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Biomedical subjects

M A Rahman

Publications and source records attributed to M A Rahman.

At least 55 records · Page 3Linked to original sources

Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors.

alpha-Latrotoxin (LTX) stimulates massive exocytosis of synaptic vesicles and may help to elucidate the mechanism of regulation of neurosecretion. We have recently isolated latrophilin, the synaptic Ca2+-independent LTX receptor. Now we demonstrate that latrophilin is a novel member of the secretin family of G protein-coupled receptors that are involved in secretion. Northern blot analysis shows that latrophilin message is present only in neuronal tissue. Upon expression in COS cells, the cloned protein is indistinguishable from brain latrophilin and binds LTX with high affinity. Latrophilin physically interacts with a Galphao subunit of heterotrimeric G proteins, because the two proteins co-purify in a two-step affinity chromatography. Interestingly, extracellular domain of latrophilin is homologous to olfactomedin, a soluble neuronal protein thought to participate in odorant binding. Our findings suggest that latrophilin may bind unidentified endogenous ligands and transduce signals into nerve terminals, thus implicating G proteins in the control of synaptic vesicle exocytosis.

Amino Acid Sequence↗

The production, binding characteristics and sequence analysis of four human IgG monoclonal antiphospholipid antibodies.

Antiphospholid antibodies (APL) have a notable association with recurrent miscarriages, arterial and venous thrombosis and thrombocytopenia. Analysis of the potential pathogenic effects of such human antibodies has been hampered by the considerable difficulty in producing IgG as opposed to IgM monoclonal immunoglobulins. We have developed four human monoclonal IgG APL (LJ1, AH2, DA3 and UK4) by fusing the peripheral blood lymphocytes of three patients with SLE with a mouse human heteromyeloma cell line, CB-F7. These antibodies bind to a variety of anionic phospholipids, two (LJ1 and AH2) bind total histones but none binds to ssDNA or dsDNA. Binding to beta 2 GPI is non-specific. UK4 alone demonstrates lupus anticoagulant activity. All four have lambda light chains, two are IgG1 (AH2 and UK4) and two are IgG3 (LJ1 and DA3). These APL utilize VH genes present in the fetally restricted repertoire and multiple somatic mutations in the CDR suggest an antigen-driven process. In contrast, there is no restriction in V lambda gene usage and only one lambda chain is extensively mutated. Two clonally related hybridomas were isolated from a single patients. This supports the theory that clonal expansion is the mechanism whereby antigen selects high affinity mutations.

Amino Acid Sequence↗

Disulfiram causes sustained behavioral and biochemical effects in rats.

The present experiment examined effects of disulfiram (Antabuse) administration on behavioral measures of nociception (hot plate and tail flick), peripheral muscular performance (grip strength), motivated performance, balance, and coordination (rotorod) in 24 male Sprague-Dawley rats during and 2 wk after an eight-day administration of disulfiram. In addition, peptidylglycine 5(-hydroxylating monooxygenase (PHM) activity in several tissues and levels of alpha-amidated alpha-melanocyte stimulating hormone (alpha-MSH) in the neurointermediate lobe of the pituitary were assayed to evaluate biochemical effects of disulfiram. These particular assays were included because it has been reported that disulfiram affects alpha-amidated peptides via alteration of PHM activity. Decrements in all behavioral measures, except tail flick, occurred after one week of disulfiram administration. Decrements in grip strength continued for the 2 wk after cessation of disulfiram. Dose-related reductions in changes in PHM activity and levels of alpha-MSH were found 2 wk after cessation of disulfiram administration. The time course of the results suggest that changes in PHM activity may underlie decrements in grip strength. The present experiment provides a paradigm for further investigations of effects of alpha-amidated peptides on behavior.

Alcohol Deterrents↗

Hyperactivity induced by prenatal nicotine exposure is associated with an increase in cortical nicotinic receptors.

Prenatal exposure to nicotine may lead to hyperactivity. To evaluate possible involvement of central nicotinic receptors in this condition, pregnant Sprague-Dawley rats were implanted with osmotic minipumps to receive nicotine (6 mg/kg/day) or saline throughout gestation. A total of 222 pups (118 males and 104 females) from 24 dams were measured for locomotor activity. Male and female hyperactive and nonhyperactive offspring from each treatment group were selected and analyzed for nicotinic receptor concentrations in various brain regions. Hyperactive male offspring that were prenatally exposed to nicotine exhibited a significant increase in the cortical receptor densities without a change in binding affinity. Hyperactive offspring of saline-treated dams did not show an increase in cortical nicotinic receptors. These results suggest that hyperactive male offspring of nicotine-exposed dams are also susceptible to neurochemical effects of intrauterine nicotine exposure.

