss (33%), and miscellaneous (7%). Perioperative (30 day) mortality was 3% and morbidity (excluding amputation or graft failure) was 5%. Patients were followed for up to eight years with a mean follow-up of 22.1 months. Grafts which remained patent, but did not prevent major amputation, were classified as "failed". Primary patency was 75% at one year and 54% at five years. Limb salvage was 88% at one year and 70% at five years. Risk factors, indication for operation and arteriographic runoff had no statistically significant impact on short- or long-term patency. However, bypass grafts to isolated popliteal segments had a significantly (p = 0.025) increased perioperative failure rate compared to all other grafts. Our data support the continued use of polytetrafluoroethylene for above-knee femoropopliteal bypass except perhaps in patients who require grafting to an isolated popliteal segment where higher early failure rates were seen.

Aged↗
PubMed1990

Evidence for 5-HT2 receptor mediation in quipazine anorexia.

Doses of d-amphetamine (3.2 mg/kg), fenfluramine (10 mg/kg) and quipazine (8 mg/kg) cause a significant reduction in food intake during a 30-min daily feeding session in food-deprived rats. Pirenperone and ritanserin, 5-HT2 receptor antagonists, significantly blocked the anorectic effect of quipazine, while d-amphetamine and fenfluramine effects were not modified. Metergoline, a non-specific blocker of 5-HT receptors, significantly blocked the anorectic effects of fenfluramine and quipazine, but not the d-amphetamine effect. Pretreatment with alpha- and beta-adrenergic receptor antagonists (prazosin, propranolol and pindolol), dopamine receptor antagonists (haloperidol and pimozide), the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine, and the opioid receptor antagonist naloxone failed to modify the anorectic effects of all three agents, with the exception that quipazine-induced anorexia was significantly reduced by pimozide. These results suggest that the quipazine anorexia is largely mediating through 5-HT2 receptors, although the effect of pimozide remains to be explained. Consistent with previous studies, the fenfluramine effect appears to be mediated through 5-HT1B receptors. Receptors involved in the anorectic effect of higher doses of d-amphetamine are still unidentified by this analysis. Further investigation is required to define the mechanisms by which quipazine and larger doses of d-amphetamine bring about a reduced appetite for food.

Amphetamine↗
PubMed1990

Protection of adults rechallenged with a human rotavirus.

Previous studies of adults challenged with human rotavirus (CJN strain) showed that 74% became infected and 55% of those infected experienced illness. Protection against infection correlated with rotavirus antibody, most significantly (P = .005) serum rotavirus IgG. In this study, 20 previously challenged subjects were reinoculated with the same virus 9-12 months after their initial challenge. Only 1 of 8 subjects not infected after the initial challenge and 2 of 12 infected after the first inoculation became infected after reinoculation; none became ill. Titers of rotavirus antibodies (serum, jejunal, and stool) at the time of reinoculation were about as high as or higher than they were before the initial inoculation. This correlated with greater protection, but the extent of protection was significantly greater (P less than .0001) than predicted based on a previous model relating protection and preinoculation titers of serum rotavirus IgG. Thus, inoculation with human rotavirus provided homotypic protection for at least 9-12 months, and protection remained correlated with higher concentrations of rotavirus antibody. However, the specific relationship between protection and rotavirus antibody was altered after the initial inoculation.

Adult↗
PubMed1990

Lead effects on postural balance of children.

The postural sway responses of 63 children with a mean age of 5.74 years were quantified with a Force Platform technique. The average maximum (max) blood lead (PbB) of these children during the first 5 years of life was 20.7 micrograms/dL (range 9.2 to 32.5). The backward stepwise regression analysis for sway area response during the eyes-closed, no-foam test with all the covariates and confounders and the PbB parameters showed a significant relationship with peak or max PbB during the second year of life. These results are consistent with our previous study with a smaller group of children. The data have been analyzed to provide some insight into the role of various afferent for the maintenance of postural balance. The results suggests a hypothesis that if the max PbB had caused some level of impairment in the functional capacities or interconnectivity of the vestibular and/or proprioception systems at 2 years of age, then it is reasonable to assume that the redundancy in the postural afferent systems would naturally adapt to rely more on the remaining intact afferent system (in this case, vision).

