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Biomedical subjects

Y Tsuji

Publications and source records attributed to Y Tsuji.

At least 289 records · Page 16Linked to original sources

Immunohistochemical localization of calmodulin in the testes of patients with idiopathic male infertility.

The localization of calmodulin in testes of patients with idiopathic male infertility was studied using the indirect immunoperoxidase method. Specimens were obtained by testicular biopsy from 55 patients. They were divided into 26 cases of hypospermatogenesis, 11 cases of maturation arrest (8 of primary spermatocyte arrest and 3 of spermatid arrest) and 18 cases of Sertoli cell-only syndrome. Regardless of the type of testicular pathology, the types of immunoreactive cell and the intensities of staining were the same as those in the normal testis. That is, staining for calmodulin was first found to be positive in early pachytene primary spermatocytes. It became intense in late pachytene primary spermatocytes and round spermatids. By contrast, elongated spermatids and spermatozoa were not stained. Sertoli cells were stained slightly or not at all. A calmodulin-staining index (CaM-S index) was defined as the proportion of primary spermatocytes that were stained intensely for calmodulin relative to the total number of primary spermatocytes. The indices for the testes of men with complete spermatocyte maturation arrest were significantly lower than those for the testes of normal controls and of men with hypospermatogenesis. Degenerating late pachytene spermatocytes observed in the testes of men with spermatocyte arrest showed low calmodulin-specific immunoreactivity. Such a decrease in numbers of normal late pachytene spermatocytes might be responsible for the low CaM-S index in cases of complete spermatocyte arrest.

Adult↗

Relationship between vitamin K dependent coagulation factors and anticoagulants (protein C and protein S) in neonatal vitamin K deficiency.

To determine the relationship between vitamin K dependent coagulation factors and natural anticoagulants, namely protein C and protein S, in various degrees of vitamin K deficiency, plasma values for clotting activity, protein induced by vitamin K absence (PIVKA-II), protein C antigen, gamma-carboxy protein C antigen, and protein S antigen including total and free fractions and activity of protein C were measured in 66 full term and healthy breast fed neonates who did not receive vitamin K supplement at birth. The 66 neonates were divided into a control group (17 cases) and a low group (49 cases) according to their values for clotting activity--that is, > or = 20% or < 20% during the first six days of life--and vitamin K was immediately given when the neonates showed values < 20%. In the low group clotting activity gamma-carboxy protein C, free protein S, and protein C activity was significantly decreased to a minimum on day 2 or 3, and increased in parallel after vitamin K administration. Furthermore, they were positively correlated with one another and inversely cor-correlated with the PIVKA-II concentrations. These findings suggest that simultaneous gamma-carboxylation of coagulation factors and proteins C and S acts to maintain both coagulation and anticoagulation activities in parallel at various concentrations of vitamin K. The breast milk intake in the group with low values of clotting activity was significantly lower than that in the control group during the first three days of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗

Expression of 92-kD type IV collagenase/gelatinase (gelatinase B) in osteoarthritic cartilage and its induction in normal human articular cartilage by interleukin 1.

We report here that a 92-kD gelatinolytic metalloproteinase is expressed as protein and mRNA in human osteoarthritic cartilage, but not in normal adult articular cartilage. Western immunoblotting demonstrated that the 92-kD gelatinolytic activity corresponded to 92-kD type IV collagenase/gelatinase (gelatinase B); mRNA for gelatinase B was identified by Northern blotting. Chondrocytes from normal cartilage also exhibited mRNA for 72-kD type IV collagenase/gelatinase (gelatinase A), tissue collagenase, and stromelysin-1, and these mRNAs were increased in osteoarthritic cartilage. Regional analysis of osteoarthritic cartilage samples from four individuals revealed that gelatinase B mRNA was expressed in grossly fibrillated areas; two of four nonfibrillated cartilage samples failed to exhibit the mRNA, but did have increased levels of mRNA for other neutral metalloproteinases. IL-1 alpha treatment of normal human cartilage explants or isolated chondrocytes induced increased levels of gelatinase B and increased mRNA for tissue collagenase and stromelysin-1. Under identical conditions, mRNA levels for gelatinase A were not increased indicating that regulation of this enzyme in human articular chondrocytes is distinct from that of other metalloproteinases. Our data showing expression of gelatinase B in fibrillated cartilage suggest that it is a marker of progressive articular cartilage degradation in osteoarthritis.

