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T Kaku

Publications and source records attributed to T Kaku.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prognostic factors in ovarian carcinosarcoma: a clinicopathological and immunohistochemical analysis of 23 cases.

UNLABELLED: Carcinosarcoma of the ovary is a rare, highly aggressive neoplasm comprising histologically of both epithelial and mesenchymal components. The aim of this study was to evaluate the clinicopathological prognostic factors in ovarian carcinosarcoma, including the immunohistochemical expression of p53 protein and Ki67. METHODS AND RESULTS: Twenty-three cases of carcinosarcoma of the ovary were studied retrospectively. The clinicopathological and immunohistochemical parameters including p53 and Ki67 staining were statistically analysed to investigate the prognostic significance of this tumour. The overall 5-year survival rate was 27.1%; 100% for stage I, 31.3% for stage II, 10.9% for stage III and 0% for stage IV. The low-stage group (stages I and II) was found to be a significant prognostic factor for patient survival (P = 0.0113). None of the other factors (tumour size, histological type of carcinomatous and sarcomatous components, mitotic count, vascular space invasion and immunoreactivity for p53 protein and Ki6 7) was found to be a statistically significant prognostic indicator. CONCLUSIONS: Ovarian carcinosarcoma is a rare malignancy with poor prognosis. In this study, advanced stage appears to be poor prognostic indicator of survival in patients with ovarian carcinosarcoma.

Adult↗
PubMed2000

Selective block of late currents in the DeltaKPQ Na(+) channel mutant by pilsicainide and lidocaine with distinct mechanisms.

The congenital long QT syndrome is an inherited disorder characterized by a delay in cardiac repolarization, leading to lethal cardiac arrhythmias such as torsade de pointes. One form of this disease involves mutations in the voltage-dependent cardiac Na(+) channel, which includes an in-frame deletion of three amino acids (Lys-1505, Pro-1506, and Gln-1507; DeltaKPQ). The potential for selective suppression of the mutant was examined by heterologous expression of DeltaKPQ-Na(+) channels in Chinese hamster fibroblast cells via single-channel recording. In a single-channel cell-attached patch study, DeltaKPQ-Na(+) channels yielded currents that peaked at approximately 1 ms after voltage steps to 0 mV with aberrant late currents, which were composed of burst and isolated openings. The affinity of certain anesthetics (pilsicainide and lidocaine) to the late currents of the mutant channels was examined. It was revealed that 1) pilsicainide (1 microM), an open channel blocker of voltage-dependent Na(+) channels, remarkably decreased the late currents primarily by the shortening of burst duration without suppressing the initial peak current; and 2) lidocaine (1 microM), an inactivated channel blocker, decreased the late currents primarily by the suppression of isolated channel openings. Because the late currents in DeltaKPQ mutants are mainly composed of the burst openings, we conclude that pilsicainide is capable of selectively blocking the late currents in the mutant Na(+) channels that show dominant abnormal burst openings such as in DeltaKPQ mutants.

Animals↗
PubMed1999

The grading of lymphovascular space invasion in endometrial carcinoma.

BACKGROUND: This study was conducted to elucidate the prognostic significance of a three-grade system for lymphovascular space invasion (LVSI). METHODS: The prognostic significance of the grading of LVSI as compared with other pathologic variables was evaluated in a study of 303 Japanese women with endometrial carcinoma. The criteria for determining the grade of LVSI were as follows: none (no LVSI), mild (a focus of LVSI was recognized around a tumor), and severe (diffuse or multifocal LVSI were recognized around the tumor or in the myometrium regardless of the degree of myometrial invasion). Both univariate and multivariate regression analyses were performed. The effects of different surgical methods and adjuvant therapies on survival were also examined. RESULTS: A univariate survival analysis showed that survival significantly correlated with surgical stage, histologic grade, depth of myometrial invasion, LVSI, cervical invasion, ovarian metastasis, and tubal metastasis. Of the three grades of LVSI, survival showed the most difference between the mild and severe groups. In multivariate analysis, the highest correlation with survival was observed for LVSI (P = 0.0008). Lymph node metastasis was also significantly associated with LVSI (P = 0. 0001). The correlation between histologic variables and survival was only slightly influenced by the differences in surgical methods and adjuvant therapies. CONCLUSIONS: The grading of LVSI was found to be an important histologic prognostic variable. The severe degree of LVSI also was found to be a good indicator of lymph node metastasis. It is therefore important to evaluate the grade of LVSI based on a histologic examination of at least one cut surface of the hysterectomy specimen that macroscopically shows the deepest myometrial invasion.

