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Biomedical subjects

R Hamid

Publications and source records attributed to R Hamid.

52 records · Page 3Linked to original sources
PubMed1997

Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis.

Several epidemiological and experimental studies have indicated a strong relationship between different types of dietary fats and risk of colon cancer. However, the modulating effects of these nutritional factors at the molecular level are not fully elucidated. It has been documented that the modulation of tumorigenesis is associated with changes in the levels of prostaglandins production. To provide an understanding of the mechanism(s) of dietary fat-induced modulation of colon tumor development, we have analyzed the expression of cyclooxygenase (COX), an enzyme that catalyzes the metabolism of omega-3 and omega-6 polyunsaturated fatty acids in a critical step in prostaglandin biosynthesis. Male F344 rats were fed the semipurified AIN-76A diet containing low-fat corn oil and were s.c. injected azoxymethane (AOM) dissolved in normal saline at a dose rate of 15 mg/kg of body weight, once weekly, for 2 weeks. Vehicle controls received s.c. equal volumes of normal saline. One day after the second AOM or saline injection, rats intended to receive experimental diets were provided high-fat corn oil (HFCO) or high-fat fish oil (HFFO) mixed in semipurified AIN-76A diet, and the remaining rats continued to receive the low-fat corn oil diet. Animals were sacrificed 1, 12, or 36 weeks after the last AOM or saline injection, and their colonic mucosa, as well as the grossly visible colon tumors from rats sacrificed 36 weeks after the last AOM injection, were analyzed for the expression levels of COX-1 and COX-2. The results indicate that AOM induced increasingly high levels of COX-2 expression with advancing stages of colon tumorigenesis. HFCO further enhanced the AOM-induced COX-2 expression. In contrast, HFFO ingestion resulted in a significant decrease in COX-2 expression both in the colonic mucosa and in tumors. These results correlate with increased incidence and multiplicity of grossly visible colon tumors in AOM-treated animals that were fed the HFCO diet versus decreased tumor incidence and lower tumor multiplicity in animals that were fed the HFFO diet. No significant differences were observed in expression levels of COX-1. The data suggest that HFCO may promote colon tumorigenesis by up-regulating the COX-2 expression, whereas HFFO may exert its antitumor effect by inhibiting the COX-2 expression.

Animals↗
PubMed1997

Dietary fat and colon cancer: modulating effect of types and amount of dietary fat on ras-p21 function during promotion and progression stages of colon cancer.

Although epidemiological and experimental studies have indicated a strong relationship between types and amount of dietary fat and colon tumorigenesis, the modulating effects of these nutritional factors at the molecular level have not been fully elucidated. Transforming proteins encoded by activated ras genes have been implicated in the etiology of many human malignancies, including colon cancer. It is now well established that the transforming ability of ras-p21 critically depends on its correct localization in plasma membrane. The posttranslational processing of the cytosolic precursor (pro-ras), as it is synthesized in the cytoplasm, and its proper anchorage to the cytoplasmic face of plasma membrane are determined by an important intermediate metabolite of dietary fat and an enzyme system that includes farnesyl protein transferase. To provide an understanding of the molecular basis of the relationship between the types and amount of dietary fat and the transforming function of ras, especially during the stages of promotion and progression of colon tumor development, we investigated the effect of various types and amount of dietary fat on the expression of ras-p21 during azoxymethane (AOM)-induced colon carcinogenesis. Male F344 rats were fed the semipurified American Institute of Nutrition-76A diet containing low-fat corn oil and were given s.c. injections of AOM dissolved in normal saline at a dose rate of 15 mg/kg body weight, once weekly, for 2 weeks. Control animals received s.c. injections of equal volumes of normal saline. Beginning 1 day after the second AOM or saline injection, groups of animals intended for the treatment with different types of high-fat dietary regimens were fed the semipurified American Institute of Nutrition-76A diets containing high levels of high-fat corn oil (HFCO) rich in omega-6 fatty acids or high levels of high-fat fish oil (HFFO) rich in omega-3 fatty acids; the remaining animals in experimental and control groups were continued on the low-fat corn oil diet until termination of the experiment. Groups of animals were sacrificed 1, 12, or 36 weeks after the last AOM or saline injection, and their colonic mucosa and grossly visible colon tumors from rats sacrificed 36 weeks after the last AOM injection were analyzed for the levels of expression of ras-p21. We found that AOM induced increasingly higher levels of ras-p21 expression with advancing stages of colon tumor development. The HFCO diet resulted in enhanced expression of AOM-induced ras-p21 as observed 36 weeks after the last AOM injection. In contrast, feeding the HFFO diet inhibited AOM-induced ras-p21 expression. These results correlate with increased incidence and multiplicity of grossly visible colon tumors in AOM-treated animals fed a HFCO diet versus decreased incidence and lower multiplicity of colon tumors in their counterparts on the HFFO diet. Further analysis of ras-p21 levels in cytosol and plasma membrane revealed that feeding a HFFO diet resulted in increasing accumulation of ras-p21 in cytoplasm with a concomitant decrease in membrane-bound ras-p21 levels as observed in animals sacrificed 12 and 36 weeks after the last AOM injection. Thus, the dietary HFCO may promote colon tumorigenesis by increasing ras-p21 expression, whereas HFFO appears to exert its antitumor activity by interfering with posttranslational modification and membrane localization of ras-p21.