Animals↗

Prenatal exposure to nicotine: effects on prepulse inhibition and central nicotinic receptors.

The present experiment examined effects of prenatal nicotine exposure (6 mg/kg/day via osmotic minipump) throughout gestation on prepulse inhibition of the acoustic startle response (PPI) and on the density of nicotinic acetylcholine receptors (nAchRs) in the brains of 5-week-old Sprague-Dawley rats. A total of 117 male and 103 female offspring were used. Prenatal nicotine reduced subsequent percent PPI to a 98 dB stimulus in female but not in male offspring. There was an inverse correlation between the percent of PPI and nAchR density in the cortex of male rats and the striatum of female rats.

Acoustic Stimulation↗

Analysis of psychiatric morbidity of outpatient children in Mitford Hospital, Dhaka.

The objective of this study was to describe the pattern of psychiatric morbidity among 97 child patients who, for the first time attended the psychiatric outpatient department of Sir Salimullah Medical College & Mitford Hospital, Dhaka, in the year 1994. Dissociative disorder (Hysteria) comprised the largest group (21.65%), followed by epilepsy (19.59%). Majority of the cases were within 7-10 years age group with mean age 9.74 (+/- 2.39) years. Male outnumbered female patients and 53.61% cases came from rural background. The findings of the study indicate the need for establishment of child psychiatric treatment centres in different parts of the country including rural areas.

Adolescent↗

Comparison of the activity of carp and rat beta-actin gene regulatory sequences in tilapia and rainbow trout embryos.

A comparative study on the level of expression of lacZ reporter constructs driven by equivalent carp and rat beta-actin regulatory sequences was carried out in embryos of tilapia and rainbow trout. DNA was microinjected into fertilised tilapia and rainbow trout eggs and the embryos/fry were assayed at various developmental stages for beta-galactosidase expression. We provide evidence to demonstrate that the carp beta-actin promoter/ lacZ reporter gene is expressed at higher levels than the equivalent rat beta-actin construct in both species.

Actins↗

Down-regulation of expression and function of the rat liver Na+/bile acid cotransporter in extrahepatic cholestasis.

BACKGROUND & AIMS: The molecular regulation of hepatic bile acid transporters during cholestasis is largely unknown. Cloning of complementary DNAs for the sinusoidal sodium-dependent taurocholate cotransporting polypeptide (ntcp), the cytosolic bile acid-binding protein 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), and a putative canalicular bile acid transporter Ca2+, Mg(2+)-ecto-adenosine triphosphatase, now facilitates such studies. METHODS: Protein mass, steady-state messenger RNA (mRNA) levels, and gene transcription were assessed in rat livers after common bile duct ligation (CBDL) from 1-7 days, and taurocholate uptake was determined in isolated hepatocytes. RESULTS: After CBDL, Na(+)-dependent taurocholate uptake (Vmax) declined by 70%. The levels of ntcp protein were reduced by more than 90%, and 3 alpha-HSD levels decreased by 66% by 7 days. Expression and canalicular localization of the ecto-adenosine triphosphatase remained unchanged. mRNA levels for both ntcp and 3 alpha-HSD diminished by about 60% 1 day after CBDL and remained unchanged up to 7 days. Transcriptional activity was decreased 1 day after CBDL only for ntcp. CONCLUSIONS: Extrahepatic cholestasis results in rapid down-regulation of Na(+)-dependent taurocholate uptake, ntcp transcription, and posttranscriptional regulation of both ntcp and 3 alpha-HSD mRNA. This selective decline of ntcp may represent a protective feedback mechanism in cholestasis to diminish uptake of potentially hepatotoxic bile acids.

3-Hydroxysteroid Dehydrogenases↗

Five patients who developed systemic sclerosis shortly after episodes of physical trauma.

We describe 5 patients in whom the onset of systemic sclerosis followed shortly after episodes of trauma. The HLA-DR52 allele was common to all these patients. This raises the possibility that trauma may be associated with the onset of the disease in predisposed individuals. If this is the case, it seems likely that it may have advanced the development of the disease rather than being fundamentally responsible for it.

