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Biomedical subjects

M K Hasan

Publications and source records attributed to M K Hasan.

At least 19 recordsLinked to original sources
PubMed1998

Large quantity production with extreme convenience of human SDF-1alpha and SDF-1beta by a Sendai virus vector.

We describe a robust expression of human stromal cell-derived factor-1alpha (SDF-1alpha) and SDF-1beta, the members of CXC-chemokine family, with a novel vector system based upon Sendai virus, a non-segmented negative strand RNA virus. Recombinant SDF-1alpha and SDF-1beta were detected as a major protein species in culture supernatants, reached as high as 10 microg/ ml. This remarkable enrichment of the products allowed us to use even the crude supernatants as the source for biological and antiviral assays without further concentration nor purification and will thus greatly facilitate to screen their genetically engineered derivatives.

Anti-HIV Agents↗
PubMed1997

Sendai virus-based expression of HIV-1 gp120: reinforcement by the V(-) version.

BACKGROUND: We have established a system for recovering Sendai virus (SeV), a nonsegmented negative strand RNA virus, entirely from cDNA at an extremely high rate, and have succeeded in creating a V(-) SeV whose gene expression was greatly enhanced by the deletion of the nonessential V gene. Because of its extreme medical importance, there has been a strong need for the establishment of a better system to express the gp120 envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) in sufficient quantity and purity. It also remains to be established to produce gp120 in in vitro natural host cells for HIV-1 such as human primary blood mononuclear cells, macrophages or established T cell lines. RESULTS: Using the above system, we created recombinant Sendai viruses expressing the gp120 in CV1 cells, a monkey kidney line. The expression level from the standard V(+) version has already reached 2.2/microg per 10(6) infected cells, which was readily purified from the culture fluid with a recovery rate of about 60%, and has so far appeared to be functionally and serologically authentic. The inserted gp120 gene was stably maintained during numerous passages of the recombinant virus. The V(-) version-based expression was even more robust, consistently reaching over 6.0 microg per 10(6) cells, a level that is one of the highest currently attainable for gp120 production in mammalian cells. Furthermore, a broad host range of SeV allowed gp120 production in all the three natural host cells for HIV-1 described above. CONCLUSIONS: SeV-based expression serves as a novel choice for producing large quantities of HIV-1 gp120 and will greatly facilitate biochemical, biological and immunological studies of this important glycoprotein.

DNA, Recombinant↗
PubMed1997

Creation of an infectious recombinant Sendai virus expressing the firefly luciferase gene from the 3' proximal first locus.

A genetic engineering approach was made to generate a recombinant non-segmented negative-strand RNA virus, Sendai virus (SeV) of the family Paramyxoviridae, that expresses firefly luciferase. The DNA construct containing the entire open reading frame (ORF) of the luciferase gene followed by the SeV transcription stop and restart signals connected with the conserved intergenic three nucleotides was inserted immediately before the ORF of the viral 3'-proximal nucleocapsid (N) protein gene in a full-length SeV cDNA copy. After intracellular expression of full-length antigenomic transcripts from the engineered cDNA and of the viral n ucleocapsid protein and RNA polymerase from the respective plasmids, a recombinant SeV expressing luciferase activity at a high level was recovered, although the tendency of this particular reporter gene product to aggregate in cells made it difficult to estimate the maximum level of expression. The increase in genome length brought about by inserting 1728 nucleotides into the 15,384 nucleotide parental SeV was associated with reduced plaque size, slightly slower replication kinetics and a severalfold decrease in yield of the virus. The inserted luciferase gene was stably maintained after numerous rounds of replication by serial passages in chick embryos. These results indicate the potential utility of SeV as a novel expression vector.

Animals↗
PubMed1997

In vivo sequence variability of human immunodeficiency virus type 1 envelope gp120: association of V2 extension with slow disease progression.

According to the rate of depletion of CD4 cell counts, we grouped 12 cases of human immunodeficiency virus type 1 (HIV-1) infection as 6 rapid (21.0 to 33.8 cells per microl per month) and 6 slow (0.9 to 7.9 cells per microl per month) progressors and determined the individual viral quasispecies patterns by sequencing the genome region encoding the V1, V2, and V3 loops of envelope protein. Although the quasispecies structures varied widely from one individual to another, a strong correlation was observed between a low rate of disease progression and a high degree of genetic diversity of HIV-1. Furthermore, the V2 loop extension was observed specifically in individuals with slow or no disease progression, whereas basic amino acid substitutions in V3 characteristic of a viral phenotype shift from non-syncytium inducing to syncytium inducing were observed in patients with advanced stages of disease regardless of their rate of disease progression. Studies with recombinant viruses suggested that elongation of V2 potentially restricts the capacity of HIV-1 to replicate in macrophages. Thus, our results suggest the association of distinct sequence features of both V3 and V2 with particular patterns of disease progression. Elongation of the V2 loop may be a good predictor of slow disease progression, while basic substitutions of V3 without elongation of V2 are characteristic of rapid progression.

Amino Acid Sequence↗
PubMed1996

Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface.

