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Biomedical subjects

S Baron

Publications and source records attributed to S Baron.

At least 127 records · Page 7Linked to original sources
PubMed1987

Alpha interferon production in patients with hairy cell leukemia: correlations with disease activity and remission status.

Nineteen patients with hairy cell leukemia (HCL) were studied for in vitro production of alpha interferon (IFN alpha). The patients were divided into three groups. The first group consisted of 8 patients with active disease, all of whom showed a severe deficiency in IFN alpha production (no detectable titers in 6 and less than 40 units/ml in the other 2) compared to normal controls (range: 320-10,500 units/ml; median: 2,560 units/ml). The second group consisted of 6 patients who achieved a partial remission (PR) after IFN alpha treatment. These 6 patients had normal numbers of mononuclear cells in the peripheral blood, but still had deficient IFN alpha production (titers of IFN alpha were below 10 units/ml in 5 of the 6 patients). The third group consisted of 5 patients in complete remission (3 after IFN alpha treatment and 1 each after splenectomy and infection). This group had IFN alpha production that was not significantly different from that of controls 35 years or older (median: 640 units/ml; range 60-2,560 units/ml for patients vs. 1,513 units/ml; range 320-5,120 units/ml for controls; p greater than 0.05). These data show a direct relationship between the activity of HCL and the capacity to produce IFN alpha in vitro. The data also suggest that deficiency of endogenous production of IFN alpha may be relevant to the induction and sustenance of remissions in this disease and that relapses may be partly associated with failure to fully restore endogenous IFN alpha production.

Adult↗
PubMed1987

Pharmacokinetic and clinical evaluation of imipenem/cilastatin in children and neonates.

Imipenem, a new carbapenem (thienamycin) beta-lactam antibiotic which is clinically used in a 1:1 combination with cilastatin, an inhibitor of renal metabolism of imipenem, was evaluated in 25 patients; 11 children and 14 neonates. A mean daily dose of 60 mg/kg was given to children and the dose in neonates was 50 mg/kg. Clinically, 21 patients were cured, two failed to respond to treatment and two were not evaluable. Pharmacokinetic studies were performed in the 11 children and in 10 of the neonates. The mean elimination half-life of imipenem was 0.87 h in children and 2.1 h in neonates. The mean cilastatin elimination half-life was 0.73 h in children and 5.1 h in neonates. This difference in half-life between children and neonates is similar to the one noted between healthy adults and adults with renal insufficiency. No accumulation of imipenem was seen in neonates studied on the first and fifth days of treatment.

Adolescent↗
PubMed1986

Interferon-mediated protection of B16 melanoma cells from cytotoxicity by activated macrophages.

Corynebacterium parvum-activated macrophages (M phi), purified by adherence, were cytotoxic for B16 melanoma cells maintained in vitro. Pretreatment of the melanoma cells for 18 hr with interferon-alpha/beta or -gamma (IFN-alpha/beta or -gamma) caused a reduced susceptibility of the B16 cells to M phi-mediated cytotoxicity. The IFN-induced protective effect of B16 cells from cytotoxic M phi was found to be dose dependent. In addition, IFN-gamma was more protective than IFN-alpha/beta. The protective effect observed with partially purified IFN was reproduced by using highly purified IFN-alpha/beta or recombinant IFN-gamma. Monoclonal antibodies to IFN-gamma neutralized the protective effect provided by IFN-gamma. These results show that the susceptibility of a tumor cell line to killing by activated M phi can be altered by IFN pretreatment.

Animals↗
PubMed1986

Role of interferon in streptococcal infection in the mouse.

