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Biomedical subjects

S Rasheed

Publications and source records attributed to S Rasheed.

At least 55 records · Page 3Linked to original sources

Type-specific immune response to human T cell lymphotropic virus (HTLV) type I and type II infections in Nigeria.

Type-specific antibody responses to human T cell lymphotropic virus type I (HTLV-I) and type II (HTLV-II) were studied in blood samples collected from 25 different locations in Nigeria between 1985 and 1991 and stored at the University College Hospital in Ibadan. A total of 4,153 sera were collected from participants in the National Immunity Survey of Viral Infections (n = 1,640), patients with tuberculosis (TB) (n = 140), patients with sexually transmitted diseases (STDs) (n = 876), patients with other medical conditions (n = 1,285), female prostitutes (n = 60), and health care workers (n = 152). The overall seroprevalence of HTLV was 5.6%, with similar rates among males and females. Using enzyme immunoassays that differentiated between antibodies to the two viruses, the seroprevalence rates were 2.5% for HTLV-I and 1.9% for HTLV-II, with an additional 1.2% of the samples dually reactive for both HTLV-I and HTLV-II. The seroprevalence rates for HTLV were low among children (0.8%) and adolescents (1.7%), with substantially higher rates among adults (range 5.0-7.4%). Age-specific patterns among adults appears to differ for HTLV-I and HTLV-II, with HTLV-I rates peaking above age 50 and HTLV-II rates peaking below age 50. The highest overall HTLV prevalence rates were observed for STD patients (16.3%), followed by female prostitutes (8.3%), TB patients (6.4%), health care workers (3.3%), patients with other medical conditions (3.2%), and immunity survey participants (1.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Inhibition of human immunodeficiency virus infection by the lectin jacalin and by a derived peptide showing a sequence similarity with gp120.

Jacalin is a plant lectin known to specifically induce the proliferation of CD4+ T lymphocytes in human. We demonstrate here that jacalin completely blocks human immunodeficiency virus type 1 (HIV-1) in vitro infection of lymphoid cells. Jacalin does not bind the viral envelope glycoprotein gp120. Besides other T cell surface molecules, it interacts with CD4, the high-affinity receptor to HIV. Binding of jacalin to CD4 does not prevent gp120-CD4 interaction and does not inhibit virus binding and syncytia formation. The anti-HIV effect of the native lectin can be reproduced by its separated alpha-subunits. More importantly, we have defined in the alpha-chain of jacalin a 14-amino acid sequence which shows high similarities with a peptide of the second conserved domain of gp120. A synthetic peptide corresponding to this similar stretch also exerts a potent anti-HIV effect. This peptide is not mitogenic for peripheral blood mononuclear cells and does not inhibit anti-CD3-induced lymphocyte proliferation. These results make jacalin alpha chain-derived peptide a potentially valuable therapeutic agent for acquired immunodeficiency syndrome.

Amino Acid Sequence↗

Prevalence of human immunodeficiency virus types 1 and 2 infections in Nigeria.

The prevalence of human immunodeficiency virus (HIV) types 1 and 2 infections in Nigeria was estimated from 3854 serum samples collected at 21 locations from 1985 to 1990. Seventy-eight samples (2.0%) were reactive for HIV-1 and 49 (1.3%) for HIV-2 antibodies; 5 samples were reactive for both viruses. The prevalence of HIV-1 and -2 infections, respectively, was highest among 60 female prostitutes, with 10% and 6.7% positive. For other groups the respective rates of positivity were 4.1% and 3.4% in 610 patients with sexually transmitted diseases, 3.6% and 1.4% in 140 tuberculosis patients, 1.6% and 0.6% of 1253 other medical patients, and 1.2% and 0.9% of 1640 volunteer blood donors. Of 153 health care workers, 1.3% were positive for HIV-1 only. The age group from 20 to 29 years had the highest prevalences of HIV-1 (3.3%) and -2 (2.2%). In Nigeria, antibody prevalence for both viruses appears to have increased > 10-fold between 1986 and 1990.

