Biomedical subjects

K Kashima

Publications and source records attributed to K Kashima.

At least 73 records · Page 4Linked to original sources

PubMed2000

Clonal analysis of the epithelial component of Warthin's tumor.

The proliferation of the epithelial component of Warthin's tumor is generally considered to represent a neoplastic condition. There has been much controversy about the histogenesis of this tumor, and the clonality of the epithelial component has not been clarified. We examined the clonal status of epithelial cells of Warthin's tumor by using a polymerase chain reaction (PCR) method based on trinucleotide repeat polymorphism of the X chromosome-linked human androgen receptor gene (HUMARA) and on random inactivation of the gene by methylation. Total DNA was isolated from formalin-fixed, paraffin-embedded tissue from 16 women with Warthin's tumor. Of the 16 cases analyzed, 7 were heterozygous for the HUMARA polymorphism and informative. The epithelial components of the tumors from the 7 cases were microdissected under the light microscope, and were subjected to extraction of DNA and HUMARA analysis. Using a permanent aqueous mounting medium during microdissection, we succeeded in reducing the rate of contamination by lymphocytes in the samples to less than 10%. All 7 cases showed patterns of polyclonal proliferation in the HUMARA analysis. Our results showed the nonclonal nature of Warthin's tumor, suggesting that Warthin's tumor is a non-neoplastic tumor-like condition. HUM PATHOL 31:1377-1380.

Adenolymphoma↗

PubMed1999

Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants.

The therapeutic efficacy of ursodeoxycholic acid (UDCA) has been widely demonstrated in various liver diseases, suggesting that UDCA might protect hepatocytes against common mechanisms of liver damage. A candidate for such protection is oxidative injury induced by reactive oxygen species. This study was designed to assess the effects of UDCA on oxidative injury and antioxidative systems in cultured rat hepatocytes. The viability of the hepatocytes dose-dependently decreased after hydrogen peroxide or cadmium administration. Pretreatment with UDCA significantly prevented this decrease in viability. The amounts of glutathione (GSH) and protein thiol increased significantly, but the activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and catalase were unchanged in UDCA-treated hepatocytes. The mRNA levels of gamma-glutamylcysteine synthetase and metallothionein (MT) were significantly higher in UDCA-treated hepatocytes than in controls. In conclusion, UDCA increased hepatocyte levels of GSH and thiol-containing proteins such as MT, thereby protecting hepatocytes against oxidative injury. Our results provide a new perspective on the hepatoprotective effect of UDCA.

Animals↗

PubMed1999

Tyrosine kinase-dependent modulation by interferon-alpha of the ATP-sensitive K+ current in rabbit ventricular myocytes.

We examined the effects of interferon-alpha on the ATP-sensitive K+ current (IK,ATP) in rabbit ventricular cells using the patch-clamp technique. IK,ATP was induced by NaCN. Whole-cell experiments indicated that interferon-alpha (5 x 10(2) - 2.4 x 10(4) U/ml) inhibited IK,ATP in a concentration-dependent manner (60.7+/-7.5% with 2.4 x 10(4) U/ml). In cell-attached configuration, interferon-alpha (2.4 x 10(4) U/ml) applied to the external solution also inhibited the activity of the single ATP-sensitive K+ (KATP) channel by 56.0+/-5.8% without affecting the single channel conductance. The inhibitory effect of IK,ATP by interferon-alpha was blocked by genistein and herbimycin A, tyrosine kinase inhibitors, but was not affected by N-(2-metylpiperazyl)-5-isoquinolinesulfoamide (H-7), an inhibitor of protein kinase C and cAMP-dependent protein kinase. These findings suggest that interferon-alpha inhibits the cardiac KATP channel through the activation of tyrosine kinase. The tyrosine kinase-mediated inhibition of IK,ATP by cytokines may aggravate cell damage during myocardial ischemia.

Adenosine Triphosphate↗

PubMed1999

Novel formula for cell kinetics in xenograft model of hepatocellular carcinoma using histologically calculable parameters.

