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Biomedical subjects

M Ho

Publications and source records attributed to M Ho.

At least 217 records · Page 12Linked to original sources

A semiquantitative microassay for measurement of relative number of blood mononuclear cells infected with human immunodeficiency virus.

A simple semiquantitative microassay was developed for the measurement of relative number of infected peripheral blood mononuclear cells (PBMC) from individuals infected with human immunodeficiency virus (HIV). The assay is based on cocultivation of serially diluted PBMC of a seropositive person with phytohemagglutinin-stimulated normal PBMC. The microassay has comparable sensitivity with the standard virus culture method in detecting positive HIV cultures. Since the microassay uses only 2-3 x 10(5) patients' PBMC, the assay is also most suitable for HIV isolation from HIV-infected infants or from AIDS patients with extremely low T-cell counts. The microassay can also be used to measure antiviral effects of a drug on persistent HIV infection in vitro. Because the microassay measures the relative number of infected PBMC, it can be readily used for following the quantitative antiviral effect of a drug in a clinical trial.

AIDS-Related Complex↗

Oxophenarsine, an antisyphilis drug inhibits HIV-1-specific protein synthesis in acutely and persistently infected lymphocytes.

The development of drugs that can inhibit both acute and persistent anti-human immunodeficiency virus type 1 (HIV-1) infection is a major goal in the treatment of patients with acquired immunodeficiency syndrome (AIDS). Most of the anti-HIV-1 drugs reported thus far, such as azidothymidine (AZT), inhibit acute HIV-1 infection but have no antiviral effect against persistent infection. We report here that oxophenarsine (3-amino-4 hydroxyphenylarsineoxide hydrochloride), an antisyphilus drug inhibits HIV-1 production in acutely infected peripheral blood lymphocytes (PBL) and persistently infected T cells. In acutely infected PBL and H9 T cells, the drug is effective at concentrations as low as 0.07-0.15 micrograms/ml with no significant cytotoxicity at concentrations of 6.0 micrograms/ml or below. It does not inhibit HIV-1 reverse transcriptase at doses up to 60 micrograms/ml. The drug has no effect on HIV-1-specific DNA and RNA synthesis. However, it inhibits HIV-1 protein synthesis in both acutely and persistently infected cells.

Anti-Infective Agents↗

Splenic Fc receptor function in host defense and anemia in acute Plasmodium falciparum malaria.

To determine splenic Fc receptor function in patients with acute Plasmodium falciparum malaria, the clearance of IgG-coated autologous 51Cr-labeled erythrocytes in 20 patients and 10 normal controls was studied. Clearance half-times were directly correlated with both the absolute parasite count (r = .635, P less than .005) and hematocrit (r = .791, P less than .001). Clearance half-times in patients varied from 1.0 to 96.3 h (median, 14.8 h) while those of controls ranged from 8.0 to 80.3 h (median, 23.1 h) (P = .10). Nine of the 20 patients had clearance half-times shorter than the lower 95% confidence limit of controls (less than 12.4 h). The clearance of IgG-coated erythrocytes was accelerated after parasites were eliminated from the circulation (P less than .05) and returned toward normal 6-8 weeks after the acute infection. Although circulating immune complexes were detectable, there was no correlation between immune complex levels and clearance half-times (P greater than .05). The failure to increase Fc receptor-mediated red cell clearance in patients with high parasitemias suggests inadequate splenic phagocytic activity in the face of considerable antigenic challenge. These findings indicate that splenic Fc receptor function may be important both in the control of infection and the development of anemia in P. falciparum malaria.

Acute Disease↗

Fatal Plasmodium falciparum malaria after an inadequate response to quinine treatment.

A 24-year-old man with severe Plasmodium falciparum malaria died after 77 h of treatment with full parenteral doses of quinine. His peripheral parasitemia at death exceeded the level on admission. Plasma concentrations of quinine were abnormally low throughout. This case emphasizes the importance of pharmacokinetic factors in determining the therapeutic response in severe P. falciparum malaria.

Adult↗

Epidemiology of genital herpes in Pittsburgh: serologic, sexual, and racial correlates of apparent and inapparent herpes simplex infections.