Adolescent↗

Maintenance of CD4+ cells by thymopentin in asymptomatic HIV-infected subjects: results of a double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and safety of thymopentin in HIV-infected patients who had not yet developed AIDS. DESIGN: Patients were stratified into asymptomatic or symptomatic groups and randomized to receive either thymopentin (50 mg) or placebo, subcutaneously, double-blind for 24 or 52 weeks, three times a week. SETTING: Patients were enrolled at three sites (two hospital clinics and one private practice). PATIENTS: Of 91 HIV-seropositive patients (52 asymptomatic and 39 symptomatic) from whom HIV could be isolated from peripheral blood, 45 were enrolled for 24 weeks and 46 for 52 weeks of double-blind evaluation. MAIN OUTCOME MEASURES: Virological, immunological and clinical evaluations were performed before and during treatment. RESULTS: Thymopentin-treated asymptomatic patients had more CD4+ cells, as demonstrated by a greater area under the percentage CD4+ cells curve (P = 0.03) and a shorter median time to a 20% increase in percentage of CD4+ cells (P = 0.04) in the first 24 weeks, with similar trends in the 52-week study. By 24 weeks no asymptomatic thymopentin-treated and two placebo-treated patients (9.1%, Kaplan-Meier estimate) had progressed to constitutional symptoms (P = 0.12; two-tailed Wilcoxon-Gehan test), with only one further progression in a placebo-treated patient in the subset followed for 52 weeks. Symptomatic patients receiving thymopentin or placebo were similar in both CD4+ cell levels and disease progression (two progressions to AIDS in each group). No serious adverse effects attributable to thymopentin were observed. CONCLUSIONS: These results, if confirmed, indicate that thymopentin, by maintaining CD4+ cells, could slow or arrest immune decline and consequent disease progression at the asymptomatic stage of HIV infection.

Amino Acid Sequence↗

Human immunodeficiency virus-related lymphoma. Prognostic factors predictive of survival.

In an attempt to determine factors predictive of survival in patients seropositive for human immunodeficiency virus (HIV) with acquired immune deficiency syndrome (AIDS)-related lymphoma, the authors studied 60 such patients, all of whom were treated with curative intent. Eleven patients presented with lymphoma primary to the brain (P-CNS); the remaining 49 had systemic AIDS-related lymphoma. Patients with P-CNS lymphoma had more severe underlying HIV-related disease than did patients with systemic lymphoma as evidenced by a higher incidence of AIDS before the diagnosis of lymphoma (73% versus 37%; P = 0.04), and lower median number of CD-4-positive lymphocytes in peripheral blood at diagnosis of lymphoma (30/dl versus 189/dl; P = 0.005). Median survival of such patients was 2.5 months versus 6.0 months for patients with systemic lymphoma (P = 0.04). Forty patients with systemic AIDS-related lymphoma have died; three factors were strongly associated with shorter survival: (1) Karnofsky performance status (KPS) of less than 70% (multivariate relative survival risk [RSR] = 3.1); (2) history of AIDS before the diagnosis of lymphoma (multivariate RSR = 3.0 for opportunistic infection plus Kaposi's sarcoma); and (3) bone marrow involvement (RSR = 3.1)). All three factors (KPS of less than 70%, prior AIDS diagnosis, and marrow involvement) were associated with early demise attributed to AIDS, whereas death attributed to lymphoma per se was associated with only two factors (KPS of less than 70% and marrow involvement). In the absence of all three risk factors, a "good prognosis" group of 17 patients was defined, with a median survival of 11.3 months; the median survival of the remaining patients ("poor prognosis") was 4.0 months (P = 0.0002). Attainment of complete response to therapy (CR) was strongly related to prolonged survival in the patients in the good prognosis group (17.8 months in patients with CR versus 5.0 months in those with less than CR); however, such meaningful prolongation of survival was not seen in patients with poor prognosis who attained CR (6.3 months versus 3.4 months). The patients with poor prognosis may be unable to tolerate the insult of multiagent chemotherapy, experiencing low CR rates (25%) and death caused by lymphoma and AIDS. However, patients in either prognostic category who attained CR remained at risk for dying of AIDS while the lymphoma was in remission. Thus, it is apparent that meaningful prolongation of survival in the patient with AIDS-related lymphoma will require not only effective antineoplastic intervention, but also control of the underlying HIV infection. In addition, future therapeutic trials should stratify patients based upon the prognostic factors defined here in an attempt to clarify the results obtained.

