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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 73 records · Page 4Linked to original sources

Sequelae after esophageal variceal ligation and sclerotherapy: a prospective randomized study.

OBJECTIVES: Esophageal variceal ligation is a new approach to the treatment of esophageal varices that does not result in transmural tissue injury and inflammation, and therefore might produce fewer sequelae and symptoms than sclerotherapy. We conducted a prospective, randomized comparison of sclerotherapy with ligation to study the relative short-term risks of these two procedures with respect to bacteremia, pulmonary and coagulation function, esophageal motility, and gastroesophageal reflux. METHODS: Patients with previously documented high grade esophageal varices were randomized to receive sclerotherapy or ligation. Blood was drawn for culture and coagulation profiles, and patients underwent pulmonary function tests, esophageal manometry, and intraesophageal pH monitoring before and after treatment. RESULTS: Six patients with Childs class B cirrhosis and one patient with pre-sinusoidal portal hypertension underwent 20 courses of therapy. Neither sclerotherapy nor ligation produced significant clinical changes in pulmonary or coagulation parameters, or bacteremia requiring treatment. The majority of ligation treatments were without worsening of motility or reflux scores, and none were associated with symptoms. Sclerotherapy was followed by significantly greater esophageal dysmotility and worsening reflux patterns. CONCLUSIONS: Patient acceptance of ligation was much greater than that for sclerotherapy. Our data define the advantages of ligation over sclerotherapy.

Bacteremia

Glutathione and glutathione linked enzymes in human small cell lung cancer cell lines.

Glutathione levels and several glutathione-linked enzyme activities have been variably correlated with cisplatin chemosensitivity in cultured neoplastic cells. In order to determine the relative contribution of the glutathione-linked enzymes towards mediating inherent cisplatin resistance in cancer cells, we have measured the chemosensitivity to cisplatin, glutathione levels and activities of glutathione S-transferase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase in 8 cultured human small cell lung cancer (SCLC) cell lines with widely differing cisplatin sensitivities. Of these parameters, only glutathione S-transferase activity correlated with degree of cisplatin resistance in a linear fashion.

Carcinoma, Small Cell

Synthetic peptides derived from the sequence around the plasmin cleavage site in vitronectin. Use in mapping the PAI-1 binding site.

A series of 8 peptides derived from the amino acid sequence accommodating the plasmin cleavage site in vitronectin were synthesized and used to map its binding site for the type I plasminogen activator inhibitor (PAI-1). This mapping assigned the inhibitor binding site to the K348-R370 region with high affinity recognition elements within the K348-R357 sequence. These results account for our previous finding that cleavage of the R361-S362 bond by plasmin significantly reduces the affinity between PAI-1 and vitronectin, since it splits the PAI-1 binding site in two. Furthermore, in the case of the two-chain form of vitronectin, this cleavage detaches the S362-R379 peptide which provides some of the affinity elements for the binding of PAI-1.

Amino Acid Sequence

Sleep-inducing function of noradrenergic fibers in the medial preoptic area.

The aim of the investigation was to find out the role of noradrenergic (NE) terminals of the medial preoptic area (mPOA), in the regulation of sleep-wakefulness. Studies were conducted on free-moving adult male rats with chronically implanted cannulae in the mPOA. Sleep-wakefulness was assessed on the basis of EEG, EMG, and EOG recordings along with behavioral observations. Lesioning of catecholamine terminals (with 6-hydroxydopamine) in the mPOA produced an increase in quiet wakefulness. Prevention of NE fiber destruction, by pretreating the rats with imipramine, prevented this effect. This demonstrated that the increased quiet wakefulness produced by 6-OHDA was the result of NE fiber destruction. Changes in sleep-wakefulness were also assessed after microinjection of NE into the mPOA, in normal and ventral noradrenergic bundle (VNA)-lesioned rats. NE administration induced sleep in VNA-lesioned rats, and arousal in normal rats. The findings suggest that the NE terminals in the mPOA, projecting via VNA, play a role in the induction of sleep.

Animals

Comparative studies on the effect of butylated hydroxyanisole on glutathione and glutathione S-transferases in the tissues of male and female CD-1 mice.

