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Biomedical subjects

H C Lane

Publications and source records attributed to H C Lane.

At least 127 records · Page 7Linked to original sources
PubMed1989

The role of immunomodulators in the treatment of patients with AIDS.

In the last several years, the biologic modification of the immune system has become one of the therapeutic alternatives in medicine. The use of interferon alpha has resulted in both antineoplastic and antiviral effects in patients with AIDS-associated Kaposi's sarcoma. Trials currently underway will determine whether or not this drug, either alone or in combination with zidovudine, is of overall value to patients with early stages of HIV-1 infection. Hematopoietic growth factors, GM-CSF and erythropoietin in particular, offer new hope that the bone marrow suppressing toxicities of certain therapeutic agents such as zidovudine and ganciclovir can be ameliorated, thus allowing the more aggressive use of these important medications. Although a variety of non-biologic immunomodulators have been evaluated in patients with HIV-1 infection, none thus far has shown the clear clinical advantage that has been demonstrated for zidovudine and a variety of clinical trials continue in this area. The area of immunologic reconstitution, although promising in concept, has been disappointing in practice, even in combination with zidovudine. Recent approaches to immunomodulation have included active immunotherapy involving immunization of HIV-1 infected individuals with either inactivated virus or recombinant HIV-1 proteins. Continued investigation of the role of immunomodulation in the therapy of patients with HIV-1 infection should be of value, not only in developing better therapies for patients with HIV-infection, but also in helping develop a better understanding of the nature of the immunologic defects seen in the context of this infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Admission of AIDS patients to a medical intensive care unit: causes and outcome.

As the number of cases of AIDS increases, it is important to determine whether ICUs can be productively and safely used for this patient population. From July 1981 to March 1987, 216 patients were admitted to the medical ICU: 166 (77%) were admitted for procedures and 50 (23%) were admitted for life-sustaining support. Most of the patients were admitted for respiratory failure (36 of 50), primarily as a result of Pneumocystis carinii pneumonia. Other patients were admitted for cardiovascular instability (six of 50 patients), CNS dysfunction (four patients), or other reasons (four patients). Of 50 patients admitted to the ICU, 13 (26%) were alive 3 months after hospital discharge. Despite 25 needle-stick injuries and 56 mucosal splashes involving human immunodeficiency virus (HIV)-infected patients and staff, no staff member converted HIV serology. These results suggest that AIDS patients may benefit from ICU admission. These patients appear to pose a low risk to the hospital staff in terms of occupationally acquired HIV infection, but strong emphasis needs to be placed on minimizing accidental exposures to potentially infected body fluids and to adhering to universal precautions.

Acquired Immunodeficiency Syndrome↗
PubMed1989

High levels of oral yeasts in early HIV-1 infection.

Ten human immunodeficiency virus-1 (HIV-1) infected homosexual or bisexual individuals (ages 24-45) with no history of opportunistic infection were examined, by culture, for the presence of yeasts in whole saliva and on oral mucosa. All were HIV-1 antibody-positive men, non-smokers, non-denture wearers, and taking no medication. The mean salivary level of yeast was four logs higher in the HIV-1 infected group compared to a control group of normal, unmedicated, non-smoking men (ages 20-41) who denied any risk behavior for HIV-1 infection. Identification of the yeast in these HIV-1 positive individuals established that Candida albicans was the predominant species found in whole saliva and on buccal mucosa and tongue. Distinct hyphae were observed with only one mucosal sample. No significant correlation was found between whole saliva yeast concentration and the T4/T8 lymphocyte ratios or absolute number of T4 cells. No correlation was observed between oral yeast concentration and anti-C. albicans IgA titers. The high level of oral yeast in these individuals prior to the development of opportunistic infections is consistent with the suggestion that oral defense mechanisms are compromised in individuals following HIV-1 infection.

Adult↗
PubMed1989

Passive hemagglutination test for detection of antibodies to human immunodeficiency virus type 1 and comparison of the test with enzyme-linked immunosorbent assay and Western blot (immunoblot) analysis.

