Biomedical subjects

R N Hiramoto

Publications and source records attributed to R N Hiramoto.

9 recordsLinked to original sources

PubMed1979

Age related changes in auto-erythrocyte rosettes in the C57BL/6J and NZB/BINJ mice.

The changes in the auto-erythrocyte rosetting thymic and splenic lymphocytes and the induction of autoimmunity was followed with age in C57BL/6J and NZB/BINJ mice. The auto-erythrocyte rosetting cells (auto-RFC) showed shifts in their pattern in both thymus and spleen in C57BL/6J and NZB/BINJ mice. Both strains had approximately the same percentage (approximately 3%) of thymic auto-RFC at 1 month of age. In C57BL/6J mice the rosette population increased to 6.6% by 2 months, declined after 3 months and subsequently increased gradually with age. In contrast, the NZB/BINJ thymic auto-rosettes peaked at 4 months and gradually declined thereafter. Both the NZB/BINJ and C57BL/6J strains were tested for the presence of anti-erythrocyte antibodies by the direct Coombs' agglutination test. The results showed that at 6 and 10 months 50% and 90% of the NZB/BINJ mice were positive for antibodies, respectively, and the thymic and splenic auto-RFC dramatically decreased in numbers. In the C57BL/6J mice during this same period, very low incidence of auto-antibodies was detected by the Coombs' test and auto-RFC increased in numbers.

Aging↗

PubMed1979

Sequential appearance of auto-erythrocyte antibody immunoglobulin classes with age.

The autoimmune, short-lived, NZB/BINJ mice were followed for the changes taking place in the number of thymic and splenic nucleated cells from day 1 up to 12 mo of age. The long-lived C57BL/6J mice were monitored in parallel with the NZB mice to see whether similar changes were reflected. Both strains of mice were investigated for the sequential appearance of anti-erythrocyte autoantibody classes by the direct Coombs' agglutination test. IgG1 was the first class of antibody detected on the erythrocytes and was followed by IgG3, IgG2 and IgA, simultaneously. IgM was the last antibody to react with erythrocytes. The C57BL strain had a very small number of mice with low levels of IgG1 antibody on erythrocytes throughout the study.

Aging↗

PubMed1979

Endotoxin toxicity in rats with 6-sulfanilamidoindazole arthritis.

Seven oral administrations of 6-sulfanilamidoindazole (6-SAI) to 10- to 12-month-old rats sensitized the animals to endotoxin, with dosages as small as 2.5 microgram causing death in 80% of animals. Endotoxin in a dosage of 3,000 microgram was not lethal for nonmedicated control animals. 6-SAI-treated 1-month-old rats were not as sensitive to endotoxin as aged animals. The sulfonamide-induced sensitivity to endotoxin could not be passively transferred and could not be explained by blockade of the reticuloendothelial system or impairment of endotoxin detoxification. 6-SAI administration was associated with both depletion of liver glycogen and lowering of blood glucose concentration without changes in blood lactic acid concentration. Disseminated intravascular coagulation is believed to be involved in the pathogenesis of shock and death as evidenced by: (i) concomitant decreases in plasma fibrinogen concentration and elevations in fibrin degradation products after endotoxin challenge; (ii) protection against lethal actions of endotoxin by pretreatment with heparin. Treatment of 6-SAI-medicated rats with glucocorticoids before endotoxin challenge protected the animals against lethal doses of endotoxin and prevented deposition of fibrin thrombi in the glomerular capillaries.

Aging↗

PubMed1979

A methodological approach to the prediction of anticancer drug effect in humans.

Tumor cells from animals and humans were treated with drugs under tissue culture conditions. Tumor cells from the sensitive L1210 model were studied first. A dose-response curve was derived between drug exposure and subsequent cytotoxicity in L1210. The concentration of drug and duration of exposure were factors critical to the subsequent development of in vitro cytotoxicity. The in vitro dosage which effected 50% leukemic cell death in L1210 cells correlated with reported in vivo drug levels. Other tumor models and human neoplastic cells were studied at this dosage level. A good correlation was noted in these studies between the in vivo responsiveness and the in vitro chemotherapy results in both animals and humans. It was suggested by these results that it may be possible to predict cancericidal drug activity for individual neoplasms by assaying the tumor cells in vitro for drug sensitivity.

Animals↗

PubMed1978

Age dependent reaction of mouse thymus cells with autologous and syngeneic erythrocytes.

