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Biomedical subjects

Z Bentwich

Publications and source records attributed to Z Bentwich.

At least 19 recordsLinked to original sources

Antibodies to reverse transcriptase in HIV infection and progression to AIDS.

Serum antibodies to the reverse transcriptase (ART) of human immunodeficiency virus 1 (HIV-1) were sequentially determined by ELISA in a group of 41 HIV-seropositive male homosexuals and 101 matched healthy controls, over 1.5-6 years (mean follow-up 3.25 years). Mean ART levels were significantly higher in the patient group as compared to the controls (195 +/- 75 vs. 75 +/- 45 absorbance (A) units; P less than 0.05). When analyzed in parallel with clinical evaluation and T-cell subset determinations, a "surge" in ART activity was associated with a more favourable course: eleven patients whose ART profile showed an increase greater than 100 A units (mean delta A 159.6 units) showed an attenuated decrease of CD4+ (T helper) lymphocytes with a mean time of 42.5 months to reach a CD4+ number of 400 cells/mm3. In contrast, 25 matched seropositive patients whose ART remained constant became CD4+ less than 400 cells/mm3 within a mean time of 10.8 months (P less than 0.05). These results as well as individual patients' data support a surge in serum ART as a favourable prognostic indicator, and may indicate a protective role for this antibody which should be followed up and possibly utilized in the treatment or in the design of a vaccine against HIV-1.

Acquired Immunodeficiency Syndrome

Elevated serum levels of soluble tumour necrosis factor receptors (sTNF-R) in patients with HIV infection.

Serum levels of the soluble form of tumour necrosis factor receptor type II (p75) (sTNF-R) were determined in HIV-infected individuals and risk groups and were then correlated with the course of infection and prognosis. sTNF-R levels were determined by an ELISA with MoAbs and polyclonal antibodies to urine-derived sTNF-R proteins. The mean +/- s.e. levels of sTNF-R in the sera of 49 HIV+ male homosexuals, 34 HIV- male homosexuals and 44 matched controls were 6.1 +/- 0.3 ng/ml, 4.4 +/- 0.3 ng/ml and 3.4 +/- 0.2 ng/ml, respectively. All these values were significantly different between each of the groups (P less than 0.001-0.05). Sequential studies of sTNF-R revealed higher levels following seroconversion in 5/8 individuals, remained persistently high during the asymptomatic phase of the infection and became even more elevated in some ARC and AIDS patients. At the same time TNF-alpha was undetectable in sera obtained from HIV+ male homosexuals and from healthy controls. This was independent of stage of HIV infection, serum sTNF-R level and type of ELISA kit used. These findings suggest that TNF-alpha/TNF-R system is turned on before and during HIV infection and raise the possibility that sTNF-R, the natural inhibitor of TNF, may be of importance in determining the course and probably prognosis of the disease.

Enzyme-Linked Immunosorbent Assay

Increased LAK activity against HIV-infected cell lines in HIV-1+ individuals.

The role of natural killer (NK) cells and their inducible counterparts, lymphokine-activated killer (LAK) cells in AIDS with regard to HIV-1 viral immunosurveillance and the control of secondary opportunistic disease has yet to be established. In this study, we have demonstrated that LAK cells derived from all HIV-1+ groups showed striking increases in their capacity to lyse HIV-1-infected U-937 cells relative to their uninfected U-937 counterparts. Surprisingly, similarly derived LAK cells from healthy seronegative controls showed no differences in their lysis of HIV-1-infected versus uninfected U-937 cells. The differential ability of LAK effectors from seropositive donors to lyse HIV-1-infected targets was demonstrable using a number of U-937 subclones and their HIV-1-infected counterparts. Again, no differences in LAK cell-mediated lysis of HIV-1-infected and uninfected U-937 subclones were observed in seronegative individuals. Our findings that HIV-1+ individuals show selective expansion of non-MHC restricted, HIV-1-directed cytotoxic LAK cells indicate that natural immunity may indeed play a role in HIV-1 viral immunosurveillance.

Antigens, CD

'Silent' HIV infection among wives of seropositive HIV carriers in the Ethiopian community in Israel.

We have previously described the phenomenon of 'silent HIV carriers', i.e. individuals with HIV specific immunity and a positive PCR for HIV-1, yet HIV seronegative. In the present study, we have looked for such 'silent' carriers among wives of individuals infected with HIV in Africa (Ethiopia). In addition to determining HIV serology, peripheral blood mononuclear cells (PBMC) were tested by PCR for HIV-1 and for their ability to generate specific antibodies to HIV upon polyclonal B-cell activation (P-BAT). Out of 16 wives so tested, three were HIV seropositive and among the 13 seronegatives, eight were P-BAT positive and five were both P-BAT and PCR positive. These findings suggest that (1) 'silent' HIV carriers may indeed be present in African populations; (2) interpretation of the 'silent' carrier phenomenon is not clear and will depend on clinical follow-up and the ability to culture virus from such carriers; and (3) results of HIV serology in this population and probably in other African populations should be viewed with caution.