A passive hemagglutination test (PHA) was developed for detecting antibodies to human immunodeficiency virus type 1 (HIV-1) utilizing sheep erythrocytes cross-linked with purified envelope glycoprotein (gp160) of HIV-1. In an analysis of 216 human serum samples, 100% correlation was observed in 86 reactive and 124 nonreactive serum samples between PHA and commercial enzyme-linked immunosorbent assays and Western blot (immunoblot) analysis. Serum samples from gp160-immunized chimpanzees also reacted equally well in PHA. The test is simple, rapid, and inexpensive, thus providing an alternate, quick method of detecting HIV antibodies. These advantages and the thermal stability of the reagents that are used make this an attractive alternative for detecting prior exposure of individuals to HIV-1.

Animals↗
PubMed1989

Detection of antibodies to human immunodeficiency virus type 1 in whole blood and saliva by using a passive hemagglutination test.

A passive hemagglutination test (PHA) for detecting human immunodeficiency virus type 1 antibodies in serum samples by using envelope glycoprotein (gp160)-coupled sheep erythrocytes was described earlier (M.B. Vasudevachari, K. U. Uffelman, T.C. Mast, R.L. Dewar, V. Natarajan, H.C. Lane, and N.P. Salzman, J. Clin. Microbiol. 27:179-181, 1989). In the study reported here, the applicability of the PHA test to the detection of antibodies in whole-blood and saliva samples has been investigated. We observed a 100% correlation between PHA and commercial enzyme-linked immunosorbent assay in 101 whole-blood samples and 98% correlation between PHA and reactivity to envelope proteins in Western blots (immunoblots) of 53 saliva samples. Furthermore, salivary antibodies could be detected in 19 of the 22 seropositive individuals. As in serum, antibodies to envelope proteins were widely prevalent in all the Western blot-reactive saliva samples.

Blotting, Western↗
PubMed1989

Integrated proviral human immunodeficiency virus type 1 is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals.

Evidence of a latent human immunodeficiency virus type 1 (HIV-1) infection in healthy, seropositive individuals who do not have viral antigens in their sera and from whom virions cannot be rescued in cocultivation experiments was examined. Proviral DNA was detected by amplification by the polymerase chain reaction procedure. In each of 10 seropositive individuals, the presence of HIV-1 proviral sequences was demonstrated in their peripheral blood mononuclear cells. By using fluorescence-activated cell sorting, we obtained highly enriched subpopulations of peripheral blood mononuclear cells and found that the CD4+ T-cell subset is the cell subset that consistently harbors the HIV-1 proviral sequences. The number of HIV-1-infected CD4+ T cells was variable among the 10 healthy individuals, ranging from 1 in 100 to 1 in 40,000. While in vitro infection of CD4+ T cells causes down regulation and eventual loss of CD4 surface molecules, this is not true in vivo where it is only the CD4+ population that harbors the virus. This disparity may reflect differences between a latent infection in vivo with the lytic response of cells infected in vitro.

Antibodies, Monoclonal↗
PubMed1989

Efficient macrophage isolation of human immunodeficiency virus from peripheral blood leukocytes from healthy seropositive individuals: implications for cell tropism.

We investigated the efficiency of HIV isolation from the PBL of 23 healthy, HIV-seropositive individuals with high (600-700/mm3) CD4+ T cell counts. Cocultivations of patients' PBL with allogeneic T lymphocyte blasts or monocytes were performed. T lymphocyte blasts allowed recovery of 4/23 (17%) HIV isolates, whereas monocytes allowed recovery of 12/23 (52%) isolates. Monocyte cultures sustained release of viral antigen for up to 70 days. Nine of the viral isolations could be accomplished only with this monocyte coculture technique. To determine the in vivo source of the macrophage-tropic HIV isolates we separated PBL from 5 of these 9 patients into T lymphocyte and monocyte fractions by cell sorting; then, we analyzed the fractions by PCR to amplify HIV proviral DNA. In 4 out of 5 patients studied HIV-1 proviral DNA was detected only in T lymphocytes but not in monocytes, although the virus was isolated exclusively by monocyte coculture technique. In the remaining patient, HIV DNA was found to be present in both T cells and monocytes. Thus, HIV can be more efficiently isolated in healthy seropositive individuals by coculture of their PBL with normal monocytes rather than T cell blasts. Of note, the most common in vivo source of viral isolates which preferentially infect monocytes in vitro ("macrophage-tropic strains") is the circulating CD4+ T lymphocyte.