Adult↗

Molecular pathology and diagnosis of infectious diseases.

The authors have reviewed and described molecular methods for the detection of etiologic agents or genetic sequences involved in the pathogenesis of various diseases. Molecular probes are now available for the rapid diagnosis of diseases caused by a large number of viruses, bacteria, fungi, spirochetes, rickettsia, and other infectious agents. Since nucleic acid probes can distinguish minute differences indicative of genetic mutations or alternations, specific probes also can be developed even for those diseases with unknown causative agents or etiologies. Further, using these techniques, specific drug-resistant and pathogenic strains associated with epidemics in widely separated areas of a country or a town have been identified. Thus, the sensitivity and specificity of molecular detection methods using both radioactive and nonradioactive probes are at a point that clinical specimens can be tested for rapid diagnosis and identification of etiologic agent(s) that may be responsible for the pathogenesis of a wide variety of diseases.

Communicable Diseases↗

A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 and 800 mg) and a placebo was performed at four medical centers geographically distributed throughout the USA. One hundred and sixty-four HIV-infected adult men with lymphadenopathy were enrolled over a 2-month period and received active treatment for 24 weeks followed by a 4-week interval during which they did not receive the study drug. A marked interlaboratory variation in HIV isolation from peripheral blood mononuclear cells was observed, underscoring the critical role of quality assurance in similar multicenter trials. Nevertheless, the combined data indicate that ribavirin did not significantly suppress HIV activity (on measurement of reverse transcriptase activity) after week 6 or reduce serum p24 antigenemia.

AIDS-Related Complex↗

AIDS and HIV associated disorders in Karachi.

In a seroepidemiological study for the prevalence of HIV infection in Pakistan, individuals from different groups were tested for HIV antibodies using ELISA. Positive results were confirmed by western blot. Out of 413 individuals screened four were found positive by ELISA, of these three were confirmed by western blot. Two cases were foreign nationals visiting Pakistan, one of them died of full blown AIDS, the other did not show any AIDS related condition. The third case was a Pakistani national who presented with full blown AIDS with toxoplasmosis. To our knowledge this is the first case of full blown AIDS reported in a Pakistani national. The fourth case was an asymptomatic promiscuous lady who could not be traced further. Blood transfusions abroad and sexual contacts were responsible for HIV infection in these cases.

Acquired Immunodeficiency Syndrome↗

Interferon-alpha maintenance therapy after cytotoxic chemotherapy for treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma.

A prospective phase I clinical trial with recombinant interferon-alpha-2b as maintenance therapy after cytotoxic chemotherapy was conducted. Twenty-one homosexual and bisexual males with extensive mucocutaneous or visceral epidemic acquired immunodeficiency syndrome (AIDS)-Kaposi's sarcoma (KS) were studied. After a complete response (6 patients) or partial response (15 patients) from chemotherapy consisting of Adriamycin (20 mg/m2), bleomycin (10 U/m2), and vincristine (1.4 mg/m2; 2 mg maximum), patients were given interferon-alpha (IFN-alpha) in an attempt to prolong disease-free survival. Three dose levels of daily IFN-alpha were tested: 5, 10, and 15 million U. The maximum tolerated dose was 10 million units. Dose-limiting toxicities included recurrent grade 3 fatigue, diarrhea, and fever, which resulted in the termination of therapy in eight patients (38%). Hematologic toxicities were infrequent (four patients; 19%). Responses were observed in two patients on IFN-alpha, both at the 10-million-U dose level. The median duration of response on IFN-alpha therapy following chemotherapy was 8 weeks (range, 3-11). We conclude that the duration of IFN-alpha maintenance response following cytotoxic chemotherapy is short with response to residual disease observed in a minority of cases at this dose and schedule. Additional trials of maintenance therapy in patients with advanced AIDS-KS combining antiretroviral agents are in progress.

