[A case of carcinoid of probable thymic origin].
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Biomedical subjects
Publications and source records attributed to H Masuda.
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Each of 5 patients with renal cell carcinoma and urinary bladder tumor who were operated on at the department of urology, Hamamatsu University School of Medicine and its affiliated hospitals, received 20 mg of 4'-O-tetrahydropyranyladriamycin (THP) intravenously at the beginning of surgery. Heparinized peripheral blood samples were collected at regular intervals and separated in plasma and blood cell fractions by centrifugation for the estimation of THP. The THP concentration of the surgical specimen was also studied. In renal cell carcinoma, the surgical specimen was divided into cytoplasm and nuclear fractions, and the THP concentration in each fraction was measured. The THP concentration gradually decreased in the plasma and blood cell fractions with passage of time after the administration in both renal cell carcinoma and urinary bladder tumor. In renal cell carcinoma, although the tumor revealed a lower concentration of THP compared with the normal renal cortex and medulla, the nuclear fraction of the tumor showed a higher concentration than those of the normal renal cortex and medulla. In contrast to renal cell carcinoma, the THP concentration of the urinary bladder tumor was found to be higher than those of the normal urinary bladder mucosa and muscle.
In vitro chemosensitivity was evaluated by SDI test in various human tumors including 1 lymph node metastasis of esophageal cancer, 10 gastric cancers, 4 colo-rectal cancers, 1 hepatoma, 2 lung cancers, 2 breast cancers and 1 gallbladder cancer. Tumor fragments cut with scissors were exposed to twelve kinds of antitumor drugs at five to ten times peak plasma concentration. After 3 days at 37 degrees C, each tumor fragment suspension was washed with phosphate-buffered saline and assayed for succinate dehydrogenase (SD) activity using 3-(4,5- dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) as a hydrogen acceptor. When the SD activity of the drug-treated cells was reduced to below 50% that of control cells, the chemosensitivity to the antitumor drug was considered positive. The chemosensitivity of each tumor varied individually. Mitomycin C or 5-fluorouracil are regularly used to treat gastric cancer patients, but, some specimens of gastric cancer in this study showed a resistance to these drugs and an unexpected sensitivity to other drugs. Our results show that the SDI test is a convenient method for clinical use and gives significant information about drug sensitivity.
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Neuromedin K and neuromedin L are novel mammalian tachykinins isolated from porcine spinal cord. We have developed a highly sensitive radioimmunoassay for neuromedin K. Since the radioimmunoassay for neuromedin K has significant crossreactivity with neuromedin L and substance P, we can simultaneously determine the tissue concentrations of neuromedin K, neuromedin L and substance P after separation of the tissue extracts by reverse phase high performance liquid chromatography. Substance P is found to be the most abundant mammalian tachykinin in every brain region. The ratio of the concentration of substance P to neuromedin K is small in cerebral cortex and large in medulla-pons, while that of substance P to neuromedin L is rather constant in a range of 2.0-2.5. In spinal cord, dorsal half contains more neuromedin K and L than ventral half as is the case with substance P. These results indicate that both neuromedin K and L are endogenous mammalian tachykinins with specific physiological functions.
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Human lung fibroblast MRC-5 cells treated with Triton X-100 (MRC-5 cell models) were able to contract in the presence of MgATP and Ca2+ of more than 1 microM. Immunofluorescence microscopy with antibodies to actin and myosin 20,000-dalton (20 Kd) light chain revealed that stress fibers were prominent in MRC-5 cell models. Use of a fluorescent actin probe, 7-nitrobenz-2-oxa-1,3-diazole-phallacidin permitted visualization of contraction of the stress fibers in the presence of MgATP and Ca2+. Of the proteins in MRC-5 cell models, only a myosin 20 Kd light chain was phosphorylated in a Ca2+-dependent manner. This Ca2+-dependent phosphorylation of the 20 Kd light chain closely corresponded with the contraction of MRC-5 cell models: 1) Both phosphorylation of the 20 Kd light chain and contraction of MRC-5 cell models were inhibited by calmodulin antagonists such as N-(6-aminohexyl)5-chloro-1-napthalene sulfonamide. 2) The threshold Ca2+ concentration for phosphorylation of the 20 Kd light chain was similar to that for contraction of MRC-5 cell models. Both were lowered by exogenous calmodulin in a concentration-dependent manner. 3) The 20 Kd light chain was thiophosphorylated by incubation of MRC-5 cell models with an ATP analogue, adenosine 5'-0-(3-thiotriphosphate) only in the presence of Ca2+. After this treatment, MRC-5 cell models lost the Ca2+-dependence for contraction. These results indicate that Ca2+-calmodulin-dependent phosphorylation of myosin 20 Kd light chain is required for contraction of MRC-5 cell models.
Pituitary hyperplasia, microadenoma or an empty sella was detected in three children with primary hypothyroidism and three with Turner syndrome with the use of high resolution contrast-enhanced computed tomography (CT) with thin slices. Hyperplasia or microadenoma of the pituitary gland frequently occurs secondary to primary hypothyroidism and gonadal dysgenesis, and recognition of these results may eliminate unnecessary surgery in favor of hormone replacement therapy. High resolution contrast-enhanced CT, especially coronal CT, with thin slices is very helpful in demonstrating these pituitary abnormalities.
