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Biomedical subjects

R Abe

Publications and source records attributed to R Abe.

At least 343 records · Page 19Linked to original sources

'Two-route chemotherapy' using intra-arterial cisplatin and intravenous sodium thiosulfate, its neutralizing agent, for hepatic malignancies.

Seventeen patients with primary or metastatic malignancy in the liver were treated with 'two-route chemotherapy' (TRC). One course of this TRC consisted of hepatic artery infusion of cisplatin, 120 mg/m2, in combination with concurrent intravenous administration of sodium thiosulfate, its neutralizing agent, at a dose of 9.0 g/m2 by a rapid push, followed by 1.2 g/m2/h by continuous infusion for 6 h. Five of 11 (45%) hepatocellular carcinoma and two of six (33%) metastatic tumors achieved partial response. Although almost all patients experienced nausea or vomiting, severe side-effects, including nephrotoxicity, peripheral neuropathy or ototoxicity, were not encountered. Myelosuppression was observed in one patient after seven courses of this TRC. The results indicate that TRC may be relatively effective against hepatic malignancies in patients without severe toxicity.

Aged↗

Ferrokinetic evaluation of erythropoiesis in patients with myelodysplastic syndromes.

Erythropoietic activity in patients with myelodysplastic syndrome (MDS) was evaluated by ferrokinetic measurements. Since the conventional plasma iron turnover of MDS patients increased with plasma iron levels after multiple blood transfusions, erythron transferrin uptake was chosen as a parameter of erythroid marrow activity. Although a correlation was shown between plasma iron level and plasma iron turnover (r = 0.50, 0.01 less than p less than 0.02), no correlation existed between the plasma iron level and erythron transferrin uptake (r = 0.25, p greater than 0.1). Erythron transferrin uptake, independent of plasma iron, was significantly higher in MDS patients than in normal subjects (110.6 +/- 67.6 and 67.6 +/- 18.8 mumol/l/dl, respectively; 0.01 less than p less than 0.02). An increased erythropoiesis occurring concomitantly with morphologically normal or increased erythroid cellularity was demonstrated in patients with MDS. The measurement of erythron transferrin uptake might be valuable as an accurate expression of erythroid activity in the hyperferremic state.

Erythropoiesis↗

Apolipoprotein E phenotypes of normo- and hyperlipoproteinemia in Japanese.

Apolipoprotein E phenotypes of normo- and hyperlipoproteinemia in Japanese were examined by the disc gel isoelectric focusing technique, which was modified according to the method of Kashyap et al. (1981). Apoprotein E isoproteins were clearly separated by this method. Six phenotypes (E2/2, E3/3, E4/4, E2/3, E2/4 and E3/4) were determined in 107 cases of normolipoproteinemia and 75 cases of hyperlipoproteinemia. In normolipoproteinemia, apoE phenotype frequencies were similar to those of the Japanese and Caucasian populations which were reported previously. In hyperlipoproteinemia, a higher frequency of phenotype E2/2 and a lower frequency of E3/3 were observed. The apo E phenotypes of type IIa and IIb were distributed similarly to that of normal subjects. In contrast, only 27.8% of type IV patients had E3/3 phenotype. Among type V patients 64.3% was homozygous or heterozygous for E-4, and only 14.3% was homozygous for E-3 (E3/3). The results suggest that the apolipoprotein E phenotypes are similarly distributed among different human races and the apolipoprotein E phenotypes could be one of the etiological factors associated with some types of hyperlipoproteinemia.

Adult↗

[Cooperative research on post-operative adjuvant therapy of breast cancer. Tohoku Society of Adjuvant Chemo-endocrine Therapy of Breast Cancer].

A randomized trial was carried out in 55 institutes in the Tohoku district to examine the significance of breast cancer post-operative adjuvant chemo-endocrine therapy in stage II and IIIa patients for possible radical mastectomy. A total of 619 patients were entered from November 1982 to November 1984, of whom 554 were eligible. Patients were administered MMC 13 mg/m2 after surgery, and randomized using the envelope method into either group A, treated with Tegafur 400 mg/m2 alone (275 patients), or group B, treated with Tegafur 400 mg/m2 and Tamoxifen 20 mg/daily (279 patients), for a year from the 7th day after operation. There was no significant difference between the two groups in the background factors of age, menopausal status, operation methods, stage or number of positive lymph nodes, but there were more patients of ER(+) in group B. A Kaplan-Meier method comparison showed no significant difference between the two groups in 3-year disease-free survival rates. There was no significant difference between the two groups compared by ER or menopausal status. However, patients with 4 or more positive lymph nodes showed a significant benefit in group B. Group B also marked a higher disease-free survival rate for ER(+) patients with 4 or more positive lymph nodes.

Antineoplastic Combined Chemotherapy Protocols↗

Mls is not a single gene, allelic system. Different stimulatory Mls determinants are the products of at least two nonallelic, unlinked genes.

