Search PubMed⌕ Search

Biomedical subjects

M Huberman

Publications and source records attributed to M Huberman.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1991

A phase I study of an outpatient regimen of recombinant human interleukin-2 and alpha-2a-interferon in patients with solid tumors.

This study was undertaken to define the maximum tolerated dose (MTD) of recombinant interleukin-2 (IL-2) that could be combined with a fixed dose of alpha-2a-interferon (alpha-IFN) in an outpatient setting. The schedule called for IL-2 to be given by a 2-hour intravenous infusion 5 days a week for 4 weeks. The alpha-IFN was given at a dose of 6 x 10(6) U/m2/d intramuscularly 3 days per week (Monday, Wednesday, and Friday). The IL-2 dose was escalated in four dose levels from 1 to 4 x 10(6) U/m2/d. The MTD in this study of 17 patients was at the fourth dose level of IL-2 (4 x 10(6) U/m2/d). In addition to the usual IL-2 toxicities, debilitating fatigue limited outpatient administration of this dose. Although the response rate was low, with partial responses seen in only 1 of 15 patients, 2 of 5 patients with melanoma treated at the higher dose levels had objective tumor shrinkage with one partial and one minor response. Thus, an IL-2 dose of 3 x 10(6) U/m2/d combined with a recombinant alpha-2a-IFN dose of 6 x 10(6) U/m2/d is recommended for Phase II studies.

Adult↗
PubMed1990

A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma.

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.

Adult↗
PubMed1990

Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial.

OBJECTIVE: To determine whether very low doses of warfarin are useful in thrombosis prophylaxis in patients with central venous catheters. DESIGN: Patients at risk for thrombosis associated with chronic indwelling central venous catheters were prospectively and randomly assigned to receive or not to receive 1 mg of warfarin, beginning 3 days before catheter insertion and continuing for 90 days. Subclavian, innominate, and superior vena cava venograms were done at onset of thrombosis symptoms or after 90 days in the study. RESULTS: One hundred twenty-one patients entered the study, and 82 patients completed the study. Of 42 patients completing the study while receiving warfarin, 4 had venogram-proven thrombosis. All 4 had symptoms from thrombosis. Of 40 patients completing the study while not receiving warfarin, 15 had venogram-proven thrombosis, and 10 had symptoms from thrombosis (P less than 0.001). There were no measurable changes in the coagulation values assayed due to this warfarin dose, except in occasional patients who had become anorectic because of their disease or chemotherapy. CONCLUSIONS: Very low doses of warfarin can protect against thrombosis without inducing a hemorrhagic state. This approach may be applicable to other groups of patients.

Adult↗
PubMed1990

Interferon system and natural killer cell activity in myasthenia gravis.

The autoimmune response in myasthenia gravis is well characterized, but little is known about the mechanisms initiating it. We have studied the interferon system and natural killer cell activity in 25 patients with myasthenia gravis and compared them to 68 healthy subjects and 96 patients with acute viral infections. Forty-four per cent of patients had circulating interferon (greater than 16 mu/ml), and in a similar proportion their peripheral blood mononuclear cells were in an antiviral state, i.e., showed low levels of viral replication when infected by vesicular stomatitis virus. Spontaneous in vitro interferon production by patients' peripheral blood mononuclear cells was also common (greater than 10 mu/ml, 32 per cent), while the response to the alpha-interferon inducer poly I:C was lower than expected, possibly reflecting the already high state of activation of the interferon system. These results were essentially similar to those obtained in patients with viral illnesses and differed significantly from healthy controls. In many myasthenia gravis patients (16 of 22, 73 per cent), a markedly deficient natural killer cell activity was found, with a median cytotoxicity of 6.5 per cent compared to 29 per cent in healthy subjects (p less than 0.005). Thus, many patients with myasthenia gravis have evidence of an activated interferon system and defective natural killer cell activity, suggesting an occult viral infection or reflecting nonspecific stimulation which may nevertheless contribute to the pathogenesis of the autoimmune response.

Acute Disease↗
PubMed1988

MRI parameters in multiple sclerosis patients.

Magnetic resonance imaging (MRI) findings of 20 patients with clinically definite multiple sclerosis (MS) are presented. The studies were performed on a 0.5 Tesla magnet using spin-echo technique. Analysis of the MRI findings included detailed linear measurements of the ventricular and the subarachnoid spaces and reading of the intensity of the grey and white matter and intensity of the MS plaques. The plaques were sorted according to their number and size. The younger patients (20-40 years) had overall more plaques than the older ones (over 40 years). The small plaques were the most numerous and the large ones were the least common. Statistically significant association was found between the number of plaques and the cella media width. The intensity ratios between the non-plaque white matter/grey matter showed a significant correlation with the ventricular score. A significant negative correlation was found between the antero-posterior diameter of the spinal cord and the number of MS plaques in the brain. The plaque/white matter ratio had a significantly negative correlation with the cervical cord's width.