Adult

[Wound healing by homeopathic silica dilutions in mice].

Highly diluted solutions of silica are widely used in homeopathic medicine to treat lesions such as chronic wounds, ulcers, and abscesses. We tested the therapeutic effects of homeopathic dilutions of silica on induced chronic wounds. Holes were made in the ears of mice by dental wire, which then remained hanging from the ear to cause persistent mechanical irritation. In each experiment 3 or 4 groups of 10 mice each were treated by adding homeopathic dilutions of silica (10(-10), 10(-60), 10(-400)) and of saline (10(-10), respectively, to the drinking water of the mice for 4-20 days. The size of the wound holes was measured every second day (grades 0-4) and/or by an objective image analysis system. The results showed that in 7/11 experiments the ear holes of the silica-treated animals were significantly smaller (p less than 0.05-0.001) and healed faster than in those treated with saline. Also the therapeutic effect increased progressively with increase in dilution of the silica (10(-10) less than 10(-60) less than 10(-400)). These results show that homeopathic dilutions of silica (even well beyond Avogadro's number) clearly have a therapeutic effect on wound healing and that our experimental model for studying wound healing is a very useful tool for such studies.

Animals

Oral colon lavage solutions containing polyethylene glycol may interfere with ELISA detection of tumor-associated antigens in colonic effluent.

Immunologic methods for detection of colorectal neoplasia based on examination of stool or colonic effluent are being developed. Most current oral lavage preparations contain polyethylene glycol (PEG), and if PEG adversely interferes with immunologic testing these tests may become less useful. We describe a decrease in sensitivity of ELISA for tumor-associated antigens (TAA) when effluent samples are diluted in PEG-electrolyte lavage solution, equivalent to a commonly used oral lavage solution based on PEG. Radioisotope-labeled antigen binding to plastic plates was decreased by dilution in the PEG lavage solution. Antigen binding, present in colonic effluent collected by the laxative purge method, was absent in effluent collected by PEG oral lavage from the same patient. We conclude that PEG and PEG-containing lavage solutions interfere with ELISA detection of TAA in colonic effluents. We speculate that the in vitro, and possibly the in vivo, effect occurs at the level of antigen binding to the plate either by a steric effect or alteration of charge by the nonpolar properties of PEG.

Absorption

Autoantibodies in male homosexuals and HIV infection.

We have used ELISA to study the frequency of autoantibodies to several antigens in the serum of 17 male homosexuals (MHS) negative for HIV (HIV-), 11 asymptomatic HIV seropositive MHS (HIV+) and patients with ARC (N = 15) or AIDS (N = 13), and compared them to 20 matched healthy heterosexual controls. Serum antibody binding to histones, cardiolipin, ss-A, ss-B and Sm was found to be significantly higher in each of the MHS groups studied as compared to controls (P less than 0.001), and was also increased in the HIV+ patients vs. the HIV- group (P less than 0.05). In contrast, no increase in autoantibodies to ss-DNA, ds-DNA, poly(I), poly(G) or RNP were found in any of the groups tested. These results enlarge the spectrum of autoimmunity previously reported in HIV infection and identify a similar pattern to a lesser degree, already present in HIV- MHS, suggesting a role for HIV or concomitant virus infections in its pathogenesis.

AIDS-Related Complex

Sequential serological studies of homosexual men with and without HIV infection. Epstein-Barr virus activation preceding and following HIV seroconversion.

Viral cofactors may be important in the pathogenesis of HIV infection and the development of AIDS, but their role is still imperfectly understood. Sequential serological studies were performed in a cohort of 100 homosexual men and 70 matched healthy controls over a mean period of 4 years. Of the patients, 18 were found to be HIV+ on admission to the study and 15 seroconverted to HIV+ during the follow up (seroconversion group). Serum antibodies of both IgG and IgA isotypes against Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were determined. IgG antibodies indicate past infection, while a marked increase in IgG titre or a positive IgA titre were taken to indicate active infection or reactivated latent infection. EBV and CMV infections were about two to four times more prevalent in the homosexual men both HIV- and HIV+, compared with controls. Active infections were increased in the homosexual men and particularly in the HIV+ patients. The seroconversion group revealed activation of both EBV and CMV following HIV infection. When the antibody profile of seroconverting patients at the time preceding seroconversion was compared with a matched group of 39 homosexual men who remained HIV-, no change was found in CMV antibodies, but four out of 15 (26.6%) of the patients had high titres of anti-EBV IgA preceding seroconversion, as compared with only one out of 39 (2.6%) of HIV- homosexual men (P less than 0.05). This suggests a role for EBV reactivation in the pathogenesis of HIV infection in some patients.