Women attending family planning clinics in western Pennsylvania were enrolled into a prospective epidemiologic study of herpes simplex virus (HSV) infection. Detection of antibodies to HSV-1 and HSV-2 was based on an immunodot assay using type-specific glycoproteins gG-1 and gG-2. Serologic and historical data at enrollment were analyzed for 4527 subjects; the seroprevalence of HSV-2 was 21.6%. By multivariate analysis, HSV-2 infection as determined by seroprevalence was significantly and independently associated with age, years of sexual activity, race, one or more episodes of other genital infections, lower annual family income, and multiple sexual partners. The presence of antibody to HSV-1 was associated with a lower frequency of antibody to HSV-2, suggesting that developed immunity to HSV-1 protected against HSV-2 infection. Of 926 participants who had antibody to HSV-2, only 117 (12.6%) reported a history of genital herpes. Hence the vast majority of HSV-2 infections were inapparent. Although seroprevalence of HSV-2 was higher among black (35.4%) than white (18.5%) women, black women appeared to have significantly less symptomatic genital herpes than white women (7.7% vs. 14.7%, P less than .01).

Adolescent↗

Interferon as an agent against herpes simplex virus.

The effectiveness and limitations of interferon as an antiviral agent in man is exemplified by its actions against herpes simplex types 1 and 2. Given in adequate doses parenterally before or shortly after infection, interferon can ameliorate or reduce clinical manifestations or reduce the virus yield. It usually cannot completely prevent disease and may be particularly problematical if used late after infection in an acute disease. It is ineffective against the state of latent infection in ganglia. Interferon may have more potential in slower virus diseases and diseases in which other pathogenetic mechanisms affected by interferon's pleiotropic actions are operative.

Herpes Genitalis↗

The otologic significance of cleft palate in a Sri Lankan population.

The otologic findings from 197 subjects with repaired and unrepaired clefts and 121 noncleft controls are presented. All data were collected in Sri Lanka during a 3-week period attached to the Sri Lanka Project in 1986. Subjects were examined otoscopically and also tested audiometrically if they were able to perform a pure-tone audiogram, a performance test, or a distraction test. Subjects with clefts of the palate were found to have fewer otoscopically normal ears than the controls. A comparison between subjects with unrepaired and repaired palates revealed a similar rate of otoscopically normal ears in subjects older than 10 years of age. Comparisons for younger ages could not be performed because of a lack of subjects less than 10 years of age who had repaired palates. The impedance data were used to verify the accuracy of otoscopy in detecting effusion.

Acoustic Impedance Tests↗

Pharmacokinetics of three commercial antivenoms in patients envenomed by the Malayan pit viper, Calloselasma rhodostoma, in Thailand.

The pharmacokinetics of 3 monospecific antivenoms were compared in patients envenomed by the Malayan pit viper, Calloselasma rhodostoma. There was a biphasic decline in serum concentrations following intravenous administration. The initial rapid decline was attributable to the formation of venom-antivenom complexes, as the fall in antivenom during this phase was positively correlated with the initial venom concentration (P = 0.045). The total apparent volume of distribution for each antivenom was 1.5-3 times larger than that of the central compartment, which suggests some tissue distribution in addition to complex formation. This was marked for antivenom from the Government Pharmaceutical Organization of Thailand which contained mostly F(ab)2 fragments. The terminal elimination half time was shorter for Twyford antivenom of caprine origin. Systemic clearance was lower for Thai Red Cross antivenom. In 8 of the 26 patients who experienced recurrence of non-clotting blood after initial response to antivenom, serial measurements of plasma venom and antivenom concentrations revealed that recurrence of venom antigenemia and non-clotting blood bore no direct relation to the elimination half-life of the antivenom used, but non-clotting blood recurred when serum antivenom levels fell below 10-20% of the total given. There is no substitute for close monitoring of envenomed patients so that indications for further antivenom can be detected promptly.

Adolescent↗

Relation of alpha and gamma interferon levels to development of AIDS in homosexual men.

Homosexual men who were human immunodeficiency virus (HIV) seropositive at enrollment into the Pittsburgh portion of the Multicenter AIDS Cohort Study had elevated titers of serum alpha and gamma interferon (IFN) within 24 months prior to development of AIDS. In contrast, subjects who developed AIDS relatively early after seroconversion to HIV during this study did not have increased levels of alpha or gamma IFN.

Acquired Immunodeficiency Syndrome↗

No association between herpes simplex virus type-2 seropositivity or anogenital lesions and HIV seroconversion among homosexual men.

