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S Rana

Publications and source records attributed to S Rana.

At least 37 records · Page 2Linked to original sources
PubMed1998

CXCR-4 is expressed by primary macrophages and supports CCR5-independent infection by dual-tropic but not T-tropic isolates of human immunodeficiency virus type 1.

Primary macrophages are infected by macrophage (M)-tropic but not T-cell line (T)-tropic human immunodeficiency virus type 1 (HIV-1) strains, and CCR5 and CXCR-4 are the principal cofactors utilized for CD4-mediated entry by M-tropic and T-tropic isolates, respectively. Macrophages from individuals homozygous for an inactivating mutation of CCR5 are resistant to prototype M-tropic strains that depend on CCR5 but are permissive for a dual-tropic isolate, 89.6, that can use both CCR5 and CXCR-4, as well as CCR2b, CCR3, and CCR8. Here we show that 89.6 entry into CCR5-deficient macrophages is blocked by an anti-CXCR-4 antibody and by the CXCR-4-specific chemokine SDF but not by the ligands to CCR2b or CCR3. Reverse transcription-PCR demonstrated expression of CXCR-4 but not CCR3 or CCR8 in macrophages, while CCR2b was variable. Macrophage surface expression of CXCR-4 was confirmed by immunofluorescence staining and flow cytometry. Thus, CXCR-4 is expressed by primary macrophages and functions as a cofactor for entry by dual-tropic but not T-tropic HIV-1 isolates, and macrophage resistance to T-tropic strains does not result from a lack of the T-tropic entry cofactor CXCR-4. Since CXCR-4 on macrophages can be used by some but not other isolates, these results indicate that HIV-1 strains differ in how they utilize chemokine receptors as cofactors for entry and that the ability of a chemokine receptor to mediate HIV-1 entry differs, depending on the cell type in which it is expressed.

Base Sequence↗
PubMed1998

Influence of the CCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4.

The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I) is associated with a 2- to 4-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor activities, and their effects on the expression and receptor activities of the major HIV-1 coreceptors. CCR2b and CCR2b-V64I were expressed at similar levels, and neither molecule affected the expression or coreceptor activity of CCR3, CCR5, or CXCR4 in cotransfected cell lines. Peripheral blood mononuclear cells (PBMCs) from CCR2-V64I heterozygotes had normal levels of CCR2b and CCR5 but slightly reduced levels of CXCR4. CCR2b and CCR2b-V64I functioned equally well as HIV-1 coreceptors, and CCR2-V64I PBMCs were permissive for HIV-1 infection regardless of viral tropism. The MCP-1-induced calcium mobilization mediated by CCR2b signaling was unaffected by the polymorphism, but MCP-1 signaling mediated by either CCR2b- or CCR2-V64I-encoded receptors resulted in heterologous desensitization (i.e., limiting the signal response of other receptors) of both CCR5 and CXCR4. The heterologous desensitization of CCR5 and CXCR4 signaling by both CCR2 allele receptor types provides a mechanistic link that might help explain the in vivo effects of CCR2 gene variants on progression to AIDS as well as the reported antiviral activity of natural CCR2 ligands.

Cell Line, Transformed↗
PubMed1998

Non-ulcer dyspepsia.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗
PubMed1998

HIV prevention among injecting drug users: responses in developing and transitional countries.

OBJECTIVE: Human immunodeficiency virus (HIV) infection associated with injecting drug use has been reported in at least 98 countries and territories worldwide. There is evidence that new epidemics are emerging in different regions, including Eastern Europe, Latin American, and the eastern Mediterranean. The authors provide a global overview of the situation of HIV infection associated with injecting drug use and responses that have been implemented in various developing and transitional countries. METHODS: Although there has been extensive documentation of the extent and nature of of HIV infection associated with injecting drug use in many developed countries and the various interventions implemented in those countries, there is very limited information on the situation in developing and transitional countries. This chapter brings together information from a broad range of sources, including published literature; "gray" or "fugitive" literature; data collected by the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations International Drug Control Programme (UNDCP); personal communications; and direct observation by the authors. The authors have traveled extensively to a wide range of developing and transitional countries and have accessed information not readily available to the international research community. RESULTS: A wide range of HIV prevention strategies targeting injecting drug users (IDUs) has been implemented in developing countries and countries in transition. Interventions include opioid substitution pharmacotherapy, needle syringe exchange and distribution, condom and bleach distribution, outreach to IDUs, peer education programs, and social network interventions. In some communities, completely new models of intervention and service delivery have developed in response to specific local needs and limitations. CONCLUSIONS: Although empirical data may currently be lacking to demonstrate the effectiveness of may HIV prevention programs targeting IDUs in developing and transitional countries, there is evidence that innovative HIV prevention initiatives are being implemented and sustained in a wide range of sociocultural settings.

