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Biomedical subjects

M Kato

Publications and source records attributed to M Kato.

At least 793 records · Page 44Linked to original sources

Nanomolar amyloid beta protein-induced inhibition of cellular redox activity in cultured astrocytes.

It has been previously reported that Alzheimer's amyloid beta protein (A beta) induces reactive astrocytosis in culture. In the present study, we found that A beta potently inhibits cellular redox activity of cultured astrocytes, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. The following comparative studies revealed several differences between these two actions of A beta on astrocytes. First, A beta-induced reactive morphological change was suppressed by the presence of serum or thrombin, and A beta inhibition of cellular redox activity was observed in either the presence or the absence of serum. Second, micromolar concentrations (10 microM or more) were required for A beta to induce reactive astrocytosis, whereas nanomolar concentrations (0.1-100 nM) were sufficient to inhibit cellular redox activity. Third, the effect of micromolar A beta was virtually irreversible, but nanomolar A beta-induced inhibition of cellular redox activity was reversed by washing out A beta. Furthermore, as it has been reported that A beta neurotoxicity is mediated by reactive oxygen species, we also examined if similar mechanisms are involved in astrocytic response to A beta. However, neither A beta-induced morphological change nor inhibition of redox activity was blocked by antioxidants, suggesting that these effects are not caused by oxidative stress.

Amyloid beta-Peptides↗

4-Nerolidylcatechol from Pothomorphe spp. scavenges peroxyl radicals and inhibits Fe(II)-dependent DNA damage.

The total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) of 4-nerolidylcatechol (4-NC) and methanolic extracts of Pothomorphe umbellata and P. peltata were determined by monitoring the intensity of luminol enhanced chemiluminescence by peroxyl radicals derived from thermolysis of 2,2'-azobis(2-amidinopropane). The highest antioxidant potential was measured in the extract of P. umbellata (TRAP = 97.2 microM) while the highest reactivity was observed in the extract of P. peltata (TAR = 5.0 microM), measured as equivalents of Trolox concentration. These results were higher than those obtained for 4-NC (TRAP = 33.6 microM, TAR = 4.9 microM). DNA sugar damage induced by Fe(II) salts was also used to determine the capacity of 4-NC to suppress hydroxyl radical-mediated degradation of DNA. Calculated IC50 values for 4-NC and catechin, used as a standard, were 25 and 17 microM, respectively.

Catechols↗

Lack of chondrotoxicity of ofloxacin otic solution on the auditory ossicle cartilages of juvenile guinea pigs.

The effect of 0.3% otic solution of ofloxacin on the cartilages constituting the epiphyses of the auditory ossicles and the wall of the auditory tube was histologically examined after 30-day repeated intratympanic administration to juvenile male guinea pigs aged 4 weeks. Ofloxacin showed no chondrotoxicity for the cartilages and, in some but not all animals, reduced haemorrhage and neutrophil infiltration in the tympanic cavity, compared with that of the control. Further, the articular cartilage of the humeral trochlea and femoral condyle also showed no change.

Animals↗

A case of liver metastasis from colon cancer masquerading as focal sparing in a fatty liver.

Focal sparing in diffusely fatty liver is a well recognized entity. However, it occasionally creates some problems in the diagnosis of hepatic mass lesions. We recently experienced a case of liver metastasis from colon cancer which appeared as a wedge-shaped hyperdense area on non-enhanced CT (computed tomography). Other imaging techniques also demonstrated a wedge-shaped area which was difficult to distinguish from mere focal sparing in the fatty liver. CT arteriography and dynamic magnetic resonance images were useful for diagnosing this metastatic tumor. CT during arterial portography showed a wedge-shaped ischemic area in the anterior segment caused by intrahepatic portal vein blockade. The histological findings eventually revealed that the tumor, an adenocarcinoma, was surrounded by fibrotic tissue that mimicked focal sparing. We present the radiological features of this case and discuss how to arrive at a correct diagnosis.

Adenocarcinoma↗

Characterization of a human placental fructose-6-phosphate, 2-kinase/fructose-2,6-bisphosphatase.

