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Biomedical subjects

M Hussain

Publications and source records attributed to M Hussain.

At least 145 records · Page 8Linked to original sources

Zinc concentration of breast milk and its diurnal variation in Bangladeshi mothers.

Little is known about the zinc content of breast milk in developing countries. Zinc content in breast milk was analyzed in 34 mothers of low socio-economic status; 17 were primiparae and 17 multiparae. Women in their 6th to 36th week of lactation provided 3 samples of breast milk at different times within a single day. The mean zinc concentration in breast milk (micrograms/ml) was 1.89 +/- 0.64 with a range from 0.17 to 4.38 micrograms/ ml. Zinc content in the morning, midday and evening samples were 2.1 +/- 0.84, 1.74 +/- 0.53, 1.84 +/- 0.69 respectively. There was significant variation between morning and midday samples (p = 0.038). Maternal age, parity, nutritional status or age of the child did not affect the zinc content of milk in the population studied.

Adolescent↗

Evaluation of 96-hour infusion fluorouracil plus cisplatin in combination with alpha interferon for patients with advanced squamous cell carcinoma of the head and neck: a Southwest Oncology Group study.

BACKGROUND: Recurrent cancer of the head and neck after primary therapy is almost always fatal. The combination of 5-fluorouracil (5-FU) and cisplatin is considered the best available therapy but complete response rates remain too low to affect survival. This study was designed to evaluate the complete response rate and toxicity of 5-FU, cisplatin, and alpha-interferon (alpha-IFN) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). METHODS: Fifty eligible patients with recurrent or metastatic SCCHN and no prior chemotherapy (40 men, 10 women; age range, 26-77 years; median, 59 years; 82% white; 88% had prior surgery and 92% had prior radiation therapy) were treated every 21 days with 96-hour infusion of 5-FU 1000 mg/m2/day; cisplatin 100 mg/m2, day 1; and alpha-IFN 5 x 10(6) units/day, days 1-4. RESULTS: One hundred fifty-seven courses of chemotherapy were administered, with a median of three courses. Thirty-seven patients experienced Grade 3 or 4 toxicity. Of the 17 patients with Grade 4 toxicity; 12 had hematologic toxicity, 3 stomatitis, and 2 vomiting. Two additional patients died of myelosuppression-related sepsis. Of the 50 patients, 3 (6%) achieved a complete response, five (10%) had a partial response, 3 (6%) had unconfirmed response (1 complete and 2 partial), 10 (20%) had stable disease, 17 (34%) progressed, and 12 (24%) were considered nonresponders owing to early death (6) or inadequate assessment (6). The median survival was 5 months. CONCLUSION: The complete response rate of patients with recurrent or metastatic SCCHN treated with 5-FU, cisplatin, and alpha-IFN does not appear to be superior to that observed for 5-FU and cisplatin. Alpha-interferon appears to augment hematologic and gastrointestinal toxicities associated with this combination.

Adult↗

Detection of brain-reactive autoantibodies in the sera of patients with systemic lupus erythematosus and cerebral involvement.

We modified, and applied to man, an ELISA established for the detection of brain-reactive autoantibodies in a murine model of SLE. We found brain-reactive antibody levels to be significantly higher in lupus patients than in healthy subjects. The antibody levels were significantly higher in lupus patients with central nervous system involvement than in those without.

Adult↗

Prostate-specific antigen messenger RNA is expressed in non-prostate cells: implications for detection of micrometastases.

Prostate specific antigen (PSA) is generally believed to be expressed only by prostate epithelium. If this were true of PSA, RNA, then detecting PSA RNA in cells outside of the prostate would indicate metastasis. PCR can detect rare prostate cancer cells. To enhance sensitivity, we developed "nested primer" PCR to detect PSA RNA. With this method, PSA RNA is present in several non-prostate cell lines, including BG-1 (ovarian), SK-MES-1 (lung), and HL-60 (myeloid leukemia), and some normal blood. A low level of PSA RNA detectable by nested primer PCR is present in some cells of non-prostate origin and may interfere with sensitive methods to detect micrometastases. Transcripts of other genes thought to be organ specific may have similar limitations.

Adenocarcinoma↗

Induction of T-helper cell response to hepatitis B core antigen in chronic hepatitis B: a major factor in activation of the host immune response to the hepatitis B virus.