Developing Countries↗
PubMed1997

Homocysteine in sickle cell disease: relationship to stroke.

PURPOSE: The risk factors and pathophysiology of stroke and other serious complications of sickle cell disease (SCD) are poorly defined. Hyperhomocysteinemia has recently been identified as a risk factor for stroke and other vascular diseases in the general population, however its role in SCD has not been investigated. PATIENTS AND METHODS: We measured serum homocysteine and red cell folate levels in 100 patients with SCD, including 16 patients with stroke. A disease severity score was determined for all patients and those without stroke were classified into mild (44 patients) or severe (40 patients) disease groups. RESULTS: Homocysteine levels for the stroke group (median 13.3 mumol/L, mean 13.1 +/- 4.3 mumol/L) were significantly higher than those in patients without stroke (median 9.7 mumol/L, mean 10.7 mumol/L) (P < 0.02), and on multiple regression analysis homocysteine level was independently correlated with stroke (P < 0.026). Homocysteine and folate levels were inversely correlated (r = -0.41, P < 0.00005). Using logistic regression, the odds ratio for stroke in patients with homocysteine levels above the median (10.1 mumol/L) was 3.5 in this group of patients (95% confidence interval 1.1 to 11.9). CONCLUSION: High homocysteine levels may be a risk factor for development of stroke in SCD patients. The role of homocysteine in the pathogenesis of stroke in SCD needs to be examined in a longitudinal, prospective study.

Adolescent↗
PubMed1997

Discontinuation of long-term transfusion therapy in patients with sickle cell disease and stroke.

Long-term transfusion therapy in patients with sickle cell disease and stroke markedly decreases the risk of stroke recurrence. However, it is not known how long the transfusions should be continued. Published reports have documented a high risk of stroke recurrence after stopping transfusion. We report on nine consecutive patients with sickle cell disease and stroke whose long-term transfusion therapy was discontinued and in whom no ischemic strokes developed during 80.75 patient years of follow-up.

Adolescent↗
PubMed1997

Classical light scattering quantitation of protein aggregates: off-line spectroscopy versus HPLC detection.

This paper describes the development and validation of a new off-line approach to quantitate both covalent and noncovalent, in-solution aggregates present in protein formulations and compares the new assay to established HPLC methods. This off-line analysis is well suited for use in QC release testing, formulation development and stability indicating applications. An inexpensive, continuous source HPLC fluorometer has been adapted with the addition of second order filters for use as a sensitive right-angle scatterometer which can determine the molecular weight of protein aggregates in solution. When used as an HPLC detector, right-angle light scattering is a sensitive method which can determine the molecular weight of peaks separable by HPLC, thus discriminating between monomers of different conformations and aggregates. The weight-averaged molecular weight of aggregate peaks can be calculated with system calibration, yielding the average number of monomers per aggregate. If the protein concentration is high enough for an adequate signal, the off-line technique of right-angle light scattering of protein formulations has advantages of convenience and speed over the HPLC approach. Samples are placed in standard fluorometer cuvettes and toluene is used as a calibrator. Data are presented which show the off-line (static) method to be extremely rapid, rugged and precise. The accuracy of this approach is demonstrated through cross-validation to traditional GPC analysis of protein aggregate distributions. This non-invasive light scattering approach is particularly useful when non-covalent protein aggregation is reversible and readily altered by chromatographic separations typically used for characterizing aggregates.

Calibration↗
PubMed1997

Role of CCR5 in infection of primary macrophages and lymphocytes by macrophage-tropic strains of human immunodeficiency virus: resistance to patient-derived and prototype isolates resulting from the delta ccr5 mutation.