The growth rate of tumors should be assessed in terms of both tumor cell proliferation and death. The former is considered to be determined by growth fraction and cell-cycle time, whereas the latter is mainly determined by apoptosis, especially in tumors with a low level of necrosis. While most hepatocellular carcinomas (HCCs) in a relatively early stage contain only a small amount of necrosis, the growth rate supposedly depends mainly on growth fraction, cell-cycle time, and apoptosis. However, their quantitative relationship remains unknown. We have derived a novel theoretical formula for determining this relationship in nonnecrotic HCC, using Ki-67-positive index, apoptotic score, and a correction factor, all calculable by histological assessment without injecting labeling agents. Furthermore, we confirmed the reliability of this formula, using a xenograft model of human HCC with less than 15% necrosis. In this model the values of cell-cycle time calculated from the formula were very close to those estimated by a conventional double-labeling method and showed high correlations. Since our novel formula can clarify the cell kinetics without cumbersome labeling procedures, it is expected to be clinically applicable to HCC with a small portion of necrosis, using the radiographically measured growth rate and the histologically assessed cell kinetic parameters.

Animals↗

PubMed1999

Histopathological features of liver damage induced by laser ablation in rabbits.

BACKGROUND AND OBJECTIVE: Possible mechanisms that promote or interfere with the effects of laser ablation of the liver have not been clarified. The aim of this study was to define the chronological alterations in the normal rabbit liver at early stages after laser ablation. STUDY DESIGN/MATERIALS AND METHODS: Rabbit livers were ablated with a laser via an optical fiber and then analyzed histopathologically by immunostaining for heat shock protein 70 (HSP70) and by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. RESULTS: The lesions increased in size progressively over the 24 h that followed ablation and the area of the lesion coincided with the area that had been heated above 43 degrees C. TUNEL-positive hepatocytes were surrounded, at some distance, by HSP70-positive hepatocytes were surrounded, at some distance, by HSP70-positive hepatocytes at 6 h, and such cells were in contact with each other at 24 h. CONCLUSIONS: Injury to hepatocytes induced by laser ablation increases for 24 h and dying cells express nuclear HSP70, with subsequent fragmentation of DNA.

Animals↗

PubMed1999

A paucity of unusual trihydroxy bile acids in the urine of patients with severe liver diseases.

To clarify the relationship between the occurrence of unusual trihydroxy bile acids, namely hyocholic acid, ursocholic acid (UCA), and omega-muricholic acid (omega-MCA) in urine and liver disease severity, urinary bile acids were analyzed by gas-liquid chromatography in acute and late phases of acute hepatitis and before and after ursodeoxycholic acid (UDCA) loading in healthy adults and liver cirrhosis patients. In 11 patients with acute hepatitis, the occurrence rates and amounts of unusual trihydroxy bile acids were increased in the late (recovery) phase, as compared with those in the early phase. In 10 patients with severe acute hepatitis who had prothrombin times exceeding 16 seconds, these bile acids had completely disappeared from the urine in the early phase but reappeared in the late phase in those who had a good outcome, though never in a patient who died. After UDCA administration for a week, the amounts of unusual bile acids, especially UCA and omega-MCA, which are thought to be synthesized through 12 alpha- and 6 alpha-hydroxylations, respectively, from UDCA, were clearly increased in 10 healthy adults but only slightly changed in 10 patients with liver cirrhosis. In conclusion, hepatic hydroxylations of dihydroxy bile acids as a detoxification reaction were impaired in severe liver diseases, which may play a role in the intensification and perpetuation of hepatocellular injuries.

Acute Disease↗

PubMed1999

Ovarian metastasis in stage IB and II cervical adenocarcinoma.