The T helper (Th) cell response to hepatitis B core antigen (HBcAg) was analyzed in 76 chronic hepatitis B virus (HBV) carriers with varying degrees of hepatic inflammation and HBV replication. Fifty-five patients had active viral replication, 28 with minimal histological changes and normal alanine transaminase (ALT) and 27 with active hepatic inflammation and elevated ALT. The remaining 21 chronic hepatitis B surface antigen (HBsAg) carriers had undetectable HBV replication, minimal histological activity, and normal ALT. In addition, 34 chronic HBV carriers were studied prospectively during treatment with alpha-interferon. The HBcAg-specific Th cell response was evaluated by a proliferative assay using 3H-thymidine uptake and gamma-interferon production by peripheral blood mononuclear cells. The proliferative response and gamma-interferon production of patients with active hepatic inflammation were significantly higher than in patients with minimal histological changes and in controls. In the longitudinal analysis during alpha-interferon treatment, 22 of 34 patients sustained an ALT flare accompanied by a parallel, significant Th cell response, which preceded or coincided with the ALT flare. The elevation in the Th cell response and the ALT flare were followed by a significant rise in the serum immunoglobulin (Ig) M anti-HBc index. Ten of twenty-two patients with an enhanced Th cell response and an ALT flare seroconverted after alpha-interferon treatment. The Th cell activity in the 10 responders rapidly subsided after hepatitis B e antigen (HBeAg) to anti-HBe seroconversion, whereas in the 12 nonresponders it remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

Removal of the financial barrier to health care: does it impact on prostate cancer at presentation and survival? A comparative study between black and white men in a Veterans Affairs system.

OBJECTIVES: African-American men are known to have a higher incidence and mortality rate from prostate cancer than American-Caucasian men. It is also known that African Americans have a higher incidence of advanced stage disease at diagnosis. One hypothesis for the latter is a delay in diagnosis due to lack of financial access to health care. Because eligibility for medical care in Veterans Affairs Medical Centers (VAMCs) is similar for both black and white patients, less disparity of stage at diagnosis, and therefore survival between blacks and whites, would be expected. METHODS: Cases for this study included only those histologically confirmed, newly diagnosed prostate cancers at the Allen Park VAMC in Wayne County, Michigan, between 1973 and 1992. Trained Surveillance, Epidemiology, and End Result (SEER) abstractors determined the stage at diagnosis, according to SEER criteria. Data analyses include descriptive statistics and survival analysis. RESULTS: The distribution of race and annual income of all male patients seen at the VAMC in Allen Park is similar. Over the entire 20-year period (1973 to 1992), there were a total of 358 prostate cancers in white patients and 383 in black patients. The ages of black and white patients were comparable. The proportion of white and black men presenting with localized disease is similar (57% and 54%, respectively). A significantly greater proportion of black patients with prostate cancer were classified as having distant disease compared with white patients (25% versus 19%; P = 0.045). A racial "crossover" effect in survival occurred around age 70 years, with white men demonstrating improved survival under 70 years of age, and black men 70 years and older tending to have better survival. CONCLUSIONS: These data suggest that financial access to care has no apparent influence on the higher proportion of distant disease and poorer survival of African-American patients with prostate cancer compared with American-Caucasian men.

Black or African American↗

Interferon-alpha 2 variants in the human genome.

Variants of human leukocyte interferon alpha 2 (IFN-alpha 2a, alpha 2b, and alpha 2c) differ from each other by changes in their coding regions at nucleotide positions 137 and 170. As a result of these nucleotide variations, the DNA sequences of the three variants can be distinguished by selective restriction enzyme analysis. Human genomic DNA obtained from over 28,000 normal healthy individuals was used as templates in the polymerase chain reaction (PCR) to amplify the human IFN-alpha 2 gene sequence. The resulting PCR products were analyzed with restriction nucleases to identify the specific IFN-alpha 2 variant sequences present in the genomic DNA of the population examined. The results show that IFN-alpha 2b was detected as the predominant species and IFN-alpha 2c as a very minor species (< 0.1%). The IFN-alpha 2a gene was not detected in this population.

Alleles↗

Induction of A- and D-type cyclins and cdc2 kinase activity during recovery from short-term hyperoxic lung injury.

