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Biomedical subjects

R Kleinman

Publications and source records attributed to R Kleinman.

At least 55 records · Page 3Linked to original sources

The use of bacteria as markers of leukemic lymphocytes and for the isolation of natural killer cells.

Human lymphocyte subpopulations as well as leukemic lymphocytes can be identified and enumerated in blood smears by using bacteria that bind spontaneously to lymphocytes or by using bacteria to which antibodies are chemically coupled. The mechanism of natural binding of bacteria to lymphocytes was shown to involve a lectin on the lymphocyte surface and a carbohydrate on the bacteria. Also, we found that natural killer (NK) cells can be separated by negative selection using monolayers of bacteria. A subpopulation of T cells, identified by their binding of B. globigii, was shown to be suppressors for NK cells.

Bacteria↗

Development of gastrointestinal mucosal barrier. I. The effect of age on intestinal permeability to macromolecules.

Indirect evidence has suggested that increased quantities of antigen may penetrate the intestinal mucosa and enter the systemic circulation during the newborn period compared to adult life. However, no direct measurement of macromolecular transport has been reported as a function of perinatal age. To study this process, we administered 100 mg of tritiated bovine serum albumin ([3H]BSA) by gavage to rabbits at birth, one wk, 2 wk, 6 wk, and one year of age and measured plasma radioactivity 4 hr after gavage. Plasma concentration of trichloroacetic acid insoluble radioactivity and immunoreactive bovine serum albumin radioactivity decreased significantly after one wk of age. When adult animals were gavaged with the same amount of [3H]BSA per body weight as the one-wk-old animals, they failed to transport as much of the antigen as the younger animals. This study, therefore, provides objective evidence that the intestinal mucosal barrier of newborns may be incompletely developed at birth and allow increased intestinal transport of antigens into the circulation.

Age Factors↗

Identification and separation by bacterial adherence of human lymphocytes that suppress natural cytotoxicity.

Human lymphocyte subpopulations (B1, B2T1, T2T3, and T4, our denomination) have been previously identified by bacterial adherence, and differences in functions (mitogen responses, specific cytotoxicity, and natural killing activity) have been associated with some of these subpopulations. The natural killing activity (NK) was located in the T4 lymphocyte subpopulation. Here we investigated the possibility that lymphocytes capable of suppressing the NK activity of the T4 cells could be identified and isolated from one of the other lymphocyte subpopulations. Freshly isolated, monocyte-depleted human peripheral blood lymphocyte (PBL) were separated into adherent and nonadherent cells after centrifugation against various bacterial monolayers. The PBL and the resulting subpopulations of PBL were tested as effector cells in a 4-hr cytotoxicity assay against the CEM lymphoblastoid cell line. The addition of viable T2 lymphocytes to either PBL or T4 lymphocytes resulted in a significant decrease in NK activity, whereas no decrease was seen when T1, T1T3, or killed T1T2 cells were added. This decrease in NK activity was not due to a simple dilution of the active NK cells, to alteration of the lymphocytes by their processing on the bacterial monolayers, or to a competition for binding to the target cells. We concluded that the T2 lymphocyte subpopulation contains the cells capable of suppressing the ability of normal human peripheral blood lymphocytes (T4 subpopulation) to perform natural killing.

Binding, Competitive↗

Isolation of human spontaneous killer lymphocytes by bacterial adherence.

Human lymphocyte subpopulations (B, T1, T2, T3, and T4 our denomination) have been identified previously by bacterial adherence and differences between them in mitogen responses and specific cytotoxic activity have been found. In this study another aspect has been investigated in order to find functions associated with these subpopulations, namely the spontaneous killing (SK) ability. Freshly isolated human peripheral blood lymphocytes (PBL) were separated into adherent and non-adherent cells following centrifugation against various bact:rial monolayers. The PBL and the resulting subpopulations of PBL were tested alone or in combination as effector cells in a 4 hr cytotoxicity assay against human lymphoblastoid cel- lines of B or T cell origin. The T3 + T4 cells or T4 cells alone showed a significantly higher SK activity against both B and T target cell lines when compared with unseparated PBL, T1 + T2, or T3 cells alone. Whe Fc portion of IgG, contain the lymphocytes responsible for SK activity and that SK cells can be purified by negative selection using bacterial adherence.

Bacteria↗

Suppression of the humoral immune response by particulate material extracted from spleen cell subpoulations of MOPC-315 tumor-bearing mice.

Particulate extracts were prepared from MOPC-315 plasmacytoma cells, from whole spleen cells or from splenic macrophages of MOPC-315 tumor-bearing mice. These preparations, when injected into normal mice, inhibited their primary humoral immune response to sheep red blood cells (SRBC). At the same time, particulate extracts from whole spleens or splenic macrophages of normal mice and T cell extracts from spleens of MOPC-315 tumor-bearing mice had no effect on the primary immune response to SRBC. The results suggest that phagocytic spleen cells of tumor-bearing mice contain immunosuppressive particles which originate from the tumor cells.

Animals↗

Congenital dislocation of the hip--prognostic implications of early diagnosis.

A retrospective analysis of 62 patients with 78 congenital dislocations of the hip (CDH) referred to Children's Hospital at Stanford was done to ascertain whether CDH was being diagnosed as early as had been thought possible and whether various treatments were effective. In this series there were a substantial number of cases of CDH that were not diagnosed within the first 48 hours of life. At Children's Hospital the Pavlik harness was the most effective form of treatment of congenital dislocations of the hip in the perinatal period.

Female↗

Protection against MOPC-315 plasmacytoma by immunization with C-type particle preparations.

Mice were given injections of C-type particles extracted from the ascitic fluid of plasmacytoma-bearing mice. These particles, extracted from MOPC-315 tumor-bearing mice and injected into BALB/c mice, protected them against challenge with MOPC-315 tumor cells. The protection was dependent upon tumor cell dose; 66% survival was observed with a lethal dose of tumor cells. No protection was observed against challenge with another plasmacytoma (S13). Attempts to protect mice against S-13 plasmacytoma by immunizing them with C-type particles originating from S-13 tumor-bearing mice were unsuccessful.

Animals↗

An improved quantitative plaque assay for lymphocytes bearing antigen-specific cell receptors.

An improved method for the determination of the number of lymphoid cells bearing antigen-specific receptors is described. The method is based on the use of hapten-coupled bacteriophage (dinitrophenyl-T4) and detection of lytic plaques formed by the action of DNP-T4 on a target E. coli strain. The method is highly specific (up to 90% specific binding) and can be adapted for use with other antigenic determinants chemically attached to an active bacteriophage.

Animals↗

RNA-instructed DNA polymerase associated with C-type particles produced in vivo by murine myeloma cells.

C-type particles secreted in vivo by MOPC-315 myeloma cells were characterized. These particles localize at a density of 1-16 g/ml in sucrose and possess a 60 to 70S RNA and an RNA-instructed DNA polymerase. Endogenous enzyme activity requires manganese and is inhibited by ribonuclease or by the omission of any of the deoxynucleoside triphosphates. The enzyme utilizes the virus 60 to 70S RNA as a template to synthesize DNA molecules which specifically hybridize to the homologous RNA.

Animals↗