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Biomedical subjects

N Alam

Publications and source records attributed to N Alam.

At least 19 recordsLinked to original sources

Substrate-inhibitor interactions in the kinetics of alpha-amylase inhibition by ragi alpha-amylase/trypsin inhibitor (RATI) and its various N-terminal fragments.

The ragi alpha-amylase/trypsin bifunctional inhibitor (RATI) from Indian finger millet, Ragi (Eleucine coracana Gaertneri), represents a new class of cereal inhibitor family. It exhibits a completely new motif of trypsin inhibitory site and is not found in any known trypsin inhibitor structures. The alpha-amylase inhibitory site resides at the N-terminal region. These two sites are independent of each other and the inhibitor forms a ternary (1:1:1) complex with trypsin and alpha-amylase. The trypsin inhibition follows a simple competitive inhibition obeying the canonical serine protease inhibitor mechanism. However, the alpha-amylase inhibition kinetics is a complex one if larger (> or =7 glucose units) substrate is used. While a complete inhibition of trypsin activity can be achieved, the inhibition of amylase is not complete even at very high molar concentration. We have isolated the N-terminal fragment (10 amino acids long) by CNBr hydrolysis of RATI. This fragment shows a simple competitive inhibition of alpha-amylase activity. We have also synthesized various peptides homologous to the N-terminal sequence of RATI. These peptides also show a normal competitive inhibition of alpha-amylase with varying potencies. It has also been shown that RATI binds to the larger substrates of alpha-amylase. In light of these observations, we have reexamined the binding of proteinaceous inhibitors to alpha-amylase and its implications on the mechanism and kinetics of inhibition.

Binding, Competitive↗

The effect of divorce on infant mortality in a remote area of Bangladesh.

The process of divorce is usually lengthy and hazardous, and can start quarrels that can lead to the abuse of women and their children. This study examines the effects of divorce on neonatal and postneonatal mortality of babies born before and after divorce in Teknaf, a remote area of Bangladesh. The longitudinal demographic surveillance system (DSS) followed 1,762 Muslim marriages in 1982-83 for 5 years to record divorce, deaths of spouse, emigration and births. It recorded 2,696 live births during the follow-up period, and their survival status during infancy. Logistic regression models were used to estimate the effect of divorce on neonatal and postneonatal mortality, controlling for maternal age at birth, parity, sex of the child and household economic status. The odds of neonatal and postneonatal deaths among babies born after divorce or less than 12 months before mothers were divorced were more than double the odds of those born to mothers of intact marriages. The odds of postneonatal deaths were two times higher among babies born more than 12 months before divorce happens than their peers. The high mortality of infants born before and after mothers were divorced may reflect how abusive marriage and divorce increase the vulnerability of women and children in rural Bangladesh. Divorce and abuse of women are difficult and intractable social and health problems that must be addressed.

Adolescent↗

Additional bioactive Lyso-PAF congeners from the sponge Spirastrella abata.

A known (1) and four new (2--5) lyso-PAF (platelet activating factor) derivatives were isolated from the sponge Spirastrella abata. Two of them are unprecedented in having a methoxy group at C-2'. The structures have been determined by combined spectroscopic methods. Their inhibitory effect on the biosynthesis of cholesterol and cytotoxicity against human solid tumor cell lines are reported.

Animals↗

Cytotoxic diacetylenes from the stony coral Montipora species.

Ten new (1, 4-6, 9-14) and four known (2, 3, 7, 8) diacetylenes have been isolated from a brine shrimp active fraction of the methanolic extract of the stony coral Montipora sp. The structures were determined by combined spectroscopic methods. The compounds exhibited significant cytotoxicity against a small panel of human solid tumor cell lines. Montiporyne A (15), a previously reported congener, was also found to induce apoptosis in human colon tumor cell.

Acetylene↗

New cytotoxic sesterterpenes from the sponge Sarcotragus species.

Five new (1-3, 5, and 7) and two known (4, 6) furanosesterterpene tetronic acids were isolated from the marine sponge Sarcotragus sp. by bioactivity-guided fractionation. These compounds showed cytotoxicity against a panel of five human tumor cell lines. The gross structures were established on the basis of NMR and MS analyses. The compounds showed interesting variations of geometry and absolute configuration.

Animals↗

Preoptic area sleep-regulating mechanisms.