Cells, Cultured↗
PubMed1989

Vitamin B12 malabsorption in patients with acquired immunodeficiency syndrome.

We have examined 11 patients with the acquired immunodeficiency syndrome (AIDS) for evidence of subclinical vitamin B12 malabsorption. Three subjects (27%) had low levels of vitamin B12. Eight subjects (73%), including these 3 subjects plus 5 others with normal vitamin B12 levels, had abnormal Schilling test results. In addition, 15% of an unselected population of 121 patients with AIDS and 7% of 27 patients without AIDS who were seropositive for human immunodeficiency virus type 1 (HIV-1) had low serum vitamin B12 levels. Stool cultures from the 8 subjects with abnormal Schilling test results revealed no pathogens. Intestinal involvement by Kaposi's sarcoma was found in only 1 patient. Biopsy specimens from 5 of 6 patients with vitamin B12 malabsorption, however, contained mononuclear cells harboring HIV-1, as indicated by in situ hybridization studies. Our observations suggest that vitamin B12 malabsorption is common in patients with AIDS and may be a very early manifestation of infection with HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Characterization of GP120 binding to CD4 and an assay that measures ability of sera to inhibit this binding.

There is evidence that the initial interaction between HIV-1 and the host that is essential for infection is the specific binding of the viral envelope glycoprotein, gp120, to the CD4 molecule found on certain T cells and monocytes. Most individuals infected with HIV develop antibodies against the gp120 protein. Although in vitro treatment of CD4+ T cells with mAb to a specific epitope of the CD4 molecule (T4a) blocks virus binding, syncytia formation, and infectivity, it is unclear if antibodies to gp120 from an infected individual that can inhibit the binding of gp120 to CD4 is in any way related to the clinical course of disease. Our present study characterizes the binding of 125I-labeled rgp120 to CD4+ cells, and describes an assay system that measures a potentially relevant form of immunity to HIV infection, i.e., the blocking of HIV binding to CD4+ cells. Optimal binding conditions included a 2-h incubation at 22 degrees C, 4 x 10(6) CD4+ cells, and 1 nM gp120. The dissociation constant (KD) for gp120 binding to cell surface CD4 was 5 nM, and was inhibited by soluble CD4 and by mAb to T4a but not to T3 or T4. For the binding inhibition assay, negative controls included healthy seronegatives, seronegatives with connective tissue diseases, patients with HTLV-1 disease, and patients infected with HIV-2. In studying over 100 sera, the assay was highly sensitive (98%) and specific (100%). The majority of HIV+ sera could inhibit binding at dilutions of 1/100 to 1/1000. No correlation was noted between binding inhibition (BI) titer in this assay and clinical stage of HIV infection. In addition, there was no correlation between BI titer and HIV neutralizing activity. The BI titer was correlated with the titer of anti-gp160 (r = 0.63) and the titer of anti-gp120 (r = 0.52) antibodies determined by Western blot dilution. As with neutralizing antibodies and other forms of immune response to HIV, it is unclear what role antibody blocking of HIV binding to CD4+ cells may play in active immunity to HIV in infected individuals. This activity may prove to have some value in protection against initial HIV infection and, thus, the assay may be of use in monitoring vaccine trials.

Animals↗
PubMed1988

Anti-retroviral effects of interferon-alpha in AIDS-associated Kaposi's sarcoma.

21 patients with AIDS and Kaposi's sarcoma were enrolled in an open therapeutic trial to determine the in vivo anti-retroviral activity of recombinant interferon-alpha (IFN-alpha). 8 (38%) showed a complete or partial anti-tumour response. The mean pretreatment CD4 count for the responders was 399 cells/microliter vs 154 cells/microliter for the non-responders. All 5 of the patients with more than 400 CD4 cells/microliter pretreatment showed a significant reduction in tumour, whereas none of the 7 patients with under 150 CD4 cells/microliter had any response. 5 of the 6 complete or partial responders with greater than 50 pg/ml of human immunodeficiency virus (HIV) p24 before IFN therapy showed a 75% or greater reduction by 12 weeks of therapy, with 3 patients having persistently negative HIV cultures. The anti-viral effects were also most pronounced in the patients with the highest CD4 counts. These data demonstrate the potential benefits, both anti-tumour and anti-retroviral, of treatment with IFN-alpha in the early stages of HIV infection and Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Frequency of myocarditis, left ventricular dysfunction and ventricular tachycardia in the acquired immune deficiency syndrome.