We performed the present study to identify those patients with adenocarcinoma of the cervix in whom ovarian preservation might be acceptable. Between January 1971 and December 1996, 82 patients with International Federation of Gynecology and Obstetrics stage IB and II cervical adenocarcinoma and adenosquamous carcinoma, treated by radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, were identified. The mean age of the patients was 44.6 years (range 27-72). The incidence of ovarian metastasis was more frequent in stage II (19.0%) than in stage IB disease (2.5%), in which only 1 patient with apparent extrauterine disease at laparotomy had an ovarian metastasis. No patients with up to inner two-thirds of stromal invasion had ovarian metastasis; however, 5 of 24 patients with outer one-third stromal invasion (20.8%) and 4 of 20 with parametrial invasion (20.0%) had ovarian metastasis. A significantly higher incidence of ovarian metastasis was also observed in 5 of 20 cases with lymph node metastasis (25.0%) than in 4 of 62 patients without lymph node metastasis (6.5%). Multivariate analysis, however, found only deep stromal invasion to be an independent risk factor for ovarian metastasis. Although it would be reasonable to conserve normal-appearing ovaries in young women undergoing radical hysterectomy for treatment of stage IB cervical adenocarcinoma and adenosquamous carcinoma, gross intraoperative inspection of the radical hysterectomy specimen may identify deep cervical invasion or extrauterine spread in those who are at increased risk of ovarian metastases.

Adenocarcinoma↗

PubMed1999

Parenchymal cells proliferate and differentiate in an organotypic slice culture of the neonatal liver.

We applied organotypic slice culture of neonatal mouse liver tissues to maintain the parenchymal cells in ontogenesis and to investigate their proliferation and differentiation. Cultured tissue spread gradually over 3 weeks. Small basophilic cells formed several layers in the center of the cultured tissues, and a monolayer of polygonal cells was seen at the periphery. Albumin- and alpha-fetoprotein-immunoreactions were seen in polygonal cells, as were proliferating cell nuclear antigen-immunoreactions. Connexin 32- and 26-immunoreactions were observed in small plaques on the membrane of the polygonal cells, and electron microscopy showed gap junctional complexes. Ultrastructurally, polygonal cells had a round nucleus and abundant cytoplasmic organelles, and bile canaliculi were seen on the cytoplasmic membrane. Cytokeratin 19-immunoreactions were scattered in clusters. There were ultrastructurally bile-duct-like structures with microvilli on the inner surface of the cavity and tight junctions between their constituent cells. Quantitative analysis of albumin-, alpha-fetoprotein- and cytokeratin 19- or proliferating cell nuclear antigen-immunoreactivity in parenchymal cells showed changes of their phenotypes or maintenance of their proliferation in tissue culture. Our slice-culture system enabled us to maintain and to develop parenchymal cells in the liver tissue for at least 3 weeks. The findings suggest that organotypic slice culture applied to liver tissues in ontogenesis may be a useful tool not only to maintain parenchymal cells but also to investigate their proliferation and differentiation.

Albumins↗

PubMed1999

Pancreatoscopy for the next generation: development of the peroral electronic pancreatoscope system.

BACKGROUND: To improve visualization of the pancreatic duct with a pancreatoscope, we have developed the smallest known electronic endoscope, that is, the peroral electronic pancreatoscope. METHODS: This instrument (2.1 mm, external diameter) was developed with a 50k-pixel interline charge coupled device. A peroral fiberoptic pancreatoscope was used as control, connected to a video converter. The visibility of both systems was studied with a test chart. The model pancreatic duct, the oral mucosa, and the pancreatic ducts of a healthy control subject and patients with chronic pancreatitis were examined with both systems. RESULTS: The smallest visible interval (with a 5 mm distance between the object and the distal end of the endoscope) was 0.07 mm with the peroral electronic pancreatoscope and 0.2 mm with the peroral fiberoptic pancreatoscope. The electronic instrument produced better images of the model pancreatic duct than the fiberoptic endoscope. A clear image of the small vessels of the oral mucosa was obtained with the electronic but not with the fiberoptic instrument. The fine vessel network of the pancreatic duct was visualized only with the electronic instrument; pancreatic duct stones and rough-surfaced pancreatic duct were shown more precisely with the electronic endoscope. CONCLUSIONS: The peroral electronic pancreatoscope provides images of the fine detail of the pancreatic duct and will contribute to the diagnosis of pancreatic diseases.