Evidence is summarized for the existence of a sleep-regulating mechanism within the preoptic area of the hypothalamus, including the results of lesion, stimulation, and neuronal recording studies. Recent findings employing the c-fos protein immunohistochemical method, have localized putative sleep-regulatory neurons to the ventrolateral preoptic area (vlPOA) and the median preoptic nucleus (MnPn). Electrophysiological studies have confirmed the presence of neurons with sleep-related discharge in the vlPOA. Neurons in the vlPOA that exhibit c-fos protein immunoreactivity during sleep contain the inhibitory neuromodulators galanin and gamma-aminobutyric acid (GABA). These neurons also project to monoaminergic arousal systems, particularly the histaminergic cell groups in the posterior hypothalamus. POA neurons can be hypothesized to provide sleep-related inhibitory control over multiple arousal systems in the forebrain and brainstem.

Action Potentials↗

Discharge patterns of neurons in cholinergic regions of the basal forebrain during waking and sleep.

A subset of neurons recorded in the magnocellular basal forebrain (mBF) of cats and rats exhibit elevated discharge rates during waking and REM sleep, and diminished discharge during sleep with cortical EEG synchrony (nonREM sleep). This pattern is observed in mBF neurons in cats with identified ascending projections, and in neurons located in cholinergic regions of the rat mBF. However, the cholinergic versus noncholinergic nature of recorded cells could not be determined with the extracellular recording method employed. During waking, discharge of mBF neurons is strongly movement-related. Peak discharge rates occur during a variety of head and limb movements. Discharge rates during waking immobility are reduced by >50% compared to rates during waking movement. The absence of movement accounts for more of the variance in discharge across the sleep-wake cycle than does the presence of cortical EEG synchronization. Several factors participate in the regulation of mBF neuronal activity across arousal states. Tonic inhibition mediated by adenosine appears to be present during both waking and sleep. In some mBF neurons, increased GABAergic inhibition contributes to nonREM sleep-related reductions in discharge rate. Fluctuations in mBF cell activity during waking behaviors may reflect changing excitatory input from neurons in the pontine and midbrain tegmentum.

Animals↗

Teenage motherhood and infant mortality in Bangladesh: maternal age-dependent effect of parity one.

Nuptiality norms in rural Bangladesh favour birth during the teenage years. An appreciable proportion of teenage births are, in fact, second births. This study examines the relationship between teenage fertility and high infant mortality. It is hypothesized that if physiological immaturity is responsible, then the younger the mother, the higher would be the mortality risk, and the effect of mother's 'teenage' on mortality in infancy, particularly in the neonatal period, would be higher for the second than the first births. Vital events recorded by the longitudinal demographic surveillance system in Matlab, Bangladesh, in 1990-92 were used. Logistic regression was used to estimate the effects on early and late neonatal (0-3 days and 4-28 days respectively) and post-neonatal mortality of the following variables: mother's age at birth, parity, education and religion, sex of the child, household economic status and exposure to a health intervention programme. The younger the mother, the higher were the odds of her child dying as a neonate, and the odds were higher for second children than first children of teenage mothers. First-born children were at higher odds of dying in infancy than second births if mothers were in their twenties. Unfavourable mother's socioeconomic conditions were weakly, but significantly, associated with higher odds of dying during late neonatal and post-neonatal periods. The results suggest that physical immaturity may be of major importance in determining the relationship between teenage fertility and high neonatal mortality.

Adolescent↗

Structure of the bifunctional inhibitor of trypsin and alpha-amylase from ragi seeds at 2.2 A resolution.

The crystal structure of a bifunctional inhibitor of alpha-amylase and trypsin (RATI) from ragi seeds (Indian finger millet, Eleusine coracana Gaertneri) has been determined by X-ray diffraction at 2.2 A resolution. The inhibitor consists of 122 amino acids, with five disulfide bridges, and belongs to the plant alpha-amylase/trypsin inhibitor family. The crystals were grown by the microdialysis method using ammonium sulfate as a precipitating agent. The structure was determined by the molecular-replacement method using as models the structures of Corn Hageman factor inhibitor (CHFI) and of RATI at 2.9 A resolution determined previously. It has been refined to an R factor of 21.9%. The structure shows an r.m.s. deviation for C(alpha) atoms of 2.0 A compared with its own NMR structure, whereas the corresponding value compared with CHFI is found to be 1.4 A. The r.m.s. difference for C(alpha) atoms when compared with the same protein in the structure of the complex with alpha-amylase is 0.7 A. The conformations of trypsin-binding loop and the alpha-amylase-binding N-terminal region were also found to be similar in the crystal structures of native RATI and its complex with alpha-amylase. These regions differed considerably in the NMR structure.