Recent reports have suggested that HSV-2 infection and associated anogenital ulcerations represent an important risk factor for acquisition of HIV infection. Although this is an appealing biological hypothesis, inferences drawn for homosexual men, as well as other at-risk populations, must be made after careful consideration of methods to control for potential confounding data. This report utilized a nested case-control study in which 49 homosexual HIV seroconverters were compared to 49 homosexual seronegative men matched on the prior level of receptive anal intercourse. No differences were observed for prior HSV-2 infection, since 21/49 (43%) of matched HIV seronegative men were HSV-2 antibody positive and 21/49 (43%) of HIV seroconverters were HSV-2 antibody positive at the visit 6 months before HIV seroconversion (odds ratio of 1.0, 95% confidence limits of 0.3-2.9) Similar findings were also observed for prior HSV-1 infection. Both self-reported symptoms and physical exam findings suggestive of HSV infection were rare during the 12 months prior to seroconversion and not associated with HIV seroconversion. These data do not support HSV-2 as a risk factor for seroconversion to HIV among homosexual men studied. These results should not be generalized to heterosexual transmission of HIV, particularly in Africa, where both an increased prevalence of genital ulcerative diseases and different etiologies have been observed.

Adult↗

Limitations of the lipid state hypothesis for atherosclerosis are revealed by X-ray diffraction measurements.

The lipid state hypothesis proposes that liquid crystalline states of cholesteryl esters play a role in the development and persistence of the fatty streak lesions characteristic of atherosclerosis. We have tested several corollaries suggested by this hypothesis and find that the ensemble of droplets in atherosclerotic tissue are predominantly in the isotropic (fluid) state at 37.0 degrees C. Furthermore, the liquid-crystalline state transition behavior of these droplets is not influenced significantly by the distribution of component cholesteryl ester species. There are no significant correlations between the transition behavior of the droplets and the age, sex, or race of the subjects from which tissue samples were taken. These results show that the lipid state hypothesis is weak, and that the origin and persistence of fatty streak lesions in humans is probably dominated by other factors.

Adolescent↗

Serum vitamin D metabolites in very low birth weight infants with and without rickets and fractures.

Seventy-one very low birth weight (less than or equal to 1500 gm) infants were studied to determine the sequential changes in serum vitamin D metabolite concentrations between infants with and without radiographically documented rickets, fractures, or both (R/F). Usual intake of vitamin D included 20 IU/kg/day from parenteral nutrition or 400 IU/day supplementation with enteral feeding. Radiographs of both forearms and serum samples were obtained at 3, 6, 9, and 12 months. Twenty-two infants had R/F. At 3 months, significantly lower mean (+/- SEM) serum phosphorus levels (4.5 +/- 0.4 vs 6.1 +/- 0.2 mg/dl), higher 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations (96 +/- 5 vs 77 +/- 4 pg/ml), and higher free 1,25-(OH)2D index (1,25-[OH]2D:vitamin D binding protein ratio; 5.2 +/- 0.3 x 10(5) vs 4.0 +/- 0.2 x 10(5] were found in the R/F group. These values returned to normal and were similar between groups on subsequent measurements. Serum calcium, magnesium, and 25-hydroxyvitamin D (25-OHD) concentrations were normal and similar between groups. In both groups, serum vitamin D binding concentrations increased initially but remained stable and normal beyond 6 months. We conclude that in very low birth weight infants with R/F, the vitamin D status (as indicated by serum 25-OHD concentrations) is normal, and that lowered serum phosphorus levels, higher serum 1,25-(OH)2D levels, and a higher free 1,25-(OH)2D index support the thesis that mineral deficiency (especially of phosphorus) may be important in the pathogenesis of R/F in small preterm infants.

Calcifediol↗

Enhanced antibody responses to Epstein-Barr virus in HIV-infected homosexual men.

We investigated the association between human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infections in 593 homosexual men. The status of EBV infection in this group was evaluated based on serological evidence of EBV-specific antibody responses. The geometric mean titers (GMT) of antibody to EBV capsid antigen (EBV-VCA) (1:154) and EBV early antigen (EA) (1:16) in 141 HIV-seropositive men were significantly higher than respective titers in 452 HIV seronegative men (1:95 and 1:12). Antibody titers to EBV were higher in HIV-infected men with lymphadenopathy than in asymptomatic HIV-seropositive men. However, these correlation were less evident in patients with AIDS-related complex. Elevated antibody titers to EBV were found to be independent of levels of total serum IgG. Cytomegalovirus (CMV) antibody titers were also found to be significantly increased among HIV-seropositive men, independent of total IgG. Antibody titers to EBV were not correlated with those to CMV in either HIV-seronegative or HIV-seropositive men. Subjects without evidence of HIV infection, but who had high antibody titers to EBV-VCA and EBV-EA, had elevated mean numbers of CD3+, CD4+, and CD8+ cells, and lower levels of CD4+/CD8+ cell ratios compared to subjects with low EBV-antibody titers. This study suggests that the elevated levels of circulating antibodies against EBV in homosexual men are associated with loss of control of latent EBV due to HIV infection.

