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Biomedical subjects

M Alam

Publications and source records attributed to M Alam.

At least 19 recordsLinked to original sources
PubMed2001

Globin-coupled sensors: a class of heme-containing sensors in Archaea and Bacteria.

The recently discovered prokaryotic signal transducer HemAT, which has been described in both Archaea and Bacteria, mediates aerotactic responses. The N-terminal regions of HemAT from the archaeon Halobacterium salinarum (HemAT-Hs) and from the Gram-positive bacterium Bacillus subtilis (HemAT-Bs) contain a myoglobin-like motif, display characteristic heme-protein absorption spectra, and bind oxygen reversibly. Recombinant HemAT-Hs and HemAT-Bs shorter than 195 and 176 residues, respectively, do not bind heme effectively. Sequence homology comparisons and three-dimensional modeling predict that His-123 is the proximal heme-binding residue in HemAT from both species. The work described here used site-specific mutagenesis and spectroscopy to confirm this prediction, thereby providing direct evidence for a functional domain of prokaryotic signal transducers that bind heme in a globin fold. We postulate that this domain is part of a globin-coupled sensor (GCS) motif that exists as a two-domain transducer having no similarity to the PER-ARNT-SIM (PAS)-domain superfamily transducers. Using the GCS motif, we have identified several two-domain sensors in a variety of prokaryotes. We have cloned, expressed, and purified two potential globin-coupled sensors and performed spectral analysis on them. Both bind heme and show myoglobin-like spectra. This observation suggests that the general function of GCS-type transducers is to bind diatomic oxygen and perhaps other gaseous ligands, and to transmit a conformational signal through a linked signaling domain.

Amino Acid Sequence↗
PubMed2001

Inelastic collapse in simple shear flow of a granular medium.

Previous investigations have shown that inelastic collapse is a common feature of inelastic, hard-sphere simulations of nondriven (or unforced) flows, provided that the coefficient of restitution is small enough. The focus of the current effort is on a driven system, namely, simple shear flow. Two-dimensional, hard-sphere simulations have been carried out over a considerable range of restitution coefficients (r), solids fractions (nu), and numbers of particles (N). The results indicate that inelastic collapse is an integral feature of the sheared system. Similar to nondriven systems, this phenomenon is characterized by a string of particles engaging in numerous, repeated collisions just prior to collapse. The collapsed string is typically oriented along a 135 degrees angle from the streamwise direction. Inelastic collapse is also found to be more likely in systems with lower r, higher nu, and higher N, as is true for unforced systems. Nonetheless, an examination of the boundary between the collapsed and noncollapsed states reveals that the sheared system is generally more "resistant" to inelastic collapse than its nondriven counterpart. Furthermore, a dimensionless number V* is identified that represents the magnitude of the initial fluctuating velocities relative to that of a characteristic steady-state velocity (i.e., the product of shear rate and particle diameter). For values of V*>>O(1), the transient portion of the simulation is found to be more reminiscent of a nondriven system (i.e., isotropic particle bunching is observed instead of diagonal particle bands).

Journal Article↗
PubMed2001

Anabolic-androgenic steroids induce apoptotic cell death in adult rat ventricular myocytes.

We tested whether exposure to anabolic-androgenic steroids (AASs) would induce apoptosis in adult rat ventricular myocytes in vitro. Myocytes were exposed to stanozolol (STZ), testosterone enanthate (TE) and testosterone (T) (0.1 micromol/L, 1 micromol/L, 10 micromol/L, and 100 micromol/L) for 20 h. The percentage of myocytes undergoing apoptosis was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and was found to be increased when compared to control myocytes at STZ 10 micromol/L 12 +/- 2% (mean +/- SD), STZ 100 micromol/L 42 +/- 3%; TE 1 micromol/L 11 +/- 2%, TE 10 micromol/L 21 +/- 3%, TE 100 micromol/L 62 +/- 2%; T 10 micromol/L 11 +/- 2%, T 100 micromol/L 40 +/- 3% (P < 0.001 vs. CTL 2 +/- 2%). The STZ-, TE- and T-induced dose-dependent apoptotic cell death was corroborated by a significantly increased DNA laddering in myocytes exposed to STZ and T > or = 10 micromol/L and TE > or = 1 micromol/L. Notably, STZ, TE, and T exposure markedly increased the expression of the pro-apoptotic oncogene Bax-alpha, as assessed by reverse transcription-polymerase chain reaction. Taken together, these results clearly show for the first time that AASs induce apoptotic cell death in a dose-dependent manner. This finding may have important implications in understanding the pathogenesis of ventricular remodeling, cardiomyopathy, and sudden cardiac death associated with AAS abuse.