Acquired Immunodeficiency Syndrome↗

A simple procedure for maximum yield of high-quality plasmid DNA.

We have established a simple procedure for the rapid isolation of high-quality plasmid DNA suitable for various molecular techniques and provided a step-by-step protocol. The DNA samples isolated by this procedure have been used successfully for double-stranded DNA sequencing, restriction enzyme mapping, subcloning, in vitro mutagenesis, generation of deletion clones and so on. The procedure is highly reproducible, and superior quality DNA can be obtained without the use of phenol, chloroform or other organic solvents.

DNA↗

Prevalence and significance of acquired immunodeficiency syndrome-related retinal microvasculopathy.

We performed ophthalmologic examinations on 127 subjects with or at risk for human immunodeficiency virus (HIV) infection over a one-year period to determine the prevalence and significance of retinal cotton-wool spots and hemorrhages (AIDS-related retinal microvasculopathy). Of 26 asymptomatic homosexual men, of whom 13 were HIV seronegative and 13 were HIV seropositive, none manifested this retinopathy. Three of 34 patients (9%) with AIDS-related complex and 29 of 67 patients (43%) with AIDS manifested retinopathy on the initial examination. This difference in the prevalence of retinopathy between groups was statistically significant (P less than .05). Patients with AIDS demonstrated 7.2 times greater odds of manifesting retinopathy than patients with AIDS-related complex (P less than .05). Within the group of patients with AIDS, the T helper (CD4) to suppressor (CD8) cell ratio was significantly associated with retinopathy at the initial ocular examination. The CD4:CD8 ratio of the total group of AIDS and AIDS-related complex patients with retinopathy was significantly lower than that of patients without retinopathy (P less than .05). There was no significant association between retinopathy and any specific past or concurrent opportunistic infection or neoplasm. The presence of retinopathy was not associated with symptoms in any patient. The lesions of AIDS-related retinal microvasculopathy may be an important finding in the evaluation of patients suspected to have HIV-related disease.

AIDS-Related Complex↗

Immunoblot reactivity of a non-HIV protein with human sera. Transfusion Safety Study Group.

Examination of serum for the presence of antibodies to the human immunodeficiency virus (HIV) by immunoblot analysis requires precise identification of reactivities with various HIV specific proteins. During a recent survey of approximately 2,000 sera, we identified 22 sera from non-HIV-reactive blood donors and 2 from individuals receiving blood products for congenital blood disorders, which consistently and exclusively reacted with a protein of a molecular weight slightly greater than 65,000 daltons (termed AT65). Since the HIV pol p65 protein reacts with specific antibodies at about the same position (i.e., 65,000 daltons), it was essential to determine the viral or nonviral origin of the AT65 reactivity. Our data indicate that the AT65 reaction is due to a protein present on normal or activated lymphocytes, which can co-purify with HIV preparations used for immunoblot analysis. Recognition of HIV-specific p65 and nonspecific AT65 reactions is important to those responsible for interpretation of HIV immunoblots and may aid in the evaluation of some "indeterminant" results.

Blood Donors↗

Studies on the mode of action of non-steroid anti-inflammatory drugs.

During the past decade the mode of action of anti-inflammatory drugs has mainly been related to the inhibition of prostaglandin (PGS) synthesis (Vane 1971). In a presentation by Burne (1982) it has been shown that PGS are not the only most important mediators of inflammation, and the inhibition of prostaglandin synthesis alone does not explain all common effects and mode of action of NSAIDs. Hence alternative concepts are presented in this paper, which may be adopted as the mode of action of NSAIDs.

Journal Article↗

Vitamin D metabolite-mediated hypercalcemia and hypercalciuria patients with AIDS- and non-AIDS-associated lymphoma.

