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Biomedical subjects

M A Khan

Publications and source records attributed to M A Khan.

At least 19 recordsLinked to original sources
PubMed1996

Depolarization-induced tyrosine phosphorylation of paxillin in PC12h cells.

Treatment of PC12h cells with a high concentration of KC1 induces depolarization of the plasma membrane and Ca2+ influx into the cells. We have previously shown that KC1 induced tyrosine phosphorylation of cellular proteins of 120, 110, 68, 44 and 42 kDa. In the present study, we found that the 68-kDa protein is paxillin, a tyrosine kinase substrate associated with the actin cytoskeleton. A calcium ionophore, A23187, also induced tyrosine phosphorylation of the 68-kDa protein, while KC1 did not in the presence of EGTA or nifedipine, indicating that the effect of KC1 was due to the Ca2+ influx into the cells. Tyrosine phosphorylation of paxillin was also induced by nerve growth factor and epidermal growth factor, but its migration patterns on an SDS/polyacrylamide gel were different, that is, nerve growth factor and epidermal growth factor caused upward shifts of the bands, while KC1 did not. However, both forms could associate with Csk and Crk. The effect of KC1 was blocked by cytochalasin D, indicating that tyrosine phosphorylation required the integrity of actin filaments. These results suggest that tyrosine phosphorylation of paxillin may be involved in Ca2+ -dependent events in neuronal and neuroendocrine cells.

Animals↗
PubMed1996

Diabetes in pregnancy in Pakistani women: prevalence and complications in an indigenous south Asian community.

The aim of this study was to determine the prevalence and complications as well as to correlate maternal and fetal outcome with glycaemic control, in a community of Pakistani women. This was a retrospective study of 6830 deliveries over a 5-year period in a tertiary care hospital in Karachi. Either a 75 g glucose tolerance test or a screening 50 g glucose challenge was administered depending on risk factors for Gestational Diabetes Mellitus (GDM). Case records of deliveries during this period were analysed for presence of GDM or pre-existing diabetes; glycaemic control and complications were ascertained for those with diabetes. During this period 267 (3.9%) of the 6380 deliveries were identified as diabetic pregnancies. Of these 223 (3.3%) had GDM and 44 (0.6%) women had pre-existing diabetes mellitus. Overall maternal complications were high; pre-eclampsia (19%), polyhydramnios (4.6%), and threatened abortion (3.4%). Fetal complications of macrosomia (13.1%), intrauterine growth retardation (7.1%), intrauterine deaths (5.3%) were noted. Complications were higher in poorly controlled groups. We conclude that the prevalence of GDM in Pakistani women in our study was comparable to their Western counterparts but complication rates were higher, possibly due to poorer glycaemic control.

Adult↗
PubMed1996

Clastogenic effects of defined numbers of 3.2 MeV alpha particles on individual CHO-K1 cells.

Research to determine the effects of defined numbers of alpha particles on individual mammalian cells is helpful in understanding risks associated with exposure to radon. This paper reports the first biological data generated using the single-particle/single-cell irradiation system developed at Pacific Northwest Laboratory. Using this apparatus, CHO-K1 cells were exposed to controlled numbers of 3.2 MeV alpha particles, and biological responses of individual cells to these irradiations were quantified. Chromosomal damage, measured by the induction of micronuclei, was evaluated after no, one, two, three or five particle traversals. Exposures of up to five alpha particles had no influence on the total numbers of cells recovered for scoring. With increased numbers of alpha particles there was a decrease in the ratio of binucleated to mononucleated cells of 3.5%/hit, suggesting that alpha particles induced dose-dependent mitotic delay. A linear hit-response relationship was observed for micronucleus induction: Micronuclei/binucleated cell = 0.013 +/- 0.036 + (0.08 +/- 0.013) x D, where D is the number of particles. When the estimated dose per alpha-particle traversal was related to the frequency of induced micronuclei, the amount of chromosomal damage per unit dose was found to be similar to that resulting from exposures to alpha particles from other types of sources. Approximately 72% of the cells exposed to five alpha particles yield no micronuclei, suggesting the potential for differential sensitivity in the cell population. Additional studies are needed to control biological variables such as stage of the cell cycle and physical parameters to ensure that each cell scored received the same number of nuclear traversals.

Alpha Particles↗
PubMed1995

Nerve growth factor stimulates tyrosine phosphorylation of paxillin in PC12h cells.