Adult↗

Pharmacological and pharmaceutical properties of freeze-dried formulations of egg albumin, indomethacin, olive oil, or fatty acids.

Formulations consisting of egg albumin, indomethacin (IND), and olive oil or fatty acids, were prepared by vigorous stirring using a high-speed homogenizer and subsequent freeze-drying. To confirm the anti-inflammatory properties and ulcerogenic effects of the formulations, we examined the action of the formulations on carrageenan-induced edema in rats as well as their ulcerogenic actions in the same species. Compared with IND alone, albumin-IND-olive oil (9:1:4.3), albumin-IND-linolenic acid (9:1:4.3), albumin-IND-linolic acid (9:1:4.3), albumin-IND-oleic acid (9:1:4.3), albumin-IND-stearic acid (9:1:4.3), and albumin-IND-tristearin (9:1:4.3) formulations all exhibited a more potent inhibitory effect on carrageenan-induced edema. In addition, the inhibitory effects on edema formation of an albumin-IND (9:1) complex was as strong as that of IND alone. These results suggested that the bioavailability of IND was increased by olive oil, fatty acid, and tristearin as absorbefacient agents. The increase in the bioavailability was evident from the fact that the mean plasma levels, maximum plasma levels (Cmax), and area under plasma concentration-time curve (AUC) values after oral administration of the albumin-IND-olive oil (9:1:4.3) formulation was significantly greater than that after administration of the drug alone. With respect to their ulcerogenic properties, the formulations were significantly less active than IND alone, suggesting that a reduction in the ulcerogenic activity of IND was by produced complexation with egg albumin.

Administration, Oral↗

Pharmacological and pharmaceutical properties of freeze-dried formulations of egg albumin, indomethacin, olive oil, or fatty acids. II.

To confirm the increased bioavailability of indomethacin (IND) when incorporated in a preparation with egg albumin and olive oil, we studied the detailed pharmaceutical characteristics of a ternary formulation consisting of egg albumin, IND and olive oil. From the results of X-ray powder diffraction measurements, the drug in the formulation was found to be in an amorphous form. When orally administered to rats, the ternary formulation significantly increased the plasma concentration and cumulative biliary and urinary excretion of IND alone as well as the urinary excretion of its major metabolite, desmethylindomethacin, compared with the drug alone. In addition, the dissolution rate of IND from the formulation was higher than that of the drug alone. These results clearly suggest that the bioavailability of IND was markedly improved by incorporating it in a protein-drug formulation containing olive oil as an absorbefacient element, and this effect may be due to an increased absorption of IND.

Administration, Oral↗

Alterations in beta-adrenergic receptor density and cyclic-AMP level in the myocardium of rats chronically treated with alcohol.

An impaired function of the myocardial beta-adrenergic receptor system has been reported in patients with end-stage heart failure and this impairment has been postulated to be a factor in further deterioration of cardiac contractile function. As ventricular dysfunction is often associated with prolonged alcohol abuse, we investigated whether or not chronic administration of ethanol could induce alterations in the beta-adrenergic receptor adenylate-cyclase system in rats. Male Wistar rats of 8 weeks of age received 33% ethanol in drinking water for 3 months. As compared with control rats drinking water, the ethanol-treated rats showed weight loss and an increase in the heart/body weight ratio. Chronic ethanol increased myocardial contents of norepinephrine and epinephrine, possibly resulting from sympathoadrenal activation. The beta-adrenergic receptor density (Bmax) of the myocardial membrane was significantly decreased in the ethanol-treated rats (27.7 +/- 9.9 vs 39.0 +/- 6.0 fmol/mg protein, p < 0.01), while the affinity (Kd) did not differ between the two groups. The myocardial content of cyclic-AMP was also reduced in the ethanol rats (865 +/- 59 vs 1055 +/- 83 pmol/g w.w., p < 0.01). These observations indicate that chronic ethanol administration depresses the function of the beta-adrenergic receptor adenylate-cyclase system. The decreased beta-adrenergic receptor density was partly attributed to down-regulation due to increased sympathetic stimulation. This impaired function may contribute to the cardiac contractile dysfunction observed in chronic alcoholics.