Anabolic Agents↗
PubMed2001

A globin-coupled oxygen sensor from the facultatively alkaliphilic Bacillus halodurans C-125.

We have recently discovered heme-containing signal transducers from the archaeon Halobacterium salinarum (HemAT-Hs) and the gram-positive bacterium Bacillus subtilis (HemAT-Bs). These proteins bind diatomic oxygen and trigger aerotactic responses. We identified that HemAT oxygen-sensing domains contain a globin-coupled sensor (GCS) motif, which exists as a two-domain transducer, having no similarity to the PAS domain (Period circadian protein, Ah receptor nuclear translocator protein, Single-minded protein) superfamily transducers. Using the GCS motif, we predicted that a 439-amino-acid protein annotated as a methyl-accepting chemotaxis protein (MCP) in the facultatively alkaliphilic bacterium Bacillus halodurans is a globin-coupled oxygen sensor. We cloned, expressed, and purified GCS(Bh), and performed its spectral analysis. GCS(Bh), binds heme and shows myoglobin-like spectra. This suggests that GCS(Bh) acts as an oxygen sensor and transmits a conformational signal through a linked signaling domain to trigger an aerotactic response in B. halodurans.

Amino Acid Sequence↗
PubMed2001

A novel cytotoxic flavonoid glycoside from Physalis angulata.

A new flavonol glycoside, myricetin 3-O-neohesperidoside (1) was isolated from a cytotoxic MeOH extract of the leaves of Physalis angulata. Compound 1 showed remarkable cytotoxicity in vitro against murine leukemia cell line P-388, epidermoid carcinoma of the nasopharynx KB-16 cells, and lung adenocarcinoma A-549 with ED(50) values of 0.048, 0.50 and 0.55 microg ml(-1), respectively.

Animals↗
PubMed2001

Analysis on distribution of insertion sequence IS431 in clinical isolates of staphylococci.

Distribution of insertion sequence IS431 in clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus was investigated. Except for methicillin susceptible-S. aureus (MSSA), IS431 was detected in all isolates of the three staphylococcal species. In MSSA, only 20% of isolates with distinct coagulase types and genetic types possessed IS431. In a few MSSA isolates, an IS431 variant with internal deletion was found.

Base Sequence↗
PubMed2001

Distribution of aminoglycoside resistance genes in recent clinical isolates of Enterococcus faecalis, Enterococcus faecium and Enterococcus avium.

Aminoglycoside modifying enzymes (AMEs) are major factors which confer aminoglycoside resistance on bacteria. Distribution of genes encoding seven AMEs was investigated by multiplex PCR for 279 recent clinical isolates of enterococci derived from a university hospital in Japan. The aac(6')-aph(2"), which is related to high level gentamicin resistance, was detected at higher frequency in Enterococcus faecalis (42.5%) than in Enterococcus faecium (4.3%). Almost half of E. faecalis and E. faecium isolates possessed ant(6)-Ia and aph(3')-IIIa. The profile of AME gene(s) detected most frequently in individual strains of E. faecalis was aac(6')aph(2") + ant(6)-Ia + aph(3')-IIIa, and isolates with this profile showed high level resistance to both gentamicin and streptomycin. In contrast, AME gene profiles of aac(6')-Ii+ ant(6)-Ia+aph(3')-IIIa, followed by aac(6')-Ii alone, were predominant in E. faecium. Only one AME gene profile of ant(6)-Ia+aph(3')-IIIa was found in Enterococcus avium. The ant(4')-Ia and ant(9)-Ia, which have been known to be distributed mostly among Staphylococcus aureus strains, were detected in a few enterococcal strains. An AME gene aph(2")-Ic was not detected in any isolates of the three enterococcal species. These findings indicated a variety of distribution profiles of AME genes among enterococci in our study site.