Endometrial Neoplasms↗
PubMed1999

7-Nitroindazole reduces nitric oxide concentration in rat hippocampus after transient forebrain ischemia.

We investigated the effects of 7-nitroindazole, a specific inhibitor of neuronal nitric oxide (NO) synthase, on NO concentration and on blood flow in rat hippocampus after transient forebrain ischemia which was induced by 4-vessel occlusion for 10 min. NO concentration was measured directly by an NO-selective electrode method. Hippocampal blood flow was also estimated by laser Doppler flowmetry. 7-Nitroindazole [0 (vehicle), 12.5, 25, 50 or 100 mg/kg] was administered intraperitoneally 20 min before ischemia. 7-Nitroindazole at any dose used did not affect basal NO levels before ischemia. 7-Nitroindazole (25, 50 and 100 mg/kg) reduced the NO concentration significantly during post-ischemic early reperfusion. Before 10 min of ischemia and during post-ischemic early reperfusion, there were no significant differences in hippocampal basal blood flow and reactive hyperemia between vehicle- and 7-nitroindazole-treated groups. These results demonstrate that the neuronal NO synthase inhibitor, 7-nitroindazole, can effectively inhibit NO synthesis in rat hippocampus during post-ischemic early reperfusion.

Animals↗
PubMed1999

Pattern of expression of beta-defensins in oral squamous cell carcinoma.

Human beta-defensin (hBD)-1 and hBD-2 are antimicrobial peptides that have been detected in certain types of epithelia, including the skin and oral epithelia. It has been suggested that bacterial infection is an important factor in the process of carcinogenesis. The expression of hBDs in oral squamous cell carcinoma (SCC) may be down-regulated. We studied the pattern of expression of hBD-1 and hBD-2 mRNA in oral (SCC) cell lines and in tumor samples obtained from four patients with oral SCC who underwent surgical resection, by reverse transcription-polymerase chain reaction (RT-PCR). Human gingival epithelial (HGE) cells were used as the control. The effect of various inflammatory cytokines on hBD-1 and hBD-2 expression in the HGE cells and SCC cell lines, was also studied. hBD-1 mRNA was detected in the Ca-9, SCC-9 and HSC-4 cell lines, but not in the SAS and KB cell lines. hBD-2 mRNA was detected in all five cell lines. All four tumor samples expressed both hBD-1 and hBD-2 mRNA, although the mRNA level of each protein varied. These results indicate that SCCs in which hBD expression is downregulated, may be susceptible to bacterial infection.

Aged↗
PubMed1999

Endometrial carcinoma associated with hyperplasia--immunohistochemical study of angiogenesis and p53 expression.

OBJECTIVE: To clarify the hypothesis that there are two pathways of endometrial carcinogenesis we compared the frequency of abnormal p53 protein expression and angiogenesis in endometrial carcinomas with and without hyperplasia. METHODS: Specimens obtained from 70 patients with stage I-IV endometrial carcinomas were available for this immunohistochemical study. Immunohistochemical staining for factor VIII-related and p53 antigens was performed using a standard immunoperoxidase technique (Histofine SAB-PO Kit, Nichirei Co., Tokyo, Japan). Microvessels were highlighted by staining endothelial cells for factor VIII-related antigen, and microvessel density (MVD) was counted in a x200 field (0.785 mm2 per field) in the area of most active neovascularization. p53 protein was detected with monoclonal anti-p53 antibodies (clone DO-7, Dako, Santa Barbara, CA). RESULTS: Twenty-six of 73 (37%) patients had hyperplasia in the endometrium adjacent to the carcinoma. Significantly more patients with low MVD (less than 60) had carcinoma with hyperplasia than those with carcinoma without hyperplasia (P = 0.0053). p53 expression was noted in a carcinomatous area in 8 of 26 patients (30. 8%) with hyperplasia compared to 26 of 44 (59.1%) without hyperplasia, and the difference was statistically significant (P = 0. 0220). CONCLUSION: The presence or absence of hyperplasia is a different pathogenesis and important in assessing the biological behavior of endometrial carcinoma, especially concerning angiogenesis and p53 expression.