1. Male CD-1 mice had about 1.6-fold higher glutathione (GSH), 2-fold higher glutathione S-transferase (GST) activity and 2.8-fold higher GST protein in their livers as compared to the female mice. 2. When mice were fed a diet containing 0.75% BHA for 2 weeks, a 1.8-fold increase was observed in GSH levels of female mice liver as opposed to only 1.2-fold increase in male mice. BHA caused 10-fold increase in GST activity and protein in livers of female mice as compared to only about 3-4-fold increase in livers of males. Differential induction of GSH and GST in males and females was also observed in other tissue besides liver but was not as remarkable. 3. Sex-related differences were also observed in the induction of the alpha- and mu- and pi-classes of GSTs by BHA; most noticeable being GST pi, which was induced to about 10-fold in female liver as opposed to only 3.4-fold in male liver.

Animals

The actions of RFamide neuroactive peptides on the isolated heart of the giant African snail, Achatina fulica.

1. The effects of a range of RFamide peptides were examined on the frequency, amplitude and tone of the isolated heart of Achatina fulica. 2. FMRFamide, FLRFamide and SDPNFLRFamide were potent excitants while LPLRFamide, KHEYLRFamide and GSFFRFamide were weak excitants. 3. DNFLRFamide and SSLFRFamide were potent inhibitory peptides while LFRFamide, GSLFRFamide and KNEFIRFamide were weak inhibitory peptides. 4. MRFamide, LRFamide and RFamide were inactive. 5. It is concluded that a tetrapeptide sequence is the minimal requirement for activity on the Achatina heart. With the exceptions of DNFLRFamide and in most preparations GSFFRFamide, LRFamide peptides are excitatory while FRFamide peptides are inhibitory. 6. Due to its inhibitory effect and high potency, the sequence DNFLRFamide warrants further investigation.

Amino Acid Sequence

A novel role for calcium and membrane-binding proteins in regulation of respiratory burst in Ehrlich ascites tumour cells.

The effect of the signals, dexamethasone and phorbol-ester (TPA) and their interplay on the respiratory burst in Ehrlich ascites tumour (EAT) cells and the effect of this interplay has on the phosphorylation state and thus function of EAT cell cytosolic calcium and membrane-binding proteins (CaMBPs) was studied. Dexamethasone (1 mg/kg body weight) inhibited basal and TPA-activated EAT cell respiratory burst. CaMBPs isolated from EAT cells under the influence of either or both signals by a membrane-affinity binding technique showed similar profiles on SDS-PAGE. Autoradiography showed that only an 11,000 M(r) protein is subject to phosphorylation and that dexamethasone brings down the extent of phosphorylation of CaMBPs isolated from control and TPA-treated EAT cells. Phosphorylated CaMBPs from control and TPA-treated cells could activate the respiratory burst in Triton-permeabilized EAT cells in a dose-dependent manner (four- and six-fold activations, respectively, at 16 micrograms protein concentration) when included in the assay, whereas dephosphorylated CaMBPs from EAT cells from mice treated with dexamethasone alone, or later activated with TPA, could not. A phosphatase activity was detected in EAT cell cytosol receiving the dual-signal, dexamethasone and TPA.

Animals

Is spermatozoan acrosin a predictor of fertilization and embryo quality in the human?

OBJECTIVE: To investigate whether acrosin is a more reliable criterion than conventional parameters for assessing semen samples. DESIGN: Total acrosin was estimated biochemically in semen samples obtained for routine screening for infertility and for IVF-ET procedures. SETTING: Assisted Conception Unit, St. James's University Hospital, Leeds, United Kingdom. PATIENTS: Four hundred sixty-three couples being investigated for causes of infertility, and 132 couples undergoing IVF-ET for any indication except antisperm antibodies between 1990 and 1991 were included in the study. INTERVENTIONS: Semen samples were collected as part of routine investigation. Samples from men with consistently high viscosity were collected in alpha-chymotrypsin. MAIN OUTCOME MEASURES: Total spermatozoan acrosin in motile spermatozoa and motile spermatozoan density in couples being assessed for IVF-ET and fertilization and embryo quality in those receiving treatment are considered. RESULTS: Total acrosin levels were less variable (within subject) than either total or motile spermatozoan concentration at ejaculation. Although severely oligozoospermic ejaculates had the lowest levels of total acrosin, overall, there was no significant correlation of spermatozoan concentration between total acrosin levels and percentage fertilization. CONCLUSIONS: Total spermatozoan acrosin activity correlates positively with fertilization rates but not with spermatozoan count. Motile spermatozoan density for insemination may be adjusted to achieve > 7.5 microIU acrosin per oocyte, without compromising fertilization or further embryo development to blastocysts in vitro.