Calculi↗

PubMed1999

Genotype of glutathione S-transferase and other genetic configurations in myelodysplasia.

We examined polymorphisms of glutathione S-transferase (GST) genes in 159 Japanese patients with myelodysplasia and compared the incidence with that in 43 normal individuals to clarify their pathogenetic significance in myelodysplasia. In individuals with the GSTT1 null genotype, the odds ratios for disease risk were elevated to 2.65 (95%CI; 1.27-5.52) in de novo MDS, 4.62 (1.48-14.4) in therapy-related AML, and 2.94 (1.07-8.07) in AML with triliniage dysplasia. Other representative polymorphisms of GSTs had a similar incidence among patients with myelodysplasia, and those of the controls and other hematological disorders. To further investigate the genetic pathway of myelodysplasia, the association between GST genotype and karyotype or configurations of TP53 and NRAS was evaluated, but no relationship was noted. These results suggest that the GSTT1 null genotype may play a role in an increased risk of myelodysplasia unrelated to other mechanisms of myelodysplasia, such as chromosomal alterations or mutation of TP53 or NRAS.

Acute Disease↗

PubMed1999

Interferon therapy lowers the rate of progression to hepatocellular carcinoma in chronic hepatitis C but not significantly in an advanced stage: a retrospective study in 1148 patients. Viral Hepatitis Therapy Study Group.

BACKGROUND/AIM: Hepatocellular carcinoma frequently develops during the advanced stages of chronic hepatitis C. We examined whether interferon prevents the development of hepatocellular carcinoma in chronic hepatitis C patients. METHODS: Japanese patients with chronic hepatitis C (n = 1.148; 117 with portal fibrous expansion (F1), 636 with bridging fibrosis (F2), 355 with bridging fibrosis and architectural distortion (F3)) and 40 cirrhotic (F4) patients were treated with interferon. These patients were followed from 1 to 7 years after interferon therapy. Blood tests and image analysis were serially performed to assess response to interferon and to detect hepatocellular carcinoma. Fifty-five cirrhotic type C patients (control F4) not receiving interferon were enrolled in this study. RESULTS: Sustained (SR: 27.5%) and transient (TR: 23.0%) responders totaled 50.5%, while 49.5% did not respond to interferon. SR showed an improvement in disease stage reflected by increased platelet counts. Fifty-two patients (9 F2, 36 F3, and 7 F4) developed hepatocellular carcinoma in the follow-up period; 3 SR, 8 TR, and 41 non-responders (NR). The cumulative incidence of hepatocellular carcinoma in F2 was significantly lower (p = 0.019) in SR compared with NR, but not in SR in F3 and F4 patients. However, the cumulative incidence of hepatocellular carcinoma was significantly decreased in all SR (p = 0.0001) and TR (p = 0.0397) compared with all NR. CONCLUSION: These results indicate that interferon therapy in chronic hepatitis C patients lowered the rate of progression of hepatocellular carcinoma in sensitive cases but not in patients in an advanced stage.

Adult↗

PubMed1999

Distinct genetic involvement of the TP53 gene in therapy-related leukemia and myelodysplasia with chromosomal losses of Nos 5 and/or 7 and its possible relationship to replication error phenotype.