Fifteen patients with lymphoma and hypercalcemia (greater than or equal to 11.0 mg/dL) were identified by screening the serum chemistry profile obtained from patients upon admission to the Los Angeles County/USC Medical Center. Seven of the 15 (47%) possessed a frankly elevated serum concentration of 1,25-dihydroxyvitamin D [1,25-(OH)2-D]. An additional patient with severe hypercalcemia (16.2 mg/dL) had a serum 1,25-(OH)2-D concentration in the midnormal range, not a suppressed value. To examine the potential existence of hypercalciuria in absence of overt hypercalcemia, prospective screening of 23 normocalcemic patients with lymphoma was undertaken. Four of the 23 patients (17%) had increased fractional urinary calcium excretion rates (0.35 +/- 0.3 mg calcium/100 mL glomerular filtrate [GF], mean +/- SE; normal, less than 0.16 mg/100 mL GF); two of the hypercalciuric patients had a frankly elevated serum 1,25-(OH)2-D concentration. Of the 19 hypercalcemic/hypercalciuric lymphoma patients identified, none had an elevated serum immunoreactive parathyroid hormone concentration. Fourteen of the 19 hypercalcemic/hypercalciuric patients (74%) suffered from B-cell neoplasms, three had Hodgkin's lymphoma, and two had adult T-cell leukemia/lymphoma. All hypercalcemic/hypercalciuric patients had widespread disease (stage III or IV). Six patients, four with hypercalcemia and two with hypercalciuria, had acquired immunodeficiency syndrome (AIDS). These data suggest that the deregulated synthesis of a 1,25-(OH)2-D-like metabolite is a common cause of hypercalcemia and hypercalciuria in patients with lymphoma including patients with AIDS-associated tumors.

Adult↗

Human immunodeficiency virus-induced cytotoxicity for CD8 cells from some normal donors and virus-specific induction of a suppressor factor.

Several aspects of human immunodeficiency virus (HIV)-induced pathology in vitro warrant close examination to ascertain their role in the development of disease in vivo. The ability of HIV to produce cytopathology of CD4 cells has been well documented, although the extent and mechanism(s) may be varied. Further, immune suppression by HIV envelope (env) is well documented in vitro, but its importance in vivo remains unknown and the role of other HIV components in immune suppression has not been examined. We have exposed peripheral blood mononuclear cells (PBMC) from normal donors to ultraviolet-irradiated HIV (uv-HIV) at concentrations similar to those found in AIDS patient serum and determined that in some normal donors (3/7) depletion of CD8 cells as well as CD4 cells is demonstrable. Abrogation of phytohemagglutinin (PHA)-induced proliferation by uv-HIV was also examined in the same normal donors. Immune suppression, unlike CD4 cell killing, does not require intact virus and occurs at physiologically relevant concentrations of HIV. Furthermore, PBMC exposed to uv-HIV in the presence of PHA produce a heat- and protease-labile suppressor factor(s) following removal of virus, whether or not they are reexposed to PHA. Our results suggest that cell killing may be a more broad event than previously described, including the killing of at least CD8 cells either directly or indirectly. In addition, suppressor factors produced following exposure of patient lymphocytes to agents that induce proliferation may exacerbate the development of opportunistic infection.

Animals↗

Human immunodeficiency virus-associated disorders in Pakistan.

We have documented evidence of the human immunodeficiency virus (HIV) infection in four individuals including a blood donor and three members of a family (husband, wife, and a child) in Karachi, Pakistan. Our data indicate that HIV has been transmitted to the wife of the seropositive male, a drug abuser, in the recent past and that she has passed the virus to her newborn child perinatally/transplacentally. The two seropositive males (blood donor and drug abuser) were diagnosed clinically as having persistent generalized lymphadenopathy, an AIDS-related condition (ARC), and the child presented with developmental disorders and neurologic manifestations. This is the first report of AIDS/ARC cases from Pakistan that can be directly related to HIV infection and its heterosexual transmission.

AIDS-Related Complex↗

Human immunodeficiency virus-associated T-cell lymphoblastic lymphoma in AIDS.

A patient with multiple infections whose serum had antibodies to a human immunodeficiency virus (HIV) developed a T-cell lymphoblastic lymphoma (T11+, Leu-1+, Leu-3a+, TdT+, B1-, common ALL-). Antibodies to human T-lymphotropic virus-I (HTLV-I) were absent. T-cell leukemia-lymphoma may be associated with HIV infection.

Acquired Immunodeficiency Syndrome↗