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Biomedical subjects

M Kasai

Publications and source records attributed to M Kasai.

At least 415 records · Page 23Linked to original sources

[T cell leukemia antigens, FT-1 and FT-2].

The understanding of the differentiation process of lymphocytes in the embryonic thymus has been based on extrapolation from adult thymic lymphocytes. The study presented here was mainly concerned with the new cell surface antigens designated FT (FT-1, FT-2), which are expressed on fetal thymocytes of all mouse strains examined, but not on thymocytes or any other lymphoid cells of adult mice. One of the interesting features of FT antigens is the timing of their expression in connection with the ontogeny of thymic lymphocytes. A majority of fetal thymocytes at the 13th day of gestation express FT antigens, whereas no positive cells are found in fetal liver. Therefore, FT antigens seem to appear as soon as the stem cells have reached the thymus. The proportion of FT+ cells then declines sharply with increase in the time of gestation, while Thy-1+ cells increase in inverse proportion. All of these results seem to support the idea that the thymocytes expressing FT antigens are replaced with Thy-1+ thymocytes, although the possibility of the transition from FT+ to Thy-1+ cells cannot be excluded. It was also demonstrated that fetal thymocytes are heterogeneous with respect to the expression of FT-1 and FT-2 antigens. Especially, thymic lymphocytes at the earlier stages of ontogeny can be divided into at least three subpopulations, FT-1+2+, FT-1+2- and FT-1-2-. With the emergence of Lyt antigens, these subpopulations seem to differentiate and acquire far more complicated features. Such cellular heterogeneity probably reflects the complexed events like selection, deletion or amplification occurring in the embryonic thymus. Another interesting aspect of FT antigens is their reappearance on the surface of thymic leukemia cells. Biochemical studies have indicated that the molecular weight of FT-1 antigen on leukemia cells is about 100,000 by means of biosynthetic labeling with either [3H]-galactose or [35S]-methionine. FT-1 antigen on fetal thymocytes also appeared as a major band with m.w. 100,000. Two-dimensional gel electrophoresis revealed that FT-1 antigenic determinants appear to reside on a family of glycoproteins with extensive charge heterogeneity. All of these results suggest that FT antigens, especially FT-1 antigen, will be useful markers for understanding the mechanism underlying the activation of normally silent genetic information in leukemia cells. In summary, further biochemical and genetic analysis of FT antigens will contribute to an understanding of the ontogenic development of T cells as well as the leukemogenesis of T cell leukemias.

Animals↗

[Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group].

A randomized study of mitomycin C (MMC)+5-FU [control group] vs MMC+5-FU+lentinan (LNT) [LNT group] was conducted in order to evaluate the effect of LNT against advanced gastric and colorectal cancers by the envelope method in 166 patients, comprising of 115 cases of gastric cancer and 51 cases of colorectal cancer. Significant increases were observed in the survival rates for the LNT group (p less than 0.05) for both patients with gastric and colorectal cancer. No significant difference was observed in response rates between the aforesaid two groups, though the response rate in the LNT group was slightly higher than the control group. These results suggest that LNT in combination with anticancer drugs prolong the survival time of patients with advanced gastric and colorectal cancer.

Adult↗

[Prevention of cancer chemotherapeutic agent-induced toxicity in postoperative breast cancer patients with glycyrrhizin (SNMC)].

It is well known that all cell lines, normal as well as malignant, have a sensitivity to the growth inhibitory effect of IFN or IFN inducers. We speculated that the antiproliferative effects of the IFN inducer SNMC might help alleviate the uncomfortable side effects of cancer chemotherapeutic agent. Fifty-seven patients with postoperative breast cancer received MMF (mitomycin, methotrexate, futraful therapy with SNMC and 60 were given MMF alone. There was only one patient (1.7%) in the former group in whom the MMF chemotherapy was discontinued because of liver dysfunction; however, 15 patients (25%) in the latter group had to stop the therapy because of its side effects. Thus, there was a significant effect of SNMC in preventing the side effects of MMF chemotherapy.

Adult↗

Assessment of host immune response in breast cancer patients.

Cell-mediated immune status of breast cancer patients was evaluated by percentage of T gamma cells, natural killer (NK) activity, and the augmentation of NK cells by interferon. The patients with breast cancer did not show impaired cell-mediated immune responses until they were in the late stage of cancer. Sixty-one patients with breast cancer revealed higher proportions of T gamma cells measured by a new method utilizing microplate compared with those of 50 healthy subjects. Reduced NK activity was seen in the patients with stage III or IV breast cancer. Natural cytotoxicity against K-562 target cells was strongly augmentated by treatment with interferon in vitro for 2 hr, both in the patients with breast cancer and in healthy donors, except for far advanced breast cancer patients. A negative correlation between the percentage of T gamma cells and T cell was significant in the patients with primary breast cancer prior to radical mastectomy.

Adult↗

[Modified radical mastectomy and lymphocyte subsets of regional lymph nodes].