Amino Acid Sequence↗

Repeated neonatal deaths in families with special reference to causes of death.

It is recognized that one infant death in a family indicates an increased risk of death of a subsequent sibling. This study examines which cause of death of a sibling is related to the mortality of the younger sibling and when. Longitudinal vital events data from the maternal and child health and family planning (MCH-FP) project and the comparison areas in Matlab, Bangladesh, were used. Primary causes of 868 neonatal deaths and 624 post-neonatal deaths resulting from 18,865 singleton live births in 1989-92 and those (967 as neonates and 708 as post-neonates) of their immediate elder siblings were categorised into infectious and non-infectious diseases. Multinomial logistic regression was used to estimate the risk of younger siblings dying in each age period from infectious and non-infectious diseases given the age and cause of deaths of older siblings and controlling for other biosocial correlates of infant mortality. A neonatal death of non-infectious causes in a family was twice as likely to be followed by another one occurring at the same age from similar causes compared with a surviving infant followed by a neonatal death from non-infectious causes. The MCH-FP project, though successful in reducing the risk of neonatal and post-neonatal mortality from infectious diseases, did not reduce the risk of dying from non-infectious diseases.

Bangladesh↗

Hepatitis B infection in Bangladeshi mothers and infants.

In order to estimate the relative importance of perinatal transmission of hepatitis B in rural Bangladesh a cross-sectional study was carried out. Paired-serum samples of infants aged 2-8 months old, a group of new born, and their mothers were tested for hepatitis B markers using a commercial ELISA test kit. In total, 107 (32.4%) positive for HBcAg, 18 (5.4%) for HBsAg, and 4 (1.2%) for HbeAg. Of the infants, 35 (10.5%) positive for HBcAg, 1 (0.3%) for HBsAg, and none for HBeAg. Of the 18 HBsAg positive mothers, 4 (22%) were HBeAg positive. All 14 children of mothers who were HBeAg negative were negative for HBsAg. Only one out of four (25%) of children of HBeAg positive mothers were HBsAg carriers (8 months old), and in three children transmission did not occur (two 8 months, one 6 months old). This survey indicates that hepatitis B is prevalent in rural Bangladesh and that the perinatal transmission mode may be relatively low.

Bangladesh↗

Sleep-waking discharge patterns of ventrolateral preoptic/anterior hypothalamic neurons in rats.

Numerous lesion, stimulation and recording studies in experimental animals demonstrate the importance of neurons within the preoptic/anterior hypothalamic area (POA) in the regulation of sleep induction and sleep maintenance. Recently, a discrete cluster of cells in the ventrolateral POA (vlPOA) of rats was found to exhibit elevated c-fos gene expression during sleep, indicating that these neurons are strongly activated during nonREM and/or REM sleep stages. We examined neuronal discharge during wakefulness and sleep throughout the dorsal to ventral extent of the lateral POA in rats, using chronic microwire technique. We found that neurons with elevated discharge rates during sleep, compared to waking, were localized to the vlPOA. As a group, vlPOA neurons displayed elevated discharge rates during both nonREM and REM sleep. Discharge of vlPOA neurons reflected the depth of sleep, i.e., discharge rates increased significantly from light to deep nonREM sleep. During recovery sleep following 12-14 h of sleep deprivation, vlPOA neurons displayed increased sleep-related discharge, compared to baseline sleep. Neurons in the vlPOA displaying increased neuronal discharge during sleep were located in the same area where neurons exhibit increased c-fos gene expression during sleep. Such neurons are likely components of a rostral hypothalamic mechanism that regulates sleep onset and sleep maintenance.

Animals↗

Malonyl-CoA and the regulation of fatty acid oxidation in soleus muscle.