Adenocarcinoma↗
PubMed1999

Comparison of p53, Ki-67, and CD44v6 expression between primary and matched metastatic lesions in ovarian cancer.

OBJECTIVE: Many studies have demonstrated that clinically evident tumor cells already carry multiple genetic alterations and further accumulation of genetic alteration causes tumor progression which plays a role in metastasis. Therefore, it could be expected that malignant potential in the metastatic site is more aggressive than that in the primary site. Using several immunohistochemical markers (p53, Ki-67, and CD44v6), we investigated an alteration of malignant potential. METHODS: We immunohistochemically examined expression of p53, Ki-67, and CD44 in primary and metastatic lesions of ovarian cancer. Fifty-six samples of primary lesions and matched metastatic sites from 56 patients with primary epithelial ovarian cancers were included in this study. RESULTS: In 16 cases (28%), the histological grade of the metastatic lesion increased. This difference was statistically significant (P = 0.0232). In 16 cases (28%), the expression of p53 increased in the metastatic lesions, in 5 pairs from negative to positive, whereas the case decrease in the metastatic lesions was only 1. This difference was statistically significant (P = 0.0046). There was no significant difference in Ki-67 labeling indices and expression of CD44v6 between the primary and matched metastatic lesions. The degree of p53 expression in the metastatic lesions significantly correlated with disease-free survival (P = 0.0482), whereas that in the primary lesions did not. Moreover, high p53 expression in the metastatic lesions significantly correlated with disease-free survival in multivariate analysis. CONCLUSIONS: The p53 expression in metastatic lesions may reflect an aggressive biologic behavior in ovarian cancer.

Adenocarcinoma↗
PubMed1999

Predicting pelvic lymph node metastasis in endometrial carcinoma.

BACKGROUND: To determine the possibility of individualizing the pelvic lymph node dissection in patients with endometrial cancer, the relationship between pelvic lymph node (PLN) metastasis and various prognostic factors was retrospectively investigated. METHODS: From 1979 to 1994, 175 patients with endometrial carcinoma were treated with either total or radical hysterectomy combined with a PLN dissection as initial therapy. The prognostic factors examined included clinical stage, patient age, histological grade, the microscopic degree of myometrial invasion (DMI), cervical invasion, adnexal metastasis, and macroscopic tumor diameter (TD). RESULTS: Of the 175 patients undergoing PLN dissection, 24 (14%) had PLN metastasis. An endometrial cancer with PLN metastasis had a significantly longer diameter than those without PLN metastasis. The frequency of PLN metastasis increased along with increases in tumor diameter. A logistic regression analysis revealed DMI and TD to be independently correlated with PLN metastasis. The formula based on the coefficients of TD and DMI obtained from the analysis also showed a good correlation, which allowed us to estimate the probability of patients having PLN metastasis. CONCLUSIONS: DMI and TD could accurately estimate the status of PLN in endometrial carcinoma patients.

Adenocarcinoma↗
PubMed1999

Prognostic significance of epithelial-stromal vascular cuffing and microvessel density in squamous cell carcinoma of the uterine cervix.