Nerve growth factor (NGF) induces tyrosine phosphorylation of various cellular proteins to activate multiple signal transduction pathways. We show that one of these proteins is paxillin, a cytoskeletal component associated with adhesion plaques. Phospho-amino acid analysis showed that NGF stimulated phosphorylation of its serine in addition to tyrosine residues. Tyrosine phosphorylation of paxillin by NGF was blocked by the pretreatment of the cells with cytochalasin D, an inhibitor of actin polymerization. These results suggest that phosphorylation of paxillin is involved in the signaling pathway of NGF in PC12 cells.

Animals↗
PubMed1995

Clinicopathological features and management of immunoproliferative small intestinal disease and primary small intestinal lymphoma in Pakistan.

This study was performed to confirm the existence of immunoproliferative small intestinal disease (IPSID) in Pakistan. Clinicopathological features of 12 patients with histologically confirmed disease were analysed. Patients were mostly young males with median age of 24.6 years. Two thirds belonged to poor socioeconomic class. Main presenting features were chronic diarrhoea and weight loss. Eleven patients had radiologic evidence of malabsorption syndrome. Endoscopic findings of mucosal thickening, edema, and flattened villi were present in the majority. Patients had both secretory and non-secretory types of disease. Six patients presented with stage A disease. Four responded to antibiotics or steroids, although mucosal abnormalities persisted in three. Two stage A patients evolved into stage C disease, one was lost to follow-up, the other is alive with disease. Three patients presented with stage B disease. Two responded completely to chemotherapy, the third refused treatment and expired after 16 months. Three patients had stage C disease at diagnosis. They received aggressive combination chemotherapy and remain in complete remission with a median follow-up of 2.2 years. This is the first series of patients with IPSID reported from Pakistan. Clinicopathological features and therapeutic results are consistent with the experience elsewhere. Increased awareness may result in early diagnosis and better management.

Adult↗
PubMed1995

Inhaled radon-induced genotoxicity in Wistar rat, Syrian hamster, and Chinese hamster deep-lung fibroblasts in vivo.

This study was performed (1) to provide a comparison of the genotoxic effects of inhaled radon and radon progeny, referred to as radon in this paper, among three species of rodents: Wistar rats, Syrian hamsters, and Chinese hamsters; (2) to determine if initial chromosome damage was related to the risk of induction of lung cancer; and (3) to evaluate the tissue repair and long-term presence of cytogenetic damage in respiratory tract cells. These species were selected because Syrian hamsters are very resistant to radon induction of lung cancer and Wistar rats are sensitive; no literature is available on the in vivo effects of radon in the Chinese hamster. Exposure-response relationships were established for the rats and Syrian hamsters while the Chinese hamsters received a single exposure of radon. At 4 h (0.2 days), 15 days, and 30 days after the highest WLM exposure to radon, Wistar rats, Chinese hamsters, and Syrian hamsters were killed, and lung fibroblasts were isolated and grown in culture to determine the frequency of induced micronuclei. Animals at each level of exposure showed an increase in the frequency of micronuclei relative to that in controls (P < 0.05). The exposure-response relationship data for rats and Syrian hamsters killed 0.2 days after the end of exposure were fit to linear equations (micronuclei/1000 binucleated cells = 15.5 +/- 14.4 + 0.53 +/- 0.06 WLM and 38.3 +/- 15.1 + 0.80 +/- 0.08 WLM, respectively). For the single exposure level used (496 WLM) in Chinese hamsters killed at 0.2 days after exposure, the frequency of micronuclei/1000 binucleated cells/WLM was 1.83 +/- 0.02. A comparison of the sensitivity for induction of micronuclei/WLM illustrated that Chinese hamsters were three times more sensitive than rats. The Syrian hamsters also showed a significantly elevated response (P < 0.05) relative to rats. These data suggest that initial chromosome damage is not the major factor responsible for the high rate of radon-induced cancer in rats relative to Syrian hamsters. The frequency of micronuclei in radon-exposed rats, Syrian hamsters, and Chinese hamsters significantly decreased (P < 0.05) as a function of time after the exposure. The rate of loss of damaged cells from the lung was greatest in the Chinese hamsters, followed by Wistar rats and Syrian hamsters, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants, Radioactive↗
PubMed1995

Effects of myotoxins on skeletal muscle fibers.

