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N Raskin

Publications and source records attributed to N Raskin.

9 recordsLinked to original sources
PubMed1998

Interaction affinity between cytokine receptor components on the cell surface.

The anti-common gamma chain (gammac) mAb CP.B8 is shown to inhibit interleukin 4 (IL-4)-dependent proliferation of phytohemagglutinin (PHA) activated T cells noncompetitively with respect to cytokine by blocking the IL-4-induced heterodimerization of IL-4Ralpha and gammac receptor chains. Affinities for the binding of IL-4 to Cos-7 cells transfected with huIL-4Ralpha, and to PHA blasts expressing both IL-4Ralpha and gammac, were used to estimate the affinity of the key interaction between gammac and the binary IL-4Ralpha.IL-4 complex on the cell surface. This affinity was defined in terms of the dimensionless ratio [IL-4Ralpha.IL-4.gammac]/[IL-4Ralpha.IL-4], which we designate KR. The results show that on PHA blasts this interaction is relatively weak; KR approximately 9, implying that approximately 10% of the limiting IL-4Ralpha chain remains free of gammac even at saturating concentrations of IL-4. This quantitative treatment establishes KR as a key measure of the coupling between ligand binding and receptor activation, providing a basis for functional distinctions between different receptors that are activated by ligand-induced receptor dimerization.

Animals↗
PubMed1998

Molecular mapping with functional antibodies localizes critical sites on the human IL receptor common gamma (gamma c) chain.

The IL receptor common gamma (gamma c) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how gamma c chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human gamma c chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-gamma c mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the gamma c chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on gamma c chain required for its association with multiple ligands.

Alanine↗
PubMed1991

Thoracic surgery in the AIDS patient.

AIDS is a syndrome caused by HIV. The virus is spread by homosexual or heterosexual transmission and by infected blood or certain body fluids. Respiratory infections are the commonest cause of death, and diagnosis may be difficult. The fiberoptic bronchoscope (FOB) plays an essential role in diagnosing respiratory infections in AIDS and is important in minimizing the need for open lung biopsies. Various problems require thoracic surgical consultation and treatment. We do not consider it ethical to deny these patients help. There can be no "double standard" in the care of patients in the hospital or in the operating room since any of our patients may have HIV without our knowledge.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Adenosine diphosphate ribosyl transferase responses to a standardized dose of hydrogen peroxide in the mononuclear leukocytes of patients with a diagnosis of cancer.

Mononuclear leukocytes from 151 patients with cancer of various organs and from 467 apparently cancer-free individuals were exposed, in vitro, to H2O2 (100 microM) and the effects of the exposure on the activity of adenosine diphosphate ribosyl transferase (ADPRT) were determined. First, the reproducibility of this test procedure was established as satisfactory, by comparing the results of assays performed independently by two investigators, and by measuring ADPRT in cells from two individuals over a 9-week period. The test data were analyzed by multiple linear regression, and the correlation of cancer diagnosis, age, sex and smoking habits with ADPRT values was determined. The strongest correlate was cancer diagnosis. We considered categorizing ADPRT values as high and low, with a cut-off value that would substantially distinguish cancer from cancer-free individuals. When a cut-off value of 1200 c.p.m. TCA ppt [3H]NAD+/5 x 10(5) cells was applied to the complete test material, it was found that ADPRT values from cancer patients were more frequently below the cut-off than values from disease-free individuals: the relative risk estimate (odds ratio) was 13.8. When a similar analysis was done on values from lung cancer patients and smoking disease-free individuals, the odds ratio was 73.5. However, a cut-off value of 2000 c.p.m. TCA ppt [3H]NAD+/5 x 10(5) cells was most effective in distinguishing lung cancer patients (the largest cancer group, n = 96) from smoking non-cancer individuals: that value provided better sensitivity (85%) and specificity (81%) than other cut-off values tested in the range 1200-2000 c.p.m. Further, in the case of lung cancer, possible effects of anatomical site, and of staging and pathology on ADPRT values was analyzed by the chi-squared test: no significant associations were found. These data support the value of the ADPRT test in detecting early stage lung cancer regardless of location or pathological type.

Adult↗
PubMed1989

Brain metastases in malignant pleural mesothelioma. Case report and review of the literature.

Recent advances in pleural malignant mesothelioma include the sequential use of palliative surgery, perioperative radiation therapy, and systemic chemotherapy. Radical treatments may not only palliate but also improve survival in some patients. The latter may be associated with the appearance of metastases in unusual sites including the central nervous system. In malignant mesothelioma, brain metastases were previously reported in 19 patients at autopsy and in only 1 patient antemortem. We detail the clinical presentation in the second patient with pleural malignant mesothelioma thus far reported to develop brain metastases. The difficulties in diagnosis, the role of immunoperoxidase stains in malignant mesothelioma, excellent tolerance of different modalities of treatment, and a review of the literature of brain metastases in mesothelioma are discussed. Based on our report, the possibility of brain metastases should be investigated by careful clinical examination prior to a radical treatment in patients with progressive refractory mesothelioma.

Aged↗