Search PubMed⌕ Search

Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 1,333 records · Page 74Linked to original sources

Stereochemistry, metabolism, and antitumor activity of 4-hydroperoxyisophosphamide (NSC-227114) and its stereoisomer.

An acid-catalyzed isomerization of 4-hydroperoxyisophosphamide, a synthetic compound with potential antitumor activity, produced a new crystalline epimer having an inverted stereochemistry at the phosphorus atom. The stereochemistry of these epimeric hydroperoxides is discussed on the basis of their chemical and nuclear magnetic resonance properties. The epimers show essentially the same metabolic behavior. This behavior is, however, different from that of isophosphamide (IP) which is metabolized in part via pathways ineffective for its activation. The newly isolated epimer shows slightly higher activity against some kinds of experimental tumors than the original hydroperoxide, suggesting that the inverted stereochemistry of the alkylating group at the phosphorus atom is effective in promoting the antitumor activity of the activated species of IP.

Animals↗

Hypophosphatasia-study on two autopsy cases.

The autopsy findings of two cases of infantile hypophosphatasia are described and compared with those of 16 previously reported cases. Histochemical and biochemical tissue analysis for alkaline phosphatase showed a marked decrease in activity in liver, kidney, and bones. However, intestinal alkaline phosphatase possessed normal or slightly elevated activity. Nephrocalcinosis is a frequent complication and its development depends on hypercalcemia and length of survival of the patient. Electron microscopic findings are illustrated, and a mechanism for the development of nephrocalcinosis is proposed. For the first time, marked elevations of parathyroid hormone was detected. This finding, coupled with the extreme difficulty in locating the parathyroid glands in cases of hypophosphatasia, is enigmatic. Areas for furture investigation are suggested.

Alkaline Phosphatase↗

Antibody production and interaction with lymphoid cells in relation to tumor immunity in the Moloney sarcoma virus system.

The temporal development of antibodies to Moloney sarcoma virus (MSV)-induced antigens in relation to tumor progression was followed with the membrane immunofluorescence (MF) and antibody-dependent normal lymphocyte cytotoxicity (ADNLC) assays. Antibody was detected at 14 days following virus infection by MF. In mice that developed primary tumors which regressed, MF titers developed to high levels following a period between 2 and 4 weeks post-innoculation during which the titers remained at low and constant levels. The increase in MF titers corresponded closely on a temporal basis to the initiation of the regression process. In contrast, antibody remained at low levels in those mice that developed progressively growing tumors. ADNLC was detected in the sera of regressor mice approximately 6 weeks post-inoculation but was not detectable at any of the time interavals in sera from mice with progressively growing tumors. Attempts to enhance the cytotoxic activity of normal spleen cells directly with immune serum were unsuccessful. The synergistic effect of serum on the cytotoxic activity of immune lymphocytes was less pronounced than with normal lymphocytes in this system. Temporal studies indicated that there was an inverse relationship between the development of cellular immunity and the capablility of these cells to be activated in the ADNLC assay.

Animals↗