A full-length cDNA, which encodes a human placental fructose-6-phosphate,2-kinase/ fructose-2,6-bisphosphatase, was constructed and expressed in Escherichia coli. The expressed protein, purified to homogeneity, showed a molecular weight of 58,000 by gel electrophoresis under denaturing conditions, compared to the deduced molecular weight of 59,410. The N-terminal sequence of 15 amino acids coincided with that of the deduced sequence. The active enzyme was a dimer as judged by molecular sieve filtration. The expressed enzyme was bifunctional with Vmax values of 142 and 0.2 milliunits/mg for the kinase and phosphatase activities, respectively. The phosphatase activity was extremely low, because one phosphatase active site residue was mutated, and consequently the kinase/phosphatase ratio was the highest among the known isozymes. Furthermore, the enzyme was phosphorylated by cAMP-dependent protein kinase, protein kinase C and also by [2-32P]fructose-2,6-bisphosphate. Phosphorylation by cAMP-dependent protein kinase and protein kinase C increased the maximal Fru-6-P,2-kinase activities by 1.8- and 1.1-fold, respectively. These results suggested that placental fructose-6-phosphate,2-kinase/ fructose-2,6-bisphosphatase is important in maintaining and regulating a relatively high rate of glycolysis in placenta.

Cyclic AMP-Dependent Protein Kinases↗

Genetic alterations in patients with esophageal cancer with short- and long-term survival rates after curative esophagectomy.

OBJECTIVE: The objective of this study was to ascertain the exact relation between specific oncogenes and long- and short-term survival rates in patients with esophageal cancer. SUMMARY BACKGROUND DATA: Recent developments in molecular biology have shown that several oncogenes and suppressor genes are involved in the development of esophageal cancer. However, the role of these genes still is unknown. METHODS: The clinical outcome of 84 cases of R0-resected esophageal carcinomas (from 1986-1993) and the molecular and biologic characteristics of these tumors were studied. The patients studied were divided into three groups, which were designated as follows: shortest term survivors (up to 6 months), short-term survivors (7-12 months), and long-term survivors (>5 years). These groups included 23, 17, and 44 subjects, respectively. For the genomic analysis, CyclinD1, int-2, murine double minute 2 (MDM2), retinoblastoma, p53, adenomatous polyposis coli (APC), deleted in colorectal carcinoma (DCC), and human papillomavirus were studied in these patients. The regrowth capability of primary cultures and the clinicopathologic characteristics of these patients also were analyzed. RESULTS: The CyclinD1 and int-2 genes, which are located in the 11q13 chromosome, and the MDM2 gene were related to short survival. However, the p53 mutation and human papillomavirus infection were not related to short-term survival. The average ratio of genomic abnormalities to genes examined was higher in the shortest and short-term survival groups than in the long-term survival group. Regrowth capability in primary cultures also was related to short-term survival. Among the long-term survival patients, 7 (16%) of 44 cases suffered further cancer after esophagectomy. CONCLUSIONS: These results suggest that the 11q13 amplicon and MDM2 may play an important role in the progression of esophageal cancer, and an accumulation of genomic abnormalities may result in poor prognosis. Careful follow-up testing for double cancer is needed in long-term survivors of esophageal cancer.

Chromosome Aberrations↗

Increased cytokine production by gastric mucosa in patients with Helicobacter pylori infection.

To determine the mechanisms of gastric mucosal injury associated with Helicobacter pylori infection, we investigated the contents of cytokines and inflammatory cell infiltration in the gastric mucosa. Ninety-six patients with dyspepsia were studied (58 gastric ulcer, 38 nonulcer dyspepsia). Of the 96 patients, 63 were infected with H. pylori as determined by microscopic examination with HE staining, culture of H. pylori, or the rapid urease test. Endoscopic biopsy specimens were obtained from both the antrum and the body to examine interleukin (IL)-8, IL-6, IL-1 beta, and tumor necrosis factor-alpha contents in the gastric mucosa by enzyme-linked immunosorbent assay. Inflammatory cell infiltration was assessed according to the Sydney system. IL-8 content was enhanced in both the antral and body mucosa of the H. pylori-positive patients compared with the H. pylori-negative patients. Furthermore, IL-8 content correlated well with the infiltration of both mononuclear cells and polymorphonuclear cells. These results suggest that IL-8 plays important roles in the pathogenesis of gastric mucosal injury associated with H. pylori infection.

