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Biomedical subjects

M Huberman

Publications and source records attributed to M Huberman.

At least 19 recordsLinked to original sources
PubMed1998

The immunomodulator AS101 restores T(H1) type of response suppressed by Babesia rodhaini in BALB/c mice.

The immunomodulator AS101 has been previously shown to confer protection upon BALB/c mice infected with the intraerythrocytic parasite Babesia rodhaini (B. rodhaini). The present study focuses on the effect of AS101 administration on the acute phase of babesial infection where T helper cell subset patterns-TH1/TH2-were assessed in heavily infected mice. Secretion of cytokines of the TH1 subset (IL-2, IFN-gamma, IL-12) and of the TH2 subset (IL-10, IL-4) as well as TGF-beta was measured following the administration of AS101 2 weeks before parasite infection. Our results demonstrate that the parasites suppress IL-2 protein and IL-12 mRNA and that AS101 upregulates their secretion: IL-2, 8 u/ml vs 34 u/ml, respectively; IFN-gamma protein, 2370 pg/ml vs 4777 pg/ml, respectively. Conversely, babesial infection results in the upregulation of IL-10 and IL-4 proteins and TGF-beta transcripts, whereas AS101 downregulates their production: IL-10, 1800 pg/ml vs 360 pg/ml, respectively; IL-4, 58.3 pg/ml vs 24.5 pg/ml, respectively. A possible escape mechanism induced by B. rodhaini is suggested, starting with IL-10 inhibition of macrophage activities leading to a suppression of the TH1 response and of IL-2 in particular. It is therefore possible that AS101 may protect infected mice by activating cellular-mediated immunity and concurrently balancing the TH subset responses. It is suggested that AS101 may be effective as an antiparasitic drug.

Adjuvants, Immunologic↗
PubMed1997

Beta-amyloid peptide induces tumor necrosis factor-alpha and nitric oxide production in murine macrophage cultures.

We investigated the effect of beta-amyloid peptide (betaA) on the activation of the murine-derived monocyte/macrophage J774 cell-line. BetaA induced tumor necrotic factor-alpha (TNF alpha) in these cells in a dose-dependent manner. Incubation of cells with betaA slightly increased nitric oxide (NO) production, an effect that was significantly enhanced by the addition of interferon-gamma (IFN gamma). Substitution of betaA4 with TFN alpha and incubation of the cultures with IFN gamma resulted in significant NO production, although this was lower than that obtained in the presence of the peptide. Incubation of cultures with a monoclonal antibody (mAb) against TNF alpha abrogated NO production. Our results suggest that betaA4-induced TNF alpha production is a crucial event in the activation of peripheral macrophages.

Amyloid beta-Peptides↗
PubMed1997

Essential fatty acid preparation improves biochemical and cognitive functions in experimental allergic encephalomyelitis rats.

This study examined the possible effects of a novel mixture of fatty acids, SR-3 (a specific ratio of alpha-linolenic acids), on brain biochemistry and on learning deficits induced by injection of an agent that induces experimental allergic encephalomyelitis. Treatment with SR-3 caused a decrease in myelin and changes in the fatty acid profile of brain synaptosomes, and a learning deficit. Eighteen days of treatment with SR-3 reversed the biochemical and learning deficit significantly, but did not restore them to normal levels. We propose that, most probably, the main action of SR-3 is the modulation of the cholesterol level, which in turn causes the modulation of the fatty acid profile and enhances learning by allowing improved neuronal communication.

Analysis of Variance↗
PubMed1996

Trials of 9-amino-20(S)-camptothecin in Boston.

9-Amino-20(S)-camptothecin (9-AC) is an analog of camptothecin with limited water solubility which has shown significant preclinical activity in a variety of human solid tumor xenografts. A Phase I trial using a soluble formulation of 9-AC, given as a 72-hour continuous infusion, has been completed. Thirty-one patients with resistant cancers received 5-60 micrograms/M2/h at three week intervals. The Maximum Tolerated Dose (MTD) was 45 micrograms/M2/hour. Neutropenia was the dose limiting toxicity, with few significant non-myelosuppressive toxicities. Minor responses were seen in 3/31 patients. Pharmacokinetic studies of 9-AC lactone (closed ring) showed substantial interpatient variability with a predicted half-life of 36 hours. A phase I/II trial of the same formulation of 9-AC is ongoing in refractory leukemia. Stomatitis and diarrhea are the non-myelosuppressive dose limiting toxicities. Evidence of antineoplastic activity has been seen in 3/15 patients. A Phase II trial in previously untreated metastatic breast cancer is also underway. A Phase I trial of a colloidal dispersion formulation, not yet completed, is better tolerated with a MTD > 45 micrograms/M2/h as a 72-hour continuous infusion. Evidence of antineoplastic activity has also been demonstrated.