In previous studies, we have shown the rapid in vitro induction of IFN gamma from human T cells by highly purified peptic extracts of M proteins from Streptococcus pyogenes. The present report extends these in vitro studies and shows that a mixture of both alpha/beta and gamma IFN were present in spleen cell homogenates after in vivo treatment with M protein wild-type (M+) or mutant (M-) S. pyogenes strains. The levels of bacterial-induced IFN were found to be greater in M+ treated animals. Additional studies in vivo showed that pretreatment of mice with heat-killed M+ S. pyogenes organisms significantly protected mice to pneumococcal infection compared to similarly treated M- or control animals (P less than 0.001). Further, antibodies to mouse IFN alpha/beta and antibodies specific to a synthetic N-terminal peptide of mouse IFN gamma enhanced the death of animals due to pneumococcal infection and blocked the protection observed in animals previously treated with heat-killed M+ organisms. Most importantly, treatment of mice with either type of IFN alone enhanced the survival of mice to levels similar to that observed by treatment with M+ organisms (P less than 0.05). The results strongly suggest that IFN can play a crucial role, directly or indirectly, in controlling infection by Streptococcus pneumoniae and perhaps other streptococci.

Animals↗
PubMed1986

An influenza virus inhibitor that acts late in the replication cycle.

An inhibitor which is active against influenza A virus was found in Neuramide, a complex tissue extract that is used as an anti-herpes zoster virus treatment. Kinetic studies showed that significant inhibition of virus production occurred when the inhibitor was added to infected cultures up to 5 h after virus penetration. Molecular sieving fractionation showed that the antiviral activity was contained in a low-molecular-weight fraction (molecular weight, less than 1,000).

Animals↗
PubMed1985

Continuous epidural narcotic analgesia for intractable pain due to malignancy.

Eighty consecutive cancer patients with severe pain, uncontrolled by conventional narcotic analgesics, received a 2-mg test dose of morphine epidurally. Thirty-four of them had significant pain relief and were thus selected to receive continuous treatment. This consisted of 2-6 mg of morphine administered every 8-24 hours through an indwelling epidural catheter. The duration of treatment was from 1 to 28 weeks with a median of 4 weeks. Twenty-five (76%) of the patients experienced complete relief of pain, while nine had only a partial analgesic response. Complications were minimal. No sepsis, hypotension, or respiratory depression occurred. It is recommended that cancer patients with intractable pain will be selected for continuous epidural analgesia by evaluating their response to a test dose of epidural morphine.

Adult↗
PubMed1985

Lymphoma arising in an adenolymphoma.

A malignant lymphoma that originated in association with an adenolymphoma (Warthin's tumor) of the parotid salivary gland is reported. The occurrence of lymphomas in salivary glands is discussed briefly.

Adenolymphoma↗
PubMed1985

Streptococcus pneumoniae cocultured with fibroblasts enhances both interferon production and cytotoxic activity by lymphocytes.

Cell-mediated cytotoxicity against normal human fibroblasts was dependent on treatment of the fibroblasts with Streptococcus pneumoniae. Both spontaneous and interferon (IFN)-enhanced lymphocytes killed human foreskin (HFS) or skin muscle cells cocultured with S. pneumoniae five- to eightfold more than control nontreated cells. Based on Percoll gradient centrifugation, the cytotoxic effector cell migrated like a large granular lymphocyte. The human IFN produced from mixtures of HFS cells, lymphocytes, and S. pneumoniae was observed to be both a mixture of IFN-alpha and IFN-gamma and in an amount 500 times greater than that observed with lymphocytes on HFS cells alone, and it was in an amount 12 times greater than when lymphocytes and bacteria were cultured together. A mixture of antibodies to IFN-alpha and -gamma added to cocultures of fibroblasts and bacteria blocked the killing of fibroblast targets by lymphocytes (47 versus 13%). Thus, endogenously produced IFN was essential for the effective killing of the fibroblasts. Treatment of HFS cells with IFN before bacterial treatment protected the HFS cells from lysis by lymphocytes. The observation that normal diploid cells exposed to bacteria can be killed by lymphocytes suggests that natural cytotoxic cells are active at the site of bacterial infection and conceivably play roles in defense or pathogenesis.

Bacterial Infections↗
PubMed1985

Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood.