Adult↗

Properties of human affect induced by static color slides (IAPS): dimensional, categorical and electromyographic analysis.

Human affect elicited by static color slides was evaluated quantitatively using dimensional (N = 60 subjects) and differential or categorical (N = 57) self report, and facial electromyography (N = 20). Mean dimensional self reports of affective responses were highly replicable across cohorts. Mean categorical response profiles over seven affective categories were monomodal for some slides, but multimodal for most, and nearly identical within the same cohort for slides of similar content. Mean categorical response profiles for individual slides were also similar across different cohorts and for different experimental conditions. Valence calculated from weighted categorical self report scores was highly correlated with the self reported valence (r = +0.98), demonstrating a simple, linear relationship between dimensional and categorical (differential) measures of affect. Categorical response strength was synergically patterned, i.e. invariably correlated positively for affect of the same dimensional valence and generally correlated negatively for affect of opposite valence. Facial electromyograms associated with affective responses to slides were correlated with valence, but smaller in magnitude than those associated with the weakest possible voluntary facial movements involving the same muscles. This study, therefore, demonstrates that self reported affective responses to color IAPS slides are replicable within and between cohorts, complex but synergically patterned, and relatively weak.

Affect↗

Effect of continuous positive airway pressure on intrathoracic and left ventricular transmural pressures in patients with congestive heart failure.

BACKGROUND: Continuous positive airway pressure (CPAP) can improve cardiac function in patients with congestive heart failure (CHF). We hypothesized that this effect might be related to CPAP-induced increases in intrathoracic pressure, which would reduce left ventricular transmural pressure (LVPtm) during systole, thereby decreasing left ventricular afterload. METHODS AND RESULTS: The effect of graduated CPAP from 0 to 10 cm H2O on the above variables was examined over a 75-minute period and compared with a 75-minute time control period without CPAP in two groups of subjects: 15 patients with CHF and 9 healthy subjects. Intrathoracic pressure was estimated from esophageal pressure (Pes), and systolic LVPtm, a determinant of left ventricular afterload, was assessed by subtracting Pes during systole from systolic blood pressure. Cardiac index (CI) was assessed by Doppler echocardiography. At baseline, inspiratory Pes amplitude, which reflects inspiratory muscle force generation, was greater in the patients with CHF than in the healthy group (9.9 +/- 0.8 versus 5.5 +/- 0.4 mm Hg, P < .001). In addition, systolic Pes, which represents the relative contribution of intrathoracic pressure to LVPtm, was more negative in the patients with CHF than in the healthy group (-4.1 +/- 0.3 versus -2.2 +/- 0.1 mm Hg, P < .001). While on CPAP of 10 cm H2O, inspiratory Pes amplitude decreased and systolic Pes increased significantly in the group with CHF (from 11.1 +/- 1.1 to 7.5 +/- 1.1 mm Hg, P < .025 and from -4.7 +/- 0.6 to 0.6 +/- 0.6 mm Hg, P < .001, respectively), but CPAP had no effect on these variables in the healthy subjects. Compared with the equivalent time control period, Pes amplitude x respiratory rate decreased significantly while on CPAP in both the group with CHF (from 188 +/- 22 to 112 +/- 17 mm Hg x breaths per minute, P < .005) and the healthy group (from 82 +/- 8 to 60 +/- 6 mm Hg x breaths per minute, P < .05). Compared with time control, systolic LVPtm decreased significantly while on CPAP, from 116.0 +/- 5.3 to 110.3 +/- 4.5 mm Hg (P < .025) in the group with CHF, but did not change in the healthy group. Moreover, systolic LVPtm x heart rate decreased significantly in the group with CHF (from 80.55 +/- 5.27 to 71.83 +/- 4.73 mm Hg x beats per minute/100, P < .005) but not in the healthy group. CI decreased significantly while on CPAP in the healthy group (P < .025) but did not change in the group with CHF. CONCLUSIONS: In patients with CHF, the inspiratory muscles generate greater force per breath and systolic Pes contributes more to LVPtm than in healthy subjects. By increasing intrathoracic pressure in patients with CHF, CPAP unloaded inspiratory muscles and reduced left ventricular afterload without compromising CI.

Adult↗

Continuous positive airway pressure increases heart rate variability in congestive heart failure.