We examined chromosomes and molecular aberrations in 21 patients with therapy-related leukemias (t-AML) or myelodysplastic syndromes (t-MDS). All patients showed abnormal karyotypes, and chromosomal losses of No. 5 and/or No. 7 (-5/5q- and/or -7/7q-) were identified in 12 patients. Among these 12, six patients (50%) harbored a TP53 mutation, and two of five examined showed microsatellite instability, suggesting replication error (RER+) phenotype. Meanwhile, among the other nine patients without -5/5q- and/or -7/7q-, none harbored a TP53 mutation, and none of five examined showed RER+ phenotype. Thus, TP53 mutations and RER+ phenotype were preferentially associated with specific chromosomal losses in t-AML/MDS. We then screened for mutational events in representative DNA mismatch repair genes; exons 5-7 and 12-15 of the hMSH2 gene and exon 9 of hMLH1. Notably, two unrelated patients showing RER+ phenotype had an identical missense alteration at codon 419 of hMSH2 in their marrow cells and fibroblasts, which were not found in 120 DNA samples from healthy volunteers or patients with other hematological disorders. Consequently, this study revealed a possible relationship of RER+ phenotype accompanying an hMSH2 alteration to the development of therapy-related AML/MDS in association with TP53 mutations and specific chromosomal losses, and suggests that some patients may be predisposed to myelodysplasia after chemotherapy for their primary tumor.

Adult↗

PubMed1999

Relationship between the cagA 3' repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH.

BACKGROUND & AIMS: The variation in size of Helicobacter pylori CagA is related to repeat sequences in the 3' region of the cagA gene. We investigated whether structural subtypes of the cagA 3' region are associated with presentation of the infection or to susceptibility to acid. METHODS: We examined 319 cagA-positive H. pylori isolates: 84 isolates from Bogota, Colombia; 83 from Houston, Texas; 24 from Siena, Italy; and 128 from Seoul, Korea. The cagA 3' region was amplified by polymerase chain reaction. Gastric histology and susceptibility to pH 3 were evaluated in relation to the number of cagA repeat regions. RESULTS: Strains with more than three repeat regions were associated with significantly higher scores for gastric mucosal atrophy and intestinal metaplasia than those with fewer repeat regions. H. pylori strains with three repeat regions were also significantly more susceptible to pH 3 than isolates with fewer repeat regions. CONCLUSIONS: H. pylori strains with more than three repeat regions in the 3' region of the cagA gene are associated with enhanced histological injury and with reduced survival in acidic conditions. It is hypothesized that these variants arise within the stomach.

Adult↗

PubMed1999

Increased pain sensitivity of the upper extremities of TMD patients with myalgia to experimentally-evoked noxious stimulation: possibility of worsened endogenous opioid systems.

The purpose of this study was to examine whether or not temporomandibular disorder (TMD) patients with chronic masticatory myalgia have increased pain sensitivity at remote sites outside of the head and neck region, and to evaluate whether the endogenous pain inhibitory systems triggered ischemic pain functions favorably in those patients. Twenty female TMD patients with chronic myalgia and 20 controls participated in this study. Ischemic pain was produced to activate endogenous opioids. The pain threshold time, pain tolerance time, pain intensity and pain unpleasantness were compared between the TMD patients and controls. The pressure pain thresholds in the hand were also compared before, between, and immediately after the ischemic pain. The TMD patients showed higher severe pain intensity and unpleasantness values and had lower pressure pain thresholds in the hand. Although both groups showed an increase in the pressure pain threshold, there was less of an increase in the pressure pain threshold in the TMD patients than in the controls. These findings indicate that TMD patients have increased pain sensitivity at remote sites, and also indicate additional evidence that the endogenous opioid systems may become impaired in TMD patients with chronic masticatory myalgia.

Adult↗

PubMed1999

Transfer of nitric oxide from the liver to erythrocytes--an ESR study using nitroglycerin-treated mice.

Nitric oxide (NO) formation in the liver and blood of the mouse following intraperitoneal treatment with nitroglycerin (glycerol trinitrate, GTN) was determined using electron spin resonance (ESR) spectroscopy. ESR signals of heme-NO complexes were detected at maximum levels within 5 min in the liver, but increased to a maximum level about 15-30 min later in the blood. GTN is not metabolized to release NO in vitro in the blood of the mouse. The hepatic microsomes which showed the heme-NO complexes ESR signals were incubated with mouse erythrocytes, with the result that a hemoglobin-NO signal was obtained from the erythrocytes. The activities of microsomal cytochrome P-450, the hepatic level of glutathione, and the reduction rate of nitroxide radicals in the in vivo liver, measured using L-band ESR spectroscopy, were temporarily decreased following GTN administration. In conclusion, NO in the liver could be scavenged by circulating erythrocytes, which might minimize NO-induced liver damage.