Animals↗

Para-aortic lymph node dissection for the treatment of advanced gastric cancer.

Para-aortic lymph node (No. 16) metastasis has been accepted as a factor responsible for non-curability in gastric cancer surgery. Recently in Japan, after detailed experimental and clinical studies of the lymph flows from the stomach and/or perigastric nodes to these No. 16 nodes, it is now considered to be curable. From 5 autopsy cases, the mean number of No. 16 nodes has been determined to be 43. The frequency of positive No. 16 metastasis (No. 16(+)) was found to be 24%, occurring in 35 of 144 cases with advanced gastric cancer following R3 gastrectomy plus No. 16 dissection. The 5 year-survival rate of R3+ No. 16 dissection was 70.1% in n1(+), 49.8% in n2(+) and 24.3% in n3(+) and had better prognoses (by Kaplan-Meier statistics) than those without dissection of the No. 16 nodes. Only 37 patients in the Japanese literature have had No. 16 dissections, and were confirmed histologically to have had No. 16(+) and subsequently survived more than 5 years. The number of those surviving No. 16(+) can be expected to increase in the near future with the adoption of R3 gastrectomy plus No. 16 dissection.

Aorta, Abdominal↗

Early gastric cancer associated with synchronous multiple liver metastasis--two rare cases.

From 1976 to 1991, 1,640 cases of gastric cancer were resected in our department. Of these, 659 (40.2%) cases were early gastric cancer (EGC). The prognosis after resection of an EGC is generally good, with a 5-year survival rate of 95%. The incidence of an EGC with synchronous liver metastasis is very rare. To our knowledge, only 15 cases of an EGC with synchronous liver metastasis have been reported in the Japanese literature. From 10 cases adequately described the EGC with synchronous liver metastasis derived only from sm-cancers (cancers confined to the submucosa) of medullary type, histologically, more commonly occurring in males than EGC generally, (of elevated type) and with positive lymph node metastasis. Here we report two additional rare cases of EGC with liver metastasis.

Aged↗

Early gastric cancer with juxta lymph node (n3) metastasis.

From 1976 to 1992, a total of 714 cases of early gastric cancer (EGC) were treated by resection in the First Department of Surgery, Kurume University Hospital. For EGC, the overall lymph node metastasis rate is generally 10%, with the lymph node metastasis observed mainly in the Group 1 perigastric nodes in both mucosal cancer and submucosal cancer. Three rare cases of an early gastric cancer with Group 3 juxta regional lymph node metastasis are described because Group 3 lymph nodes are rarely discovered. To our knowledge, only 14 other cases of EGC with juxta regional lymph node metastasis have been reported in the Japanese literature.

Aged↗

Retrospective studies of synchronous double early gastric cancer.

From 1984 to 1990, 922 cases of gastric cancer underwent resection in the First Department of Surgery, at Kurume University Hospital. Of these, 381 (41.3%) cases were early gastric cancer (EGC). Among these EGC, synchronous double early gastric cancer (double EGC), according to the diagnostic criteria of Moertel, was found in 49 (12.9%) cases involving 98 foci. In cases of a double EGC, the primary and secondary foci can be distinguished. Double EGC occurred more frequently in males than females (7.1:1). In the elderly, the incidence of a double EGC was higher than the incidence of a single EGC. Double EGC occurred more frequently in the lower third of the stomach than a single EGC. And a macroscopically elevated and histologically differentiated type primary focus was more frequently found in double EGC than in single EGC. Of the 49 secondary foci in the double EGC, 12 (24.5%) foci were a microcarcinoma of less than 5 mm in greatest diameter, and 48 (98%) were limited to the mucosa (m-cancer). Therefore, a preoperative detailed examination of the whole stomach by endoscopy and an intraoperative careful search under gastrotomy must be made in the remnant of the stomach in cases of distal or proximal partial gastrectomy to ensure adequate excision.

