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K Matsuzawa

Publications and source records attributed to K Matsuzawa.

At least 19 recordsLinked to original sources
PubMed2001

Histone H3 mRNA in situ hybridization for identifying proliferating cells in human pancreas, with special reference to the ductal system.

In general, the incidence of proliferating cells parallels that of carcinogenesis. We have investigated proliferating activity and phenotype expression in epithelial cells in normal tissue, mucinous metaplasia and ductal adenocarcinoma of the pancreas. Twenty-eight resected pancreases (15 cases of pancreatic ductal adenocarcinoma and 13 cases of other diseases) were examined. Formalin-fixed, paraffin-embedded tissue sections were examined for proliferating cell activity using histone H3 mRNA in situ hybridization and immunostaining for Ki-67. In the normal pancreas, the labelling indices for proliferating cells were low and no generating zone was found. The following progressive increase was found in the labelling indices: normal ductal epithelium < mucinous metaplasia without papillary hyperplasia < mucinous metaplasia with papillary hyperplasia < ductal carcinoma. In the pancreatic ductal adenocarcinomas, the S-phase fraction, as defined by the ratio H3-mRNA-labelling index/Ki-67-labelling index, increased as the degree of differentiation decreased. Mucinous metaplasia with papillary hyperplasia showed organoid differentiation toward pyloric mucosa. If used in combination with other proliferative markers on paraffin-embedded tissue sections, histone H3 mRNA in situ hybridization could open broader perspectives on the biology of cell proliferation in the pancreatic ductal system.

Adenocarcinoma↗
PubMed2001

Helicobacter pylori and two ultrastructurally distinct layers of gastric mucous cell mucins in the surface mucous gel layer.

BACKGROUND AND AIMS: Helicobacter pylori locate not only on the apical surface of surface mucous cells but also in the mucous gel layer covering the gastric mucosa. The present study was undertaken to observe the mucous gel layer itself and any H pylori in this layer at the electron microscopic level, and to determine whether H pylori proliferate in this layer. METHODS: We examined resected human stomachs (five cases, fixed in Carnoy's solution, paraffin embedded) under the light microscope, and gastric biopsy specimens (10 cases, fixed in glutaraldehyde with or without osmium, epoxy embedded) under the electron microscope. We performed histochemical staining for gastric mucins and immunostaining for H pylori, gastric gland mucous type mucins, and intestinal mucins. RESULTS: Under the electron microscope, surface mucous cell type mucins and gland mucous cell type mucins in the mucous gel layer covering gastric mucosa without intestinal metaplasia showed reticular and band like structures, respectively. H pylori were frequently found as small aggregates within the mucous gel layer of surface mucous cell type mucins, and H pylori within these aggregates were seen dividing. H pylori were frequently found in the mucous gel layer of the surface mucous cell type mucins along the border with the layer of gland mucous cell mucins. Occasionally, H pylori were trapped by frayed thin threads of the gland mucous cell type mucins. CONCLUSIONS: The two types of gastric mucins in the mucous gel layer differ in ultrastructure. H pylori preferentially colonise and form microcolonies within the mucous gel layer of surface mucous cell type mucins. Mucins from gland mucous cells may disturb the movement of H pylori within the mucous gel layer.

Adult↗
PubMed2000

The diagnostic significance of left auricular thrombus in F344/N rats.

In the process of assessing the main cause of death in F344/N rats from the aging farm of our institute, we have often found left auricular thrombus in autopsy cases of moribund animals. In 319 autopsy cases, 45 were of left auricular thrombus and 44 were accompanied by hematopoietic neoplasms, including overt leukemia and a pre-leukemic condition of leukemia. In cases without splenomegaly, this lesion was found in 13 of 21 animals (61.9%) whereas, in cases with splenomegaly, 31 of 239 were positive for this lesion (13.0%). Thus, left auricular thrombus may be an important macroscopic diagnostic criteria of hematopoietic neoplasms, especially when splenomegaly is absent. Furthermore, this lesion tended to arise in aged animals despite the presence of splenomegaly. These results would therefore greatly contribute to aging science by confirming the health condition of experimental rats and the accuracy of subsequent results.

Journal Article↗
PubMed2000

Cancer incidence in old age.

