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Biomedical subjects

S Litwin

Publications and source records attributed to S Litwin.

At least 109 records · Page 6Linked to original sources
PubMed1986

Biologic effects of gamma interferon pre-treatment followed by monoclonal antibody 17-1A administration in patients with gastrointestinal carcinoma.

Twenty-seven patients with metastatic adenocarcinoma of the colon or pancreas were treated with 400mg of monoclonal antibody 17-1A. This antibody, which binds to a cell surface glycoprotein moiety preferentially expressed by adenocarcinomas of the rectum, colon, pancreas, and stomach, is postulated to induce antibody-dependent monocyte cytotoxicity (ADMC) as a mechanism of tumor lysis. Therapy was preceded by four days of gamma interferon infusions, with the intent of activating peripheral blood monocytes, enhancing monocyte Fc receptor expression and increasing the likelihood of tumor lysis as reflected by enhanced ADMC directed against a colon carcinoma cell line (SW1116) which expresses 17-1A's target antigen. In this Phase I study patients were treated daily at one of the following gamma interferon dose levels (X 10(6) U/M2/day): 0.001, 0.01, 0.1, 1.0, 10.0, 40.0, 60.0, 80.0. Addition of 100 U/ml of rIFN-gamma in vitro to monocytes isolated from normal controls or from patients prior to treatment significantly enhanced monocyte Fc receptor expression and ADMC. in vitro tumor cell killing by monocytes and monoclonal antibody was enhanced by treatment with low doses of rIFN-gamma, while treatment with high doses of rIFN-gamma did not enhance ADMC. No objective clinical responses were noted, although serum tumor markers dropped transiently in 36% of the treated patients. Seven of 11 assayed patients developed human anti-idiotype antibodies. With better scheduling of rIFN- and 17-1A we hope to duplicate optimal in vitro conditions for antibody-mediated cytotoxicity, hopefully enhancing in vivo antibody mediated tumor lysis.

Adenocarcinoma↗
PubMed1986

Multiparameter evaluation of the expression in situ of normal and tumor-associated antigens in human colorectal carcinoma.

The immunoreactivity of a panel of monoclonal antibodies (MoAb) was studied in a series of patients with colorectal carcinomas to test the association of antigen expression with other parameters such as histopathologic stage, differentiation, and clinical outcome. Low-level binding to normal tissue and high-level binding to malignant tissue were observed with MoAb defining, respectively, a gastrointestinal cancer antigen (GICA), Leb (distal colon only), A, H type 2 antigen, X-like antigen, and the 200-kilodalton (Kd) protein of carcinoembryonic antigen (CEA). The degree of histologic differentiation correlated with the expression of Lea antigen, A, and Y haptens, whereas a progressive loss of these antigens coincided with loss of differentiation. Two undifferentiated carcinomas expressed only two, H type 2 antigen and a highly glycosylated protein of 20-50 Kd, of the 14 antigens investigated. An interesting, but not significant, association between Leb antigen expression and more extensive disease was found: Whereas 71% of Dukes C tumors were positive for Leb, only 48% of patients with Dukes A and B2 tumors showed the presence of Leb antigen. On the other hand, the presence of B72.3-defined antigen is significantly associated with an earlier stage of disease. Chi-square tests to assess the association of antigen positivity with disease recurrence indicated a significant binding association with tumor recurrence over a broad range of percent positive cells for two MoAb defining different determinants of GICA. Similar associations, but over a narrow range of positive cells, were found for H type 2 antigen and the 200-Kd protein of CEA.

ABO Blood-Group System↗
PubMed1984

Monoclonal derivation of mouse myeloid and lymphoid lineages from totipotent hematopoietic stem cells experimentally engrafted in fetal hosts.