Aged↗

[Antibiotic prophylaxis for transurethral resection of the prostate--comparison of oral administration therapy with intravenous administration therapy].

To compare the prophylactic effect of oral and intravenous antibiotics against postoperative fever and urinary tract infection (UTI) after transurethral resection of the prostate (TUR-P), we conducted a multi-center prospective randomized study. The incidence of pyrexia over 38 degrees C was defined as the primary endpoint. One hundred and fifty patients with sterile urine before TUR-P were entered into this study. The patients were allocated randomly into the two arms; arm A cefotiam 4 g a day for 7 days, arm B tosufloxacin 300 mg a day for 7 days, based on the stratification into the 4 groups determined with/without preoperative indwelling catheters and with/without the history of preoperative UTI. Of these patients, 143 were eligible. We divided 124 patients without preoperative UTI and without indwelling catheters as the "low risk group", and the other 19 patients with preoperative UTI and/or with indwelling catheters as the "high risk group". In the low risk group, 9 patients out of 63 (14.3%) in arm A and 6 out of 61 (9.8%) in arm B had pyrexia during 7 postoperative days. The incidence of fever in arm B was 4.4% less than that in arm A and the 95% confidence limit was from -7% to 16%. In the high risk group, 4 out of 11 (36.4%) patients in arm A and none of 8 in arm B had fever but the difference was not significant. The incidence of post operative UTI in the low risk group on the 4 to 5, 9 to 12, 23 to 26 and 37 to 40 postoperative days was 8.3, 16.4, 25.0 and 23.9% in arm A and 6.7, 16.7, 29.6 and 36.7% in arm B, respectively. The prophylactic effect of oral administration of tosufloxacin is equivalent to that of the intravenous administration of cefotiam. The use of oral antibiotics is beneficial to reducing the cost of medication.

Administration, Oral↗

[NEO-MACOP-B chemotherapy for the treatment of advanced-stage aggressive non-Hodgkin's lymphoma].

We conducted a new chemotherapy, NEO-MAC OP-B (addition of etoposide and mitoxantrone to MACOP-B with half dose of methotrexate and half administration of doxorubicin), to reduce severe mucositis, which is a major toxic effect of MACOP-B, and to increase its effect with etoposide and mitoxantrone as new non-cross resistant drugs. Between Jan. 1989 and Mar. 1993, 12 patients with previously untreated advanced aggressive non-Hodgkin's lymphoma (NHL), 2 patients with adult T cell lymphoma, and 3 patients with relapsed NHL, were treated with NEO-MACOP-B. After termination of NEO-MACOP-B therapy, 83.3% of 12 patients with previously untreated NHL were in complete remission (CR). After median follow-up of 22 months, Kaplan-Meier estimates showed that overall survival of 12 previously untreated patients was 71.4%, and relapse-free survival of complete responder was 83.3%. Toxic effects on all 17 patients were moderate with a lower incidence of severe mucositis (only one patient with relatively severe stomatitis, WHO Grade 3). No treatment related deaths were observed. Thus, NEO-MACOP-B is an effective and safe treatment for advanced stage aggressive NHL.

Adult↗

Evidence for active transport of 3H-androgens across the epididymal epithelium in the rat.

The effect of metabolic inhibitors on transepithelial movement of 3H-androgens was investigated by in vivo perifusion and subsequent micropuncture of caput and cauda epididymal tubules. Epididymal tissue (adenosine triphosphate (ATP) concentrations were determined at 1 h after exposure of perifusion fluid with metabolic inhibitor. To determine whether or not metabolic inhibitor alters intraluminal androgen-binding protein concentration or androgen binding to interstitial proteins in the caput epididymis, 3H-dihydrotestosterone (DHT) binding to interaluminal androgen-binding protein and bound vs free androgen ratio in the interstitial fluid after 1 h perifusion with fluid containing metabolic inhibitor around caput epididymal tubules were examined. Proluminal movement of 3H-androgens and tissue ATP concentrations in the caput and cauda epididymis were significantly decreased by addition of dinitrophenol (DNP) or potassium cyanide to the perifusion fluid. Relative intraluminal androgen-binding protein protein concentration and bound vs free 3H-androgen ratio in the interstitial fluid were not altered when DNP or potassium cyanide was added to the perifusion fluid. These results demonstrate for the first time that an energy-dependent mechanism may be involved in the epididymal androgen uptake.