Case-Control Studies↗

Performance characteristics of chronic schizophrenia on attention tests sensitive to unilateral brain damage.

The aims of this study were to investigate the lateralization hypothesis of schizophrenia, comparing chronic schizophrenics with unilateral brain-damaged subjects and normal controls, using attentional tests sensitive to the unilateral brain damage. Three attentional tests with different modes of stimuli, two vigilance tasks that require the self-paced or nonself-paced responses of subjects and one divided attention task, were administered to 28 chronic schizophrenics, 26 right and 24 left unilateral brain-damaged subjects, and 20 normal controls. The results indicated that schizophrenics performed a possible right-hemisphere damages pattern and also a left pattern in part, with failure of all tasks to show either pattern related to a number of differences between the three tasks. Furthermore, the attention deficits of schizophrenics are less than those of brain-damaged subjects but are clearly abnormal compared with the normal controls.

Attention↗

Comparison of hemodynamic effects of nitric oxide (NO) donors with different NO-releasing properties in rats.

The aim of this study was to compare the hemodynamic effects of three nitric oxide (NO) donors [i.e., (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5-nitro-3-he ptenyl]-3-pyridinecarboxamide (FR 146801) and isosorbide dinitrate (ISDN)] in rats. In in vitro experiments, FK409 had a higher spontaneous NO-releasing rate in solution and more potent vasorelaxant activity in isolated rat aorta than other drugs. FR146801 and ISDN showed almost the same vasorelaxant activity. In in vivo experiments, FK409 significantly decreased hematocrit at 1.0 mg/kg p.o., whereas FR146801 and ISDN significantly decreased it at 10 mg/kg p.o., suggesting that these NO-donating agents cause significant plasma volume expansion. However, only FK409 showed significant hypotensive effects immediately after oral administration even at 0.32 mg/kg; FR146801 and ISDN did not cause any significant hypotension at 10 mg/kg, suggesting that FK409 induces much more potent arterial vasodilation than other drugs. These findings suggest that NO donors induce significant plasma volume expansion and that the differences in the selectivities between these effects and their hypotensive effects is probably produced by their different NO-releasing activities.

Animals↗

Change of pancreatic enzymes, pancreatic stone protein (PSP), and plasma alpha(2)-macroglobulin-trypsin complex-like substance (MTLS) in the activation of pancreatic juice.

To characterize the activation of pancreatic zymogens (trypsinogen, chymotrypsinogen, and proelastase 1) in acute pancreatitis, we studied the activation of pancreatic juice with porcine enteropeptidase in vitro, and then enzymatic activities and the generation of pancreatic stone protein (PSP) S1 form in pancreatic juice were investigated. Further, we determined immunoreactive trypsin, immunoreactive elastase 1, PSP, and alpha(2)-macroglobulin-trypsin complex-like substance (MTLS) levels in plasma to which the activated juice was added. In the present report, we demonstrate that the plasma MTLS level reflected the activation of pancreatic trypsinogen in pancreatic juice. Further, the generation of PSP S1 form was found at an early stage of activation. Therefore, the plasma MTLS level and the generation of PSP S1 form may offer new diagnostic information on the amounts of activated proteases and subsequently on the severity of acute pancreatitis.

Animals↗

Diagnosis of chronic pancreatitis using noninvasive tests of exocrine pancreatic function--comparison to duodenal intubation tests.