To evaluate possible relations between clinical and histopathologic cardiac findings in patients with the acquired immune deficiency syndrome (AIDS), 58 consecutively autopsied AIDS patients were reviewed retrospectively. Twenty-six (45%) had histopathologic myocarditis. Fifteen of these 26 (58%) had greater than or equal to 1 clinical cardiac abnormalities: 6 had congestive heart failure or left ventricular (LV) dysfunction, or both, 4 had ventricular tachycardia (VT), 10 had electrocardiographic abnormalities and 4 had pericardial abnormalities. Of the 32 patients without myocarditis, 6 (19%) had pericardial or electrocardiographic abnormalities, or both, but none had congestive heart failure, LV dysfunction or VT. Overall, clinical cardiac abnormalities were found in 21 patients (36%). Patients with myocarditis had a significantly higher incidence of clinical cardiac abnormalities than patients without myocarditis (58 vs 19%, p less than 0.01). All patients with congestive heart failure, LV dysfunction or VT had myocarditis. Thus, serious clinical cardiac abnormalities were common in patients with AIDS and were associated with myocarditis.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes.

Monocytes were maintained in tissue culture for greater than 3 mo in media supplemented with rCSF-1. These cultures provided susceptible target cells for isolation and propagation of virus from PBMC of HIV-infected patients. HIV isolated into monocytes readily infected other rCSF-1-treated monocytes but only inefficiently infected PHA-stimulated lymphoblasts. Similarly, laboratory HIV strains passaged in T cell lines or virus isolated from patients' leukocytes into PHA-stimulated lymphoblasts inefficiently infected rCSF-1-treated monocytes. Persistent, low-level virion production was detected in macrophage culture fluids by reverse transcriptase activity or HIV antigen capture through 6-7 wk. Marked changes in cell morphology with cell death, syncytia, and giant cell formation were observed in monocyte cultures 2 wk after infection, but at 4-6 wk, all cells appeared morphologically normal. However, the frequency of infected cells in these cultures at 6 wk was 60-90% as quantified by in situ hybridization with HIV RNA probes or by immunofluorescence with AIDS patients' sera. Ultrastructural analysis by EM also showed a high frequency of infected cells; virtually all HIV budded into and accumulated within cytoplasmic vacuoles and virus particles were only infrequently associated with the plasma membrane. Retention of virus within macrophages and the macrophage tropism of HIV variants may explain mechanisms of both virus persistence and dissemination during disease.

Cells, Cultured↗
PubMed1988

Diagnosis of Pneumocystis carinii pneumonia: improved detection in sputum with use of monoclonal antibodies.

With the dramatic increase in the frequency of Pneumocystis carinii pneumonia associated with human immunodeficiency virus infection, there has been a need for more rapid and less invasive diagnostic techniques. Recent studies have shown that examination of induced sputum can establish the diagnosis of P. carinii pneumonia in about 55 percent of cases. To assess whether a recently developed indirect immunofluorescent stain using monoclonal antibodies was more sensitive than Giemsa or toluidine blue O stains in detecting P. carinii in sputum, we undertook two prospective studies. Of 63 patients at one institution from whom sputum specimens were obtained, 49 were ultimately given a diagnosis of P. carinii pneumonia, 46 of them by staining of sputum. The sensitivity of the three stains in detecting P. carinii was 45 of 49 (92 percent) for immunofluorescence; 37 of 49 (76 percent) for Diff-Quik (a Giemsa-type stain); and 39 of 49 (80 percent) for toluidine blue O. There were no false positive immunofluorescent stains. In a similar study of a series of 25 patients at another institution, a diagnosis of P. carinii pneumonia was made in 23 of 25 patients by staining of induced sputum. We conclude that examination of induced sputum is a rapid, sensitive, and inexpensive method for diagnosing P. carinii pneumonia and that indirect immunofluorescence is a practical and highly sensitive staining technique for establishing this diagnosis.

Animals↗
PubMed1988

Neuropsychiatric consequences of AIDS.