Antibodies, Viral

[Screening for colorectal neoplasms].

We screened groups at high risk for colorectal neoplasms, determining the efficacy of the leukocyte adherence inhibition test (LAI) for early detection, in comparison with that of the fecal occult blood (Hemoccult) test and sigmoidoscopy or colonoscopy. Those screened included 549 first-degree relatives of patients with colorectal cancer, 190 patients with a past history of colorectal adenoma or carcinoma and 67 with a past history of breast or gynecological cancer or inflammatory bowel disease. 146 normal volunteers served as controls. In 782 of those fully screened during a 3-year period, 121 had adenomas (15.5%) and 5 had invasive cancer (0.6%). The LAI test was positive in 21% of those at high risk and in 7.5% of the controls. The hemoccult test was positive in only 4.8%, but in 1/3 of them neoplasms were found. This predictive value of 33% compares with only 16% for the LAI test. That most of the neoplasms found were adenomas and not invasive cancer may be due to the relative youth of most of those screened. We conclude that the groups studied were indeed at high risk. The LAI test is not sensitive enough to identify benign adenomas but might serve as another risk-market for colorectal neoplasms. Long-term follow-up of those at high-risk with positive LAI tests may prove that we have identified a subgroup truly at risk.

Adenoma

Leukotriene C4 decreases the activity of respiratory cilia in vitro.

In the present study we assessed the effect of leukotriene C4 on ciliary beat frequency in vitro. Chicken tracheas were sliced into thin rings and ciliary activity was viewed microscopically. Ciliary beat frequency was measured through an optical fibre by a fast Fourier transformer analyser and recorded on an oscilloscope. Ciliary beat frequency was measured at one fixed point during 30 min at room temperature in RPMI-HEPES medium alone and in medium containing leukotriene C4 at a range of concentrations (10(-6)-10(-9) M). Our results demonstrate that leukotriene C4 (10(-7) and 10(-8) M) caused a significant decrease in ciliary beat frequency in all tracheal rings tested (mean decrease of 24%). The specificity and Ca2(+)-dependency of leukotriene C4 activity was elucidated by the ability of FPL 55712 (SRS-A specific antagonist), Ca2(+)-free medium, calcium channel blockers (nifedipine and verapamil) and the calmodulin inhibitor trifluroperazine to abrogate its effect on ciliary beating.

Adenosine Triphosphate

Absence of T cell impairments in a unique group of anal-receptive transvestite and male prostitutes in Israel.

High rates of immunologic abnormalities in asymptomatic, clinically healthy urban homosexual men have been associated with promiscuous, unprotected receptive rectal intercourse, and related to infection by the human immunodeficiency virus (HIV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cohort studies in Israel, which is still a low risk country for HIV infection and AIDS, about 40% of asymptomatic, clinically healthy male homosexuals consistently showed T cell defects that were not correlated with anal-receptive sexual behavior and were independent of HIV antibody status. Since pre-existing immune impairments in HIV-seronegative individuals have been implicated as a risk factor for seroconversion, we have attempted to investigate more precisely the role of anal-receptive homosexual activity as a risk factor for the acquisition of immune defects. We compared T lymphocyte profiles and mean geometric titers of EBV and CMV in a homogeneous group of 14 transvestite and male anal-receptive homosexual prostitutes with those of 77 HIV-seronegative male homosexuals who were not exclusively anally passive with multiple sex partners. While 44% of the control group showed a decrease of total T cells or their subpopulations as compared with normal heterosexual men (P less than 0.001), T lymphocyte values of the anal-receptive prostitutes were within the normal range. In the prostitutes, serum antibodies to HIV were detected in only 1 individual, to CMV in 12 of 13, and to EBV in all. Despite high mean geometric titers of antibodies to CMV (86.6) and EBV (25.8), frequent anal-receptive intercourse was not sufficient, in itself, to cause immune impairment in this unique group. The results suggest that the problem of cofactors contributing to immune deficiency in male homosexuals should be reexamined in countries with a low incidence for HIV seropositivity and AIDS.

Adolescent

Adult respiratory distress syndrome: roles of leukotriene C4 and platelet activating factor.