The diagnosis of chronic pancreatitis usually is based on imaging studies, pancreatic function tests, and the presence of characteristic clinical features. In Japan, diagnostic criteria for chronic pancreatitis were established in 1983 and revised in 1995. Under the new criteria, the secretin test (a duodenal intubation test) and the combination of noninvasive tests, N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) and fecal chymotrypsin (FCT), have been recommended for evaluating exocrine pancreatic function in patients with chronic pancreatitis. In the present study, the diagnostic value of these two noninvasive tests was compared to the secretin test. Although noninvasive tests are less sensitive and specific for determining exocrine pancreatic impairment than the secretin test, greater reliability for diagnosing chronic pancreatitis can be obtained by performing the BT-PABA and fecal chymotrypsin tests simultaneously. Combining BT-PABA and FCT is easy and useful and should be performed at least twice to obtain reliable results.

4-Aminobenzoic Acid↗

Experimental studies on potentiation of the antitumor activity of 5-fluorouracil with 3'-azido-3'-deoxythymidine for the gastric cancer cell line MKN28 in vivo.

A new method of biochemical modulation of 5-fluorouracil (5-FU) with 3'-azido-3'-deoxythymidine (AZT) was studied experimentally. Nude mice transplanted with cells of the human gastric cancer cell line MKN28 were divided into 4 groups, i.e., control, 5-FU, AZT, and 5-FU plus AZT, and the antitumor activities were compared. Based on the assessment of tumor volume, significant suppression of tumor growth was observed in the 5-FU and 5-FU plus AZT groups (P<0.05, P<0.01, versus control, respectively). The thymidylate synthase (TS) inhibition rate, an index of inhibition of the de novo pathway, was significantly higher in the 5-FU and 5-FU plus AZT groups than in the control group (P<0.01), but it did not differ from the control in the AZT group. TS-bound FdUMP tended to be higher in the 5-FU plus AZT group than in the 5-FU group. The activity of thymidine kinase (TK) and the uptake ratio of 5-bromo-2'-deoxyuridine (BrdU), indices of salvage pathway activity, were significantly lower in the AZT and 5-FU plus AZT groups than in the control group (TK, P< 0.05, P < 0.01; uptake ratio of BrdU, P < 0.01, P < 0.05, respectively). There were slight losses of body weight in the 5-FU and 5-FU plus AZT groups compared with that in the control group, but no difference between the AZT and control groups in weight loss. These findings suggest that addition of AZT plays an important role in potentiating the antitumor activity of 5-FU through both blockage of a compensatory increase of activity in the salvage pathway and also an increase in TS-bound FdUMP, and has no adverse effects. Thus, the combination of 5-FU and AZT could be useful as a new modality in gastric cancer chemotherapy.

Animals↗

Significant correlation of telomerase activity in thyroid papillary carcinomas with cell differentiation, proliferation and extrathyroidal extension.

Telomerase activity was examined by telomeric repeat amplification protocol assay in thyroid disease states, including adenomas and carcinomas, and correlated with clinicopathological features. Of a total of 26 papillary carcinomas, 16 cases (61.5%) were positive, with the poorly differentiated subtype being predominant (P < 0.05). A significantly more shortened terminal restriction fragment length (P < 0.05), higher incidence of extrathyroidal extension (P < 0.001), and more elevated Ki-67 labeling indices (P < 0.002) were also found in telomerase-positive than in telomerase-negative papillary carcinomas. Of four follicular carcinomas, 3 cases (75.0%) were positive. Positive telomerase activity in follicular adenomas (9/23 cases, 39.1%) and lymphocytic thyroiditis (12/22 cases, 54.5%) appeared to be mainly caused by infiltrating lymphocytes. However, three cases of atypical adenoma with relatively increased Ki-67 labeling indices were positive, suggesting a possibility of malignant potential. The good correlations with extrathyroidal invasiveness, Ki-67 labeling indices and poor differentiation of papillary carcinomas, established by multivariate analysis, suggest that this parameter might have potential application in the estimation of tumor progression and prognosis, and in clinical management.

Adenoma↗

The classification of idiopathic spasmodic torticollis: three types based on social adaptation and frustration tolerance.

