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Biomedical subjects

M Tamai

Publications and source records attributed to M Tamai.

At least 19 recordsLinked to original sources

Defective autologous mixed lymphocyte reaction (AMLR) and killer activity generated in the AMLR in cancer patients.

The autologous mixed lymphocyte reaction (AMLR) and the killer activity generated in the AMLR (AMLR-killer) in the spleen and the peripheral blood of patients with gastric cancer were investigated. The AMLR in cancer patients was suppressed, especially in the spleen, compared to that seen in controls. There was no correlation between AMLR activity and the stage status of the cancer. The cytotoxic activity of AMLR-killer cells against various tumor-cell lines was also suppressed in the spleen, and had a tendency to be suppressed in the peripheral blood of cancer patients. The autologous tumor-killing activity of AMLR-killer cells was developed in cancer patients with high AMLR activity, but was not induced in patients with low AMLR activity. Autotumor killing activity was decreased by the elimination of CD4+ cells, whereas the elimination of CD16+ cells resulted in a marked reduction in cytotoxicity against K562, indicating that the non-specific killer cells which lysed K562 were different from the specific killer cells that lysed autotumor cells. This suggests that AMLR activity is related to the differentiation and proliferation of lymphocytes with specific or non-specific cytotoxic activity and that this activity plays an important role in immune surveillance against tumors.

Adult

Inhibition of interleukin 1-stimulated cartilage proteoglycan degradation by a lipophilic inactivator of cysteine endopeptidases.

Inactivators of cysteine endopeptidases were tested as inhibitors of the cytokine-stimulated release of proteoglycan from cartilage. The test system consisted of bovine nasal septum cartilage maintained in organ culture, and the stimulus was provided by recombinant human interleukin 1 alpha. L-3-Carboxy-2,3-trans-epoxypropionyl-leucylamido-(4-guanidin o)butane (E64) and L-3-carboxy-2,3-trans-epoxypropionyl-leucylamido-(3-methyl)b utane (Ep475) showed no inhibition at concentrations up to 100 microM. In contrast, trans-epoxysuccinyl-leucylamido-(3-methyl)butane ethyl ester (Ep453), a 'prodrug' of Ep475, was an effective inhibitor. The LL-, LD- and DL-isomers gave significant inhibition at 10 microM, and the DD-isomer was inhibitory at 100 microM. None of the isomers had any detectable effect on protein synthesis or glycolysis, and their inhibitory effects were reversible. Iodoacetate inhibited proteoglycan release by a general toxic effect. Our results suggest that cysteine endopeptidase(s) play a part in cytokine-stimulated cartilage breakdown, but that effective inhibitors must pass through membranes.

Animals

Clinical and immunological evaluation of intraoperative radiation therapy for patients with unresectable pancreatic cancer.

The clinical efficacy of intraoperative radiation therapy (IORT) and the changes of immunological parameters were investigated. Nine patients with unresectable pancreatic cancer were treated with IORT (2,500-3,500 cGy) and the changes of various immunological parameters were compared with those in 11 patients with advanced cancer who received external beam irradiation therapy (XRT), 2,500-3,500 cGy. After IORT, 71% of patients obtained pain relief, two of the nine patients showed a partial response, and the serum CA 19-9 level decreased in six patients. However, the median survival was only 210 days. Natural killer activity, lymphokine-activated killer activity, and interferon gamma-activated killer activity were not inhibited by IORT, and phytohemagglutinin-induced blastogenesis was actually augmented after IORT, whereas all these parameters were inhibited by XRT. Thus, it is suggested that IORT may augment or at least stabilize systemic antitumor immunity.

Aged

Distribution of histologic subtypes and sex ratio in various primary sites of lymphocytic lymphoma.

To examine the distribution of histologic subtypes and sex ratio in each primary site of lymphoma, 1,169 histologically proven cases of lymphocytic lymphoma were analyzed. The location of tumor was nodal in 615(53%) and extranodal in 517(44%), patients with the gastrointestinal tract being the most common. The incidence was predominantly in males for all histologic types and in nodal and extranodal sites, except for a predominance of females in extranodal lymphoplasmacytic(Lp-cytic), lymphoplasmacytoid(Lp-cytoid) tumors. Frequency of the Lp-cytic/Lp-cytoid type among all types of lymphoma in females was about 2.7 times more frequent in extranodal than in nodal sites. The most striking example was thyroid lymphoma in which the frequency of Lp-cytic/Lp-cytoid type was 36% in female and 0% in male patients. Including this type of lymphoma, frequency of low grade lymphoma in females was higher in extranodal sites than in nodal sites.

Adolescent

Abnormal sclerocytes in nanophthalmos.

Scleral tissue from a nanophthalmic patient was examined morphologically and by a tissue culture method. Collagen in the unusually thickened scleral tissue was arranged in irregularly interlacing bundles. Results of tissue culture studies showed sclerocytes that seemed to secrete many granules that stained positively with Alcian blue and periodic acid-Schiff (PAS). No granules were seen in cells of scleral tissue cultured from two control eyes. These findings may be the result of the modified glycosaminoglycan metabolism, which in turn contributes to the abnormal packing of collagen bundles and thickening of sclera in nanophthalmos.