The age dependent events influencing the rosette forming capacity of Balb/c thymus and spleen cells against autologous or syngeneic erythrocytes were examined. A large number of autologous and syngeneic rosette forming cells (RFC) were observed in normal Balb/c mice in vitro. RFC were significantly greater in the thymus than in the spleen. The rosette forming T-cells (T-RFC) have the following characteristics: newborn Balb/c thymus has T-cells which react syngeneic erythrocytes from older donors. The T-RFC showed broad cross-reactivity with erythrocytes from other mouse strains but low reactivity with human or sheep erythrocytes. The auto and syngeneic T-RFC could be enhanced by non-specific serum proteins (FCS or BSA) or EDTA but was effectively inhibited by normal mouse serum. T-RFC resided in the cortisone sensitive population. The data indicate that the development of autologous and syngeneic rosette formation of thymus cells is dependent on the age of the erythrocyte donor. The age dependent change on the erythrocyte surface occurred relatively early in the life of the animal. The results also imply that certain subpopulations of thymus lymphocytes are capable of recognizing possible surface antigenic changes of the erythrocytes.

Aging↗

PubMed1978

Tumor immunology of experimental osteosarcoma.

A spontaneous AP positive C3H murine OS was used to determine the effects of various treatment modalities. AP served as a useful circulating biomarker of the in vivo tumor growth. In animals whose tumor was amputated, the elevation of the marker indicated the presence of pulmonary metastases. It was used to establish the time of recurrence after a partially effective chemotherapy or combination modality. In this model, when the neoplasm was surgically excised at 10 days posttransplantation, 70--80% of the mice showed presence of lung metastases. Specific immunotherapy with irradiated tumor cells did not alter the course of the disease. Passively transferred immune allogeneic cells to tumor bearing mice at an effector to target cell ratio of 1:1 in vivo were ineffective. The murine OS model is extremely useful to plan and institute different combinations of treatment modalities and optimize the conditions for an effective treatment in a relatively short time.

Alkaline Phosphatase↗

PubMed1977

Autoimmune disease antigens.

The first step towards understanding the cellular interaction which results in autoimmune disease is to determine what triggers the recognition between a specific autoimmune antigen determinant and the cellular receptor. In this review, we have focused on the antigen inducing experimental allergic encephalitis (EAE) because the antigen has been characterized and a relatively large body of information on its biological activities has been accumulated. Clearly, a specific allergic encephalitis-producing determinant is present and is represented on a relatively small portion of the molecule. The determinant induces a wide variety of biological reactivities, some of which are classed as cellular mediated. An attempt is made to dissect activities such as blast transformation (BT), migration inhibitory factor (MIF), in vivo delayed type hypersensitivity reaction (DTH) and EAE and to relate them to the structural requirements which the determinants possess. The complexities which arise indicate that subpopulations of cells with different receptor activities may respond selectively and that recognition of the receptor is produced by an EAE determinant consisting of three amino acids in a specific linear sequence. Furthermore, under experimental circumstances the EAE activity can be dissociated from the other activities (BT, MIF, DTH), indicating that while these tests are used generally to follow various human autoimmune disease activities, they may represent the reaction of a broad spectrum of cells.

Amino Acid Sequence↗

PubMed1977

An experimental approach to relate a tumor-associated enzyme marker to tumor cell numbers.

Alkaline phosphatase was monitored in 17 mice with s.c.-implanted tumors to relate the total circulating alkaline phosphatase to the total number of tumor cells in each mouse. There was a semilogarithmic relationship between the alkaline phosphatase units and the number of tumor cells. A time-independent standard plot of alkaline phosphatase and the number of tumor cells was used to estimate the size of disseminated and localized tumors. In animals treated with cyclophosphamide, the alkaline phosphatase marker was used to monitor the regression and recurrence of the neoplasm in vivo.

Alkaline Phosphatase↗

PubMed1977

cis-dichlorodiammineplatinum(II) chemotherapy in experimental murine myeloma MOPC 104E.

Data are presented indicating marked antineoplastic activity for cis-dichlorodiammineplatinum(II) in MOPC 104E myeloma. One-eighteenth of the dose that produced 100% cures can be combined with noncurative, low doses of cyclophosphamide and 1,3-bis(2-chloroethyl)-1-nitrosourea to produce antineoplastic activity of the same degree as that produced by much higher dose regimens which regularly produce cures. Since, in the past, results of therapeutic trials in plasma cell tumors in humans have paralleled results in this animal model, clinical trials of cis-dichlorodiammineplatinum in multiple myeloma appear warranted.

Animals↗