1. Rat soleus strips were incubated with 5 mM glucose, after which tissue metabolites were measured. Alternatively, muscle strips were incubated with 5 mM glucose and 0.2 mM palmitate, and the formation of 14CO2 from exogenous palmitate or from fatty acids released from prelabelled glycerolipids was measured. 2. Etomoxir, which inhibits the mitochondrial overt form of carnitine palmitoyltransferase (CPT1), increased the tissue content of long-chain fatty acyl-CoA esters and decreased the ratio of fatty acylcarnitine to fatty acyl-CoA, suggesting that such changes could be a diagnostic for the inhibition of CPT1 3. Over a range of incubation conditions there was a positive correlation between the tissue contents of malonyl-CoA and long-chain fatty acyl-CoA esters. Under conditions in which these two metabolites increased in content (i.e. with insulin or with 3 mM dichloroacetate) there was a corresponding decrease in the ratio of fatty acylcarnitine to fatty acyl-CoA and a decrease in beta-oxidation. Isoprenaline or palmitate (0.5 mM) opposed the effect of insulin, decreasing the contents of malonyl-CoA and long-chain fatty acyl-CoA, increasing the ratio of fatty acylcarnitine to fatty acyl-CoA and increasing beta-oxidation. These findings are consistent with the notion that all of these agents can cause the acute regulation of CPT1 in Type I skeletal muscle. 4. The addition of 5-amino-4-imidazolecarboxamide ribonucleoside (AICAriboside) to cause activation of the AMP-activated protein kinase decreased the tissue content of malonyl-CoA. AICAriboside also had an antilipolytic effect in the muscle strips. 5. Measurements were made of the activities of ATP-citrate lyase, acetyl-CoA carboxylase, fatty acid synthase and malonyl-CoA decarboxylase in soleus muscle and in representative Type IIa and Type IIb muscles. A cytosolic activity of malonyl-CoA decarboxylase would seem to offer a feasible route for the disposal of malonyl-CoA in skeletal muscle.

ATP Citrate (pro-S)-Lyase↗

Infant and child mortality in Bangladesh: age-specific effects of previous child's death.

This study examines whether mortality of two adjacent siblings in families is age-specific and is modified by the MCH-FP programme and fertility and mortality declines in Matlab, Bangladesh, using data for singleton births during 1977-78, 1985-86 and 1989-90 in the treatment (MCH-FP) and comparison areas. Logistic regression was used to estimate the net effects of survival status of elder siblings on mortality of younger siblings in the neonatal, postneonatal and toddler periods, controlling for birth order, previous birth interval, maternal age, education and religion, household possession of valuable items and sex of the child. Odds of neonatal and postneonatal deaths of younger siblings were found to be higher if the elder sibling had died at the same age than if the sibling had survived infancy. Toddler mortality was lower if the elder sibling had died in infancy. The association between two siblings'mortality risks did not decline over time in either area. The results suggest that a family history of child deaths by age is important to identify when subsequent infants would be at a higher risk of dying.

Age Distribution↗

Effect of transdermal application of nicotine on colonic transit in healthy nonsmoking volunteers.

The radio-opaque marker technique (ROMT) is a safe and noninvasive method to determine total colonic (TCTT) and segmental colonic transit times (SCTT). Previous results have shown that smoking volunteers had significantly longer TCTT than nonsmokers, but the underlying mechanism was not clear. We investigated the effect of transdermal nicotine application in two different doses in a non-blind randomized experiment involving three distinct phases. In phase 1 baseline transit times were determined with an abdominal X-ray after a 6-day period of marker ingestion and again after the following bowel movement to study the influence of a bowel movement just before the X-ray. TCTT was nearly twice as high before than after defaecation (42.6 h vs. 25.1 h, P < 0.05). The main acceleration was found in the rectosigmoid (RS) (18.6 h vs 7.1 h, P < 0.05) with no significant changes in right (RC) and left colon (LC). In phase 2 and 3 nicotine was applied in two doses of 17.5 mg day-1 and 35 mg day-1 in random order. Both doses resulted in a significant decrease of TCTT compared to the predefaecation baseline (42.6 h vs 32.2 h/28.2 h, respectively, P < 0.05). Again the main effect was located in the RS (18.6 h vs 9.9 h/7.6 h, P < 0.05). Short-term application nicotine results in a decrease of TCTT which is due to an accelerated transit in the RS.

Administration, Cutaneous↗

Intracranial aneurysm surgery in Bangladesh.

In this study of 1000 cerebrovascular disease patients, the commonest age are 50 to 70 years with male predominance. The urban patients are large in number and the risk factors are sedentary life, stress and strain, smoking, and hypertension. The patients are more chronic than acute and transport facilities are poor. Fifteen percent are hemorrhagic stroke, some of them may be due to intracranial aneurysm. In the absence of proper diagnostic facilities and adequate neurosurgeons, infrequent surgical treatment, and lack of statistics of intracranial aneurysm, this study may be a basis for further study of aneurysmal surgery in Bangladesh.

Acute Disease↗