OBJECTIVE: Tumor angiogenesis has been shown to play an important role in tumor growth and metastasis. This study examines the prognostic significance of two histological markers of angiogenesis, i.e., vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, and microvessel density (MVD), the number of microvessels in a unit area, in cervical squamous cell carcinoma. METHODS: One hundred twenty-two specimens from surgically resected uteri with cervical squamous cell carcinoma were histologically reviewed and immunostained for CD34. VC was graded into "none," "incomplete," and "complete." The MVD was determined by counting the microvessels with a light microscope within a x200 field area where neovascularization occurred most actively. Stromal inflammation was also split into three grades. The relationship of VC or MVD to clinicopathological prognostic factors such as FIGO stage, cervical stromal invasion, lymph-vascular space invasion, pelvic lymph node metastasis, and parametrial invasion was evaluated using univariate and multivariate analyses. RESULTS: The patients with a complete VC pattern showed a significantly worse prognosis compared to those with a pattern graded as either none or incomplete (P<0.011 and P<0.0001, respectively). The Cox regression analysis revealed the complete VC pattern, together with parametrial invasion, to be an independent prognostic indicator for overall survival. MVD and the grading of stromal inflammation showed no significant relationship with VC or overall survival. CONCLUSIONS: The complete VC pattern may therefore be a useful prognostic indicator in cervical squamous cell carcinoma.

Adult↗
PubMed1999

Ischio-spinal dysostosis: a previously unrecognised combination of malformations.

BACKGROUND: Ischial hypoplasia is an extremely rare malformation, both as an isolated anomaly and as a syndromic constituent. OBJECTIVE: To elucidate the clinical and radiological characteristics in five patients with the combination of ischial hypoplasia and spinal malformations. MATERIALS AND METHODS: The clinical records and radiographs of two females and three males, ranging in age from 3 months to 38 years, were evaluated. RESULTS: Ossification defects of the ischial rami were symmetrical and total in four patients, whereas the right ischial ramus was partly ossified in the other patient. All patients possessed multiple segmental defects of the spine, with rib anomalies of varying severity. One patient characteristically showed multiple rib gaps, resulting in respiratory distress. Severe anomalies of the cervical spine were evident in two patients. Four patients exhibited lumbosacral hypoplasia, which ultimately led to cauda equina syndrome in three older patients. One patient had mild facial dysmorphism and another had a diversity of anomalies, including ichthyosiform skin changes. Four patients were sporadic cases, whereas the other patient was born to consanguineous parents. CONCLUSIONS: The combination of anomalies in these patients constitutes a recognisable pattern of malformations but may represent a heterogeneous group of disorders.

Abnormalities, Multiple↗
PubMed1999

In situ detection of gelatinolytic activity in developing craniofacial tissues.

Frozen tissue sections of developing and adult rat heads were incubated on a film coated with a gelatin-containing colloidal silver emulsion in order to detect gelatinolytic activity present in the different tissues. The method, termed film in situ zymography, is based on the ability of the thiol group of the propeptide released from the degraded gelatin to induce a structural change in the colloidal silver and thereby a visible change in color. The frozen tissue sections mounted on the coated film were incubated at 37 degrees C overnight. Gelatinolytic activity was detected as a color change from yellow to red. The activity of gelatinase was completely blocked by phenanthroline, which inhibits matrix metalloproteinases. Gelatinolytic activity was widely present in the oral epithelium, tooth buds, tongue, Meckel's cartilage, salivary glands, and other tissues. The intensity of the gelatinolytic activity varied among the different tissue types. The present study demonstrated gelatinolytic activity in both developing and adult craniofacial tissues. These results suggest that gelatinolytic activity plays an important role in normal turn-over in several tissues. Whereas some of the activity also in the developing rats may be related to this turn-over process, some of it is probably directly associated with developmental changes.

Animals↗
PubMed1999

Stimulation by low concentrations of fluoride of the proliferation and alkaline phosphatase activity of human dental pulp cells in vitro.