Animals↗
PubMed1997

Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition.

Oligofructose and inulin, naturally-occurring fermentable chicory fructans, have been shown to stimulate the growth of bifidobacteria which are regarded as beneficial strains in the colon and inhibit colon carcinogenesis in the laboratory animal models. The present study was designed to determine the effect of oligofructose and inulin on the azoxymethane (AOM)-induced preneoplastic lesions such as aberrant crypt foci (ACF) formation in the colon of male F344 rats. At 5 weeks of age, groups of animals were fed the AIN-76A (control) and the experimental diets containing 10% oligofructose or inulin. At 7 weeks of age, all animals received s.c. injection of AOM dissolved in normal saline at a dose rate of 15 mg/kg body wt, once weekly for 2 weeks. The animals were necropsied 7 weeks after the last AOM injection, and the ACF were visualized under light microscopy in the formalin-fixed, unsectioned methylene blue-stained colons. They were distinguished by their increased size, more prominent epithelial cells and pericryptal space. The feeding of oligofructose or inulin significantly inhibited the ACF formation and the crypt multiplicity in the colon. The degree of ACF inhibition was more pronounced in animals fed inulin than in those fed oligofructose. The findings suggest that chicory fructan supplements inhibit ACF formation, an early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

Animals↗
PubMed1997

Prevalence of chlamydial infection in females attending antenatal and family planning clinics in Karachi Pakistan.

A prospective study was undertaken to investigate the relative prevalence of Chlamydia trachomatis in asymptomatic pregnant women of 2 socioeconomic groups and those attending the family planning clinics. Group 1 consisted of women attending the antenatal clinics of the Aga Khan University Hospital which caters to the affluent strata of our society (n = 100). Group 2 comprised women attending the antenatal clinics of Lady Dufferin Hospital which provides free obstetric care to women belonging to the lower socioeconomic groups of Karachi (n = 100). Group 3 consisted of sexually active women attending the family planning clinics of Lady Dufferin Hospital (n = 100). Endocervical swabs were taken from women assigned to each group. Chlamydiazyme, an enzyme linked immunoassay, was used to detect chlamydia antigen. The positive samples were retested by using the direct fluorescent monoclonal antibody technique. Chlamydia positive patients and their sexual partners were treated with Erythromycin stearate 500 mg 8-hourly for 7 days. These patients were retested after antibiotic therapy to assess the efficacy of the therapy. In groups 1 and 2, 2% and in Group 3, 12% of the females tested positive. Selective screening of sexually active women for chlamydial infection is advocated as a cost-effective public health measure.

Adult↗
PubMed1997

Crack users in east Harlem, New York and Philadelphia, Pennsylvania: HIV-related risk behaviors and predictors of serostatus.