Afferent Pathways↗
PubMed1989

Evaluation of the yield stress of normal blood as a function of fibrinogen concentration and hematocrit.

The yield stress is a sensitive index of blood fluidity at low shear. Seven healthy adults were studied at hematocrits varying between 40 and 80% and fibrinogen concentrations from 0.0 to 0.935 g/dl. Multivariable analysis was used to determine the functional dependence of yield stress on hematocrit and fibrinogen level. The major findings from this analysis include a decreasing effect of fibrinogen at high concentrations (saturation effect), a relative insensitivity of yield stress to fibrinogen at low concentration (threshold effect), and a strong interaction between the effects of hematocrit and fibrinogen concentration on yield stress. Our results give the normal range of yield stress for a given value of fibrinogen and hematocrit and can be used to predict the effect of reductions in hematocrit or fibrinogen on the yield stress of normal blood.

Adult↗
PubMed1989

Mechanisms by which lead depresses linear and ponderal growth in weanling rats.

Lead is known to reduce linear and ponderal growth in children, even at levels of exposure common in the general population. The mechanism involved is not known. The present study was conducted in order to establish the role of food consumption and insulin-like growth factor (IGFI), also commonly known as somatomedin C (SmC), in lead-induced reduction in growth in weanling rats. A further purpose was to test the hypothesis that depressed growth could be prevented by administration of growth hormone and thyroxine, a procedure which prevents arrested growth due to hypophysectomy. Treatment with growth hormone in combination with thyroxine had no effect on depressed growth or food consumption. The reduction in linear and ponderal growth due to lead (approximately 17%) could be largely though not completely accounted for on the basis of reduced food consumption, apparently by a mechanism not involving growth hormone or thyroxine (see above). Plasma SmC was reduced in proportion to reduced food intake, regardless of whether due to Pb or to restriction of food intake in a pair-feeding experiment thereby ruling out an effect of lead on SmC synthesis or activity other than through reduced food consumption. The experiments leading to these conclusions all involved administration of lead in the drinking water, suggesting the possibility that reduced food consumption was peripherally mediated as a result of contact of lead with appetite-depressant receptors in the gastrointestinal tract, e.g., taste receptors. An additional experiment therefore was conducted comparing food consumption and growth resulting from oral lead administration to subcutaneous administration. Similar depressant effects on food consumption and growth resulted at similar concentrations of lead and zinc protoporphyrin in blood. These effects were significantly greater following oral administration, however, suggesting that lead depresses appetite by both a systemic mechanism and one operating at the level of the gastrointestinal tract.

Animals↗
PubMed1989

Disruption of FR-40 by 5-HT agonists. I. Effects of chronic imipramine or trazodone.

Doses of LSD, quipazine, 8-OHDPAT and TFMPP were established that prominently disrupted FR-40 operant response pattern in two groups of rats. Subsequently, one group received daily intraperitoneal (IP) injections of imipramine, 2.5 mg/kg, for 4 weeks, then 10 mg/kg for 2 additional weeks. The second group received 5 mg/kg/day, IP, of trazodone for the first 4 weeks, then 20 mg/kg/day for the next two weeks. For these periods and the 3 weeks after discontinuing the chronic drug treatments (washout), test doses of the 4 agonists were evaluated twice weekly in random order for their effects to decrease FR-40 reinforcements and increase pauses. No consistent, systematic changes in sensitivity to the agonist effects on FR-40 behavior were observed during chronic drug treatments, although significant effects were at times observed. However, during the washout period in the imipramine group, both LSD and 8-OHDPAT effects on reinforcements were reversed to baseline levels. The effect of 5-OHDPAT on pauses during washout in this group was also attenuated. During washout in the trazodone group, the 8-OHDPAT-induced pausing and loss of reinforcements was reduced so as to be not significantly different from baseline values. Previous studies have demonstrated antagonism of LSD- and quipazine-induced disruption of FR-40 by pretreating with the 5-HT2-selective antagonist pirenperone (28). Since chronic antidepressants down-regulate brain 5-HT2 binding sites, the effects of LSD and quipazine were expected to be attenuated, which was not the case.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Disruption of FR-40 by 5-HT agonists. II. Effects of chronic phenelzine or isocarboxazid.