The alpha-chemokine receptor fusin (CXCR-4) and beta-chemokine receptor CCR5 serve as entry cofactors for T-cell (T)-tropic and macrophage (M)-tropic human immunodeficiency virus type 1 (HIV-1) strains, respectively, when expressed with CD4 in otherwise nonpermissive cells. Some M-tropic and dual-tropic strains can also utilize other beta-chemokine receptors, such as CCR2b and CCR3. A mutation of CCR5 (delta ccr5) was recently found to be common in certain populations and appears to confer protection against HIV-1 in vivo. Here, we show that this mutation results in a protein that is expressed intracellularly but not on the cell surface. Primary CD4 T cells from delta ccr5 homozygous individuals were highly resistant to infection with prototype M-tropic HIV-1 strains, including an isolate (YU-2) that uses CCR5 and CCR3, but were permissive for both a T-tropic strain (3B) and a dual-tropic variant (89.6) that uses CXCR-4, CCR5, CCR3, or CCR2b. These cells were also resistant to M-tropic patient isolates but were readily infected by T-tropic patient isolates. Primary macrophages from delta ccr5 homozygous individuals were also resistant to infection with M-tropic strains, including YU-2, but the dual-tropic strain 89.6 was able to replicate in them even though macrophages are highly resistant to CXCR-4-dependent T-tropic isolates. These data show that CCR5 is the essential cofactor for infection of both primary macrophages and T lymphocytes by most M-tropic strains of HIV-1. They also suggest that CCR3 does not function for HIV-1 entry in primary lymphocytes or macrophages, but that a molecule(s) other than CCR5 can support entry into macrophages by certain virus isolates. These studies further define the cellular basis for the resistance to HIV-1 infection of individuals lacking functional CCR5.

CD4 Antigens↗
PubMed1997

Study of oxidative-stress in rifampicin-induced hepatic injury in growing rats with and without protein-energy malnutrition.

1. Rifampicin (RMP) induced hepatic injury was investigated in growing rats. The interaction of moderate and severe protein-energy malnutrition (PEM) was also investigated. 2. Status of oxidative/antioxidative profile was studied by the mechanistic approach, to enumerate the nature of injury. 3. Successful hepatic injury in rats was produced by giving intraperitoneal injection of RMP (50 mg/kg/day). 4. Hepatic lipid peroxidation was significantly increased in all the RMP treated rats. 5. Superoxide dismutase, catalase and glutathione peroxidase activities in the hepatic tissue decreased with RMP treatment. 6. Hepatic thiols represented as total and protein-bound thiols, showed significant elevation, whereas the non protein thiols remain unchanged with RMP treatment. 7. Glutathione-S-transferases also showed significant elevation against 1,2-dichloro-4 nitrobenzene (DCNB) and ethacrynic acid (EA) as substrates. 8. The oxidative/antioxidative profile was observed to be more severely affected with coexistence of malnutrition. 9. Histopathological correlation showed an additional fatty infiltration of hepatocytes with coexistence of malnutrition. 10. Thus, in conclusion, it can be speculated that an altered oxidative/antioxidative profile is the closely associated with production of RMP induced hepatic injury.

Alanine Transaminase↗
PubMed1996

Involvement of an efflux system in mediating high level of fluoroquinolone resistance in Mycobacterium smegmatis.

A wild type strain of Mycobacterium smegmatis mc2 155 was serially adapted to 64 fold of minimal inhibitory concentration of an antimycobacterial agent, ciprofloxacin. This clone (CIPr) exhibited cross resistance to ofloxacin and ethidium bromide. The rate of drug efflux was accelerated in CIPr compared to the wild type strain. Verapamil, a calcium channel blocker, enhanced the drug accumulation in CIPr by diminishing the efflux and thus reversed the resistant phenotype. Additionally, a missense mutation was detected in the quinolone resistance determining region of the DNA-gyrase A subunit of CIPr. Taken together, these results suggest that drug efflux plays a major role in conferring such a high level of resistance in CIPr, in addition to the mutation in the DNA-gyrase locus.

Amino Acid Sequence↗
PubMed1996

Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene.

HIV-1 and related viruses require co-receptors, in addition to CD4, to infect target cells. The chemokine receptor CCR-5 (ref.1) was recently demonstrated to be a co-receptor for macrophage-tropic (M-tropic) HIV-1 strains, and the orphan receptor LESTR (also called fusin) allows infection by strains adapted for growth in transformed T-cell lines (T-tropic strains). Here we show that a mutant allele of CCR-5 is present at a high frequency in caucasian populations (allele frequency, 0.092), but is absent in black populations from Western and Central Africa and Japanese populations. A 32-base-pair deletion within the coding region results in a frame shift, and generates a non-functional receptor that does not support membrane fusion or infection by macrophage- and dual-tropic HIV-1 strains. In a cohort of HIV-1 infected caucasian subjects, no individual homozygous for the mutation was found, and the frequency of heterozygotes was 35% lower than in the general population. White blood cells from an individual homozygous for the null allele were found to be highly resistant to infection by M-tropic HIV-1 viruses, confirming that CCR-5 is the major co-receptor for primary HIV-1 strains. The lower frequency of heterozygotes in seropositive patients may indicate partial resistance.