The incidence of all cancer increases with age through most of the human life span, but its real incidence at very old ages has not been well elucidated to date. Clarification of the real incidence of cancer in old age, especially among centenarians, may well provide pivotal information to understand the characteristics of humankind. In this study, autopsy records of the Annual of the Pathological Autopsy Cases in Japan, 1991-1996, vols. 34-39 (Japanese Society of Pathology, Tokyo) were used. Cases over 90 years old were studied individually for accurate analysis. The incidence of cancer peaked in the 6th decade and that of multiple cases in the 8th decade. In groups over 90 years of age, the incidence at 5-year intervals did not show any significant decrement. Moreover, the metastatic rate and rate of death due to cancer among centenarians was about three-fourths and two-thirds, respectively, of that of cases aged 90-94 years. The decrease in the metastatic ratio and less mortality due to cancer occurring at the oldest ages are considered due to the nature of cancer itself. The fact that the incidence of cancer does not increase would suggest that certain people among those of advanced age have a special resistance to it.

Aged↗
PubMed2000

Randomized trial of cisplatin and carboplatin versus cisplatin, vinblastine and bleomycin in ovarian cancer.

Between January 1992 and July 1997, 202 cases of epithelial ovarian cancer were registered and assigned randomly to a combination of cisplatin and carboplatin (PP group), or cisplatin, vinblastine and bleomycin (PVB group). We analyzed 189 patients whose clinical records were available. The PP chemotherapeutic regimen was advantageous in terms of overall survival compared to the PVB regimen until 4 years after the initial operation. However, the 5-year survival rates were almost the same in both groups. However, in stage III patients, the mean survival time in the PP group was 51.4 months and that in the PVB group was 23.3 months, and there was a statistically significant difference in the survival curves between the two groups (p = 0.0158). The 5-year survival rates were 31.1 and 20.4% in the PP and PVB groups, respectively, in stage III patients. The PP regimen was also significantly superior in patients with macroscopic residual tumor after the initial operation, and the 5-year survival rates were 25.7 and 10.1% in the PP and PVB groups, respectively (p = 0.0128). However, there was no significant difference between the two regimens in patients without macroscopic residual tumor. Cox's proportional hazards regression analysis showed that tumor stage, presence of macroscopic residual tumor, and the chemotherapeutic regimen used were significant prognostic factors. In conclusion, the PP chemotherapeutic regimen is superior to the PVB regimen especially in the treatment of advanced ovarian cancer.

Adult↗
PubMed2000

Differences in survivability among F344 rats.

Important parameters to identify and develop appropriate animal models for longevity science include survivability, age-related disorders, and easy handling of aged individuals. It is found that F334/Du and F344/N have distinctive strain difference in these parameters. The finding suggests F334/Du and F344/N, even though they are historically siblings, need clearly separate identification when used as animal models for aging science, in particular, longevity science.

Aging↗
PubMed2000

Efficacy of neuroendoscopic procedures in minimally invasive preferential management of pineal region tumors: a prospective study.

OBJECT: This prospective study is based on a consecutive series of 20 patients with pineal region tumors who underwent minimally invasive preferential management. The purpose of this report is to discuss the role of neuroendoscopic procedures in the management of pineal region tumors. METHODS: If the tumor markers alpha-fetoprotein and human chorionic gonadotropin were not detected in serum and there was significant ventricular dilation visualized on neuroimages, neuroendoscopic surgery was first applied for tumor debulking with tissue diagnosis and gross morphological analysis of the tumor and the intraventricular structures, followed by third ventriculostomy. Subsequent procedures were determined on the basis of verified individual tumors. For treatment of germinomas and pineoblastomas, if no tumor dissemination was confirmed by pre-, intra-, or postoperative findings, stereotactic radiotherapy or radiosurgery was performed after one course of chemotherapy with the ICE regimen (isofomid, cisplatin, and etoposide) and followed by two additional courses of chemotherapy. For treatment of malignant germ cell tumors, after extensive surgery, adjuvant chemotherapy with the ICE regimen was performed in three courses in all cases. Then radiotherapy was started using various methods, depending on the evidence of tumor dissemination. For treatment of teratomatous and neuroectodermal tumors other than pineoblastomas, extensive surgical removal was performed. As for adjuvant therapy, if the tumor was a low-grade glioma or if the patient was younger than 5 years of age, postoperative treatment did not include radiotherapy. If the tumor was a malignant teratoma or high-grade glioma, conventional focal radiotherapy was performed, followed by chemotherapy with ICE for 1 year. All but two treated patients had ventriculomegaly. Neuroendoscopic procedures were performed in six of 15 treated patients. Neuroendoscopic biopsy with tumor debulking offered enough material for tissue diagnosis, including immunohistochemical analysis and, in one case, revealed evidence of tumor dissemination undetectable on neuroimaging. With one exception, no shunt was required in any patient undergoing endoscopic third ventriculostomy. Stereotactic radiotherapy was performed in indicated cases. Favorable therapeutic outcomes were obtained in all cases of germinoma and pineoblastoma, with follow-up periods ranging from 24 months to 6.5 years. CONCLUSIONS: Our minimally invasive preferential regimen clarified the precise indication for neuroendoscopic procedures, and the majority of our patients with dilated ventricles and no evidence of tumor markers were treated satisfactorily with effective neuroendoscopic procedures as the initial procedure, avoiding unnecessary craniotomy and radiotherapy and promising excellent therapeutic outcomes. The treatment for malignant pineal region tumors remains a subject for further study.