Hyperoxia causes a reproducible pattern of lung injury and repair in rodents, in which proliferation of alveolar epithelial cells (AEC) and fibroblasts is observed during recovery. We postulated that if quiescent cells are stimulated to reenter the cell cycle, then cyclin expression and cyclin-dependent protein kinase activity would be reactivated in AEC during the repair process after hyperoxic lung injury. To test this hypothesis, we exposed adult rats to short-term hyperoxia, followed by recovery for various times in room air. Cellular proliferation in vivo was confirmed by 1) flow cytometric analysis of DNA content (FACS) of freshly isolated AEC and 2) immunohistochemistry of proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation into DNA on lung sections. The percentage of freshly isolated AEC in S phase and G2/M phase on FACS analysis increased twofold to a maximum of 16.5%, after 48 h in 100% oxygen and 48 h recovery in air. Cyclins A and D and p34cdc2 protein expression were also increased during the recovery period; while p33cdk2 and p34cdk4 increased only slightly. p34cdc2 histone H1 kinase activity, both in whole lung and in AEC, decreased initially after 48 h in oxygen. However, a marked increase in p34cdc2 kinase activity was observed at 48 h recovery in whole lung and returned to baseline by 72 h. In isolated and cultured AEC, p34cdc2 kinase activity was maximal at 24 h of recovery in air. We conclude that cyclins A and D and p34cdc2 protein expression and p34cdc2 kinase activity are increased in vivo during recovery from hyperoxic lung injury in both adult rat lungs and in AEC isolated from these lungs. We speculate that the induction of cyclin-dependent protein kinase activity is a key event in mediating the proliferative cellular repair response to lung injury.

Acute Disease↗

Intravenously injected insulin-like growth factor (IGF) I/IGF binding protein-3 complex exerts insulin-like effects in hypophysectomized, but not in normal rats.

Insulin-like growth factor (IGF) circulates in blood in two large molecular mass forms of 150 and 40 kD. Under normal conditions, most of the IGF is bound to the 150-kD complex by which it is retained in the circulation and therefore unable to exert acute insulin-like actions. The aim of this study was to answer the question whether or not IGF in the 40-kD complex is bioavailable to insulin target tissues and thus can cause acute insulin-like effects in vivo. Intravenously injected 1:1 molar recombinant human (rh) IGF I/rhIGF binding protein (BP)-3 complex lowered blood glucose and stimulated glycogen synthesis in diaphragm of hypophysectomized, but not of normal rats. The serum half-lives of the two components of the complex were similar to each other, but considerably shorter in hypox than in normal rats. On neutral gel filtration of serum both components of the injected complex appeared predominantly in the 150-kD region in normal rats. In hypox rats which lack the 150-kD complex they were found in the 40-kD region and disappeared rapidly from the circulation. We conclude that in the absence of the 150-kD complex, IGF associated with the 40-kD complex can rapidly leave the vascular compartment, reach insulin or type 1 IGF receptors and exert acute insulin-like effects.

Animals↗

Comparison of intraocular lens power calculation using the Binkhorst and SRK formulae: a clinical study.

Comparison of results of intraocular lens implants with IOL powers obtained by Binkhorst and SRK Linear Regression formulae was done using various models and brands of intraocular lenses. Of 887 pseudophakic patients. 415 patients received IOL's with their powers calculated for planned emmetropia, by means of theoretic formula devised by R.D. Binkhorst and in the remaining 472 eyes the IOL power was calculated with the SRK Linear Regression method. No significant difference (P < 0.05) was found between visual acuities, obtained with IOL's alone or after postoperative overcorrection of residual refractive errors between the two groups.

Cataract Extraction↗

Management of urinary calculi associated with renal failure.

Three hundred and sixty patients of urinary calculi associated with renal failure were included in this prospective study. The male to female ratio was 4.1:1 while adult to paediatric ratio was 6.5:1. One hundred and eighteen (32.8%) patients presented with calculus anuria while 242 (67.2%) were admitted with symptoms of chronic renal failure. Serum creatinine at the time of first admission ranged from 3-35 mg/100 ml. In the initial management, percutaneous needle nephrostomy was done in 217 cases, dialysis in 106, dialysis and PCN in 22 and retrograde catheterisation followed by JJ stent in 15. Definitive surgical procedures were undertaken in 277 cases; 29 passed stones spontaneously after PCN. At two year follow-up 72% patients of calculus anuria and 49.5% of calculus renal failure improved their renal function and remained with serum creatinine below 2 mg/100 ml. There was 13.6% mortality in calculus anuria group and 17.4% in calculus renal failure. Overall loss to follow-up was 7.6% and 12% in the two groups respectively.