Acquired Immunodeficiency Syndrome↗

Infection with human immunodeficiency virus in the Pittsburgh transplant population. A study of 583 donors and 1043 recipients, 1981-1986.

We performed a retrospective serologic survey of 583 organ donors and 1043 transplant recipients for antibodies to human immunodeficiency virus type 1 (HIV-1). Two (0.34%) of the 583 donors and 18 (1.7%) of the 1043 recipients had HIV-1 antibodies by enzyme immunoassay and by Western blot. Two of 5 seropositive recipients tested also had blood cultures positive for HIV-1. Seven (0.7%) of the 1043 transplant recipients had antibodies to HIV-1 before transplantation; 2 of these had hemophilia A, and 5 had previous transfusions. Eleven (1.3%) of 860 recipients followed for 45 days or more seroconverted to HIV-1 a mean of 96 days after transplantation. Likely sources of HIV-1 infection for 3 of these 11 recipients included a seropositive organ donor in 1 patient and high-risk blood donors in 2 patients. A definite source of HIV-1 infection was not found for the other 8 recipients, 3 of whom seroconverted to HIV-1 after institution of blood donor screening for HIV-1 antibodies. Seroconversion to HIV-1 was less common in kidney recipients than in liver, heart, or multiple-organ recipients (P less than 0.02). Nine (50%) of the 18 HIV-1 seropositive transplant recipients died a mean of 6 months after transplant surgery, and 9 (50%) are still alive a mean of 43 months after transplantation. AIDS-like illnesses occurred in 3 of the dead and 1 of the living patients and included pneumocystis pneumonia (3 cases), miliary tuberculosis (1 case), and recurrent cytomegalovirus infection (1 case). These data suggest that the course of HIV-1 infection is not more severe in transplant recipients receiving cyclosporine than in other hosts and that, despite screening of blood and organ donors, a small number of transplant recipients will become infected with HIV-1.

Blotting, Western↗

Antibody-dependent red cell removal during P. falciparum malaria: the clearance of red cells sensitized with an IgG anti-D.

The clearance of autologous red cells sensitized with an IgG anti-D has been studied in patients during and after an attack of P. falciparum malaria, and in 11 uninfected control subjects. In most patients with P. falciparum malaria there was evidence of increased clearance of sensitized red cells, compared to controls. Clearance half-times of IgG sensitized red cells were significantly decreased (P less than 0.01) in 16 patients with acute falciparum malaria (median 21 min, range 11-53 min) compared to 11 control subjects (median 37 min, range 20-60 min). This difference was independent of the degree of IgG sensitization of red cells. In patients with acute falciparum malaria, clearance half-times were positively correlated with venous haematocrit (P less than 0.05). In 11 patients studied between 1 and 9 weeks after the attack, clearance half-times (median 17 min, range 11-56 min) were also significantly decreased compared to controls (P less than 0.01). In the majority of acute and convalescent patients, there was further evidence for early destruction of an additional substantial proportion of sensitized red cells. Our data indicate that in most patients with uncomplicated P. falciparum malaria, IgG sensitized red cells are rapidly removed from the peripheral circulation by the spleen, and that rapid clearance persists during recovery.

Adolescent↗

Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody.

Very few peripheral blood lymphocytes of seropositive individuals are presumably actively infected with human immunodeficiency virus type 1 (HIV-1). During coculture of lymphocytes of a seropositive individual with mitogen-stimulated normal peripheral blood lymphocytes, the number of infected cells becomes amplified such that detectable HIV-1 is produced. We report here that in addition to transmission by extracellular virus, cell-to-cell transmission is responsible for spreading HIV-1 infection from infected to uninfected cells. Azidothymidine and virus-neutralizing antibody had no effect on cell-to-cell transmission of HIV-1. Monoclonal antibodies to the CD4 receptor, but not to the CD3 receptor, prevented cell-to-cell transmission, which suggests that CD4 receptor-mediated cell fusion is involved in cell-to-cell transmission. Spread of infection in a cell-to-cell manner may be important in development of drug therapies for HIV-1 infection.

Acquired Immunodeficiency Syndrome↗