Effects of chronic treatment with the monoamine oxidase inhibitors phenelzine and isocarboxazid on disruption of FR-40 operant responses by 5-HT agonists have been studied. Three groups of rats that were trained in the FR-40 operant schedule showed marked disruption by 0.1 mg/kg IP lysergic acid diethylamide (LSD), 2 mg/kg IP quipazine (Q), 0.05 mg/kg SC 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), and 1 mg/kg SC (m-trifluoromethyl-phenyl)piperazine (TFMPP), administered twice weekly in random order. Subsequently, one group received daily IP injection of phenelzine (5 and 10 mg/kg), the second group received 5 mg/kg IP of isocarboxazid, and the third group received vehicle (0.5% methyl cellulose) for 24 days (Period 1 and Period 2). For these periods and 12 days after discontinuing the MAOI treatments (Washout Period), test doses of 5-HT agonists were evaluated for their effects to decrease reinforcements (R) and increase pauses (P). No change in sensitivity to the LSD, Q and TFMPP effects on FR-40 behavior was observed in the vehicle-treated group. However, an attenuated effect of 8-OHDPAT was found in this group. In phenelzine- and isocarboxazid-treated rats the disruption of FR-40 responses by LSD and 8-OHDPAT were significantly reduced during Period 1, Period 2 and Washout Period. A significantly less effect on disruption in FR-40 responses by quipazine and TFMPP during Period 2 and the Washout Period was also seen. Since MAO inhibitors appear to down-regulate both 5-HT1 and 5-HT2 binding sites in brain, the attenuated effects of the 5-HT agonists were anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of antibody to rotavirus on protection of adults challenged with a human rotavirus.

Effects of preinoculation rotavirus antibody titers on the probability of infection and illness were evaluated in adults challenged orally with different doses of a virulent human rotavirus (CJN strain). Preinoculation titers considered were serum neutralizing antibody, serum rotavirus IgA, serum rotavirus IgG, jejunal neutralizing antibody, jejunal rotavirus IgA, and stool rotavirus IgA. Doses of virus of either 9 x 10(1) or 9 x 10(3) focus-forming units were administered to 19 subjects each. Twenty-six were infected; 15 experienced illness. The probability of either outcome was unrelated to dose. Stool rotavirus IgA titers could not be correlated to either infection or illness, but the mean titers of the other five antibodies were significantly or nearly significantly lower in subjects infected or ill, when compared with those negative for either outcome. When analyzed by stepwise logistic regression, only serum rotavirus IgG remained significantly (P = .005) related to the probability of infection, and only jejunal neutralizing antibody remained significantly (P = .01) related to the probability of illness.

Adult↗
PubMed1989

Neurobehavioural effects of short duration exposures to acetone and methyl ethyl ketone.

A total of 137 volunteers were recruited and tested for neurobehavioural performance before, during, and after a short duration (4 h) exposure to acetone at 250 ppm, methyl ethyl ketone (MEK) at 200 ppm, acetone at 125 ppm with MEK at 100 ppm, or a placebo. Ethanol (95%-0.84 ml/kg) was used as a positive control. Performance testing was computer controlled and took place in an environmental chamber with four test stations. The total test regimen before, during, and after exposure covered 10 hours and 32 measures were collected. The measurements were extracted from two biochemical (venous blood and alveolar breath) tests, four psychomotor (choice reaction time, visual vigilance, dual task (auditory tone discrimination and tracking), memory scanning) tests, one sensorimotor (postural sway) test, and one psychological (profile of mood states (POMS] test. The exposure to 250 ppm acetone produced small but statistically significant changes in performance from controls in two measures of the auditory tone discrimination task and on the anger hostility scale (men only) of the POMS test. Neither MEK nor the combined acetone/MEK exposures produced statistically significant interpretable results. The combination exposure provides some indication that there was no potentiation of the acetone effects with the coexposure to MEK or vice versa. More pronounced performance decrements occurred with ethanol at 0.07-0.08% BAC. Significant (less than 0.05) differences were evident on both the auditory tone and tracking tests in the dual task and there was partial significance on the visual vigilance test (0.05-0.06) and some postural sway measures (less than 0.09). These findings agree with an earlier Japanese study in showing some mild decrements on behavioural performance tests with exposures to acetone at 250 ppm.

Acetone↗