This review highlights various aspects of a number of experimental myological alterations, induced by different chemical toxicants, including anticholinesterase, colchicine, vincristine, chloroquine, tetanus toxin, botulinum toxin, reserpine and emetine. Despite their chemical diversity and mechanism(s) of action, it is evident from the data discussed here that remarkably different toxic agents exert quite similar effects and induce toxic myopathies. The latter include preferential involvement of slow-twitch red muscle, mitochondrial derangement, denervation-like alterations, formation of membranous whorls, tubular aggregates, autophagic vacuoles and axonal sprouts. The non-invasive experimental models discussed here are valuable in studying various aspects of myopathology in the absence of any mechanical damage to the innervating elements from neurons to axonal terminals.

Chloroquine↗
PubMed1995

Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: results of a prospective randomized trial.

PURPOSE: We recently demonstrated the efficacy of single-agent oral ofloxacin in the management of hospitalized neutropenic febrile patients. Ofloxacin was particularly effective in patients with short duration of neutropenia and fever of undetermined origin. These results prompted us to study the feasibility of outpatient management of neutropenic febrile patients who are otherwise at low risk of morbidity and mortality. PATIENTS AND METHODS: This multi-institutional, prospective, randomized trial included 182 low-risk neutropenic febrile episodes. After an initial work-up for fever, patients were randomized to receive oral ofloxacin 400 mg immediately and twice daily thereafter in the hospital or as outpatients. Close monitoring and follow-up were carried out in all patients. Those who failed to respond and remained febrile were given parenteral antibiotics. Nonresponding outpatients were admitted to the hospital for parenteral therapy. RESULTS: One hundred sixty-nine episodes were evaluable. The hospital and outpatient treatment groups had comparable clinical characteristics. Pyrexias of undetermined origin (PUO) comprised 69% of episodes managed in hospital and 73% of episodes treated outside. The success rate with PUO was similar with inpatient and outpatient management. Patients with clinical and microbiologic infections fared less well than those with PUO. Overall, 78% of inpatient and 77% of outpatient fevers resolved with no modification of the initial treatment. Twenty-one percent of patients originally assigned to outside management required hospitalization. Mortality was 2% among inpatients and 4% among outpatients. One early death in a nonhospitalized patient underscores the need for close monitoring and surveillance in these cases. CONCLUSIONS: Outpatient management of low-risk neutropenic febrile patients with ofloxacin is as effective as inpatient management with the same agent. This approach should be limited to the subset of patients with low-risk factors who are not otherwise on quinolone prophylaxis.

Adult↗
PubMed1995

The effects of medically-orientated labour ward routines on prefeeding behaviour and body temperature in newborn infants.

The effects of medically-orientated labour ward routines were studied during the the first hour after birth, in 48 vaginal, single deliveries. All infants were immediately separated from their mothers and left on a resuscitation table. There was no significant difference in onset of crying if the infant received cutaneous stimulation or not. It was found that 17 infants, not showing hand-to-mouth activity, were bathed at an average time of 17 min (12-23 min) after birth, while those who did were bathed at 28.5 (24.5-41.5) min (P = 0.002). One infant was breastfed during the first hour. Being separated from its mother, bathed early, and swaddled after birth seemed to interfere with the infant's inborn ability to signal hunger. Forty-one infants were hypothermic at 1 hour. According to a multiple regression analysis infant body temperature at 60 min of age corresponded positively with birth weight (P = 0.0001) and time of oxygen administration (P = 0.0002). A plausible explanation for the effect of oxygen exposure is that there is brown fat inactivation in normal newborn infants and administration of oxygen activates the brown fat. It might be advantageous to let the mother keep the baby warm, rather than manipulate the baby's metabolism with oxygen.

Birth Weight↗
PubMed1995

Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial.

Nausea and vomiting are extremely common and most distressing side effects of high-dose cisplatin therapy. Cisplatin induces anticipatory and acute, as well as, delayed emesis. High doses of metoclopramide can effectively decrease the intensity of these symptoms in up to 70% of cases. Several agents, including dexamethasone and antihistamines have been demonstrated to either increase the efficacy of metoclopramide or decrease the side effects. Lorazepam, a benzodiazepine, has both antiemetic and anxiolytic properties. It can be useful as an adjunct to metoclopramide-based therapy. We conducted a randomized trial to evaluate the efficacy of lorazepam in managing anticipatory, acute, and delayed emesis induced by high doses of cisplatin. A total of 180 events involving cisplatin administration (100 mg/m2 as a 24-hour continuous infusion) were randomized to receive metoclopramide along with dexamethasone and clemastine with and without lorazepam. Categorical scales were utilized to document the incidence of nausea and vomiting and side effects related to antiemetic therapy. All episodes are evaluable. Lorazepam significantly reduced the incidence of anticipatory nausea and vomiting (P < .05) as well as acute emesis (P = .05) induced by cisplatin. Delayed emesis was also decreased; however, it was statistically significant on day 3 only (P < .05). Side effects were few except for mild sedation and amnesia, which were significantly more common in those receiving lorazepam (P < .001). We conclude that lorazepam increases the efficacy of metoclopramide against cisplatin-induced anticipatory, acute, and delayed nausea and vomiting. This four-drug regimen may offer one of the best combinations to be utilized in comparative trials against the newly introduced serotonin antagonists.