Aminoglycosides↗
PubMed2001

A psychometric study of patients with nail dystrophies.

BACKGROUND: Survey studies suggest that patients with various dermatologic conditions experience concomitant psychologic distress. OBJECTIVE: The purpose of this study was to determine which types of psychologic distress may be correlated with dystrophic disease of the nail in nonpsychiatric patients. METHODS: Fifty-seven adult subjects presenting for treatment of nail dystrophies completed a survey instrument, which included 5 psychometric measures. RESULTS: On average, patients rated the severity of their nail dystrophy and functional deficit higher (7.40/10 and 6.00, respectively) than investigators (6.15 and 3.75, respectively). Compared with age- and sex-matched nonpsychiatric patients, subjects in the study were moderately more anxious and minimally to mildly more depressed. Subjects had moderately depressed total self-concept, but their body image was approximately normal. Overall, subjects exhibited markedly more severe psychologic symptoms (84th percentile) than the normal sample, with the scores on the psychoticism, obsessive-compulsive, and paranoid ideation subscales being the most elevated. CONCLUSION: The subjects with nail dystrophy had markedly exacerbated psychologic symptoms compared with age- and sex-matched nonpsychiatric patients.

Adult↗
PubMed2001

Abnormal implantation of permanent pacemaker lead in the left ventricle via a patent foramen ovale: clinical and echocardiographic recognition of a rare complication.

An 84-year-old man with a history of permanent pacemaker placement had a preoperative cardiac evaluation for prostate cancer surgery. The patient was asymptomatic, and the results of a physical examination were consistent with a right bundle branch block, which was confirmed by electro-cardiogram as his paced rhythm. A chest radiograph raised the possibility of an abnormal lead location, and transthoracic echocardiography confirmed the mechanism of an abnormal placement of the pacemaker lead. Left ventricular location of pacemaker is rare, and awareness of its clinical and imaging findings, complications, and management options is important for clinicians involved in the care of patients with pacemakers.

Aged↗
PubMed2001

Pharmacotherapy of ectoparasitic infections.

Epizoonoses such as scabies, lice and cimicosis are common, vexing disorders that occur worldwide. Historically, many treatment modalities have been employed in the management of these disorders, and most of the drugs described in this review are of historical interest and no longer recommended or in widespread use because of their wide spectrum of adverse effects. More recently, reports documenting resistance against various antiectoparasite drugs, complicated and severe courses of the diseases, and adverse effects of drug therapy have prompted the development of new treatment strategies and drugs for optimal disease management. Because the strategies currently recommended for the treatment of ectoparasites differ worldwide, this review proposes a rational approach to selecting the best therapeutic agent by comparing the pharmacokinetics, pharmacodynamics, drug efficacy and adverse effects. A literature search of the currently Internet accessible libraries PubMed, Medline and Ideal library, of citations of articles found there, and from communications with the Federal Institute for Drugs and Medical Devices, Germany, was conducted based on this approach. One major observation of this literature search is that permethrin is the treatment of choice for lice and scabies in the US and in Great Britain, whereas lindane is still recommended for scabies in most other European countries because of its longer-standing record of effectiveness. Although permethrin has not yet been proven to be more effective than lindane in treating infections with these ectoparasites, it currently appears to have the best efficacy versus safety profile of topical treatments for scabies and lice. Ivermectin is a newer oral drug for the treatment of ectoparasites, which has been used with great success in the treatment of onchocercosis and other endoparasites. Although ivermectin appears to be a promising drug, its role in the treatment of ectoparasitic infections will be clarified as more study data become available. Finally, it is important to emphasise the clinical aspects of ectoparasite therapy and that providing the patient with optimal instructions on the use of topical therapeutics is of great importance in avoiding adverse effects and assuring complete removal of the ectoparasite, thereby avoiding the development of drug-resistance.