Crack use has been associated with increased risk for HIV seropositivity. This study was undertaken to examine HIV-related risk behaviors among crack users in East Harlem, New York and Philadelphia, Pennsylvania, two northeastern communities which have reported extensive crack use. Crack users recruited in East Harlem (n = 1434) and Philadelphia (n = 694) were compared on demographics, drug and sex-related risk behaviors, health-related behaviors, and HIV serostatus. Many significant differences were found, and seropositivity was higher in the New York sample (25% vs. 11%, chi 2 = 36.28, p < .001). Being a recent drug injector was a significant predictors of seropositivity in both communities, and differences between communities were found in additional predictors of serostatus. Results suggest that tailored HIV interventions may be needed for different communities. In addition, aggregate data across communities, even those that may be in geographical proximity, may obfuscate differences important to incorporate in developing prevention/intervention efforts.

Adult↗
PubMed1997

The role of apoptosis in the modulation of colon carcinogenesis by dietary fat and by the organoselenium compound 1,4-phenylenebis(methylene)selenocyanate.

Studies in laboratory animals have demonstrated that dietary supplements of organoselenium, 1,4-phenylenebis(methylene)selenocyanate (p-XSC) inhibit colon carcinogenesis. Diverse chemopreventive agents and clinically used anticancer drugs have been shown to induce apoptosis in colonic tumors. Inducing apoptosis is a key mechanism for the effectiveness of some chemopreventive agents; however, failure of apoptosis is now believed to contribute to the development of human cancer. In this study, we determined the number of apoptotic bodies in the colon tumors of rats fed a low-fat (LF) or a high-fat (HF) diet with or without p-XSC treatment. At 5 weeks of age, male F344 rats were divided into four groups, which were then maintained on one of the following diets: LF, 5% corn oil; HF, 23.5% corn oil; and LF and HF supplemented with 20 ppm p-XSC. In addition, the LF or HF diet with p-XSC supplements was administered either during the initiation stage or postinitiation. At 7 weeks of age, all rats except those intended for vehicle (normal saline) treatment were given 15 mg/kg of body weight of azoxymethane once weekly for 2 weeks. The animals were sacrificed 38 weeks after carcinogen treatment, and their colonic tumors were examined for appearance of apoptosis. The LF diet significantly increased the percentage of apoptosis as compared to the HF diet; the percentage of apoptosis in LF and HF diets were 12.4 and 2.9. The colon tumors that were present in the groups fed p-XSC together with a LF or a HF diet after carcinogen administration (postinitiation period) had a higher number of apoptotic bodies than those that were present in the animals fed p-XSC before carcinogen treatment (initiation period). The extent of apoptosis was weak when p-XSC was given with a HF diet (4.4%) during the initiation phase, but it was high significant when p-XSC was administered with LF diet (25.2%). Taken together, our data suggest that administration of LF diet supplemented with p-XSC increases apoptosis as compared to a HF diet alone.

Animals↗
PubMed1995

Phenotypic determinants of adenovirus E1A gene autoregulation: variable region between conserved coding domains 2 and 3.

Different serotypes and evolutionary variants of human adenoviruses exhibit distinctive patterns of positive and negative autoregulation of the viral E1A gene. An autoregulatory E1A promoter mutation of the adenovirus type 3 (Ad3) E1A gene renders Ad3hr15 incapable of growth in normally permissive cells. The promoter mutation is complemented in trans by E1A products of the heterologous helper adenovirus type 5 (Ad5). Second-site revertants of Ad3hr15 restore viability with high levels of E1A gene expression. The revertant E1A genotypes retain the mutant E1A promoter and have small in-frame deletions in the nonconserved region between the repression- and activation-associated conserved domains CR2 and CR3. Plasmid expression vectors were constructed as 12S and 13S cDNA forms of revertant E1A genes. These were used in cotransfection experiments with a reporter gene plasmid under transcriptional control of the mutant Ad3hr15 E1A promoter. The repression of the Ad3hr15 E1A promoter by helper Ad5 or revertant 12S E1A cDNA was consistently greater than that effected wild-type Ad3 12S cDNAs expression. Significantly greater levels of positive transactivation were observed in cotransfections with 13S cDNAs of Ad5 or with the 13S E1A cDNA of Ad3hr15 revertants, compared to the transactivation observed with the mutant-encoded wild-type Ad3 13S E1A cDNA. The Ad5 helper and dI-revertant phenotype of Ad3hr15 appear to be related to transactivation activities of coexpressed E1A genes. The nonconserved region which separates the conserved coding regions CR2 and CR3 of the type 3 E1A gene acts to attenuate E1A-mediated repression and transactivation of transcription.