Whether or not regional lymph nodes in tumor-bearing hosts possess special immunological properties, still remains an important problem in the management of breast cancer. Regional lymph node cells from 22 patients with breast cancer were immunologically studied using monoclonal antibodies, OKT-3, 4, 8, OK-M 1, Leu-7, and laser flow cytometry. Among these patients, 13 early cancer patients underwent modified radical mastectomy (Auchincloss operation or Patey operation) and 9 underwent standard radical mastectomy (resection of breast, pectoralis major muscle and axillary dissection). More helper T lymphocytes defined by OKT-4 were found in regional lymph nodes in modified radical mastectomy patients in comparison with standard radical mastectomy patients. In patients given the modified operations, NK activity defined by OK-M 1 or Leu-7 were significantly increased, especially in lateral axillary lymph nodes. Also, OK-M 1 lymphocytes and Leu-7 lymphocytes were increased in lymph nodes without metastasis rather than those with metastasis. These findings suggest that regional lymph nodes may have defence mechanisms against the spread of tumor cells in early cancer patients.

Axilla↗

[Modulation of the anti-tumor effect of BRM under various nutritional or endocrine conditions].

Immuno-chemotherapeutic effects on the growth of MM-48 mammary tumor were studied in syngeneic C3H/He mice fed diets containing a low (D), normal (N) or arginine-supplemented (NA) protein content. The serum protein levels were 5.7 g/dl in N-mice and 3.7 g/dl in D-mice, respectively. On the other hand, no difference was seen between the two groups, with regard to intra-tumoral protein concentrations. The natural killer (NK) activity of spleen cells was significantly lower in D-mice than in N-or NA-mice. Augmentation of NK activity was detected following the i.p. injection of OK-432 or LENTINAN, while no augmentation was recognized in D-mice. Interferon production of cultured spleen cells was significantly reduced in D-mice, and significantly increased in NA-mice compared with N-mice. NK activity was markedly augmented at 7 days after bilateral oophorectomy in N-mice. Both NK and IFN titers were significantly reduced following administration of estradiol every 7 days. The growth of MM-48 tumor was inhibited by daily administration of OK-432 or LENTINAN in N-mice. However, the tumor growth was paradoxically accelerated after administration of the same drugs in D-mice. These findings indicated that the nutritional or endocrine environment of cancer-bearing mice plays an important role in the effect of some kinds of BRMs. A clinical randomized study of advanced and recurrent gastric cancer patients treated with MMC and FT (MF) with or without LENTINAN, was then performed. We recognized excellent end-point results only in LENTINAN-administered patients with normal protein levels, while no effect of LENTINAN was seen in patients with low protein levels (below 6.0 g/dl).

Animals↗

Reconstruction using pedicled jejunal segments after resection for carcinoma of the cervical esophagus.

During the past 21 years, 45 (76.3 per cent) of 59 instances of cervical and hypopharyngeal carcinomas were treated by resection. The standard operative procedure for reconstruction after resection was interposition of pedicled jejunal segments between the cervical esophagus or the hypopharynx and the upper part of the thoracic esophagus with or without total laryngectomy, a procedure developed by one of the authors. The five year survival rate of 11 patients who underwent this operation which preserves the larynx was 33.3 per cent and that of 19 patients who underwent the operation with laryngectomy was 19.7 per cent. Therefore, the interposition of jejunal segments preserving the larynx is shown to be an appropriate operation for carcinoma localized in the cervical esophagus. In addition, reconstruction with free jejunal segments using microvascular operations in instances of recurrent malignant tumors of the thoracic esophagus in the cervical esophagus is introduced.

Adult↗

[Phase II study of cisplatin in esophageal carcinoma].

A multi-institutional cooperative phase II study of Cisplatin for esophageal carcinoma was conducted. Cisplatin was administered by i.v. infusion at 10-20 mg/m2 body surface area daily for 5 days and repeated every 3-4 weeks (method A) or at 50-100 mg/m2 body surface area once every 3-4 weeks (method B). Out of 78 cases entered, 47 were evaluable. No complete response (CR) was obtained and partial responses (PR) were observed in 10 cases, the overall response rate being 21.3%. Response rates by administration methods A and B were 12.5% and 25.8%, respectively. Responders to treatment exhibited significantly longer survival periods compared to non-responders (p less than 0.05, generalized Wilcoxon test). Major adverse reactions were gastrointestinal symptoms, generalized malaise, bone marrow suppression and renal disorders. One case of leukopenia leading to eventual death from pneumonia was observed.

Adult↗

[Phase II study of THP (2''R)-4'-0-tetrahydropyranyladriamycin) in breast cancer].

In a phase II study of THP, fifty-six patients with advanced or recurrent breast cancer were evaluated, and a response rate of 23.2% including 1.8% with complete response and 21.4% with partial response, was obtained. Response rates of THP varied according to the location of metastasis and the highest rate was shown to be 38.5% in patients with soft tissue metastasis. The median dose for inducing response was 100 mg with a range from 60 mg to 160 mg. Toxicities such as leukopenia and gastrointestinal disorders were observed during THP treatment. The favorable response to THP was close to that of adriamycin, but it was noteworthy that a lower frequency of alopecia occurred.

Adult↗

FT-2 antigen for distinguishing lymphocyte subpopulations in the developing thymus.

The surface phenotypes of lymphoid cells in the developing embryonic thymus were characterized by using monoclonal antibodies. FT-2 antigen thus defined was predominantly expressed on thymocytes in the earlier embryonic stages in all the inbred mouse strains tested. The immunofluorescence and immunoperoxidase tests indicated that, like FT-1 antigen, the proportion of FT-2+ fetal thymocytes rapidly decreased with increase in gestation time, and these cells disappeared by day 19 of gestation. The treatment of fetal thymocytes with anti-FT-1 plus complement eliminated not only FT-1+, but also FT-2+ cells, whereas the treatment with anti-FT-2 failed to eliminate approximately 40% of FT-1+ cells, suggesting that embryonic thymocytes can be provisionally divided into at least three subpopulations, FT-1+2+, FT-1+2- and FT-1-2-.

Animals↗

Reoperation in patients with biliary atresia.

Twenty-seven reoperations were done on 23 patients among 100 infants with biliary atresia who have been treated at Tohoku University Hospital between 1971 and 1981. Nineteen patients had a single reoperation and 4 patients had 2 reoperations. We present the results and the role of reoperation in biliary atresia patients in our institution. Excellent bile drainage after reoperation was obtained in 13 of 15 patients with good bile flow after the initial operation. On the contrary, good bile drainage was not obtained by reoperation in 8 of 12 cases without active bile flow after the initial operation. Cessation of bile flow after successful initial operation is an absolute indication for reoperation. Aggressive reoperations under proper indications improve the surgical results in biliary atresia patients.

Age Factors↗

Changes of intrahepatic bile duct dilatation after surgery for congenital dilatation of the bile duct.

Of 47 patients suffering from congenital dilatation of the bile duct whose intrahepatic bile ducts could be clearly demonstrated by operative cholangiogram or preoperative ERCP, 39 patients (83%) had dilatation of the intrahepatic bile ducts. Follow-up studies in infants and children ranging from 1 year to 11 years after their corrective operation for congenital dilatation of the common bile duct showed no morbidity that was attributed to the presence of the dilatation of the intrahepatic bile ducts. ECHO grams in 21 patients revealed marked decrease in size of the intrahepatic bile ducts except for two patients with huge cystic dilatation of the intrahepatic bile ducts. These findings justify the employment of the standard operative procedure for the treatment of congenital dilatation of the bile duct even if it is associated with dilatation of the intrahepatic bile ducts.

Adolescent↗

Short term histological liver changes in extrahepatic biliary atresia with good postoperative bile drainage.

Short term histological liver changes were studied in 13 patients with congenital biliary atresia, who showed good bile drainage after radical operation. Biopsies obtained at the time of the corrective surgery and at the second operation to convert from external total to partial bile drainage (undertaken once the bilirubin concentration was less than 30.8 mumol/l) were compared. A significant correlation was found between histological findings and the clinical course. In particular, at the second biopsy an increase in hepatic fibrosis and cell infiltration was observed mainly in patients whose bilirubin concentration decreased slowly or who had cholangitis, or both. Hepatic fibrosis and cell infiltration had decreased, however, in an appreciable number of patients whose postoperative course had been characterised by a rapid reduction in the bilirubin concentration and no cholangitis.

Bile↗

Studies on the changes of serum bilirubin level after surgery in biliary atresia.

In biliary atresia, one-fourth of the patients showed prolonged jaundice in spite of a good excretion of bile after surgery. To investigate the cause of jaundice, factors related to the serum bilirubin level were examined in 28 recent cases. Furthermore, clinical analysis was performed in 86 cases of good excretion of bile after surgery. The following results were obtained: The daily amount of bilirubin excretion in bile and bilirubin concentration play an important role in decreasing the serum bilirubin level. The most important factor for prolonged jaundice is ascending cholangitis. Shortening of the life span of the red blood cells is one of the causes of prolonged jaundice.

Bile Ducts↗

[Evaluation of the malignancy of breast carcinoma using flow cytometry].

Flow cytometric DNA analyses of single cell nuclei were performed on nuclear suspensions prepared from tumors of primary breast carcinomas in 40 patients operated on in our hospital. Fluorescence intensities of propidium-iodide stained cell nuclei were analyzed in a SHOWA DENKO SC-20 cell sorter. The DNA index and the percentage of S-phase cells and DNA aneuploidy were calculated from each DNA histogram. There was a tendency for more advanced nodal tumor involvement to have a higher DNA index, increasing DNA aneuploidy proportions and significantly larger percent of S-phase cells.

Adenocarcinoma, Mucinous↗