Adult↗
PubMed1996

5-Fluorouracil and alpha-interferon in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of mortality worldwide, and no effective systematic therapy currently exists. Recombinant alpha-interferon (IFN) has been suggested to have some antitumor efficacy in this illness, and synergism with 5-fluorouracil (5-FU) has been reported in several gastrointestinal malignancies. We therefore treated 10 patients with advanced HCC with combination therapy consisting of 5-FU 750/mg/m(2) weekly and IFN 9 X 10(6) units three times weekly. Toxicity was substantial in this cirrhotic population, and included mucositis as well as neurologic and hematologic side effects. There were no sustained antitumor responses. Median survival among this heavily pretreated population was 10 months. We were therefore unable to demonstrate any significant benefit to treatment with 5-FU and IFN in patients with HCC.

Antimetabolites, Antineoplastic↗
PubMed1995

T lymphocyte subpopulations and activation markers correlate with severity of Alzheimer's disease.

In this study we investigated immune-associated antigens of peripheral lymphocytes from patients with Alzheimer's disease (AD). The patients were divided into two groups--mild and moderately severe--according to severity of disease stage, and their lymphocytes were compared to those of elderly controls. In the mild stage of the disease we observed a slight increase in the HLA-DR marker (9.5 +/- 2.4% vs 6.5 +/- 1.1%; P = 0.06), but no changes in the CD4, CD8, and interleukin-2 receptor (IL-2R) markers. In the moderately severe stage, we observed a significant increase in the HLA-DR (18.5 +/- 2.7%) and CD4 markers (55.2 +/- 3.5% vs 43.5 +/- 2.1%, P < 0.01), and a slight decrease in the CD8 subset (19.5 +/- 1.4% vs 22.3 +/- 1.3%, P = 0.05). In the same group, following stimulation with the mitogen PHA, we observed a marked reduction in IL-2R expression (30.9 +/- 4.7% vs 41.1 +/- 2.7%, P = 0.05) and in the proliferative ability of lymphocytes (21131 +/- 4676 cpm vs 47909 +/- 1107 cpm, P < 0.04). However, mitogen-induced IL-2 secretion levels from the same lymphocytes were significantly elevated (17.4 +/- 4.8 U/ml vs 8.6 +/- 4.3 U/ml, P < 0.01). Marked changes in immunological parameters in the moderately severe group support the hypothesis of a peripheral immune reaction in AD which may be correlated with the clinical stage of the disease.

Aged↗
PubMed1995

IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease.

The production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (MNC) was assessed in patients with Alzheimer's disease (AD) who were subdivided into two groups--mild and moderately-severe--according to the severity of the disease, probable vascular dementia (VaD) patients and elderly control subjects. No differences in IL-2 secretion were found between mild AD patients and controls. However, there was a significant increase in IL-2 production both in the moderately-severe AD group and in the VaD group. IL-6 levels in AD patients of both groups were similar and significantly higher than those of VaD and controls. Our results suggest that increased levels of IL-2-production correlate with severity of the dementia, whereas increased levels of IL-6 production seem to be related to AD and thus may play a role in AD pathogenesis.

Aged↗
PubMed1995

Cisplatin and chronic oral etoposide as salvage therapy for advanced colorectal carcinoma.

Patients with metastatic colorectal carcinoma who have failed 5-fluorouracil-based chemotherapy have no effective second-line treatment available. Recent studies demonstrating clinical synergy between cisplatin and etoposide, and others exploring the efficacy of etoposide regimens utilizing chronic oral administration, suggested the utility of a new regimen incorporating these elements to treat refractory colorectal carcinoma. Fourteen patients were treated with weekly cisplatin and daily oral etoposide for 21 days in cycles of 28-35 days. Toxicity was significant, both hematologic and gastrointestinal in these pretreated patients. There were no objective responses, and median survival was 9.5 months. Weekly cisplatin and daily oral etoposide are poorly tolerated and ineffective in the treatment of refractory colorectal carcinoma. Further studies are needed to discover effective therapy for this disease.

Adenocarcinoma↗
PubMed1995

Improved detection of auditory P3 abnormality in dementia using a variety of stimuli.