Adenovirus E1A Proteins↗
PubMed1995

Enhancement of experimental colon carcinogenesis by dietary 6-phenylhexyl isothiocyanate.

Naturally occurring and related synthetic isothiocyanates are known to exert chemopreventive effects in several organs in rodent models. The present study was designed to investigate the efficacy of 6-phenylhexyl isothiocyanate (PHITC), a potent chemopreventive agent in the lung tumor model in strain A mice, on azoxymethane-induced colon tumorigenesis. Another aim was to study the modulating effect of PHITC on colonic mucosal and tumor phospholipase A2 (PLA2), phosphatidylinositol-specific phospholipase C (PI-PLC), lipoxygenase (LOX), and cyclooxygenase (COX) activities. At 5 weeks of age, groups of male F344 rats were fed control diet or diets containing 320 or 640 ppm of PHITC representing 40 and 80% maximum tolerated dose levels, respectively. At 7 weeks of age, all animals except those in the vehicle-treated groups were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight/week. All animals continued on their respective dietary regimen for 52 weeks after the carcinogen treatment; then the study was terminated. Colonic mucosa and tumors were analyzed for PLA2, PI-PLC, prostaglandin (PG) E2, COX, and LOX activities. Intestinal tumors were evaluated histopathologically and classified as invasive or noninvasive adenocarcinomas. Intestinal tumor incidence (percentage of animals with tumors) and tumor multiplicity (tumors/animal; tumors/tumor-bearing animal) were compared among the dietary groups. At the 640-ppm dose level, dietary PHITC significantly increased the incidence of intestinal (small intestine plus colon) adenocarcinomas (P < 0.05) as well as the multiplicities of invasive and noninvasive adenocarcinomas of the colon (P < 0.05 to 0.01). At the 320-ppm dose level, PHITC increased the multiplicity (tumors/animal) of noninvasive adenocarcinomas and total (invasive plus noninvasive) adenocarcinomas of the colon (P < 0.05). Dietary PHITC also increased the colon tumor volume (2- to 4.3-fold) in a dose-dependent manner. Moreover, PHITC significantly enhanced the activities of PLA2 (50-100%) and levels of PGE2 (2-fold) in the colonic mucosa and in tumors, but it had no significant effect (P > 0.05) on PI-PLC activity. The formation of COX metabolites, particularly PGE2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, and thromboxane B2, as well as LOX metabolites such as 8(S)-, 12(S)- and 15 (S)-hydroxyeicosatetraenoic acids, were significantly increased in the colonic mucosa and tumors of animals that were fed 640 ppm of PHITC. Although the exact mechanism by which PHITC promotes colon tumorigenesis remains to be elucidated, it is likely that the tumor-promoting effects of PHITC may, at least in part, be related to increased eicosanoid metabolism in the colon.

Animals↗
PubMed1994

Doppler ultrasound of the uteroplacental circulation in the prediction of pregnancy outcome in women with raised maternal serum alpha-fetoprotein.

OBJECTIVE: To determine whether Doppler waveforms from the uteroplacental circulation could improve the prediction of pregnancy outcome in women with raised maternal serum alpha-fetoprotein and a structurally normal fetus. The study further attempts to determine whether the presence of an early diastolic notch would constitute a better screening test than waveform patterns. DESIGN: An observational study. SETTING: A tertiary referral obstetric service. SUBJECTS: All women referred to St George's Hospital with a raised maternal serum alpha-fetoprotein had waveform measurements from the uteroplacental circulation after exclusion of fetal abnormalities. Pregnancy outcome was determined by questionnaire sent to the referring clinicians. MAIN OUTCOME MEASURES: Adverse perinatal outcome in the form of preterm labour, low birthweight and perinatal mortality. RESULTS: Data from 332 cases were available for analysis. Women with a normal pattern of uteroplacental waveforms had a perinatal mortality of 9.6/1000. Women with a uniform high resistance pattern had a perinatal mortality of 846/1000, and those with a mixed resistance pattern had a perinatal mortality of 268/1000. Overall there were 27 cases of placental abruption which accounted for eight of the 50 perinatal deaths. The remainder were due to prematurity or low birthweight or both. The presence of the early diastolic notch did not improve on the waveform patterns in the prediction of perinatal death. CONCLUSION: Women with raised maternal serum alpha-fetoprotein and normal Doppler waveform patterns from the uteroplacental circulation can be reassured, but mixed or uniform high resistance patterns should encourage increased surveillance and a search for intervention therapies.