Adult↗
PubMed1986

Vinblastine plus cisplatin in advanced non-small cell lung cancer: lack of advantage for vinblastine infusion schedule.

We have evaluated 31 patients with advanced non-small cell lung cancer treated by short-term 5-day vinblastine infusion combined with bolus cisplatin. Nine of 31 patients (29%) had partial and complete responses. Although five of nine (55%) of the responders were alive at greater than or equal to 1 year, three of the 31 patients experienced drug-related mortality. Our experience, as well as a review of previously reported trials in the literature, suggests that the infusion schedule of vinblastine offers no advantage over the bolus schedule.

Adenocarcinoma↗
PubMed1985

Randomized trial of estrogen vs. tamoxifen therapy for advanced breast cancer.

Forty-three postmenopausal females with advanced breast cancer were studied in a prospective comparative trial of estrogen vs. an anti-estrogen (tamoxifen) therapy with a crossover to the alternative hormone with progressive disease. Ten of 19 patients (53%) responded to primary tamoxifen therapy and six of 24 (25%) responded to primary estrogen therapy. Crossover responses were observed in seven of 19 (37%) on the secondary tamoxifen therapy and in two of 10 (20%) on secondary estrogen therapy, and were not related to the response to the primary hormonal maneuver. Responses were related to the presence of estrogen receptor protein (ERP), particularly for tamoxifen therapy, although responses were observed in three of six ERP negative patients receiving estrogen and in seven of 25 (28%) of patients with an unknown ERP status. Complications were observed in 35 instances with estrogen therapy and in only five instances with tamoxifen therapy. Initial hormonal therapy with tamoxifen in postmenopausal patients with advanced breast cancer and ERP status positive or unknown is superior to primary estrogen treatment. Secondary therapy and response to estrogen or tamoxifen is not necessarily predicted by the initial hormone response, and crossover to the alternative therapy is generally indicated.

Aged↗
PubMed1984

Fate and structure of DNA microinjected into mouse TK-L cells.

Co-microinjection of single linearized molecules of plasmids containing the human beta-globin gene (pRK1) and the herpes simplex virus (HSV) type I thymidine kinase gene (pX1) into the mouse TK-L cell nucleus results in covalent linkage between these (or derived) molecules within the nucleus as revealed by Southern blotting, plasmid rescue, and recovery of plasmid-derived DNA from a Charon 4A phage library of cellular DNA. The microinjected DNA is predominantly found as high molecular weight DNA as determined by Hirt fractionation. Southern blotting data and recombinants from the Charon 4A library suggest that the plasmid DNA is in the form of a head-to-tail linear concatamer of up to 80 copies. Passage of these microinjected cells in selective medium (HAT) results in coordinate amplification of both plasmids, which are maintained in an approx. 3:1 molar ratio of pRK1 to pX1-derived molecules. Hybridization in situ shows the DNA to be integrated on a translocation chromosome, t(4;4). Integration does not appear to be site-specific, since plasmid DNA from another microinjected cell line, C2B, appears on a different translocation chromosome, t(8?;14). Plasmid rescue experiments confirm a previous finding that passage of pBR322 DNA through eukaryotic cells may result in deletions of normally stable plasmid DNA upon subsequent transformation of E. coli. These deletions appear to occur in the bacteria, and originate in a 128 bp region between the Sal I and Hae II sites of pBR322.

Animals↗
PubMed1984

Recurrent neuroleptic malignant syndrome due to tiapride and haloperidol: the possible role of D-2 dopamine receptors.

Two typical recurrent episodes of neuroleptic malignant syndrome (NMS) in the same patient are described. The first episode was caused by a sulpiride derivative, tiapride. This is the first case in which a drug of the benzamide group has been reported to have caused such adverse drug reaction. In the second episode, NMS occurred due to haloperidol in the lowest dose ever reported and was accompanied by highly excessive levels of various muscle enzymes. Involvement of hypothalamic and striatal dopamine system, and particularly of D-2 subtype receptors, is suggested by this case.

Basal Ganglia↗
PubMed1984

Pithiness in plants: I. The effect of mechanical perturbation and the involvement of ethylene in petiole pithiness in celery.

Mechanical perturbation (MP) applied to celery (Appium graveolens L. cv. Florida 683) leaf petioles or ethephon application to the plant did not induce thigmomorphogenesis (inhibition of elongation and increase in thickness of the petiole). However, the two treatments did cause the parenchyma breakdown which leads to pithiness or increased natural pithiness, mainly at the base of the petiole. Nevertheless, MP (but not ethephon) decreased the severity of drought-stress or GA3-induced pithiness. Although MP stimulates ethylene production, mainly at the middle part of the petiole, it seems that the protection by MP of the petiole may not be directly mediated by ethylene production. The exposure of the plant to drought stress brought about an increase in ethylene evolution. Upon reirrigating the plants, the first steps of pithiness were accompanied by a sharp decline in ethylene production. This decrease might be due to membrane disruption. The increase in ethylene production during drought stress may be one of the events which stimulate pithiness of the celery leaf petiole.

Apiaceae↗