Acrosin

Identification of photo-inactive phytochrome A in etiolated seedlings and photo-active phytochrome B in green leaves of the aurea mutant of tomato.

The contents of spectrophotometrically measurable phytochrome A (PhyA) and phytochrome B (PhyB) and the corresponding immunochemically detectable apoproteins (PHYA and PHYB) were examined in dark- and light-grown tissues of the aurea mutant of tomato and its wild-type (WT). The amount of PHYA in etiolated aurea seedlings was found to be about 20% of that in the WT; this PHYA showed no photo-reversible changes in absorbance, no downregulation of the level of PHYA in light-grown seedlings, and no differential proteolysis of Pr and Pfr species in vitro which was seen in the case of the WT. By contrast, the amount of PHYB in aurea seedlings was not significantly different from that in WT seedlings. Phytochrome isolated from green leaves of the aurea mutant and purified by ion-exchange chromatography showed a red/far-red reversible spectral change, and its elution profile during chromatography was essentially similar to that of PHYB. The results indicate that aurea is a mutant that is deficient in photoactive PhyA at the etiolated stage, when it contains a spectrally inactive PHYA. However, the mutant contains spectrally active PhyB in its green tissue as does the WT.

Enzyme Activation

Effect of radiation on glyoxalase I and glyoxalase II activities in spleen and liver of mice.

Swiss albino mice (7-8 weeks old) were irradiated with different doses (0-25 Gy) of gamma-radiation at a dose-rate of 0.05 Gy/s. The specific activities of glyoxalase I (GI) and glyoxalase II (GII) were determined in the spleen and liver immediately and on the 3rd and 6th day postirradiation. The results indicate that the glyoxalase system is radiosensitive, particularly glyoxalase I whose activity was enhanced even at low doses (0.5 Gy). The magnitude and mode of the radiation effect depends on dose and tissue. The patterns of the GI/GII ratio in the liver and spleen was very similar when measured immediately after irradiation. The radiation effect on the glyoxalase system persists even in the postirradiation period and was inversely related to the dose-rate. GSH and caffeine increased and chlorpromazine decreased the radiation-induced activity of GI, but all three modifiers enhanced radiation-induced inactivation of GII. Since the glyoxalase system may play an important role in the regulation of cell division and differentiation, radiation effects on this system may have some biochemical consequences.

Animals

Postpartum hemorrhage producing acute ischemic optic neuropathy.

A rare case of bilateral peripartum blindness due to acute ischemic optic neuropathy (AION) occurring after an episode of postpartum hemorrhage is described. Massive blood loss and the resultant hypotension was instrumental in reducing the perfusion pressure at the optic nerve head and producing ischemic damage to it.

Acute Disease

Solid tumours of the ovary.

One hundred seventeen solid ovarian tumours, diagnosed histologically during the period between 1971 and 1990, were studied. The overall incidence of solid ovarian tumours was 23.4% of all the ovarian tumours (500 cases) studied. Of 117 solid ovarian tumours 19 (16.2%) were benign and the rest 98 (83.8%) were malignant. Epithelial tumours were the commonest (28.2%) followed by germ cell tumours (22.2%), sex cord stromal tumours (21.4%), metastatic tumours (19.7%) and non-specific tumours (8.5%). The average age (26.8 years) was comparatively low for germ cell tumours otherwise in other groups it ranged between 42 and 45 years. Below 15 years immature teratoma was diagnosed in 4 cases and granulosa cell tumour in 2 cases. Bilateral tumours were seen in 22 cases (23.2%) out of 95 cases observed. Pain and fullness in the pelvic region were observed in 94.9% cases. Varied morphological picture was seen in 6 cases of endometrioid carcinoma. Dysgerminoma constituted 6.8% of solid ovarian tumours. Gliomatosis peritonei was noticed in one case of immature teratoma. Granulosa cell tumour accounted for 11.1% of solid ovarian tumours. Of 23 cases of metastatic tumours, Krukenberg tumour was noticed in 88.9% cases. Diagnostic problems as well as prognostic factors of solid ovarian tumours have been discussed.

Adolescent

GABA B mediated analgesia in tonic pain in monkeys.