Mls determinants share with MHC products the unique property of stimulating T cells at extraordinarily high precursor frequencies. The Mls system was originally described as a single locus on chromosome 1, with four alleles, Mlsa, Mlsb, Mlsc, and Mlsd, that encode polymorphic cell surface structures. However, the fundamental issues of polymorphism and allelism in the Mls system remain controversial. To clarify these questions, a formal segregation analysis of the genes encoding Mlsa and Mlsc determinants was carried out by testing the capacity of spleen cells from progeny of (Mlsa X Mlsc)F1 X Mlsb breedings to stimulate responses by unprimed T cells and by Mlsa- and Mlsc-specific cloned T cells. The results of this analysis indicated that the gene encoding Mlsa determinants is neither allelic to nor linked to the gene encoding Mlsc determinants. Together with previous findings, these results also suggest that another strongly stimulatory type, Mlsd, in fact results from the independent expression of unlinked Mlsa and Mlsc gene products. Based on these observations, it is concluded that, contrary to conventional concepts, the stimulatory phenotypes designated as Mlsa, Mlsc, and Mlsd can be accounted for by the independent expression of the products of at least two unlinked gene loci.

Alleles↗

MHC-restricted minimal regulatory circuit initiated by a class II-autoreactive T cell clone.

The in vivo administration of a self-class II-reactive Th clone MS202 derived from C3H into syngeneic mice resulted in the suppression of both primary and early secondary antibody responses against T cell-dependent antigens. The suppression was due to the generation of antigen-nonspecific Ts cells in the recipient, as the splenic T cells from the mice treated with MS202 were able to strongly suppress the in vitro secondary antibody response of primed syngeneic spleen cells. The dose-response curve of suppression indicated the generation of an effector type Ts that directly suppressed Th. The surface phenotype of Ts was Ly-1+,2-, L3T4+, I-J-. The presence of Ly-1+,2+ T cells was not required to induce the suppression. The suppression was strictly restricted to H-2k, as F1 Ts cells were able to suppress the response of C3H but not of B6 B cells helped by the same F1 Th cells. The experiments with chimeric mice indicated that the direct target of Ts is an MHC-restricted Th but not a B cell or APC. The results indicate the existence of a minimal regulatory circuit where an MHC-restricted Th induces a preprogrammed Ts that in turn directly suppresses Th with the same MHC-restriction specificity. The induction of and suppression by Ts appeared to be due to the direct recognition of MHC restriction sites of Th cells.

Animals↗

Epitopes associated with the MHC restriction site of T cells. I. Selective expression of Iat epitopes on H-2-restricted helper T cells.

We previously established monoclonal antibodies (mAb) that are putatively directed to the I region of H-2k but are reactive only with T cells. Because of their specificity to the unique epitopes different from class II antigens, they are designated as anti-Iat reagents. The present study demonstrated that these anti-Iat inhibit the H-2k-restricted helper T (Th) cell function by acting on the very H-2 restriction site of both H-2k and H-2kxb F1 T cells. This was determined by both the cytotoxic treatment and blocking of antigen-primed Th cells. In the F1 Th population, only those restricted to H-2k were eliminated, leaving the H-2b-restricted Th cells uninhibited. The inhibition of the response was not due to the induction of suppressor T cells, but to the elimination of the function of radioresistant Lyt-1+,2- Th cells. Iatk epitopes were also found on an H-2k-restricted but not on H-2b-restricted Th cell clone established from the same H-2kxb F1 animal. None of the anti-Iatk were reactive with class II antigens on B cells. These results indicate that Iat epitopes are not directly encoded by the I region genes, but are associated with the H-2 restriction site of T cells, which see the self class II polymorphism. Thus, Iat epitopes are expressed clonally in high frequency on H-2k-restricted Th cells of F1, being excluded from the H-2b-restricted Th population. The relationship between Iat and T cell receptor molecules is unknown.

Animals↗

Clonal analysis of the Mls system. A reappraisal of polymorphism and allelism among Mlsa, Mlsc, and Mlsd.

Only two sets of antigenic determinants are recognized by T lymphocytes at uniquely high precursor frequencies: those encoded by the MHC and those encoded by Mls. The structural as well as functional characteristics of MHC products have been extensively analyzed. In contrast, little information concerning the nature of Mls genes or their products is available. Although it was originally described (5, 6) that the Mls locus on chromosome 1 is composed of four alleles that encode polymorphic cell surface structures, the issues of polymorphism and allelism in the Mls system have been controversial for some time. In the present study, T cell clones were generated by continuous stimulation of B10.BR (H-2k, Mlsb) T cells by CBA/J (H-2k, Mlsd) stimulators and they were used to analyze the relationship of putative Mlsa, Mlsc, and Mlsd determinants. All clones proliferated in response to determinants expressed by CBA/J stimulators. In addition, each of these clones exhibited a second reactivity to either AKR/J (H-2k, Mlsa) or C3H/HeJ (H-2k, Mlsc) stimulators. No clone responded to both AKR/J and C3H/HeJ. These second specificities were defined to be for Mlsa or Mlsc determinants, respectively, by the response patterns of clones and unprimed T cells to stimulators derived from congenic strains, recombinant inbred (RI) strains, and backcross mice. Moreover, a segregation analysis of the (CBA/J X B10.BR)F1 X B10.BR backcross indicated that the Mlsa-like and Mlsc-like determinants expressed on CBA/J (Mlsd) cells are in fact encoded by nonallelic, unlinked genes. These findings suggest a new concept of the polymorphism and genetics of the Mls system. It is proposed that two distinct and nonallelic gene products express, respectively, the noncrossreacting Mlsa and Mlsc determinants, and that the Mlsd phenotype does not represent an independent genotype but rather reflects the concurrent expression of Mlsa and Mlsc. The Mls system, therefore, consists of at least two systems that are distinct both genetically and antigenically, and that may be of different biologic or physiologic significance as well.