Mutant mouse fetuses with a hematopoietic stem cell defect were injected with a mixture of two normal strains of fetal liver cells to test the possibility of seeding with single stem cells and of deriving all hematopoietic lineages clonally. Recipients were either Wf/Wf, with a mild endogenous defect offering only marginal selective advantage to a normal donor cell, or W/W, with a severe defect. Among 11 Wf/Wf animals with long-term grafts, 8 had only one or the other of the donor strains. Some of these individuals must have been seeded by only a single donor cell (P = 0.1); the frequency of this event was at least 20% (90% confidence) and most likely 50% of the cases. Cell-specific strain markers in myeloid and lymphoid lineages reinforced the likelihood that renewal and differentiation had occurred from a totipotent hematopoietic stem cell. In a smaller W/W group, some hosts were seeded by at most two cells (P = 0.1), and single-cell seeding could not be ruled out. The experiment allows stem cell pedigrees to be examined during the normal developmental progression. In both groups observed here, some mice displayed a regular and complementary rise and fall in proportions of cells of different genotypes, thereby suggesting clonal succession in a hierarchy of stem cell compartments. This transplant system also offers advantages for future experiments on regulated expression in vivo of genes transferred (in vitro) into totipotent hematopoietic stem cells.

Animals↗
PubMed1983

Influence of Sendai virus on carcinogenesis in strain A mice.

An alkylating derivative of a hydrocarbon, 10-chloromethyl-9-chloroanthracene, gave rise to reduced numbers of chemically induced pulmonary adenomas in strain A mice enzootically infected with Sendai virus, while in the case of 7,12-dimethylbenz(a)anthracene, the opposite relationship was observed. Therefore, the presence or absence of viral infection was demonstrated to have a strong influence on carcinogenic susceptibility.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Indications for platelet transfusion in children with acute leukemia.

In an attempt ot determine the indications for platelet transfusion in thrombocytopenic patients, we randomized 56 children with acute leukemia to one of two regimens of platelet transfusion. The prophylactic group received platelets when the platelet count fell below 20,000 per mm3 irrespective of clinical events. The therapeutic group was transfused only when significant bleeding occurred and not for thrombocytopenia alone. The time to first bleeding episode was significantly longer and the number of bleeding episodes were significantly reduced in the prophylactic group. The survival curves of the two groups could not be distinguished from each other. Prior to the last month of life, the total number of days on which bleeding was present was significantly reduced by prophylactic therapy. However, in the terminal phase (last month of life), the duration of bleeding episodes was significantly longer in the prophylactic group. This may have been due to a higher incidence of immunologic refractoriness to platelet transfusion. Because of this terminal bleeding, comparison of the two groups for total number of days on which bleeding was present did not show a significant difference over the entire study period.

Actuarial Analysis↗
PubMed1980

Monte Carlo simulation of particle adsorption rates at high cell concentration.

A practical method of simulating Brownian diffusion of small particles and their adsorption by randomly placed cells is used to estimate the adsorption process rate constant. The ratio of the rate constant to its classical value, 4 pi RD for dilute perfectly adsorbing spheres, is found to be determined by cellular excluded volume. This ratio varies from 1 for dilute solutions of spheres to approximately 40 for spheres in the maximum possible concentration. A function that usefully estimates the rate constant for all possible values of cell concentration, cell radius, and particle diffusion constant is given for random fields of identical spherical cells. The method is also applied to primitive cubic, body centered, and face centered lattices of spheres. At any given excluded volume and concentration the face and body centered lattices have about the same adsorption rate constant whereas the primitive cubic lattices has a smaller one which is, in turn, greater than that for randomly placed spheres. The results will be useful in determining diffusion limited reaction rates under high excluded volume conditions. These include adsorption by red blood cells at normal concentration, the adsorption of molecules by beads in a column, and adsorption of bacteriophage at very high bacterial concentrations.

Adsorption↗
PubMed1980

Nature of the open state in long polynucleotide double helices: possibility of soliton excitations.

The existence of transiently open states in DNA and synthetic polynucleotide double helices has been demonstrated by hydrogen exchange measurements; base pairs reversibly separate and reclose, exposing nucleotide protons to exchange with solvent protons. Recently it has been possible to define the equilibrium, kinetic, and activation parameters of the major open state that determines base pair hydrogen exchange. However, there is no direct information at the moment about the conformation of the open form. Here we consider the possibility that the low energy and slow opening and closing rates observed reflect a deformation involving several adjacent base pairs. Assuming a mobile open unit capable of diffusing along the double helix, we find that available data are consistent with structures of 10 or so adjacent open pairs. It is further suggested that these structures correspond to thermally induced soliton excitations of the double helix, which retain coherence by sharing the energy of a twist deformation among several base pairs. Solitons are nonlinear excitations that can travel as coherent solitary waves, and have been recognized as an important mechanism for mediating conformational changes in polymers and condensed systems generally. Comparison of the double helix with simple mechanical analogs suggests that soliton excitations may well exist within DNA chains, and the present analysis shows that the hydrogen exchange open state is consistent with these.