Adolescent↗
PubMed1999

Specific accumulation of Rho-associated kinase at the cleavage furrow during cytokinesis: cleavage furrow-specific phosphorylation of intermediate filaments.

The small GTPase Rho and one of its targets, Rho-associated kinase (Rho-kinase), are implicated in a wide spectrum of cellular functions, including cytoskeletal rearrangements, transcriptional activation and smooth muscle contraction. Since Rho also plays an essential role in cytokinesis, Rho-kinase may possibly mediate some biological aspects of cytokinesis. Here, using a series of monoclonal antibodies that can specifically recognize distinct phosphorylated sites on glial fibrillary acidic protein (GFAP) and vimentin, phosphorylation sites by Rho-kinase in vitro were revealed to be identical to in vivo phosphorylation sites on these intermediate filament (IF) proteins at the cleavage furrow in dividing cells. We then found, by preparing two types of anti-Rho-kinase antibodies, that Rho-kinase accumulated highly and circumferentially at the cleavage furrow in various cell lines. This subcellular distribution during cytokinesis was very similar to that of ezrin/radixin/moesin (ERM) proteins and Ser19-phosphorylated myosin light chain. These results raise the possibility that Rho-kinase might be involved in the formation of the contractile ring by modulating these F-actin-binding proteins during cytokinesis and in the phosphorylation and regulation of IF proteins at the cleavage furrow.

Cell Division↗
PubMed1998

Cell cycle- and chromatin binding state-dependent phosphorylation of human MCM heterohexameric complexes. A role for cdc2 kinase.

The mammalian MCM protein family, presently with six members, exists in the nuclei in two forms, chromatin-bound and unbound. The former dissociates from chromatin with progression through the S phase. Recently, we have established a procedure to isolate chromatin-bound and unbound complexes containing all six human MCM (hMCM) proteins by immunoprecipitation. In the present study, we applied this procedure to HeLa cells synchronized in each of the G1, S, and G2/M phases and could detect hMCM heterohexameric complexes in all three. In addition, depending on the cell cycle and the state of chromatin association, hMCM2 and 4 in the complexes were found to variously change their phosphorylation states. Concentrating attention on G2/M phase hyperphosphorylation, we found hMCM2 and 4 in the complexes to be good substrates for cdc2/cyclin B in vitro. Furthermore, when cdc2 kinase was inactivated in temperature-sensitive mutant murine FT210 cells, the G2/M hyperphosphorylation of the murine MCM2 and MCM4 and release of the MCMs from chromatin in the G2 phase were severely impaired. Taken together, the data suggest that the six mammalian MCM proteins function and undergo cell cycle-dependent regulation as heterohexameric complexes and that phosphorylation of the complexes by cdc2 kinase may be one of mechanisms negatively regulating the MCM complex-chromatin association.

Biopolymers↗
PubMed1998

Churg-Strauss syndrome (allergic granulomatous angitis) presenting with ileus caused by ischemic ileal ulcer.