Adult↗
PubMed1995

HLA-B27 and its subtypes in world populations.

Twenty-five years ago, HLA-B27 was recognized as a new HLA specificity. It is present throughout Eurasia but is virtually absent among the genetically unmixed native populations of South America, the Bantus and Sans (Bushmen) of equatorial and southern Africa, and the aborigines of Australia. B27 is a serologically determined specificity that encompasses nine different allotypes (subtypes), B*2701 to B*2709. Ankylosing spondylitis or related spondyloarthropathies thus far have been documented in individuals with any of the following five subtypes: B*2701, B*2702, B*2704, B*2705, or B*2707.

Africa↗
PubMed1995

Atlantoaxial instability in Down's syndrome: a five year follow up study.

In 1986 all 90 children aged 4-19 years with Down's syndrome attending school in the area served by the Southern Derbyshire Health Authority underwent radiography to identify atlantoaxial instability (AAI). This study details repeat observations five years later. Full results were available on 67 (74%), information on health status was available on the remaining 19 (21%); four (4%) were untraced. There was an overall significant reduction in the atlanto-axial gap over five years. No one developed AAI on repeat testing who had not had it earlier. One child who had previously had normal neck radiography developed acute symptomatic AAI after ear, nose, and throat surgery. Radiographs were done on three occasions on the same day in 49 individuals, ensuring full flexion of the upper neck. There were no significant differences between the radiographs, even in five subjects with AAI. Management of AAI in Down's syndrome is discussed in the light of these findings. Radiography can reliably detect children with chronic AAI who may be at risk of gradually developing symptoms; this may justify a screening programme. This must be distinguished from those who develop symptoms after acute trauma or anaesthesia, for which specific precautions are needed, and previous screening radiographs are unhelpful.

Adolescent↗
PubMed1995

Atrial arrhythmias and pacing after orthotopic heart transplantation: bicaval versus standard atrial anastomosis.

BACKGROUND: Right and left atrial configuration is more normal when the donor left atrium is anastomosed to a recipient left atrial cuff with direct anastomoses of the donor and recipient vena cavas on the right side. The right atrium and sinus node may be less disturbed by the technique of bicaval anastomosis than by the standard procedure. OBJECTIVE: To compare the incidence of atrial arrhythmias and pacing after bicaval and standard anastomoses. METHODS: 75 patients had heart transplants between January 1991 and December 1993. The notes were reviewed. Nine patients who died within the first 30 days were excluded from further analysis (seven patients with standard anastomoses, one with bicaval anastomosis, and one with a hybrid technique). RESULTS: 66 patients survived for more than 30 days. Thirty five patients had standard anastomoses and 31 bicaval anastomoses. Atrial tachyarrhythmias (atrial fibrillation, atrial flutter, atrial tachycardia, or supraventricular tachycardia) occurred on four days in three patients in the bicaval group compared with 27 days in 13 patients in the standard group (P = 0.009). The relative risk of atrial tachyarrhythmias with standard anastomosis was 5.52 (P = 0.015) compared with that of bicaval anastomosis. Atrial tachyarrhythmias requiring treatment occurred less often in the bicaval group (four episodes in three patients in the bicaval group and eight episodes in four patients in the standard group), and fewer patients with a bicaval anastomosis required temporary pacing (pacing on 20 days in 10 patients in the bicaval group, but pacing on 49 days in 16 patients in the standard group) and late permanent pacing (no patients in the bicaval group and three patients in the standard group), although these differences were not statistically significant. Patients in the bicaval group were discharged from hospital sooner than those in the standard group (mean 24.1 v 29.1 days, P = 0.024). CONCLUSIONS: The technique of bicaval anastomosis, in addition to theoretical advantages from maintaining a more normal atrial configuration, has a lower incidence of postoperative atrial tachyarrhythmias, may reduce the need for pacing, and allows earlier discharge from hospital.

Adult↗