OBJECTIVES: Our objective was to determine whether continuous positive airway pressure augments the low heart rate variability of congestive heart failure, a marker of poor prognosis. BACKGROUND: Nasal continuous positive airway pressure improves ventricular function in selected patients with heart failure. METHODS: In 21 sessions in 16 men (mean [+/- SE] age 56 +/- 2 years) with New York Heart Association functional class II to IV heart failure, we assessed the effects of 45 min with (n = 14) and without (as a time control, n = 7) nasal continuous positive airway pressure (10 cm of water) on heart rate variability and end-expiratory lung volume. Coarse-graining spectral analysis was used to derive total spectral power (PT), its nonharmonic component (fractal power [PF]) and the low (0.0 to 0.15 Hz [PL]) and high (0.15 to 0.50 Hz [PH]) frequency components of harmonic power. Standard deviation of the RR interval, high frequency power and the PH/PT ratio were used to estimate parasympathetic activity in the time and frequency domains, and the PL/PH ratio was used to estimate cardiac sympathetic activity in the frequency domain. RESULTS: Use of continuous positive airway pressure increased end-expiratory lung volume by 445 +/- 82 ml (p < 0.01) and both time (p < 0.006) and frequency domain indexes of heart rate variability: Total spectral power (p < 0.01), nonharmonic power (p < 0.023) and low (p < 0.04) and high (p < 0.05) frequency components of harmonic power all increased. Time alone had no effect on these variables. By comparison, the PH/PT ratio increased during nasal continuous positive airway pressure (p < 0.004), whereas the PL/PH ratio was unchanged. Breathing rate remained constant in both groups. CONCLUSIONS: Short-term application of nasal continuous positive airway pressure increases heart rate variability and time and frequency domain indexes of parasympathetic activity without influencing cardiac sympathetic activity. This increase may occur reflexively, through stimulation of pulmonary mechanoreceptor afferents.

Adult↗

Target-peptide-induced changes in the structure and dynamics of calmodulin as probed by frequency domain fluorimetry of bound Tb(III).

Tb(III) luminescence is used to probe the conformational change induced in the calcium regulatory protein calmodulin upon binding to a target peptide. The luminescence lifetime for Tb(III) measured by frequency domain fluorimetry increases from 1278 microseconds for the calmodulin complex to 1496 microsecond for the complex of calmodulin and M13, a peptide derived from the calmodulin target protein myosin light chain kinase. The intensity of the Tb(III) emission increases over the solution value by a factor of 726 and 891 when bound to calmodulin and to the complex of calmodulin and M13 respectively. The sensitivity of the Tb(III) decay rate to deuterated solvent was also measured and is consistent with a single water molecule bound to the metal in both the calmodulin and calmodulin-M13 complex. The most dramatic change induced by M13 is the threefold reduction in the width of the Tb(III) lifetime distribution, which is interpreted to be a target-peptide-induced annealing of the previously flexible metal-binding site.

Amino Acid Sequence↗

Effects of observed correlation structure among tumor types on experimentwise false positive rate in animal carcinogenicity studies.

Probabilities P1, P2, ..., Pn of n events E1, E2, ..., En can impose constraints on the probability of a further event E. deFinetti's fundamental theorem of probability characterizes the interval of coherent probability of E. Lad, Dickey, and Rahman (5) extended deFinetti's theorem in a few directions. In this work we will show some applications of these results to the calculation of experimentwise false positive error rate in multiple hypotheses testing procedure.

Animals↗

Escherichia coli peptide methionine sulfoxide reductase gene: regulation of expression and role in protecting against oxidative damage.

The Escherichia coli peptide methionine sulfoxide reductase gene (msrA) encodes a single-subunit polypeptide of 212 amino acid residues (M. A. Rahman, H. Nelson, H. Weissbach, and N. Brot, J. Biol. Chem. 267:15549-15551, 1992). RNA blot analysis showed that the gene is transcribed into an mRNA of about 850 nucleotides. The promoter region was characterized, and the transcription initiation site was identified by primer extension. The synthesis of the MsrA protein increased about threefold in a growth-phase-dependent fashion. In an attempt to define the in vivo role of msrA, a chromosomal disruption was constructed. This mutant was more sensitive to oxidative stress, suggesting that oxidation of methionine in proteins plays an important role in oxidative damage.

Base Sequence↗