Adult

Vitreous, retinal and subretinal hemorrhages associated with von Willebrand's syndrome.

Two patients with von Willebrand's syndrome had intraocular hemorrhages without trauma or neovascularization. A 13-year-old Japanese girl complained of sudden spotted vision in her left eye. Vitreous, peripapillary retinal, and subretinal hemorrhages were seen by ophthalmoscopy in the affected eye. In addition, a 19-year-old Japanese man had repeated vitreous hemorrhage and epistaxis. Also noted was gyrate atrophy of the choroid and retina. Analysis of the coagulation-fibrinolysis system revealed decreased activities of Factor VIII and von Willebrand's factor in both patients. The amount of von Willebrand's factor antigen also was decreased. These results suggested that the patients had von Willebrand's syndrome. The bleeding tendency in the disorder appeared to be responsible for the pathogenesis of the intraocular hemorrhages seen in these patients.

Adolescent

In vitro generation of activated natural killer cells and cytotoxic macrophages with lentinan.

The in vitro effect of lentinan in inducing activation of killer cells and cytotoxic macrophages has been examined. Human peripheral blood mononuclear cells were cultured with lentinan for 2, 4 and 8 days. After 4 days cytotoxicity was increased 4% by lentinan less than 1,000 ng/ml. After 8 days, it was increased 12% by 25 and 1,000 ng/ml lentinan. The phenotype of the killer cells induced by lentinan was CD2+, CD16+ and CD56+, suggesting that they were natural killer cells. Macrophages separated from the spleens of 6 patients with gastric cancer were cultured with lentinan for 7 days, and their cytotoxicity increased 19%. The optimal concentration of lentinan was from 25 to 100 ng/ml. The findings suggest that the antitumour effect of lentinan is due to the activation of killer cells in vivo, because the optimal concentration of lentinan for the induction of killer cells in vitro was equivalent to the plasma concentration obtained after clinical doses of this agent.

Antigens, Surface

Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP).

The mutations of codon 17, 23, 58, and 347 of rhodopsin gene were investigated in 24 unrelated Japanese families including 33 patients with autosomal dominant retinitis pigmentosa (ADRP). A patient with codon 17 mutation (Thr-17-Met, ACG-->ATG) and a family including 4 patients with codon 347 mutation (Pro-347-Leu, CCG-->CTG) were detected among them. Their clinical findings were extremely different between the two mutations. The former showed type 2 and the latter showed type 1 ADRP. No mutation of codon 23 and 58 was detected in any families so far analyzed in the present study. Clinical findings associated with the mutation in codon 17 and 347 of the rhodopsin gene show an existence of allelic heterogeneity.

Adolescent

The promotive effect of interleukin 4 with interleukin 2 in the proliferation of tumor-infiltrating lymphocytes from patients with malignant tumor.

In adoptive immunotherapy, the number of effector cells is one of the major factors relating to the therapeutic efficacy. We demonstrated that tumor-infiltrating lymphocytes (TILs) were stimulated to proliferate by incubation with interleukin 2 (IL-2) plus interleukin 4 (IL-4). TILs cultured with IL-2 plus IL-4 increased 3.1-fold more than TILs cultured with IL-2 alone. However, IL-4 did not alter the cytotoxic activity of TILs against autologous tumor cells and established tumor cell lines. It is suggested that IL-2 receptor is related to the mechanism of the proliferation of activated TILs cultured by combination with IL-2 and IL-4. Thus, the combination of IL-2 and IL-4 may increase the efficacy of adoptive immunotherapy using activated TILs.

Cytotoxicity, Immunologic

Enhancement of tumor cell susceptibility to lymphokine-activated killer cells by treatment with the streptococcal preparation OK432.

We investigated whether tumor cell lysis by LAK cells was augmented by treatment with OK432 in vitro. NK and LAK activity against K562 cells was not enhanced by their treatment with OK432. In contrast, the susceptibility of OK432-treated Daudi and KATO-III cells to lysis by LAK cells was enhanced. Succinate dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III cells by treatment with OK432, and moreover the expression of HLA Class I antigen and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells. Thus, it is suggested that the enhancement of the susceptibility of OK432-treated tumor cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA Class I antigen expression.

Antigens, Neoplasm

In vitro augmentation of the cytotoxic activity of peripheral blood mononuclear cells and tumor-infiltrating lymphocytes by famotidine in cancer patients.

We investigated the in vitro effects of famotidine on the cytotoxic activity of peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs). The cytotoxic activity of PBMC was augmented by famotidine at a concentration of 10 ng/ml, which is equivalent to the serum level achieved by the intravenous administration of a dose of 20 mg. This response to famotidine was seen only in cancer patients. Both the cytotoxic activity and DNA synthesis of activated TILs were increased by the combination of interleukin-2 and 1 microgram/ml of famotidine. Augmentation of cytotoxic activity by famotidine occurred independently of any decrease in the population of suppressor T-cells. Thus, famotidine may have the potential to be used in adoptive immunotherapy with TILs for cancer patients.