Several aspects of interleukin-2 (IL-2) generation and function were studied employing mononuclear cells from synovial fluid (SF), synovial tissue (ST) and peripheral blood (PB) of patients with rheumatoid arthritis (RA). Decreased PHA stimulated IL-2 production by lymphocytes from rheumatoid ST, SF (P less than 0.02), and PB (P less than 0.01) was observed when compared to normal blood and SF of patients with gout. The proliferative response of rheumatoid lymphocyte blasts exposed to exogenous IL-2 was also defective (P less than 0.05-0.001). This defect was greater in SF than in rheumatoid PB (P less than 0.05-0.001). In addition to the proliferative response, the effect of IL-2 on interferon-gamma (IFN-gamma) production was also examined. Rheumatoid lymphocytes from both PB and SF produced less IFN-gamma after overnight treatment with IL-2 than did normal PB lymphocytes. This decreased IFN-gamma induction was discordant with the excellent enhancement by IL-2 of natural killer activity. Removal of adherent cells in synovial fluid did not correct this deficit. Abnormalities in the biology of IL-2 and IFN-gamma suggest that impaired T cell function could contribute to the immunopathogenesis of RA.

Adult↗
PubMed1985

Genetic differences in avoidance learning by Rattus norvegicus: escape/avoidance responding, sensitivity to electric shock, discrimination learning, and open-field behavior.

The behaviors of rats selectively bred for either good or poor shuttle box avoidance learning were studied. The results of Experiment 1 indicated that the phenotypic difference in avoidance learning is not associated with differences in speed of escape or avoidance responding. Differences between the lines in frequency of intertrial responses (ITRs), which appear during training but not during pretest, suggest that ITRs in animals of the low-avoidance (SLA) line are more suppressed by electric shock than in animals of the high-avoidance (SHA) line. This result suggests that SLA animals may be more emotionally responsive than SHA animals. Experiment 2 demonstrated that the animals of the two lines do not differ in absolute sensitivity to electric shock, and Experiment 3 showed that the poor performance of the SLA line is not due to an inability to learn. Experiment 3 also provided evidence which suggests that the poor avoidance learning by SLA animals is due to their emotional reactivity. Observations of open-field behavior in Experiment 4 are consistent with this hypothesis. The major consistent correlate of the phenotypic difference in avoidance learning is greater emotionality or emotional reactivity in SLA than in SHA animals.

Animals↗
PubMed1984

Interleukin 2 enhances natural killing of normal lymphocytes.

Purified Interleukin 2 (IL-2), free of interferon (IFN), significantly enhanced NK activity of normal human peripheral blood mononuclear cells (PBMC). This enhancing activity was absorbed by IL-2 receptor-bearing cells but was not blocked by antibody to alpha-IFN. IFN in the culture supernatants was greatly increased after stimulation with poly(I:C) plus IL-2. There was less IFN produced by either modulator acting alone. Stimulation of PBMC with IL-2 and/or poly(I:C) increased the proportion of OKM1+ cells and anti-Leu-7+ cells. When cells expressing either surface antigen were specifically lysed to deplete NK, cytotoxic activity could be restored by overnight incubation in IL-2. This result suggests that IL-2 stimulates the development of NK cells from precursors that lack cell surface OKM1 or Leu-7. IL-2 acted directly on large granular lymphocytes and did not require the presence of adherent cells. These results suggest that IL-2 may act synergistically with other IFN inducers and may play an important role in the regulation of NK cells.

Absorption↗
PubMed1984

Size and stability of a naturally occurring virus inhibitor.

We recently described a virus inhibitor (contact-blocking virus inhibitor) which was produced spontaneously by untransformed human and murine cells in tissue culture (S. Baron and L. McKerlie , Infect. Immun . 32:449-453, 1981). This contact-blocking virus inhibitor was characterized by broad antiviral activity, high potency, and reversible inhibition of viral attachment. Unlike interferon, the antiviral activity of the contact-blocking virus inhibitor is not species specific. An inhibitor with similar properties can also be demonstrated in many body fluids and surface secretions. We report here studies on the stability of the antiviral species which indicate that it is resistant to denaturation by heat (100 degrees C), acid (pH 2), and alkali (pH 12). The antiviral activity against all viruses tested resides in a low-molecular-weight molecule. The range of characteristics so far determined for the contact-blocking virus inhibitor distinguishes it from other virus inhibitors reported in the literature.

Animals↗