Adolescent↗

Mechanism of action of a K+ channel activator BRL 38227 on ATP-sensitive K+ channels in mouse skeletal muscle fibres.

1. Investigations were made into the effects of BRL 38227, a potassium channel activator, on ATP-sensitive potassium channels (K+ATP channels) in single fibres dissociated from the flexor digitorum brevis muscle of C57BL/6J mice. 2. In cell-attached patches BRL 38227 (100 microM) caused activation of a glibenclamide-sensitive potassium current. Linear slope conductance of the inward current, partial rectification of the outward current and glibenclamide sensitivity indicate that K+ATP channels are the site of action of BRL 38227. 3. In the absence of ATP at the cytoplasmic side of excised inside-out patches, BRL 38227 caused direct and magnesium-dependent activation of K+ATP channels. The degree of activation diminished with successive applications of BRL 38227. 4. BRL 38227 also caused activation of K+ATP channels in the presence of low (< 100 microM) but not high (1.0 mM) ATP, particularly in patches containing large numbers of channels. 5. BRL 38227 and 5 microM MgATP failed to activate channels following complete run-down. 6. Results show that BRL 38227 caused direct activation of K+ATP in skeletal muscle and that this was mediated through a magnesium-dependent binding site rather than alleviation of inhibition by competitive displacement of ATP from the inhibitory site.

Adenosine Triphosphate↗

Rundown and reactivation of ATP-sensitive potassium channels (KATP) in mouse skeletal muscle.

Dissociated single fibers from the mouse flexor digitorum brevis (FDB) muscle were used in patch clamp experiments to investigate the mechanisms of activation and inactivation of KATP in mammalian skeletal muscle. Spontaneous rundown of channel activity, in many excised patches, occurred gradually over a period of 10-20 min. Application of 1.0 mM free-Ca2+ to the cytoplasmic side of the patch caused irreversible inactivation of KATP within 15 sec. Ca(2+)-induced rundown was not prevented by the presence of 1.0 microM okadaic acid or 2.0 mg ml-1 of an inhibitor of calcium-activated neutral proteases, a result consistent with the conclusion that phosphatases or calcium-activated neutral proteases were not involved in the rundown process. Application of 1.0 mM Mg.ATP to Ca(2+)-inactivated KATP caused inhibition of residual activity but little or no reactivation of the channels upon washout of ATP, even in the presence of the catalytic subunit of cyclic AMP-dependent protein kinase (10 U ml-1). Mg.ATP also failed to reactivate KATP, even after only partial spontaneous rundown, despite the presence of channels that could be activated by the potassium channel opener BRL 38227. Nucleotide diphosphates (500 microM; CDP, UDP, GDP and IDP) caused immediate and reversible opening of Ca(2+)-inactivated KATP. Reactivation of KATP by ADP (100 microM) increased further upon removal of the nucleotide. In contrast to KATP from cardiac and pancreatic cells, there was no evidence for phosphorylation of KATP from the surface sarcolemma of dissociated single fibers from mouse skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Recombinant human insulin-like growth factor-I: a therapeutic challenge for diabetes mellitus.

Insulin-like growth factor I (IGF I) is an endocrine hormone that mediates most of the effects of pituitary growth hormone. Other important regulatory factors of serum IGF I levels are insulin and nutrition. Most of the circulating IGF I is bound to three IGF binding proteins (BP), mostly IGFBP-3, BP-2 and BP-1. IGF I is also produced by many cells in the body where it exerts autocrine and/or paracrine effects. IGF I has a specific receptor on most cells, the so-called type 1 IGF receptor. When IGF I is administered intravenously as a bolus it leads to acute hypoglycaemia in a similar way to insulin and mainly with the insulin receptor. Chronic administration of IGF I to hypophysectomized or diabetic rats leads to prominent anabolic effects and growth. In this manuscript, metabolic and endocrine effects of recombinant IGF I are discussed. Recombinant IGF I therapy increases energy expenditure and lipid oxidation and decreases proteolysis and protein oxidation. These effects occur despite a partial inhibition of insulin and growth hormone secretion. The therapeutic spectrum of recombinant IGF I, consisting of inhibition of catabolism, stimulation of anabolism, decreases of triglyceride and cholesterol levels and a striking increase in insulin sensitivity, renders IGF I a very interesting, powerful tool for insulin-resistant states such as non-insulin-dependent diabetes mellitus.

Animals↗