Animals↗

PubMed1999

Mutations of p53 in thyroid carcinoma with an insular component.

Thyroid carcinoma with an insular component (TCIC) is considered noteworthy in view of its peculiar histopathological features and clinicopathological behavior. The purpose of the present study was to clarify the rate of mutation in the p53 gene in TCIC as compared with rates in papillary and follicular carcinomas of the thyroid. Formalin-fixed and paraffin-embedded blocks of tissue from 46 cases of TCIC were analyzed. DNA was extracted from tissues and exons 5 through 8 of the p53 gene were amplified by the polymerase chain reaction. Mutations were detected by analysis of single-strand conformation polymorphism. Of the 46 cases of TCIC, 6 had a mutation in exon 5, 2 in exon 7, and 5 in exon 8, while 1 case had mutations in all exons examined. The mutation rate of the p53 gene in TCIC was 38%. Immunostaining revealed overexpression of p53 in nuclei that were mainly in areas of the insular component rather than in surrounding areas of well-differentiated carcinoma. The frequency of positive immunostaining in TCIC was 53%. Considering that TCIC is intermediate between papillary plus follicular carcinoma and anaplastic carcinoma in terms of survival and the rate of mutation of the p53 gene, we can speculate that mutation in the p53 gene might be associated with the insular component and might play an important role in the clinicopathological behavior of thyroid carcinoma.

Adolescent↗

PubMed1999

Morules with biotin-containing optically clear nuclei in colonic tubular adenoma.

Morules have been reported in pulmonary endodermal tumors (PET) resembling fetal lung, in thyroid carcinoma, and in endometrial and colonic neoplasms. A morule has biotin-containing optically clear nuclei (OCN) in PET and thyroid carcinoma. Biotin-containing OCN have been also reported in endometrial tissue during pregnancy and in endometrioid carcinoma of the ovary, and it has been postulated that morules or OCN develop under the influence of female sex hormones. The authors report here the first case, to their knowledge, of morules with OCN in a colonic adenoma from a 68-year-old man. The colonic polyp consisted of ordinary tubular adenomatous tissue and morules. Many cells in the morules contained OCN. The OCN were immunopositive for biotin and reacted with streptavidin. The neoplastic cells in the morules were immunopositive for oncofetal antigens. Serum levels of female sex hormones were within the normal range, and no cells in the adenoma were immunopositive for receptors for progesterone and estrogen. The results indicate that OCN are rich in biotin and that morules may be embryologically immature elements that develop independently of influence by female sex hormones.

Adenoma↗

PubMed1999

Cholestatic jaundice in two patients with primary amyloidosis: ultrastructural findings of the liver.

Two patients with primary amyloidosis (amyloid light chain case) and severe cholestatic jaundice are described. Liver biopsy in the preterminal stage demonstrated amyloid deposits in the perisinusoidal space and in portal tracts, and hepatocytes were atrophic because of compression by amyloid fibrils. Ultrastructural findings showed amyloid fibrils not only in Disse's space but also in the sinusoids, and the hepatocyte microvilli facing the amyloid fibrils were spicular. There were aggregates of lysosomal granules in the vicinity of bile canaliculi and some bile canaliculi were dilated with loss of microvilli. Amyloid fibrils in the portal tract compressed bile ductules, causing wide intercellular space and separated basement membranes from their epitheliums. These findings suggested disturbance in transporting not only of essential materials from sinusoids to hepatocytes but also of secretory vesicles into bile canaliculi and leakage of bile juice from small bile ductules in preterminal stage of primary amyloidosis.

Aged↗