Antigens, CD

Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay.

A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5-FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response).

Adult

Intraductal growth of malignant mammary myoepithelioma.

This report describes the histologic and immunohistologic features of an intraductal myoepithelial tumor that developed in the breast of a 61-year-old woman. Histologically, the tumor proliferated intraductally, with both a comedo or doughnut pattern and a solid pattern containing narrow fibrovascular cores, mimicking what appeared to be a conventional intraductal carcinoma. No fine papillary or arborizing growth or cribriform formation was observed. Tumor cells at the ductal peripheral zone were polygonal and clear with abundant glycogen in the cytoplasm; they were transformed into nonclear cells with slightly eosinophilic cytoplasm toward the center of the involved ducts. Occasionally, nonclear cells were elongated, with a centrally located cigar-shaped nucleus. These elongated or spindle cells tended to show a fascicular and streaming pattern similar to that of a smooth muscle tumor. Immunohistochemically, alpha smooth muscle actin (alpha-SM-actin) and S-100 protein were expressed in most of the nonclear cells. While clear cells also had a positive reaction for S-100 protein, they were mostly negative or barely positive for alpha-SM-actin. Epithelial membrane antigen (EMA) was also positive in a certain number of polygonal cells. These results support the myoepithelial nature of the present tumor, and some cells might also be immunologically differentiated into ductal epithelial cells. In addition to cytological atypia, frequent mitoses, and central necrosis within ducts, there was a minimal but evident stromal invasion, suggesting histological malignancy in this peculiar tumor.

Breast Neoplasms

Spontaneous orbital hemorrhage in adult females. A report of three cases.

Three cases of spontaneous orbital hemorrhages in 3 adult females are reported. All of the patients had acute radiating pain in the orbit, vomiting and proptosis with a limitation of motility and ecchymosis of the eyelids. One was due to a large orbital varix with a preceding history of intermittent exophthalmos; the causes of the other cases could not be determined from their backgrounds. Within a few weeks, all of them had recovered from hematoma and had good prognoses without surgery. Orbital venous bleeding with 40 mm Hg pressure will cause more than 500 g tension on the four rectus muscles. To treat this clinical emergency, hemostasis with compression in the early phase and waiting for its spontaneous absorption are recommended.

Adult

Molecular design of potent inhibitor specific for cathepsin B based on the tertiary structure prediction.

To design a potent inhibitor specific for cathepsin B (rat liver), the tertiary structure was predicted based on the crystal structure of the papain complexed with (+)-(2S,3S)-3-(1-[N-(3-methylbutyl)amino]leucylcarbonyl)oxirane-2- carbolylic acid (E-64-c), a thiol protease inhibitor. Taking advantage of the structural characteristics of the predicted active site, seventeen inhibitors were chemically synthesized by molecular modeling, and one of them, N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-p rol ine (CA-074) was shown to be the first potent inhibitor specific for cathepsin B. The relationship between the structure and inhibitory activity is discussed based on the model structure of the cathepsin B-inhibitor complex.

Amino Acid Sequence

Two cases of hypothyroidism associated with alpha-interferon therapy.

Alpha-interferon was used for anti-cancer or anti-viral therapy in two patients with preexisting autoimmune thyroid disease and in seven patients with chronic viral hepatitis who had no history of thyroid dysfunction. Primary hypothyroidism developed in the two patients who had a history of autoimmune thyroid disease, while no changes in thyroid function were observed in the other seven patients. Modulation of the immune system by alpha-interferon may have been responsible for the development of hypothyroidism in these two patients. Therefore, autoantibodies to the thyroid and the thyroid function should be assessed in patients undergoing alpha-interferon therapy.

Adenocarcinoma

Ouabain-sensitive Na-K ATPase response in the rabbit iris-ciliary body after lensectomy-vitrectomy.

We studied ouabain-sensitive Na-K adenosine triphosphatase (ATPase) activities in the iris-ciliary body of rabbit eyes after lensectomy-vitrectomy. Changes in enzyme activities were quantitatively investigated in the plasma membrane of iris-ciliary body at 0 or 7 hours and at days 1, 3, 7, and 14. The specific activity of Na-K ATPase rose to significantly higher levels than the control value at 7 hours following surgery, but returned to the baseline value after 7 days. In addition, we evaluated enzyme activities after lensectomy-vitrectomy during which SF6 or silicone oil was injected. The specific activity of Na-K ATPase following the injection of SF6 or silicone oil was significantly higher than the control value at 7 hours and did not return to the normal value even after 14 days. Consensual reaction, demonstrated by increased Na-K ATPase activity, also was found in the contralateral unoperated eyes of SF6- and silicone oil-injected rabbits. The increased Na-K ATPase activity in the iris-ciliary body after experimental surgery may play an important role in restoring swollen tissues.

Animals