Fluoride has been used for decades, either systemically or topically, to prevent dental caries. The purpose of this study was to clarify the effects of low concentrations of fluoride on proliferation, differentiation and extracellular-matrix synthesis in normal human dental pulp cells (DP-1 and DP-2) in vitro. The effects were compared with those on a human osteoblastic osteosarcoma cell line, TE-85. Fluoride at micromolar concentrations significantly and dose-dependently stimulated [3H]thymidine incorporation into DNA in DP-1, DP-2 and TE-85 cells, with optimal effects around 50 microM, by 127 +/- 7%, 124 +/- 0.6% and 152 +/- 13.4%, respectively. To assess the potential influence of fluoride on cell differentiation, the effects of mitogenic concentrations on alkaline phosphatase activity were measured. Fluoride significantly increased the enzyme's activity in DP-1 and TE-85 by 177 +/- 12% and 144 +/- 12.3%. To evaluate the effect on extracellular-matrix synthesis, the synthesis of type I collagen was indirectly determined by an assay of procollagen type I c-peptide production. Fluoride significantly increased that production by 150 +/- 8.7% in TE-85, but not in either DP-1 or DP-2. These observations suggest that fluoride, if used at low concentrations, could be a useful therapeutic agent where increased regeneration of dentine is desired, such as after pulp amputation, by stimulating the proliferation and differentiation of the dental pulp cells.

Alkaline Phosphatase↗
PubMed1999

A follicle-stimulating hormone-secreting gonadotroph adenoma with ovarian enlargement in a 10-year-old girl.

OBJECTIVE: To report a rare case of gonadotroph adenoma accompanied by ovarian enlargement in a child. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 10-year-old Japanese girl with multiple cysts of both ovaries. INTERVENTION(S): Endocrinologic assays, immunohistochemical staining, ultrastructural observations, and in vitro analysis. MAIN OUTCOME MEASURE(S): The endocrinologic assays showed an elevated serum FSH level. The tumor cells excised from the gonadotroph adenoma were immunohistochemically positive for antihuman FSH monoclonal antibody. When cultured in vitro, the tumor cells secreted FSH in the primary culture. RESULT(S): The gonadotroph adenoma produced FSH. After transsphenoidal surgery, both ovaries decreased in size. CONCLUSION(S): The ovarian enlargement was induced by endogenous FSH from the gonadotroph adenoma. To our knowledge, this is the first reported case of gonadotroph adenoma accompanied by ovarian enlargement in childhood or adolescence.

Adenoma↗
PubMed1999

Alpha1-antitrypsin deficiency and toxic shock: a Japanese autopsy case.

A 74-year-old Japanese female presented with the sudden appearance of hemorrhagic purpuric ecchymoses on her lower extremities and with fever and chills, and died on the fifth day of hospitalization. A diagnosis of alpha1-antitrypsin (AT) deficiency was made postmortem. The liver weighed 1260 g. Histological sections from the liver revealed rather severe fatty changes of the hepatocytic parenchyma and partial loss of the normal hepatic architecture with fibrosis. The hepatocytes contained periodic acid-Schiff (PAS)-positive, diastase-resistant and alpha1-AT-positive intracytoplasmic globules. There was markedly increased inflammatory infiltration with severe edema and congestion, accompanied by fibrous, thickened pulmonary alveolar walls with fibrin deposition in the lungs (right, 410 g; left, 280 g), which suggest findings similar to those seen in multiple organ failure. Mild pulmonary emphysema was also present in the upper lobes of the lungs. Histological sections from the hemorrhagic necrotic ecchymoses of the skin showed marked neutrophil infiltration over the subcutaneous tissue with bleeding and blistering. A finding of thrombophlebitis was also found in the subcutaneous tissue. No bacteria were detected in the ecchymoses, the urine or the blood. Plasma protein analysis revealed a lower level (9.5 micromol/L) of alpha1-AT and a higher level (330 U) of anti-streptolysin O (ASO). These findings suggest that the patient died of toxic shock-like syndrome and that alpha1-AT deficiency might have facilitated the development of the toxic shock. To our knowledge, this is the first case of toxic shock associated with alpha1-AT deficiency.

Adult↗
PubMed1999

Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro.