We report a rare case of Churg-Strauss syndrome (CSS) in a 41-year-old Japanese man with a history of middle-age onset of bronchial asthma who had severe abdominal pain. He presented with ileus caused by an annular ulcer of the ileum, attributable to mucosal ischemia resulting from necrotizing vasculitis of the mesenteric artery. He also had marked hypereosinophilia (51.5%), elevated serum IgE levels (34040 IU/ml), and generalized enlargement of the superficial cervical lymph nodes, containing eosinophilic granulomas. A stenotic lesion caused by an annular ulcer in the ileum was found and resected by laparotomy. Microscopic examination of the resected specimen revealed luminal narrowing or occlusion of small arteries in the ulcer base, subserosa, and mesenterium resulting from marked fibrotic intimal thickening with fragmentation or lack of the internal elastic lamina. These findings were diagnosed as vasculitis, scar stage. The postoperative course was uneventful, with the patient receiving a maintenance dose of prednisolone (10-15 mg/day) for 7 years subsequently. We must carefully diagnose and treat patients with middle-age onset asthma, because the symptom may be a lung manifestation of CSS, in which various organs including gastrointestinal tract are involved as a result of systemic necrotizing vasculitis.

Adult↗
PubMed1998

Immunosuppressive and antiparasitic effects of cyclosporin A on Hymenolepis nana infection in mice.

The effect of cyclosporin A, which is known to act both as immunosuppressant and as an antiparasitic drug in many host-parasite systems, was examined in a mouse-Hymenolepis nana system. When BDF1 mice were injected s.c. with cyclosporin A (100 mg kg-1 day-1) every 48 h from 11 days p.i. with eggs, expulsion of the adult worms from the intestines of mice was prevented completely until at least 30 days p.i. Worm burden, dry weight and the number of gravid proglottids were not significantly reduced. By contrast, in untreated mice most of the worms were eliminated by 19 days p.i. The drug also completely abolished acquired resistance to a challenge infection with eggs when mice were injected s.c. with cyclosporin A (100 mg kg-1 day-1) around the time of challenge infection (Days -2, -1, 0, 1 and 2 relative to challenge). Such immunosuppressive effects of cyclosporin A on worm expulsion and protective immunity to reinfection were similar to those of another immunosuppressant, cyclophosphamide. As for the antiparasitic action of cyclosporin A against H. nana, a smaller number of cysticercoids developed from eggs in mice given cyclosporin A (100 mg kg-1 day-1) for 5 days beginning 1 day before infection, than in untreated controls.

Animals↗
PubMed1998

Does binding of ouabain to human alpha1-subunit of Na+, K+-ATPase affect the ATPase activity of adjacent rat alpha1-subunit?

To ascertain whether ouabain binding to human alpha1-subunit influences coexpression of rat alpha1-subunit, the ouabain-sensitive profiles of Na+,K+-ATPase activity and 86Rb+ uptake activity and ouabain binding capacity were measured in HeLa cells stably expressing rat alpha1-subunit. The ouabain-sensitive profile of ATPase and 86Rb+ uptake activity seemed to be the sum of two components, one with high and one with low apparent affinity to ouabain, which were similar to that observed in HeLa and NRK-52E cells derived from human and rat, respectively. The ATPase activity with low sensitivity to ouabain increased in simple proportion to the amount of the rat alpha1 mRNA derived from transfected cDNA, which was determined by the reverse transcription-polymerase chain reaction method. The turnover number of the human Na+,K+-ATPase activity obtained from the ratio of the Na+,K+-ATPase activity to the ouabain binding capacity is about 150/sec. The expression of the rat alpha1-subunit had no effect on the turnover numbers of the Na+,K+-ATPase activity with high affinity to ouabain estimated from the ouabain binding capacity as the active site concentration. These results suggested that the ouabain bound to human alpha1-subunit did not inhibit the ATPase activity of the coexpressing rat alpha1 in these cells.

Animals↗
PubMed1997

Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN.

PKN is a serine/threonine protein kinase with a catalytic domain homologous to the protein kinase C family and unique N-terminal leucine zipper-like sequences. Using analyses with the yeast two-hybrid system and in vitro binding assay, we found that the regulatory domain of PKN interacted with vimentin. We then examined whether PKN would phosphorylate vimentin in vitro. Vimentin proved to be an excellent substrate for PKN, and the phosphorylation of vimentin by PKN occurred in the head domain with the result of a nearly complete inhibition of its filament formation in vitro. Similar results were also obtained with another type III intermediate filament protein, glial fibrillary acidic protein (GFAP). These results raise the possibility that PKN may regulate filament structures of vimentin and GFAP by domain-specific phosphorylation.