The envelope protein, gp120, of human immunodeficiency virus type 1 (HIV-1) is heavily glycosylated and sialylated. The heavy sialylation greatly affects the physical properties of the protein, as it resolves into a wide acidic pH range despite the basic pI value predicted for its polypeptide backbone (B. S. Stein and E. G. Engleman, J. Biol. Chem. 265:2640-2649, 1990). However, the functional significance of the heavy sialylation remains elusive. Here, we show that desialylation of HIV-1 with neuraminidase greatly augments the initial virus-cell interaction, leading to remarkably enhanced viral replication and cytopathogenicity. This enhancement appeared to be a direct result of the removal of negatively charged sialic acids but not of the exposure of galactose residues or complement activation. Complementing these results, studies with inhibitors of mannosidase I and mannosidase II showed that the processing of HIV-1 oligosaccharides into the complex type to acquire the terminal sialic acid residues impeded the full replication capacity of the virus and that its prevention also enhanced virus replication and cytopathogenicity. Enhancement of infection by desialylation was found widely, with HIV-1 laboratory strains of different cell tropisms and primary isolates as well as HIV-2 and simian immunodeficiency virus. Thus, the sialylation catalyzed by host cell pathways appeared to reduce the infectivity of human and nonhuman primate lentiviruses. Our results further suggested that desialylation would help increase the titers of HIV-based vectors.

1-Deoxynojirimycin↗
PubMed1994

Isolation of Vibrio cholerae O139 synonym Bengal from the aquatic environment in Bangladesh: implications for disease transmission.

Currently, Bangladesh is experiencing an epidemic of acute watery diarrhea caused by Vibrio cholerae O139. Surface waters were collected and cultured for vibrious following enrichment. Twelve percent (11 of 92) of samples yielded V. cholerae O139, and all of them were positive for cholera toxin. The data suggest that V. cholerae O139 is easily culturable from surface water samples.

Bangladesh↗
PubMed1994

Alzheimer's disease: a new hope.

Until recently, the diagnosis and treatment of Alzheimer's disease was limited. This article describes the outcome of new research and advances in the pharmacological treatment of this disease, especially the use of Cognex (tacrine). It also reports on a multicenter study of tacrine we participated in with patients at Raleigh Psychiatric Services, Inc. in Beckley.

Aged↗
PubMed1993

Use of the polymerase chain reaction and fluorescent-antibody methods for detecting viable but nonculturable Shigella dysenteriae type 1 in laboratory microcosms.

Epidemiological studies of shigellosis in Bangladesh have demonstrated that surface-water sources can act as foci of infection. Studies of laboratory microcosms have shown that shigellae become nonculturable but remain viable when exposed to environmental samples of water. The present study was carried out to detect viable but nonculturable Shigella dysenteriae 1 from laboratory microcosms by the polymerase chain reaction and the fluorescent-antibody techniques. S. dysenteriae 1 was inoculated into laboratory microcosms consisting of water samples collected from ponds, lakes, rivers, and drains in Bangladesh. The survival of S. dysenteriae in microcosms was assessed by viable counting on MacConkey agar. After 2 to 3 weeks, S. dysenteriae 1 became nonculturable but remained viable. After 6 weeks, this nonculturable but viable S. dysenteriae 1 was detected by both the polymerase chain reaction and the fluorescent-antibody methods. The viable but nonculturable state of S. dysenteriae 1 demonstrated in this study may be important for understanding the epidemiology of shigellosis.

Base Sequence↗
PubMed1993

Growth and survival of Shigella flexneri in common Bangladeshi foods under various conditions of time and temperature.

Survival and growth of Shigella flexneri were assessed in various foods, including boiled rice, lentil soup, milk, cooked beef, cooked fish, mashed potato, mashed brinjal, and raw cucumber. Growth at 25 and 37 degrees C and survival at 5 degrees C were observed by viable counts on MacConkey agar. The organism grew well in all tested foods and growth increased from 10(5) to 10(8) to 10(10) cells per ml or g within 6 to 18 h after inoculation at 25 and 37 degrees C.

Bangladesh↗
PubMed1993

Competency assessment in the elderly.

Although brain changes and functional capacity impairment occur in both normal and abnormal aging, it is the extent of change which determines competency status. Dementia to some degree afflicts 10 percent to 15 percent of 30 million Americans over age 65. History, age-normed neuropsychological testing, and laboratory investigations are essential to competency assessment since physical and personality dysfunctions may masquerade as dementia. Since competency decisions profoundly impact the lives of the elderly, our fastest growing segment of national population, psychiatrists, psychologists, family physicians, and lawyers will become increasingly involved in competency issues.

Aged↗
PubMed1990

Neuroleptic malignant syndrome.

Neuroleptic malignant syndrome is a potentially life-threatening reaction to neuroleptic agents. Its symptoms develop rapidly and may occur at the initiation of the neuroleptics or after long-term use. The pathogenesis remains unclear. The authors reviewed 93 documented cases published in the literature over the past five years. Demographic and clinical features of the syndrome are identified. Diagnostic criteria are proposed along with recommendations for treatment and further research.

Aged↗
PubMed1981

Once-a-day drug regimen for psychiatric patients.

Patient compliance can be improved by reducing the complexity of drug dosage and by better labeling, packaging and informational exchange. Single bedtime doses not only increase compliance but also decrease side effects. The once-a-day regimen can reduce drug automatism and thus decrease acute confusional states, especially in the elderly.

Adult↗