The effects of splenectomy on tumor growth following inoculation with a relatively large number of cells (1 X 10(7) ) and a smaller number of cells (5 X 10(5) ) of Meth I tumor were studied. When 1 X 10(7) tumor cells were inoculated, tumor growth in splenectomized mice was depressed, while tumor in sham-operated mice grew progressively. On the contrary, when 5 X 10(5) tumor cells were inoculated, the tumor take was lower in sham-operated than in splenectomized mice. The spleen cells from mice inoculated with either a large or small number of tumor cells, showed an equally potent cytotoxic activity, but no detectable suppressor cell activity. On the other hand, the activity of immunosuppressive factor was detected in sera from mice inoculated with 1 X 10(7) tumor cells, but not in those given 5 X 10(5) cells. The effect of splenectomy on tumor growth is, thus, bidirectional, depending on the dose of tumor cells inoculated.
A study has been made of the glycosaminoglycan composition of the mitral valve of the normal human heart. Five glycosaminoglycans were isolated from tryptic digest of the material and were assayed by determining the carbohydrate content. Separation of these five polymers was achieved by Dowex 1 X 2 column chromatography. They were identified as hyaluronic acid, heparan sulfate, chondroitin-4-sulfate, dermatan sulfate and chondroitin-6-sulfate, respectively. As far as the authors are aware, this is the first isolation of heparan sulfate from the preparation of the mitral valve of the normal human heart.
Tumor scintigraphy, using Tc(V)-99m dimercaptosuccinic acid (Tc(V)-DMS) was performed in 58 patients with soft tissue tumors, and the results were compared with that of Ga-67 citrate. Tc(V)-DMS was found to have a sensitivity of 90% for malignant tumors including aggressive fibromatosis compared to that of Ga-67 citrate, which was 56%. However, the specificity of Tc(V)-DMS for these tumors was 71% but with Ga-67 citrate the specificity was 80%. The imaging accuracy in soft tissue tumors with Tc(V)-DMS and Ga-67 citrate was 78% and 71%, respectively. Although the accumulation of Tc(V)-DMS has been detected in some benign soft tissue tumors, the reduced accumulation in inflammatory lesions compared to Ga-67 citrate was recognized, and Tc(V)-DMS could be of great use in the detection of extension or location of malignant soft tissue tumors.
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A small necrotic focus with regeneration of myocardial cells in an aneurysmectomized ventricular wall was observed in a 46-year-old man. Marginating the area of necrosis were myocardial cells with mitosis, with frequent multinucleated and binucleated cells. In the area of necrosis, there was a proliferation of many round, oval to polygonal cells with a high mitotic activity. These cells had eosinophilic granular cytoplasm and one prominent nucleus. Some cells were solitary while others clustered in and around the damaged myocardial fibers. Some cells formed a syncytium and were attached to the perimysial tubes with protoplasmic extensions. These proliferated cells are believed to be a single-cell line and to originate from the damaged myocardial cells. This observation suggests that human myocardial cells may regenerate continuously from surviving myocardial cells and proliferate discontinuously.
Disulfiram-like reactions have been reported in patients receiving cephem antibiotics which possess a mercaptomethyltetrazole (Me-TZ) side chain in their molecular structure. The present study focused on the elucidation of the relationship between the formation of Me-TZ and its inhibitory action on alcohol metabolism after treatment with the cephem antibiotics. The cumulative urinary excretion of Me-TZ was determined in healthy volunteers and laboratory animals after i.v. administration of the cephem antibiotics: cefmetazole (CMZ), cefoperazone (CPZ) and latamoxef (LMOX). In humans, monkeys and rodents, the extent of urinary excretion of Me-TZ was found in the order of CPZ greater than LMOX greater than CMZ-treatment. To assess their influences on dehydrogenation of ethanol (EtOH) and acetaldehyde (AcH), rats and monkeys were treated with a single or multiple i.v. dose of Me-TZ and cephem antibiotics prior to the EtOH treatment. The blood EtOH levels were not affected with either the Me-TZ or the cephem pretreatments. On the contrary, the AcH levels were significantly elevated with each of the pretreatments. The dose response curves for AcH levels showed parallel lines corresponding to the urinary excretion of Me-TZ, i.e., CPZ greater than LMOX greater than CMZ-treatment. These results suggest that there are some differences in the disulfiram-like reactions among animal species and antibiotics, which will be attributed to the intrinsic distribution and stability of each of the antibiotics in the body.
Between 1964 and 1981, 100 in-patients with recurrent gastric carcinoma following curative resection were investigated in the Second Department of Surgery, Kyushu University Hospital. The disease-free interval after initial operation and the advancement of the carcinoma correlated. The mean disease free interval of cases with local recurrence was 4 years and 1 month, that is 2 years longer than in cases of peritoneal dissemination or hematogenous metastasis. The disease free interval and the survival time after recurrence also correlated. Patients with a relapse more than 2 years after initial operation survived statistically longer than did those with a relapse in less than 2 years (p less than 0.01). One and 2 year survival rates after recurrence in the second resection group was 41.4 per cent and 17.2 per cent, respectively. Almost all patients in the other group died within one year after recurrence. The average survival in patients on a combination of chemotherapy and resection of the recurrent tumor was about 2 years and longer than in cases of resection but without chemotherapy.