Administration, Oral↗
PubMed2001

Differential effects of doxorubicin on atrial natriuretic peptide expression in vivo and in vitro.

Doxorubicin (Dox) is a potent anti-cancer agent with cardiotoxic side-effects but the mechanism of its cardiotoxicity and its effect on expression of the vasoactive atrial natriuretic peptide (ANP), an important marker for cardiac hypertrophy, are little understood. The present study examined Dox-induced changes in vivo in hearts of 6 mongrel dogs and 5 Sprague-Dawley rats and in vitro in cardiac cultures of neonatal rats. Quantitative RT-PCR analysis using gamma 32-p labeled primers for beta-actin, phospholamban (PLB) and ANP showed a selective 5-fold increase of ANP mRNA in Dox-treated dog hearts in comparison to controls. Similarly, northern analysis of GAPD, beta-actin, cardiac alpha-actin and ANP gave a selective 4.5-fold increase in ANP transcripts in Dox-treated rat hearts. On the other hand, there was a selective decrease (approximately 39%) of ANP transcripts in Dox-treated cardiac cultures relative to controls. Immunohistochemistry localized the ANP changes both in tissue sections and in cultures to the cardiomyocytes. The data clearly showed that Dox selectively increases ANP expression in dog and rat hearts in absence of cardiocyte hypertrophy but selectively decreases it in cardiac cultures. This differential effect of Dox on cardiocytes in vivo and in vitro should be a useful parameter for studies of transcriptional control of ANP expression.

Animals↗
PubMed2001

Direct medical costs for surgical and medical treatment of condylomata acuminata.

OBJECTIVE: To determine which treatment modalities for condylomata acuminata are associated with the lowest direct medical costs. DESIGN: Cost-effectiveness analysis. SETTING: Ambulatory private practice, primary or specialty care. PATIENTS OR OTHER PARTICIPANTS: Adults with no presenting complaints other than condylomata acuminata. INTERVENTIONS: Construction of a cost-effectiveness model. From a literature review, extraction of commonly accepted guidelines regarding duration and frequency as well as reports of efficacies of typical treatment regimens; from Medicare physician fee schedules, costs of physician visits and physician-administered treatments; from published data, average wholesale prices of medications. MAIN OUTCOME MEASURE: Estimated direct medical costs per complete clearance associated with different treatment options for condylomata acuminata. RESULTS: Mean direct medical costs per complete clearance are lowest for surgical excision ($285). Other low-cost modalities are loop electrosurgical excision procedure ($316), electrodesiccation ($347), carbon dioxide laser ($416), podofilox ($424), and pulsed-dye laser ($479). Higher-cost modalities are cryotherapy ($951), trichloroacetic acid ($986), imiquimod ($1255), podophyllum resin ($1632), and interferon alfa-2b ($6665). CONCLUSION: Surgical modalities, including excision, electrodesiccation, loop electrosurgical excision procedure, and laser, as well as podofilox are low-cost options for the treatment of condylomata acuminata.

Condylomata Acuminata↗
PubMed2001

Kwashiorkor in patients with AIDS.

Kwashiorkor, a form of severe protein-energy malnutrition that entails loss of lean body weight, occurs endemically among children in many parts of the world but also has been documented in adults. We report a case of kwashiorkor in an HIV-positive adult male. Cutaneous findings are striking, and skin, hair, and nails are affected. Although kwashiorkor occurs in patients with HIV-AIDS, the skin manifestations have not been emphasized in the dermatologic literature. Indeed, dermatologists may play a vital role in diagnosing this treatable condition.

Acquired Immunodeficiency Syndrome↗