Alleles↗
PubMed1996

Protein-energy malnutrition and oxidative injury in growing rats.

1. Weaning rats were fed ad libitum isocaloric diets containing 5% and 20% casein based proteins. 5% protein diet was protein deficient diet. Pair fed rats with the 5% protein group were maintained simultaneously on 20% protein diet but the amount restricted to the amount taken up by PEM group. 2. Glutathione, antioxidative enzymes, lipid peroxidation and histopathological studies in liver and only glutathione and antioxidative enzymes in blood were carried out. 3. Rats fed the 5% protein diet developed a severe protein energy malnutrition (PEM) whereas those on pair-fed diet developed mild to moderate PEM. 4. Glutathione related thiols superoxide dismutase, glutathione peroxidase, catalase and glutathione-Stransferase with (1 Chloro 2,4-dinitro benzene (CDNB) substrate) were decreased in liver with concomitant increase of lipid peroxidation in severe PEM. In blood glutathione, glutathione peroxidase and catalase were decreased while superoxide dismutase was increased in severe PEM group. 5. Mild to moderate PEM (pair-fed group) also resulted in similar changes in liver except glutathione peroxidase, lipid peroxidation in liver and superoxide dismutase in blood. 6. Hepatic injury was detectable only in the severe PEM group. 7. Oxidative-stress and hepatic injury occurred in severe PEM and to a lesser degree in mild to moderate PEM.

Animals↗
PubMed1996

Thyroid dysfunction in HIV-infected children: is L-thyroxine therapy beneficial?

PURPOSE: To assess thyroid function in symptomatic HIV-infected infants and children with failure to thrive and to evaluate clinical response in patients with hyperthyrotropinemia to levothyroxine. METHODS: We evaluated 11 children (mean age: 1.5 years; males = 5, females = 6) with HIV infection and failure to thrive (weight and height > 2 SD below the mean) for presence of hypothyroidism. Thyroid-stimulating hormone (TSH) and thyroxine (T4) were measured. Four children with high basal TSH and one child with a normal basal TSH underwent the Thyrotropin-releasing hormone (TRH) stimulation test as well. Four children received treatment with L-thyroxine. RESULTS: Eight of the 11 children had high basal TSH levels. All patients had normal or increased T4 values. The TRH stimulation test showed an exaggerated response in all four patients with high basal TSH values and a normal response in one patient with normal basal THS values. All four patients who received treatment with L-thyroxine showed normalization of the TSH. Increased growth velocity was noted in 3 of 4 patients. The fourth patient died within two weeks following initiation of therapy for overwhelming candida sepsis. The autopsy of this patient showed atrophy of the thyroid gland. Two of the four patients with high TSH levels, who did not receive L-thyroxine, died; the other two did not show any improvement in their height z scores. Two patients with a high TSH also had high thyroid-binding hormone (TBG) levels. Both patients with the high TBG died within 2 to 3 months of the study. CONCLUSIONS: Hypothyroidism as indicated by elevated basal TSH and abnormal TRH response was common in the HIV-infected children in this study and may have contributed to failure of growth in these children. Replacement therapy resulted in correction of abnormal TSH and improvement of height z scores during the period of observation. The significance of these findings needs to be confirmed in a larger prospective study.

Child, Preschool↗
PubMed1995

Declining risk for HIV among injecting drug users in Kathmandu, Nepal: the impact of a harm-reduction programme.

OBJECTIVE: To measure changes in self-reported risk behaviour for HIV infections and HIV seroprevalence among injecting drug user (IDU) clients of an outreach harm-reduction programme in Kathmandu, Nepal. METHODS: The Lifesaving and Lifegiving Society (LALS) of Kathmandu began providing sterile injecting equipment and education to Nepalese IDU in 1991. A sample of these IDU were interviewed and tested for HIV each year from 1991 through 1994. RESULTS: Indicators of unsafe injecting fell, as knowledge of HIV rose more in 1994 for those who had been in touch with LALS for longer. Indicators of unsafe sex did not change. HIV seroprevalence remained low, 1.6% in 1991 and 0% in 1994. CONCLUSION: We conclude that programmes for the prevention of HIV spread among IDU are possible and effective in Asia, and are urgently needed.

Adult↗