The present study was designed to characterise the analgesia produced by the GABA B agonist baclofen in tonic pain in monkeys. The effect of various doses of baclofen was studied on formalin induced pain. Baclofen was injected intraperitoneally 30 min prior to formalin injection in five doses of 2, 4, 6, 8, and 10 mg/kg and the pain was quantified for a period of one hour. Baclofen produced dose related analgesia, 6 mg/kg having maximal effect. The antinociceptive effect of baclofen could be attributed to the effect of baclofen on GABA B receptors producing presynaptic inhibition of primary nociceptive afferents in the dorsal horn of the spinal cord.

Analgesics

Evaluation of radionuclide gastroesophagography as a suitable screening test for detection of gastroesophageal reflux.

Thirty cases of recurrent pulmonary infection and ten control cases underwent radionuclide gastroesophagography endoscopy, histopathology and barium esophagography to evaluate the clinical efficacy of scintigraphic technique in, detection of gastroesophageal reflux. After ingesting 500 micro curie of Tc-Sulphur colloid mixed in milk, patients esophageal activity was monitored using the gamma camera for forty-five minutes continuously. By using histopathology as standard of comparison, the sensitivity and specificity of radionuclide esophagography was 78.54 and 81.25%, respectively. Because of its physiologic nature, low radiation exposure and convenience, radionuclide esophagography is recommended as a suitable screening test for detecting gastroesophageal reflux where available.

Barium Sulfate

WAGR complex.

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Child, Preschool

A hospital-based study on the use of paramedical personnel for clinical downstaging of cancer cervix.

Two auxiliary nurse midwives (ANMs) were recruited and trained to recognize normal and different types of abnormal cervices. A total of 2102 women were examined by a gynaecologist and ANM independently and their findings were noted. Comparison of their findings showed an overall agreement of 89.6 per cent (Kappa 0.84 with standard error of 0.015 and a significantly large Z value of 55.6). Gross examination of 4679 women attending the Gynaecology OPD revealed normal cervix in 49.6 per cent and suspected lesions or malignant cervix in 3.4 per cent of women. Cytology smears were taken in 3608 women. Adequacy of smears was 97 per cent. Comparing the group clinically diagnosed as highly suspected or malignant to the cytologically diagnosed suspected group (atypical and malignant), clinical examination had a sensitivity of 81.7 per cent and specificity of 97.3 per cent; while comparison of the group clinically diagnosed as abnormal cervix to abnormal cytology (all grades of dysplasia, atypical and malignant cells), the clinical examination had a sensitivity of 92.5 per cent and specificity of 37.4 per cent. It was concluded that paramedical staff (ANMs) can be relied upon to do speculum examination in women in the community and take cytology smears in selected cases.

Allied Health Personnel

Effect of superoxide exposure on albumin permeability of isolated rat glomeruli.

Reactive oxygen radicals generated by mesangial cells or by resident or infiltrating macrophages may contribute to glomerular injury in glomerulonephritis. To determine whether superoxide anions have an effect on the glomerular barrier to macromolecules, we studied the responses of isolated glomeruli after exposure to superoxide generated by xanthine and xanthine oxidase or by activated macrophages. Glomerular volumetric responses to oncotic gradients of bovine serum albumin or an impermeant neutral dextran (mol wt 252 kd0 were used to calculate the albumin reflection coefficient (sigma albumin) and convectional permeability to albumin (1-sigma albumin) of control and superoxide-treated glomeruli. Albumin permeability of control glomeruli was not different from 0 (0.02 +/- 0.01, N = 50). After 10 minutes of exposure of glomeruli to superoxide generated by xanthine oxidase, albumin permeability was increased to 0.06 +/- 0.01 (N = 50). Albumin permeability did not increase further after incubations with xanthine and xanthine oxidase for up to 60 minutes. The increase in albumin permeability was prevented by superoxide dismutase (-0.02 +/- 0.01, N = 48) but was not affected by catalase or by indomethacin pretreatment. Coincubation of glomeruli with activated macrophages also increased albumin permeability to a maximum of 0.80 +/- 0.05 (N = 17). Albumin permeability was not increased by incubation of glomeruli with phorbol myristate acetate alone or with macrophages in the absence of phorbol myristate acetate. The effect of activated macrophages on albumin permeability, like that of superoxide generated chemically, was prevented by superoxide dismutase but not by catalase or indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins