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T Hirota

Publications and source records attributed to T Hirota.

At least 109 records · Page 6Linked to original sources
PubMed1996

Evidence of direct recognition subset in xeno-reactive helper T cells.

There are two functional subsets of alloreactive helper T cells: one recognizes the alloantigens on self-antigen-presenting cells (APCs), and the other recognizes the alloantigens on allo-APCs. In this study, we analyzed which specific Th cells have a possible effect on concordant-xenograft rejection responses and how Th cells recognize xeno-antigens. In the proliferative response stimulated with spleen cells obtained from rats (r-SPC), mouse T cells (m-Tc) were not inhibited by GK1.5 (CD4) or 2.43 (CD8) antibodies. In a xeno-mixed lymphocyte reaction, m-Tc that included APC (APC(+)) proliferated when stimulated with r-SPC APC(+) or APC(-). In contrast, B6 T cell APC(-) proliferated only when stimulated with r-APC(+)SPC but not when stimulated with APC(-). The m-Tc lines responded to F344 SPC APC(+) but not to SPC APC(-); however, the m-Tc line did not respond to SPC from another rat strain. We hypothesize that both CD4+ Th and CD8+ Th are included in the concordant xeno-reactive Th; there are both xeno-APC-restricted Th and self-APC-restricted Th; and xeno-APC-restricted Th recognizes xeno-major histocompatibility complexes.

Animals↗
PubMed1996

[Oral single-dose toxicity study of a new antineoplastic agent S-1, and its components, CDHP, and Oxo].

S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that produced by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, the single-dose toxicity of S-1 as well as that of its components, CDHP and Oxo, was investigated in mice, rats, and dogs. The following results were obtained. 1. In mice and rats, excretion of diarrheal stools, salivation, and alopecia were observed after S-1 administration. In severe cases, the animals subsequently showed emaciation due to weight loss or suppressed weight gain, decreased spontaneous motor activity, an anemic appearance, bradypnea, prone position, and death. In the CDHP and Oxo treatment groups of rats, the only toxic signs were soft or diarrheal stools on the dosing day. 2. In dogs, vomiting and excretion of diarrheal, mucous, or soft stools was observed after S-1 administration. In the CDHP and Oxo treatment groups, excretion of soft and diarrheal stools and vomiting were observed relatively frequently from the dosing day until day 1. 3. In the pathological examination of the animals given S-1, mice and rats showed pulmonary congestion/edema, dark red discoloration of the mesenteric lymph nodes, atrophy of lymphatic tissues such as the thymus and lymph nodes, decreases of lymphocytes in the splenic white pulp and mesenteric lymph nodes, a decrease in bone marrow cells, congestion of the glandular stomach, and aggregates of bacteria in the lung, liver, or spleen. In dogs, abnormal changes were observed mainly in the lymphatic organs such as the thymus and lymph nodes. 4. The LD50 values of S-1 in terms of the amount FT they contained were estimated to be 549 mg/kg for mice(male), 441-551 mg/kg for rats (both sexes) and about 53 mg/kg for dogs (male). The LD50 values of CDHP and Oxo were 2000 mg/kg or higher for both rats (both sexes) and dogs (male). 5. Hematopoietic and lymphatic impairments, immunosuppression associated with respiratory were considered to be the cause of death from S-1. The toxicity of S-1 reflects the toxicity of 5-FU and was not found the different toxicity by the addition of CDHP and Oxo.

Administration, Oral↗
PubMed1996

[An oral repeated dose toxicity study of a new antineoplastic agent S-1 in dogs. I. A 13-week repeated dose toxicity study. II. An ophthalmologic toxicity recovery study].

S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that producted by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, a 13-week repeated dose toxicity study and a recovery study of opthalmologic effects were conducted in dogs. The following results were obtained. All S-1 doses are expressed in terms of their FT content. 1. Concerning the general condition, dark brown pigment was deposited on the sclera of the eye in all S-1 treated groups starting at the second week of treatment, and clouding of the cornea was noted in the 3 mg/kg/day group starting after 3-4 weeks of treatment. In the 3 and 6 mg/kg/day groups, general signs such as salivation, reduction in spontaneous movements, and sedation appeared, and 1 male and 2 females of the 3 mg/kg/day group died or were moribund 4-5 weeks after treatment began. All animals of the 6 mg/kg/day died or were sacrificed within 2 weeks of the start of the study. 2. Food consumption and body weight were reduced in the groups administered 1 mg/kg/day or more S-1. 3. No apparent drug-induced changes were observed on electrocardiography, urinalysis, fecal occult blood test, hematological examination, liver and kidney function tests, or ocular mucosa infection tests. 4. Blood biochemical examinations showed decreases in creatinine and chloride levels in males, an increase in LDH activity, and decreases in the albumin level and A/G ratio in females of the 3 mg/kg/day group. 5. Organ weighing showed that the relative weight of the kidney was increased in males and females of the 3 mg/kg/day group. 6. Histopathological examination revealed melanin deposition in the conjunctiva or cornea and atrophy inflammation, neutrophil infiltration, and neovascularization in the corneal epithelium. Atrophy of lymphatic tissues, such as the thymus, spleen and various lymph nodes, and changes in the reproductive system such as aspermatogenesis and uterine atrophy, which are commonly observed side effects of anticancer drugs, were also noted. 7. In the group administered FT, vacuolation of the cerebral fornix and commissura anterior was observed in 1 animal, but no changes were observed in other examinations. 8. The toxic effects of S-1 appeared primarily in the eyes, lymphatic tissues, and reproductive organs, and deaths were ascribed to weakening due to exacerbation of the general effects accompanied by disorders of immunological function. The NOAEL of S-1 in this study was estimated to be the dose that delivered less than 0.5 mg/kg/day in both males and females. 9. Changes in the eye observed after S-1 administration are such as pigmentation of the sclera and white turbidity of the cornea. Though it may be produced vision decreased, these changes are considered to be unaccompanied by functional disorders and to be reversible.

Administration, Oral↗
PubMed1996

[A method to calculate the probability of paternity between relatives--a paternity case where the putative father was a deceased granduncle].

To test paternity in a case where the putative father was a deceased uncle of mother (plaintiff's granduncle), we designed a new method to calculate the probability of paternity likelihood. The putative father's genotypes of red cell antigens, HLA and short tandem repeat (STR) polymorphism were estimated from those of mother and sister of the plaintiff. When the probability was calculated from the frequencies in the unrelated individuals (the standard method), a significant bias might be introduced since the putative father and the plaintiff were likely to have the same alleles come from their common ancestry. Therefore, we designed a new method to calculate the likelihood ratio from the frequencies in the group of mother's uncles estimated from mother's genotypes. The probability (0.9299) calculated with our method was found to be lower than that (0.9992) done with the standard method indicating that the new method could remove the bias introduced from the incest.

Adult↗
PubMed1996

[Large granular lymphocyte leukemia].

Large granular lymphocyte leukemia (LGLL) is defined as clonal proliferation of LGLs in peripheral blood. The following studies were conducted to address some issues in chronic LGLL. (1) Chronic LGLL is characterized by the indolent course, and the diagnosis of leukemia is difficult in such patients as those without distinct organomegaly and/or any evidence of monoclonality. We performed immunohistological studies in a patient with persistent NK lymphocytosis. No organomegaly had been seen in the patient during a three-year-observation, who died from cerebrovascular accident. The autopsy findings revealed multi-organ infiltration including spleen, liver, bone marrow, lymph nodes and lung. These findings suggest that the cells of chronic LGLL have infiltrative capacity characteristic of malignant cells. (2) Lymphocytosis in chronic LGLL is usually stable for a long period. We found that both T- and NK-LGLL cells strongly expressed CD95, an apoptosis related protein. Anit-CD95 did not induce apoptosis, but suppressed proliferation induced by IL-2 or anti-CD3. These results suggest that CD95-CD95 ligand system is involved in the slow cell growth characteristic of chronic LGLL. (3) CD4+CD8+ double positive (DP) cases are rarely seen in LGLL, and the physiologic counterpart of the leukemic cells has not been determined yet. We found that the DP-LGLL had alpha alpha type in the CD8 subunit and did not express RAG-1, these findings being characteristic of peripheral T cells. We also found that they expressed IL-4 mRNA and secreted IL-4 on activation. These results strongly suggest that DP-T-LGLL represents an expansion of a rare subset of peripheral DP-T cells, possibly derived from IL-4 activated CD4 single positive T cells.

Aged↗
PubMed1996

Anti-tumor effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in seborrheic keratosis.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a drug with potent antiproliferative action on keratinocytes that have nuclear receptors for 1,25(OH)2D3. We investigated the effects of 1,25(OH)2D3 on widespread seborrheic keratoses in 51 patients with these tumors. The data indicated that resolution of these tumors was dependent on both tumor size and dose of 1,25(OH)2D3. Among 15 patients treated with a high dose (0.5 microgram/d) of oral 1,25(OH)2D3, the lesions of widespread seborrheic keratoses changed from brown-black papules to brownish papules with erythema and/or crust as early as 2 wk after the start of treatment. The tumors finally developed into an atrophic scar or brownish pigmented macule. Histologically, vacuolation of the spinous cells, vesicle formation, and liquefaction degeneration of the basaloid cells were observed. Numerous lymphocytes had infiltrated in the papillary dermis. Among 36 patients treated with a low dose (0.25 microgram/d) of 1,25(OH)2D3, brownish papules became pale to normal in color and reduced in size, without erythematous change. Histologically, acanthosis of the epidermis was reduced, but degenerative change of the tumor cells was not observed. These data suggest that oral therapy of 1,25(OH)2D3 is an acceptable method well suited to the removal of seborrheic keratoses, especially those that are predominantly small tumors.

Adult↗
PubMed1995

Histochemical differences of the lectin affinities of backbone polylactosamine structures carrying the ABO blood group antigens in papillary carcinoma and other types of thyroid neoplasm.

Endo-beta-galactosidase from Escherichia freundii cleaves linear polylactosamine structure as follows: R-GlcNAc-beta 1-3Gal-beta 1-4GlcNAc-beta 1-R' + H2O-->R-GlcNAc-beta 1-3Gal + GlcNAc-beta 1-R'. Staining with Griffonia simplicifolia agglutinin II (GSA-II) following enzyme digestion reveals the distribution of R-GlcNac-beta 1-3Gal-beta 1-4GlcNAc-beta 1-R' structures in tissue sections. In this study, the procedure was applied to formalin-fixed, paraffin-embedded tissue sections from 26 cases of papillary carcinomas including 2 follicular variants, 8 follicular carcinomas, 7 adenomas, 1 anaplastic carcinoma and 1 medullary carcinoma in order to investigate whether different types of polyactosamine-containing structure are produced in these thyroid neoplasms. Simultaneously, the susceptibility of the ABH antigens expressed in these neoplastic cells to endo-beta-galactosidase digestion was examined. Most of the papillary carcinoma cells from all the individuals examined were strongly stained by GSA-II following enzyme digestion. Without enzyme digestion, little or no reactivity with GSA-II was observed. Among other types of neoplasms, only one case of follicular carcinoma exhibited reactivity with GSA-II following enzyme digestion. ABH antigens were expressed in 22 cases of papillary carcinomas, 2 adenomas, 5 follicular carcinomas and 1 anaplastic carcinoma, and their expression was dependent on the ABO blood group of the patients. Endo-beta-galactosidase digestion resulted in the elimination of these antigens not only in papillary carcinomas but also in other neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1995

Malignant melanoma with mesenteric metastasis causing an intrapelvic abscess: report of a case.

We present herein the case of a 66-year-old woman with disseminated malignant melanoma in whom a metastasis in the ileal mesentery ruptured into the peritoneal cavity causing an acute abdomen. The patient suddenly developed lower abdominal pain and a computed tomography (CT) scan of the pelvis confirmed the presence of an intrapelvic abscess. At emergency laparotomy, a 10 x 10 cm ruptured metastatic melanoma was found in the ileal mesentery, which demonstrated no communication with the ileum itself. To our knowledge, no other case of an acute abdomen being caused by the rupture of mesenteric metastatic melanoma lacking any communication with the bowel lumen has ever been reported.

Abdomen, Acute↗
PubMed1995

Comparison of the in vitro skin penetration of propiverine with that of terodiline.

This study was designed to clarify the relationship between the properties of propiverine and skin penetration, and to compare the in vitro penetration characteristics of propiverine and terodiline through rat skin. Propiverine in both hydrochloride and free forms penetrated across the skin extremely slowly, with a 2.6 times higher flux in the hydrochloride than that in the free base, in the absence of enhancers. Various enhancers failed to enhance the penetration of propiverine hydrochloride, whereas the same agents slightly increased the flux of the free form, these being due to the slow release rate of the free form from the gel formulations, an extremely high lipophilicity (log Poct/water > 4.97), much less solubility (0.141 mg/ml) and a large partition capacity of the drug to skin components. Terodiline in both forms was able to rapidly penetrate through the skin, even in the absence of enhancers, with 20.2 and 9.8 times higher fluxes respectively, than the corresponding forms of propiverine. The high penetration characteristics of terodiline would be due to a suitable lipophilicity, low binding property as well as the structural masking from the binding to the epidermal components. Propiverine hydrochloride penetrated through the stratum corneum 4.4 times and viable skin 3.1 times higher than through full-thickness skin, while the fluxes of terodiline through the stratum corneum and viable skin were similar to each other, with high penetration rates for each form.

Administration, Cutaneous↗
PubMed1995

Calcitonin-like polypeptides without apparent biological activity in a patient with recurrent medullary thyroid carcinoma.

A 51-year-old male with a recurrent medullary thyroid carcinoma (MTC) showed high serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) but with concomitant normocalcemia. The CT activities of the patient's serum in vivo (hypocalcemic activity in rats) and in vitro (cyclic AMP-increasing activity in cultured human mammary tumor, T47D) were much lower than those expected from the patient's CT level. High performance liquid chromatography (HPLC) with radioimmunoassay (RIA) detection gave a broad spectrum of molecular weights of CT-like polypeptides in the 3 kDa to 200 kDa range with separation from CEA, suggesting that the mechanism for CT production in MTC is an obscure one.

Animals↗
PubMed1995

Histochemical demonstration of different types of poly-N-acetyllactosamine structures in human thyroid neoplasms using lectins and endo-beta-galactosidase digestion.

Blood-group-related antigens expressed in papillary carcinomas and other types of neoplasm of the human thyroid glands have been shown to be carried by poly-N-acetyllactosamines containing a linear domain susceptible to endo-beta-galactosidase digestion. To make clear more precisely the backbone poly-N-acetyllactosamine structures, labelled lectins specific to different types of these structures and specific to core structures with beta 1-6GlcNAc branching of N- and O-linked glycoproteins were employed in conjunction with prior endo-beta-galactosidase digestion on formalin-fixed, paraffin-embedded neoplasms of the human thyroid glands. In papillary carcinomas, Datura stramonium agglutinin (DSA) and succinyl wheat germ agglutinin (Suc-WGA) reacted most consistently and frequently with papillary carcinomas from all the individuals examined. Pokeweed mitogen (PWM) likewise stained the cells of papillary carcinomas from all the individuals examined, but in some individuals the number of lectin-reactive cells were very small. Lycoperscion esculentum aggultinin (LEA), Solanum tuberosum agglutinin (STA), Phaseolus vulgaris agglutinin L (PHA-L) and Artocarpus integrifolia agglutinin (jacalin) similarly bound to the cancer cells from most of the individuals, and in these cases the number of reactive cells was usually much more restricted than was the case with DSA or PWM. In adenoma and other types of carcinoma, such as follicular carcinomas, these lectins specific to poly-N-acetyllactosamine exhibited slight or no reactivity with the cells, whereas PHA-L and jacalin similarly bound to the cells of adenomas and carcinomas from most of the individuals examined. Prior digestion with endo-beta-galactosidase completely eliminated or markedly reduced the reactivity with PWM and LEA in papillary carcinomas. Reactivity with DSA, Suc-WGA, STA, PHA-L and jacalin was slightly reduced or not at all affected by enzyme digestion. These results confirmed that poly-N-acetyllactosamine species found in papillary carcinomas are quite different from those in other types of thyroid neoplasm, suggesting that at least three different types of poly-N-acetyllactosamine, that is, linear unbranched short and long sequences and highly branched ones are produced in these cells.

Adult↗
PubMed1994

Localization of blood-group-related linear poly-N-acetyllactosamine structure in different human tissues by Griffonia simplicifolia agglutinin-II staining following endo-beta-galactosidase digestion.

Endo-beta-galactosidase from Escherichia freundii cleaves polylactosaminyl structures as follows: R-GlcNAc beta I-3Gal beta I-4GlcNac beta I-R' + H2O-->R-GlcNAc beta I-3Gal + GlcNAc beta I-R'. By staining with Griffonia simplicifolia agglutinin-II following the enzyme digestion, the distribution of R-GlcNAc beta I-3Gal beta I-4GlcNAc can be demonstrated in tissue sections. This carbohydrate chain is one of the backbone structures carrying the blood-group-related antigens and, thus, localization of this structure may provide detailed information about the distribution of variants with different backbone structures. Various formalin-fixed, paraffin-embedded tissue sections were stained by Griffonia simplicifolia agglutinin-II with or without prior enzyme digestion and the reactivity of the agglutinin imparted by enzyme digestion was studied in the following tissues and cells: pancreatic acinar cells, gastric surface mucosae, duct cells and mucous cells of salivary glands and tracheal glands, surface epithelium of trachea, goblet cells of large intestine, columnar epithelium of uterine cervical glands, distal and collecting tubules of kidney, certain cells of anterior lobe and colloid of middle lobe of pituitary glands, epithelial reticular cells and Hassall's corpuscles of thymus and Kupffer cells of liver. In gastric surface mucosae, the reactivity of the agglutinin appeared in non-secretor individuals but not in the secretor individuals, and in mucous cells of salivary and tracheal glands the reactivity appeared in Le(a- b-) non-secretor individuals but not in Le(a + b-) non-secretor or secretor individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Bone marrow transplantation for erythroleukemia: a case report.

A 2 year old girl was diagnosed as having erythroleukemia (EL; M6 according to the French-American-British classification). After one course of low-dose cytosine arabinoside (Ara-C), complete remission was obtained. After three courses of low-dose Ara-C for consolidation, allogeneic bone marrow transplantation was performed from HLA-identical sibling. The course of post-transplantation was uneventful. Two years after transplantation, she continues to have durable engraftment and remission. In children with EL, conventional chemotherapy appears to be inadequate for producing durable long-term disease-free survival. Bone marrow transplantation should be considered in children with EL, in cases where suitable donors are available.

Bone Marrow Transplantation↗
PubMed1994

[Interferon-associated retinopathy].

During interferon (IFN) treatment for chronic hepatitis C, retinopathy develops in about one half of the patients. This "IFN-associated retinopathy" is characterized by cotton-wool spots (ischemic lesions) and superficial hemorrhage around the optic disc. It usually occurs 1 to 3 months after initiation of IFN therapy. Most of the patients with retinopathy have no symptoms, while some complain of impairment of visual acuity or flying specks. IFN-associated retinopathy tends to improve without any ophthalmic treatment and IFN therapy can be continued under careful observation. A complication of diabetes mellitus or a decrease in platelet count during IFN treatment may aggravate IFN-associated retinopathy. We emphasize that careful ophthalmologic follow-up is needed for all patients under IFN therapy.

Adult↗
PubMed1994

"Very well differentiated tubular adenocarcinoma" of the stomach: its endoscopic and histopathological characteristics.

Between 1986 and 1991, 31 patients having tubular adenocarcinoma with low cellular and structural atypism ("very well differentiated tubular adenocarcinoma:" tub 0) underwent surgery at the National Cancer Center Hospital (NCCH). Histologically, the 31 lesions in the 31 patients were very similar to those observed in gastric adenoma (World Health Organization) with severe atypism. Their malignancy could be diagnosed only on the basis of cellular atypism, i.e., uneven distribution of chromatin in the nucleus accompanied by irregularity in the size or shape of the spindle-form nucleus, abnormal nuclear polarity and/or obvious nucleoli. Histologically, the border between the tub 0 and adenomatous areas ('front line' of carcinoma) could not be identified within the neoplastic lesion, which showed relatively regularly shaped tubuli (less structural atypism). Of the 31 cases, 30 were solitary early gastric cancer (EGC). Their clinicopathological features were compared with those of 34 cases of gastric adenoma, 237 cases of solitary well differentiated (tub 1) and 127 cases of moderately differentiated (tub 2) tubular adenocarcinoma which had been resected at the NCCH during the same period. Most (75%) of the 30 tub 0 EGCs were type IIc (depressed) macroscopically, despite their histological similarity to gastric adenoma which showed a high (90%) elevated appearance incidence. The incidence of small lesions, < 2 cm in diameter, was highest in gastric adenoma (82%), followed by tub 0 (64%), although the tub 0 lesions showed a wide range of sizes. Small lesions were less frequent in the tub 1 (43%) and tub 2 (33%) cases. The incidence of submucosal invasion was significantly lower in tub 0 cases (17%) than in tub 1 (39%) and tub 2 (46%) cases (P < 0.05). No lymph node metastasis was seen in tub 0 cases, but was seen in 6.4% and 9.4% of tub 1 and tub 2 cases, respectively. With regard to the endoscopic appearance of depressed mucosal cancer, the incidence of encroachment (moth-eaten appearance) on the tips of folds was significantly lower (10%) and the appearance of marginal elevation was significantly higher (79%) in tub 0 than in tub 1 (each P < 0.05) or tub 2 (each P < 0.01). The results suggest that 'tub 0' can be regarded as a less malignant but not benign tumor, and that its endoscopic characteristics provide valuable information which can be used to ensure that patients receive suitable treatment.

Adenocarcinoma↗
PubMed1994

[Patients acceptance of immediate breast reconstruction after subcutaneous mastectomy in breast disease].

Most profound emotional impact for the women with breast carcinoma is experienced as loss of femininity as a result of surgical mutilation. From this point of view, the recommendation for reconstructive surgery provide the amelioration to patient's anxiety. Two hundred women with breast carcinoma including huge nonepithelial malignant and/or benign tumors who adopted the breast reconstruction were treated during a 13-year period in 1982-1994 at NCCH. The breast reconstruction was mainly created by latissmus dorsi musculocutaneous (LDMC) flap in one sitting (modified mastectomy plus simultaneous reconstruction). Thirty patients treated with subcutaneous mastectomy (conserving the nipple-areolar complex) among them, were followed by deepithelialized LDMC flap without implant as the procedure of choice in early carcinoma located in lateral half at a distance of at least 4-5 cm from the areola and in huge benign tumors. Although one patient was dissatisfied with ischemia of LDMC flap, this approach was safe, simple, and possible to produce the patient's satisfaction. There was a positive effect on life style and on sexual, social or work relationships.

Adolescent↗