Animals↗

Transepithelial movement of 3H-androgen in rat seminiferous and caput epididymal tubules: saturability and effect of competition with estradiol.

Proluminal movement of 3H-testosterone from peritubular space to intratubular fluids of the adult rat testis and epididymis was studied by using in vivo microperfusion and subsequent micropuncture of seminiferous tubules and caput epididymal tubules. Tubules were perifused with Minimum Essential Medium containing 3H-testosterone. To determine if androgen transport is saturable, 40, 80, 160, and 320 microCi 3H-testosterone were included in the perfusion fluid. Radioactivity of 3H-androgens in the intraluminal fluids was determined at 1 hour after perfusion. Transepithelial 3H-androgen movement in the testis was linear (r = 0.735, p < 0.001, y = 0.17 x +5.6). The movement of 3H-androgen across the epididymal epithelium was saturable (Vmax of 326.5 nM/hr and Km of 77 nM). To determine the effect of estradiol on proluminal androgen movement, estradiol at 10X the cocentration of 3H-testosterone was incorporated in the perifusion fluid. Proluminal 3H-androgen movement into the seminiferous and epididymal tubules was not affected by addition of estradiol to the perifusion fluid. These findings support our previous observations that proluminal transepithelial movement of 3H-androgens could be mediated by its binding to a specific intraluminal androgen binding protein.

Animals↗

[Clinical studies of S-1108, a new oral cephem, in pediatric patients].

Clinical studies of S-1108, a new oral cephem, in pediatric patients were conducted and results are summarized below. 1) Clinical effects of S-1108 against 18 cases of bacterial infections were excellent in 5 cases, good in 10 cases, fair in 1 case and poor in 2 cases, thus the clinical efficacy rates was 83.3%. 2) Bacteriological effects were evaluated in 16 strains. The elimination rate was 100%. 3) No adverse effects nor abnormal laboratory test results were observed in any of the cases.

Administration, Oral↗

Microassay of sperm concentration in the rat epididymis by micropuncture technique.

Micropuncture samples taken from the rete testis, caput, corpus and cauda epididymidis of adult rats were assayed for intraluminal sperm concentrations. The amount of fluid resorbed from the efferent duct and epididymal lumen was calculated based on the sperm concentration. Epididymal sperm concentrations increased from the rete fluid to the cauda fluid through the caput fluid. Eighty-nine percent of the fluid leaving the rete testis is resorbed by the efferent ducts and proximal epididymal tubule, and 96% of the fluid leaving the rete testis is resorbed in the distal cauda epididymidis. Resorption is important for the control of intraluminal fluid by the epididymis.

Animals↗

Preparation of a human monoclonal antibody derived from cervical lymph nodes of a patient with anaplastic carcinoma of the thyroid.

An anaplastic carcinoma cell line, KOA-2, was established from a 59-year-old patient with anaplastic carcinoma of the thyroid who died only one month after diagnosis in association with rapid progress of her disease. A human monoclonal antibody, 3C5 (IgM), was generated by a fusion of human B lymphoblastoid cell line, HO-323, with lymphocytes from cervical lymph nodes of the patient, who had been treated with local immunotherapy. Immunocytostaining demonstrated that 3C5 reacted with KOA-2, and membrane immunofluorescence demonstrated that 3C5 reacted with cell membranes. Immunohistochemical staining studies demonstrated selective reaction of 3C5 with three malignant tumors, anaplastic carcinoma of the thyroid (2/4 sampled tested), papillary carcinoma of the thyroid (8/12), and breast cancer (2/6), but no reaction with specimens of benign thyroid disease or normal thyroid gland was demonstrated. The monoclonal antibody and the cell line established from one patient have potential use in the analysis of carcinogenesis and applications to therapy of anaplastic carcinoma of the thyroid.

Antibodies, Monoclonal↗