Base Sequence↗
PubMed1977

Use of specific radioactive probes to study transcription and replication of the influenza virus genome.

Specific radioactive probes have been obtained for both influenza virion RNA (vRNA) and for its complement (complementary RNA or cRNA): 32P-labeled complementary DNA (cDNA) synthesized with the avian sarcoma virus reverse transcriptase, and [125I]vRNA, respectively. From the kinetics of annealing of these two probes to RNA from canine kidney cells infected with the WSN strain of influenza virus, we have determined the average number of cRNA and vRNA sequences in the nucleus and cytoplasm as a function of time after infection. Immediately after infection, a small amount of vRNA is detected, presumably from the inoculum virus. As expected, the amount of cRNA is insignificant. During the first 1.75 h of infection, the most significant increase observed is in cRNA sequences. Most of these cRNA sequences are found in the cytoplasm, but a significant amount (30%) is found in the nucleus. During this time, a small but significant increase in vRNA is also detected in the nucleus and cytoplasm. From 1.75 to 2.75 h, the absolute amounts of both cRNA and vRNA increase, predominantly in the cytoplasm, with cRNA remaining as the majority species. Subsequently, the amount of vRNA increases with respect to cRNA and becomes the majority species. At 3.75 h, 95% of both cRNA and vRNA are found in the cytoplasm. Addition of actinomycin D at 1.75 h completely suppresses the subsequent ninefold increase in cRNA and does not have a significant effect on the subsequent 14-fold increase in cytoplasmic vRNA. This assay is also able to detect the cRNA produced as a result of primary transcription, operationally defined as the cRNA produced in the presence of 100 mug of cycloheximide per ml added at zero time of infection. Increases in cRNA in the presence of cycloheximide are detectable in both the nucleus and the cytoplasm. Addition of actinomycin D as well as cycloheximide at zero time completely suppresses the appearance of cRNA in the cytoplasm, whereas a large fraction (50%) of the increase in nuclear cRNA still occurs.

Cell Line↗
PubMed1976

Height and personality characteristics of 47, XYY males in a sample of tall non-institutionalized males.

A sample of 471 enlisted men 183 cm or taller serving in the US Navy, Coast Guard, and Marine Corps was screened for Y-chromosome aneuploidy by use of quinacrine fluorescence of peripheral blood smears. Two 47,XYY males were detected, resulting in a prevalence of 00425 or approximately 1 in 236. The prevalence of 47,XYY males (00331) in a number of samples of tall, non-institutionalized males is significantly higher than the incidence in newborn males (00061), indicating that 47,XYY males are disproportionately represented in tall male populations. The 47,XYY males had significantly higher scores than 46,XY males on the Schizophrenia, Schizophrenia+1K, and Prejudice scales of the Minnesota Multiphasic Personality Inventory and significantly lower scores on the Dominance scale. Since the probability that a randomly selected pair of subjects in the sample had four or more scale scores significantly different from the remainder of the group was greater than 05, it is possible that the differences between the 47,XYY and 46,XY males occurred by chance. On the other hand, one or more of these scales may measure personality dimensions on which non-institutionalized 47,XYY males may, in fact, differ from 46,XY males.

Adolescent↗
PubMed1975

Susceptibility to persistence of Australia antigen.

To test the hypothesis that liver function is different in populations with inherited susceptibility to persistent Australia antigen (hepatitis B surface antigen [HBsAg]), Sardinians living in Turin, Italy, were compared with their native Turinese neighbors. The study was controlled for age, sex, place of birth, and presence or absence of persistent HBsAg. Slight differences in liver function were found in the Sardinians compared with the Turinese. Their values were in the direction of abnormality. Sardinians also had considerably higher serum gamma-globulin levels than the Turinese. The levels of alpha2-globulin by electrophoresis correlated with the presence of HBsAg.

Alanine Transaminase↗