In this study, idiopathic spasmodic torticollis (ST) has been classfied into three types from the opinion of social adaptation and the differences of frustration tolerance. The three types were as follows: type I (overadaptive type), type II (maladaptive type), and type III (compatible type). Type I is a typical psychosomatic with high frustration tolerance. Type II is personality disorder with low frustration tolerance. In type III, frustration tolerance varies depending on social circumstances (i.e., different at home and at the office). In type I, the prognosis of ST is generally unfavorable, since it is associated with recurrence and prolongation of the symptoms. In type II, the prognosis of ST is generally favorable. However, type II patients experience relationship or social difficulties. One characteristic of type III is that the onset of symptoms is usually found in an older person because of proper use of frustration tolerance at home and at the office.

Adaptation, Psychological↗

Pannus resection through the tilting disc prosthesis: successful treatment preserving the prosthesis.

A 59-year-old woman was admitted to our hospital because of heart failure. In 1988, she underwent aortic valve replacement with an Omnicarbon valve and mitral valve replacement with a bioprosthetic valve. She was doing well until July in 1996 when she developed heart failure. Echocardiography revealed massive mitral valve regurgitation, and cinefluoroscopy showed implanted Omnicarbon valve dysfunction with a leaflet opening angle of 35 degrees. At reoperation, it was revealed that pannus formation prevented the valve from functioning well. The pannus was resected through the major orifice, and the leaflet was rotated toward the right anterolateral orientation. The worn bioprosthetic valve was replaced with a mechanical one. Postoperative cinefluoroscopy of the rotated Ominicarbon valve showed the opening angle to be 61 degrees.

Aortic Valve↗

Folie à deux in Japan -- analysis of 97 cases in the Japanese literature.

In order to clarify the characteristics of folie à deux in Japan, we examined a total of 97 cases of folie à deux in the Japanese literature covering a period of 90 years, and compared them with the cases reported in Western countries. About 75% of the Japanese cases occur in two individuals, and of these are family cases. The most common combinations are mother-child and married couple. Mother-child combinations are much more common than father-child combinations. Female subjects are more often involved than males. The most common diagnosis for the dominant partner is schizophrenia, and the most common diagnosis for the submissive partner is paranoid reaction. Delusion is the most common symptom shared by both partners in Japan. Comparing these Japanese cases to Western ones, sister-sister combinations are less frequent, younger subjects influence the older ones more, and acute religious delusion is more common in Japan than in Western countries.

Adolescent↗

Characterization of fluoroquinolone-induced Achilles tendon toxicity in rats: comparison of toxicities of 10 fluoroquinolones and effects of anti-inflammatory compounds.

Fluoroquinolone antibacterial agents have been reported to induce tendon lesions in juvenile rats. In the present study, we characterized fluoroquinolone-induced Achilles tendon lesions by comparing the effects of 10 fluoroquinolones and examining the potential of one of these antimicrobial agents, pefloxacin, to induce tendon lesions when coadministered with one of nine anti-inflammatory compounds. Among the 10 fluoroquinolones tested, fleroxacin and pefloxacin were the most toxic, inducing lesions at a dose of 100 mg/kg of body weight or more, while lomefloxacin, levofloxacin, and ofloxacin or sparfloxacin and enoxacin induced lesions at 300 mg/kg or more and 900 mg/kg, respectively. In contrast, norfloxacin, ciprofloxacin, and tosufloxacin had no effect even at the high dose of 900 mg/kg. The severity of the Achilles tendon lesions appeared to correlate with the structure of the substituent at the seventh position. Furthermore, pefloxacin-induced tendon lesions were inhibited by coadministration with dexamethasone and N-nitro-L-arginine methyl ester. Phenidone (1-phenyl-3-pyrazolidinone) and 2-(12-hydroxydodeca-5,10-diynyl)3,5,6-trimethyl-1,4-benzoqui none (AA861) also decreased the incidence of tendon lesions. In contrast, catalase, dimethyl sulfoxide, indomethacin, pyrilamine, and cimetidine did not modify these tendon lesions. These results suggest that nitric oxide and 5-lipoxigenase products partly mediate fluoroquinolone-induced tendon lesions.

4-Quinolones↗