The relationship between leukotriene C4 (LTC4), platelet activating factor (PAF), and adult respiratory distress syndrome (ARDS) was studied in nine patients and 84 control subjects. A leukocyte adherence inhibition (LAI) assay induced by each of the ligands was used to monitor the subjects for 3 consecutive days or until clinical recovery was noted. LAI was considered to be positive if the nonadherence index (NAI) was greater than 30 for LTC4 or greater than 20 for PAF. LAI was negative in all healthy subjects using both ligands. LTC4-induced LAI was positive in all nine ARDS patients and reverted to negative after recovery from the syndrome, while three (33.3%) of nine patients responded to PAF. In contrast, of the 84 control subjects, LAI was induced by LTC4 in only three (3.3%) and by PAF in five (5.9%). The mean NAI (52.2 +/- 18) of LTC4-induced LAI in ARDS patients was significantly (p less than .05) higher when compared with the control group (-5 +/- 6.4), whereas that of PAF-induced LAI was less than 20 in both groups, indicating that LTC4 is a more specific ligand than PAF. All three patients in whom ARDS was caused by sepsis responded to both LTC4 and PAF, but results of specific receptor-antagonist experiments indicated that each compound acted independently. The mean NAI for LTC4 (58.5 +/- 10) and PAF (49.1 +/- 12) in patients with septic ARDS were significantly (p less than .05) higher when compared with those of patients with sepsis alone (0.5 +/- 9.9 and 4.4 +/- 17, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Possible role of natural cytotoxic activity in the pathogenesis of AIDS.

In an attempt to assess the role of immune cytotoxic activity in the sequence of events leading to the acquired immunodeficiency syndrome (AIDS), natural cytotoxic activity was studied in 17 asymptomatic homosexual males, seropositive for anti-human immunodeficiency virus (HIV) antibodies, as compared to 16 of their seronegative counterparts and to 14 control healthy heterosexual individuals. Cell (contact)-mediated cytotoxicity (CMC) as well as cytotoxin (CTX) production by lipopolysaccharide (LPS)-stimulated, phytohemagglutinin (PHA)-stimulated, HeLa tumor cell-stimulated, and unstimulated peripheral blood mononuclear cells (PBMC) were determined using HeLa cell monolayer cultures, sensitized with cycloheximide, as targets. The CMC was markedly enhanced in the seropositive group (28 +/- 21 (mean +/- SD) lytic units/10(6) PBMC) as compared to the seronegative group (17 +/- 7; P less than 0.005) and to the heterosexual group (13 +/- 6; P less than 0.05). Likewise, CTX production by unstimulated PBMC from seropositive homosexuals (19 +/- 26 units/ml) was higher than that observed in the other groups (both 4 +/- 4 units/ml; P less than 0.05). CTX production by PHA-stimulated, LPS-stimulated, and HeLa cell-stimulated PBMC was significantly enhanced in both the seropositive and seronegative groups in comparison to the normal heterosexual controls. These results suggest that increased cytotoxic activity may be present in homosexuals prior to their exposure to HIV, and may be further enhanced after HIV infection.

Acquired Immunodeficiency Syndrome

Fulminant streptococcal myositis.

A previously healthy 70-year-old woman was hospitalized for acute pain and edema of her right leg. Deep vein thrombosis was suspected, and she was put on anticoagulant therapy. Ten hours later, she developed a massive swelling of the leg with a well-demarcated violaceous discoloration of the skin and hemorrhagic bullae. She was in deep shock with signs of disseminated intravascular coagulation and adult respiratory distress syndrome. Gram stain of an aspirate from the bullae revealed short chains of Gram-positive cocci, and multiple blood cultures showed abundant growth of Streptococcus pyogenes. Despite intensive treatment, the patient died within hours. Autopsy findings showed extensive pyomyonecrosis of the leg muscles and changes secondary to septicemia. The misleading initial clinical picture and the rarity of this disease entity in temperate climates delayed the correct diagnosis and resulted in a fatal outcome.

Acute Disease

The role of acupuncture in asthma: changes in airways dynamics and LTC4 induced LAI.

A cohort of nine extrinsic asthma patients were treated by means of acupuncture. Patients were followed up for changes in medical treatment, spirometry, skin reactivity to immediate type reactions, total serum IgE levels and reactivity of their leukocytes to leukotriene C4 challenge (LTC4 induced leukocyte adherence inhibition (LAI) assay). Our results show that after acupuncture, treated patients were able to reduce bronchodilator and taper completely corticosteroid therapy. No change in skin reactivity or in IgE levels were noted. However, acupuncture treatment was able to negate, in 66.6%, the positive LTC4 induced responses.

Acupuncture Therapy