The pineal secretory product melatonin reportedly regulates release of growth hormone in humans and prevents phototherapy-induced hypocalcemia in newborn rats, suggesting that melatonin affects bone metabolism. Little is known about the effects of melatonin on bone in vitro or in vivo. The present study was undertaken to examine whether melatonin acts directly on normal human bone cells (HOB-M cells) and human osteoblastic cell line (SV-HFO cells) to affect osteogenic action in vitro. The effect of melatonin on bone cell proliferation was determined using the 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carbo xanilide (XTT) assay after a 24 hr incubation with melatonin. Melatonin significantly and dose-dependently increased the proliferation in HOB-M cells and SV-HFO cells by 215 +/- 22.1%, and 193 +/- 6.4%), respectively, with a maximal effect at a concentration of 50 microM. To evaluate the effect of melatonin on bone cell differentiation, alkaline phosphatase (ALP) activity, osteocalcin secretion and procollagen type I c-peptide (PICP) production (a measure of type I collagen synthesis) were measured after a 48 hr treatment. While melatonin at micromolar concentrations did not significantly affect either the ALP activity or the osteocalcin secretion, it significantly and dose-dependently increased the PICP production in HOB-M cells and SV-HFO cells by 983 +/- 42.2%, and 139 +/- 4.2%, respectively, with the maximal stimulatory doses between 50 and 100 microM. These results provide new evidence that melatonin stimulates the proliferation and type I collagen synthesis in human bone cells in vitro, suggesting that melatonin may act to stimulate bone formation.

Alkaline Phosphatase↗
PubMed1999

Cerebral gumma showing spontaneous regression on magnetic resonance imaging study--case report.

A 75-year-old male presented with the complaint of headache. Magnetic resonance (MR) imaging demonstrated a low-signal intensity area on both T1- and T2-weighted images with ring-like enhancement and adhesion of the dura appearing as dural tail sign. Follow-up MR imaging demonstrated spontaneous regression, so the preoperative diagnosis was malignant lymphoma. Histological examination revealed typical granuloma. Treponema pallidum hemagglutination assay tests of serum and cerebrospinal fluid were positive for active syphilis. The enhanced mass totally disappeared after 4 months of erythromycin therapy. The final diagnosis was cerebral gumma. The incidence of syphilis is increasing, so cerebral gumma should be included in the differential diagnosis of hypovascular tumors that involve both the parenchyma and dura even in the presence of spontaneous regression.

Aged↗
PubMed1999

Histopathological factors influencing pelvic lymph node metastases in two or more sites in patients with cervical carcinoma undergoing radical hysterectomy.

BACKGROUND: Lymph node metastasis has been one of the strongest prognostic factors in patients with cervical cancer. In order to select patients with high risk for recurrence, a relationship between status of lymph node and other histopathological parameters was investigated in the patients treated with radical hysterectomy with pelvic lymph adnectomy. METHODS: Of 483 patients undergoing radical hysterectomy with pelvic lymph adnectomy, 309 had stage Ib disease, 62 stage IIa, and 112 stage IIb. RESULTS: Pelvic lymph node metastasis(PLNM) was positive in 98 patients (20%). Of those positive patients, 51(56%) had metastasis in one site, 25 (26%) in two sites, and 22 (22%) in three or more sites. There was a significant difference in survival between patients with metastasis in one or no sites and those in two or more sites (p<0.0001). There was a relationship between PLNM in more than two sites and histological parameters such as histologic subtype, longitudinal diameter of cervical lesion, degree of stromal invasion, depth of stromal invasion, lymph-vascular space invasion, parametrial invasion, and corpus invasion. All of these parameters except for histologic subtype were significantly correlated with the number of positive lymph node sites. Multivariate analysis revealed that among these parameters, longitudinal diameter of the cervical lesion, parametrial invasion, and lymph-vascular space invasion were independently significantly correlated with PLNM in two or more sites. CONCLUSIONS: From these results, patients having these three histopathological parameters could be considered as those with extensive disease distribution.

Adenocarcinoma↗