The purpose of this study was to test the improved sensitivity of P3 abnormality in the detection of dementia using a variety of auditory stimuli. Improved detection was obtained using auditory stimuli that differed in their cognitive attributes and by using several P3 measures. These measures included P3 latencies and amplitudes relative to pure tone evoked P3s. Fourteen demented patients (mean age 79.2 years) and a matched normative group were tested. Abnormality of P3 latency for pure tone targets was found in ten patients, equivalent to a hit-rate of 72%. The hit-rate could be further increased by using phonemically and phonetically different types of auditory stimuli, thought to vary in their cognitive attributes. These findings underscore the importance of using a variety of stimuli in testing demented patients.

Acoustic Stimulation↗
PubMed1994

Elevated interleukin-6 secretion levels by mononuclear cells of Alzheimer's patients.

It has been suggested in recent research that interleukin-1 (IL-1) and interleukin-6 (IL-6) play a role in the pathogenesis of Alzheimer's disease (AD). Production of IL-1, by lipopolysaccharide (LPS)-stimulated monocytes, and IL-6, by phytohaemagglutinin (PHA)-stimulated mononuclear cells, was assessed in patients with AD divided into two groups--mild and moderately severe--according to severity of disease, and elderly controls. No differences in IL-1 production were found among AD patients and controls. However, significant elevation in IL-6 secretion levels was observed in both the mild and moderately severe AD patients. Our results suggest that peripheral IL-6 secretion levels may be responsible for acute-phase proteins observed in the serum of AD patients.

Aged↗
PubMed1994

Correlation of cytokine secretion by mononuclear cells of Alzheimer patients and their disease stage.

Cytokine secretion by human mononuclear cells (MNC) was investigated in age-matched controls and in patients with Alzheimer's disease (AD). AD patients were divided into two study groups: 'mild' and 'moderately severe'. A significant increase in interleukin-2 (IL-2) and gamma interferon (IFN-gamma) secretion was found in AD patients in the moderately severe stage of the disease, whereas in the mild stage of the disease there was a significant decrease in interleukin-3 activity (IL-3) and tumor necrosis factor (TNF) levels. No significant differences were found in the level of production of interleukin-1 (IL-1 beta). Our results demonstrate the existence of defective immune functions in AD patients which are correlated with the clinical condition of these patients.

Aged↗
PubMed1994

Fibrosing alveolitis associated with primary antiphospholipid syndrome.

The spectrum of the primary antiphospholipid syndrome has expanded in recent years. It has been associated with a number of non-thrombotic syndromes such as pulmonary hypertension, adrenal insufficiency, chorea and avascular necrosis of bone. Yet, it has not been described in association with inflammatory pulmonary disease. We describe a young male with definite primary antiphospholipid syndrome who developed insidious diffuse pulmonary infiltrates. The histopathologic examination of the involved lung demonstrated alveolitis and fibrosis. We suggest that this pulmonary involvement may represent another manifestation of the primary antiphospholipid syndrome.

Adult↗
PubMed1994

Myasthenia gravis: rarity of gallstone formation.

There is an increase in the production of gallbladder stones (cholelithiasis) following gastrectomy associated with vagotomy; we hypothesized that in the presence of constant stimulation of the vagal system, there should be decreased production of gallstones. Forty-two myasthenia gravis patients taking continuous anticholinesterase medications underwent ultrasound study of the gallbladder; only one patient, aged 62, had gallstones. In the control group of 112 nonmyasthenics matched for age and ethnic origin, 45 had stones. This study suggests that cholinergic medications protect against gallstones.

Adolescent↗
PubMed1993

Decreased IL-3 production by peripheral blood mononuclear cells in patients with multiple sclerosis.

The production of interleukin-3 by peripheral blood mononuclear cells (MNC) was assessed in patients with relapsing multiple sclerosis (MS) in both the active and the stable state, and in healthy controls. IL-3 levels were compared to levels of production of interleukin-2 (IL-2), tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN). No significant differences in IL-3 levels were observed between stable-state patients and controls. When levels of cytokine production of patients in the inactive phase were compared to those of the same patients during relapse a significant decrease in IL-3 levels was observed, as opposed to significant increases in gamma-IFN and TNF levels, and an increase, though a non-significant, in IL-2 levels. The functional significance of lowered IL-3 production is unknown. However, the findings support the hypothesis of a highly complex interaction of overlapping regulatory influences within the cytokine network which parallels MS disease activity.

Adult↗