Animals↗
PubMed1997

Myosin binding subunit of smooth muscle myosin phosphatase at the cell-cell adhesion sites in MDCK cells.

We examined the intracellular localization of the myosin binding subunit (MBS) of smooth muscle myosin phosphatase. In MDCK cells in a confluent monolayer of polarized epithelial sheet, MBS was concentrated to the cell-cell adhesion sites. Double-immunofluorescence analysis with anti-MBS and anti-beta-catenin antibodies showed that MBS was mainly localized at the adherens junction. Furthermore, MBS was translocated reversibly between the cytosol and the cell-cell adhesion sites during the formation and disappearance of cell-cell contacts. These data suggest that MBS may play an important role in the regulation of the cell-cell adhesion.

Animals↗
PubMed1997

Timing of insults causing abnormal outcome in preterm infants 1989-1992.

OBJECTIVE: The purpose of this study was to clarify the influence of timing of brain insults causing abnormal outcome in preterm infants. METHODS: One hundred and thirty-one preterm infants were examined. The timing of brain insult was estimated from EEG or clinical findings. Development was assessed until a corrected age of 48 months. RESULTS: 39% and 4% of infants, respectively, born before and after the 28-week time point subsequently died (P < 0.05). Abnormal development was observed in 16% of the first group and 13% of the second (N.S.). None of those born before 28 weeks showed intrauterine injuries while nine of the infants which were born after this time showed intrauterine injuries (P < 0.05). Fetal distress was noted in all infants suffering neonatal death born after 28 weeks. CONCLUSION: Intrauterine brain insult was concluded to be the cause of neonatal death or abnormal development in many infants born after 28 weeks.

Brain Injuries↗
PubMed1997

Protective effect of mucosal administration of recombinant human macrophage colony-stimulating factor (rhM-CSF) on mucosal infection of Sendai virus in mice.

We investigated the protection confered by the mucosal administration of recombinant human macrophage colony-stimulating factor (rhM-CSF) against mucosal infection of Sendai virus in mice. In an experimental infection model using Sendai virus, an intranasal (i.n.) administration of rhM-CSF (20 micrograms per mouse) 2 days before injection induced significant protection against a lethal infection of this virus. Also, its antiviral activity was dependent upon the dose of rhM-CSF. However, a subcutaneous (s.c.) administration of rhM-CSF with an effective dose (20 micrograms per mouse) i.n. did not confer protection. In a time course analysis of virus growth in the lungs, mice given rhM-CSF. i.n. significantly inhibited the early period of infection, compared with the untreated mice. Moreover, the level of interferon-gamma (IFN-gamma) in lung wash fluids from the rhM-CSF-treated mice was higher than that of the untreated mice. These results suggested that the mucosal (i.n.), but not the systemic (s.c.) administration of rhM-CSF augments host resistance against mucosal infection with Sendai virus, and that its prophylactic activity is related to growth inhibition of the virus and enhanced IFN-gamma secretion in the lungs.

Animals↗
PubMed1997

Distribution of platinum in human gynecologic tissues and pelvic lymph nodes after administration of cisplatin.

BACKGROUND: Defining tissue accumulation of platinum may be of importance, since it may provide a pharmacological explanation for organ-specific cisplatin activity. This study was conducted to evaluate the efficacy of cisplatin at the tissue level in different gynecologic organs. The doses administered were equivalent to those used in neoadjuvant chemotherapy regimens. STUDY DESIGN: Cisplatin was administered intravenously to patients with cervical or endometrial cancer 1 h before operation, and platinum accumulations in tissues were assayed by the atomic absorption method. RESULTS: Platinum accumulation was highest in the cervix and next highest in the myometrium in both cancers. Platinum accumulation in ovary and lymph node was only 0.58 and 0.57 times that in the myometrium, respectively. In patients with cervical cancer, the platinum accumulations in the myometrium and cervix were significantly higher than in the ovary and lymph node. Platinum accumulation in cervical cancer tissue was lower than in the myometrium and cervix, suggesting that delivery of cisplatin to a cervical cancer is somewhat more difficult than to the normal cervix. In patients with endometrial cancer, there was significantly more accumulation in the cervix than in the ovary and lymph node. CONCLUSIONS: These data indicated that cisplatin was easily distributed to the cervix and myometrium, but not to the ovary, lymph node, and cancer tissues.

Adult↗