Blood Flow Velocity↗
PubMed1994

Low dose aspirin in women with raised maternal serum alpha-fetoprotein and abnormal Doppler waveform patterns from the uteroplacental circulation.

OBJECTIVE: To investigate the use of low dose aspirin in the reduction of perinatal morbidity and mortality in women with unexplained raised maternal serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns. DESIGN: Prospective randomised controlled trial. SETTING: A tertiary referral obstetric service. SUBJECTS: One hundred and sixty-four women referred to our unit with raised maternal serum alpha-fetoprotein and a structurally normal fetus had abnormal uteroplacental Doppler waveform patterns at 24 weeks of gestation. INTERVENTION: Women were randomly allocated to two groups, receiving either low dose aspirin 75 mg (n = 76) or placebo (n = 88) daily until delivery. MAIN OUTCOME MEASURES: Preterm labour, low birthweight, the occurrence of placental abruptions and perinatal mortality. RESULTS: The frequency of severely small for gestational age infants (birthweight < 5th centile) was reduced in the aspirin treated group to 16% compared with 25% in the placebo group (95% CI-21% to 13%). The frequency of delivery before 34 weeks of gestation was 26% in the aspirin group and 42% in the placebo group (95% CI--30% to 1%). The perinatal mortality was 240/1000 in the aspirin group and 320/1000 in the placebo group (95% CI--22% to 6%). None of these reductions was statistically significant. Although the frequency of placental abruptions was similar in the two groups, significantly more babies died from abruption in the aspirin treated group (91% versus 30%, 95% CI 28% to 94%). Low dose aspirin did cause a significant reduction (P = 0.008) in deaths from causes other than placental abruption. CONCLUSION: This trial revealed a benefit of low dose aspirin therapy in women with raised maternal serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns, but the effect was smaller than expected. Although a reduction in deaths from small preterm babies was observed, there was an increase in the number of deaths following placental abruption without a significant increase in the number of abruptions. We recommend that this should be considered before giving aspirin to these high risk women and that other investigators should specifically look for this effect.

Adult↗
PubMed1994

Laparoscopic appraisal of infertility and pelvic pain in Pakistani women: a 5 years audit.

Five hundred and nine Laparoscopic examinations performed between 1987-91, (147 procedures for evaluation of gynaecologic pelvic pain and 313 for infertility) revealed ectopic pregnancy (27%), twisted ovarian cyst (18%) and acute pelvic inflammatory disease (14%) in cases of acute gynaecologic pain, and endometriosis (17%) and chronic pelvic inflammatory disease (16%) in chronic pelvic pain. Adhesions (20%), tubal block (15%), endometriosis (9%) and polycystic ovary (7%) were common findings in cases of infertility. These data support the usefulness of this minimally invasive procedure in accurate diagnosis of gynaecological disorders and provides insight into the spectra of diseases seen in Pakistani women with pelvic pain and infertility.

Acute Disease↗
PubMedDate not supplied

Management of colonic injury following percutaneous nephrolithotomy.

Injury to the colon during percutaneous nephrolithotomy is rare. There are no definitive management guidelines for this injury. We report a case of left-sided colonic injury diagnosed following percutaneous nephrolithotomy and suggest a treatment algorithm.

Aged↗
PubMedDate not supplied

General anesthesia with isoflurane for diaphragmatic hernia repair during ECMO.

Isoflurane has been administered via the oxygenator of the extracorporeal membrane oxygenation (ECMO) circuit to provide anesthesia and prevent hemodynamic instability during surgical repair of congenital diaphragmatic hernia. A comparison of a series of patients treated with isoflurane demonstrates that there is less fluctuation in heart rate and blood pressure than when surgery is performed under fentanyl analgesia alone.

Anesthesia, General↗