Alleles↗

T cell recognition of Mls. T cell clones demonstrate polymorphism between Mlsa, Mlsc, and Mlsd.

The determinants encoded by the minor lymphocyte stimulating locus (Mls) are defined as determinants that induce strong T cell proliferative responses in primary mixed lymphocyte reactions. Although the Mls locus was originally described as having four alleles, a, b, c, and d, a number of recent observations have led several investigators to challenge the idea that Mls is truly a polymorphic system. To better define this system of determinants recognized at high frequency by T cells, the present studies were undertaken to evaluate the polymorphism of Mls products. In the present study, the in vitro proliferative responses of Mlsa- and Mlsc-specific T cell clones were employed to analyze Mls products. The identification of determinants recognized by Mlsa- and Mlsc-reactive clones was established by the pattern of responses to stimulators derived from congenic strains, recombinant inbred strains, and backcross mice. T cell clones and unprimed T cells gave concordant responses that confirmed the Mlsa or Mlsc specificity of the cloned populations. With the use of these two sets of Mls-specific T cell clones, the existence or absence of polymorphism of Mls-encoded gene products was examined. It was found that Mlsa-specific cloned T cells responded to Mlsa but not Mlsc stimulators, whereas Mlsc-specific clones responded to Mlsc but not Mlsa. This reciprocal pattern of specificity indicates that the Mls system as currently defined is therefore truly polymorphic. In addition, it was observed that both Mlsa- and Mlsc-specific clones were stimulated by Mlsd stimulators. In particular, the possibility that Mlsa and Mlsc are not alleles but products of different loci and that Mlsd strains are those that express both Mlsa and Mlsc is considered.

Animals↗

Shared idiotopes between anti-class II monoclonal antibodies and major histocompatibility complex recognition site of T cells.

We have raised a number of monoclonal antibodies (mAb) against idiotopes (Id) on monoclonal anti-murine class II (anti-Ak or Ek) antibodies. Two anti-Id mAb among 31 were found to cross-react with some T cells but not with macrophages and B cells of H-2k animals. They were able to block syngeneic mixed lymphocyte reaction (SMLR) and antigen-induced major histocompatibility complex (MHC)-restricted T cell proliferation of H-2k but not of other haplotypes. These results indicated that antibodies were recognizing Id associated with the MHC restriction site of T cells. The injection of these anti-Id mAb into H-2k mice resulted in the stimulation of self-class II-reactive T cell clones as determined by SMLR. They were also able to stimulate in non-H-2k strains to prime H-2k alloreactive T cell clones. Some animals developed anti-class II (anti-Iak) antibodies by the injection of anti-Id. These results indicated that certain anti-Id (anti-anti-class II) antibodies cross-reacted with T cell receptors which carried class II restriction specificity and were involved in allorecognition. These antibodies were found to have an ability to alter the T cell repertoire in vivo by stimulating such MHC-restricted clones.

Animals↗

Flow cytometric analysis for assessing the malignant potential of breast cancer.

Flow cytometric analysis was performed on 60 patients with breast cancer to investigate the relationship between DNA histogram and the malignant potential of breast cancer. DNA aneuploidy of breast cancer tended to increase with increasing stage and degree of nodal metastasis. The percent of cells in the S phase was significantly increased in the patients with metastasis compared to those without metastasis. Patients exhibiting percent S phase value of more than 20% showed a high frequency of metastasis even when breast tumors were small (T1, less than 2.0 cm in diameter). Thus, flow cytometric analysis may give additional information on biological characteristics and may be useful for predicting the prognosis of breast cancer in some patients.

Adult↗

Mobile unit for use in mass screening for breast cancer.

Since 1977, mass screening for breast cancer has been carried out in Miyagi prefecture, Japan. The main activities involve itinerant screening in the communities and group screening at the workplaces. The first step in this screening is the physical examination; the second step, for women with suspicious findings, is examination by mammography and ultrasonography, in a specially equipped mobile unit. The number of subjects screened over a seven-year period ending in March, 1984, was 94,953. Mammography was performed on 4,485 subjects (4.7 per cent) Breast cancer was detected in 116 subjects (0.12 per cent). Since 1980, 2,292 high risk subjects have undergone mammography as the first step screening. The detection rate (0.35 per cent) for this group was higher than for the general subjects examined. Therefore, mammography performed in a mobile unit is a suitable approach for the detecting and diagnosing of breast cancer.

Breast Neoplasms↗