As part of a study in progress, neuropsychological tests have been administered to 13 patients with clinical acquired immunodeficiency syndrome, 9 human immunodeficiency virus-seropositive patients, 4 seropositive patients with chronic active hepatitis, 5 seronegative patients with chronic active hepatitis, and 6 healthy controls. Consistent with findings in earlier patient and control groups, the acquired immunodeficiency syndrome patients had substantially lower scores on a variety of cognitive tests. Although the acquired immunodeficiency syndrome group is not education-matched at present, the results are nonetheless consistent with impairments of language function and timed, self-paced performance. Test results obtained may reflect focal and global cognitive impairment as well as motivational decrements in patients with the acquired immunodeficiency syndrome relative to seropositive patients or controls.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Host defense against Mycobacterium-avium complex.

Mycobacterium-avium complex (MAC) is an intracellular pathogen and the most common cause of widely disseminated bacterial infection in patients with the acquired immunodeficiency syndrome (AIDS). MAC is infrequently seen in other immunocompromised adults, suggesting that the host defense defect allowing for MAC infection is relatively unique for AIDS. A system was developed for studying the immune response to MAC infection, utilizing MAC isolated from patients with AIDS and monocytes from normal controls and patients with AIDS. Phagocytosis, superoxide anion (SOA) production, and killing were measured. Monocytes from normal controls and AIDS patients were identical with respect to phagocytosis of MAC. In contrast, baseline SOA production was elevated in monocytes from patients compared to normal monocytes and was minimally augmented in response to either phorbol myristate acetate or MAC. Fourteen-day kinetic studies revealed in patients and controls a biphasic pattern with 50-99% killing of AIDS-derived MAC initially, followed always by a rapid outgrowth of surviving bacilli. Despite a modest enhancement of MAC killing by normal but not patients' monocytes pretreated with either recombinant interferon-gamma or recombinant tumor necrosis factor-alpha, outgrowth of MAC was always observed in both, typically faster in patients than in controls. Even monocytes in the presence of lymphocytes stimulated with interleukin-2 did not demonstrate enhanced MAC killing. In contrast, high-titered anti-MAC immune serum derived from a patient with polymyositis and disseminated MAC significantly enhanced the killing of MAC by monocytes from both AIDS patients and healthy controls and prevented their outgrowth. These findings suggest that the host defense defect allowing for MAC infection appears not to reside in the monocyte and that the in vitro lymphocyte functions examined in this study do not appear to play a major role. What role specific antibody plays in vivo in preventing disseminated MAC is uncertain, but the lack of such antibody may help explain the propensity for AIDS patients to develop systemic infection.

Adjuvants, Immunologic↗
PubMed1988

Disseminated Mycobacterium haemophilum infection in two patients with the acquired immunodeficiency syndrome.

In two patients with the acquired immunodeficiency syndrome (AIDS), multiple erythematous cutaneous lesions developed, revealing acid-fast organisms on Fite's stain. Initial culture results on the first patient were negative; however, repeat cultures on hemin-enriched media were positive for Mycobacterium haemophilum. Despite antimycobacterial therapy, lesions persisted until the patients' death. M. haemophilum should be a diagnostic consideration when smears of peripheral (especially skin) lesions from AIDS patients show acid-fast organisms. Cultures in such patients should be done with iron hemin- or ferric ammonium citrate-enriched media.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Bioavailability of oral trimetrexate in patients with acquired immunodeficiency syndrome.

The combination of the lipophilic antifolate trimetrexate and the rescue agent leucovorin has shown promise in the treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. The pharmacokinetic behavior of trimetrexate administered either by intravenous bolus or orally was studied in six patients with acquired immunodeficiency syndrome with a reversed-phase high-pressure liquid chromatography assay. The mean clearance following bolus injection was 38 ml/min per m2, with a range of 15 to 55 ml/min per m2. The postdistributive half-life ranged from 6 to 16 h. With oral administration, the mean bioavailability was 44% (range, 19 to 67%). An oral dose of 60 mg/m2 (162 mumol/m2) resulted in concentrations in plasma that approximated those achieved with a 30-mg/m2 (81-mumol/m2) intravenous dose. The toxicity of this combination regimen was minimal. It appears that the oral route is a practical route of administration for trimetrexate in patients with acquired immunodeficiency syndrome requiring long-term outpatient treatment or prophylaxis for P. carinii pneumonia.

Acquired Immunodeficiency Syndrome↗