Biomedical subjects

N Kato

Publications and source records attributed to N Kato.

At least 541 records · Page 30Linked to original sources

PubMed1995

Clonality in hepatocellular carcinoma: analysis of methylation pattern of polymorphic X-chromosome-linked phosphoglycerate kinase gene in females.

Analysis of X-chromosome inactivation patterns in women has been used to assess the clonality of various tumors. In this report, we analyzed 27 liver tumors in women, including 18 samples obtained by the performance of ultrasonically guided thin-needle biopsies. By analysis of the heterogeneity of phosphoglycerate kinase gene, 11 of 27 (41%) cases were found to be heterozygous at the gene. Of these informative 11 cases with liver tumors, 7 cases were "large" tumors (> 25 mm in diameter) and 4 cases were "small" tumors (< 25 mm in diameter). All 7 large tumors showed monoclonal patterns by the phosphoglycerate kinase gene analysis. Of the 4 small tumors, 2 showed monoclonal, and 2 showed polyclonal patterns. The 2 with monoclonal patterns were pathologically diagnosed as hepatocellular carcinoma despite their small sizes (20 mm and 23 mm). Of the two with polyclonal patterns, the smallest one (15 mm) was diagnosed as benign adenomatous hyperplasia, and the other as hepatocellular carcinoma heavily infiltrated by lymphocytes. These data suggest that analysis of the methylation pattern of the phosphoglycerate kinase gene may be helpful on rare occasions in elucidating the nature of liver tumors but must in fact be used in conjunction with histological appearances to avoid errors secondary to inflammatory infiltrates.

Base Sequence↗

PubMed1995

Processing of the hepatitis C virus precursor protein.

Proteins of hepatitis C virus (HCV) are produced from a polyprotein precursor by post-translational processing. Production of HCV proteins was analyzed with in vitro translation, as well as plasmid-based transient gene expression, in mammalian cell lines. A minimum of three different processing pathways yielded at least 10 viral proteins from the polyprotein precursor. One pathway depended on signal protease processing, and the other two pathways utilized viral proteinases. The signal peptidase cleaved the viral structural proteins, and two viral activities broke up the viral nonstructural proteins. With staggered cleavages, the signal peptidase produced two E2 products from the E2 region, gp70 type A and type B, differing in the C-terminal structure. Two viral proteinases partially overlapped in the N-terminal region of NS3; the functional amino acid residues required for those two activities differed. Most of the processed viral proteins bound together; some of the associated proteins were membrane bound.

Amino Acid Sequence↗

PubMed1995

[Changes in serum calcium concentration following eel calcitonin analogue administration as an index of osteoclastic bone resorption in patients with secondary hyperparathyroidism].

It has been suggested that the intensity of hypocalcemic response to administration of calcitonin may reflect the magnitude of osteoclastic activity. To determine whether this hypothesis is correct or not, I performed a calcitonin-loading test in twenty dialysis patients with secondary hyperparathyroidism. The test involved the intravenous injection of 120 MRC units of synthetic eel calcitonin analogue for 3 hours. Serum calcium concentration fell from 9.6 +/- 0.9 mg/dl to 8.7 +/- 0.9 mg/dl following calcitonin administration (p < 0.001). There was a statistically significant correlation between the fall in serum calcium concentration and the baseline intact parathyroid hormone levels (r = 0.661, p < 0.002), as well as the fall in serum calcium concentration and baseline serum alkaline phosphatase activity (r = 0.817, p < 0.001), respectively. From these findings, it was concluded that calcitonin lowers serum calcium concentration in proportional to the activity of osteoclastic bone resorption. To determine whether the effect of calcitonin on calcium concentration related to PTH secretion, same test was performed before and after parathyroidectomy (PTX) in 9 patients with severe secondary hyperparathyroidism required surgery. The fall in serum calcium concentration during calcitonin administration before PTX was significantly greater than that of after PTX (p < 0.05). Thus, it is concluded that calcitonin-loading test is clinically usefull index to estimate osteoclastic activity in patients with secondary hyperparathyroidism.

Adult↗

PubMed1995

[Relative hypoparathyroidism associated with CAPD treatment using normo-calcemic (3.5mEq/1) dialysate: an approach from transperitoneal calcium balance].

We investigated factors affecting net transperitoneal calcium balance (Ca-BL) and the level of parathyroid hormone in relation to stepwise changes in serum calcium, by short PET (peritoneal equibrium test during 240 min: using 2000 ml of 2.5% dextrose dialysate containing 1.75 mmol/L Ca) in uremic patients undergoing stable CAPD. We calculated Ca-BL (mg/effluent/PET) of 244 effluents obtained from 90 patients receiving calcium carbonate as a phosphate binder without vitamin D supplementation. Their serum calcium level corrected with albumin (cSCa), alkaline phosphatase activity (ALP) and intact-PTH level was 9.7 +/- 0.9 mg/dl, 236 +/- 83 mIU/ml and 153.0 +/- 172.4 pg/ml, respectively. We proposed two statistic significant regression lines between Ca-BL and total drainage effluent volume (Ca-BL = 133X - 0.056: r = 0.981, P < 0.001), cSCa (Ca-BL = -12.9X + 123.6: r = 0.941, P < 0.01). Total drainage volume (TDV) and cSCa were two major factors affecting Ca-BL. A TDV level of 2430 ml/240 min-PET or more was required for positive Ca-BL in cases with 9.5-10.0 mg/dl of cSCa, using this linear regression analysis. A cSCa level of 9.6 mg/dl or more was also required for positive Ca-BL in cases with 2400-2600 ml/240min-PET. We also proposed a significant linear regression line between the intact-PTH level and cSCa (i-PTH = -90.5X + 1015.8, r = 0.973, P < 0.01). This line suggest that 200 pg/ml of intact PTH was obtained by 9.0 mg/dl or less of cSCa level in 90 CAPD uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

[Clinical outcome of radical prostatectomy and pelvic lymph node dissection].

Between September, 1987 and September, 1993, a total of 44 consecutive patients had undergone radical retropubic prostatectomy and pelvic lymphadenectomy for the treatment of prostate cancer. The patients were between 56 and 77 years (mean, 68 years). Eleven patients had clinical state A2 disease, 21 had stage B disease, and 12 had stage C disease. Fourteen of the 44 patients (32%) had positive lymph node metastases. The 5-year survival rate for patients with pT1, pT2 and pT3 was 100%, 71% and 87%, respectively. It was 77% in patients with positive node disease and 90% in patients with negative node disease. The 5-year disease-free survival rate for patients with pT1, pT2 and pT3 was 82%, and 78%, respectively. It was 54% in patients with positive node disease and 88% in patients with negative node disease. In 14 positive node patients, metastases were located in obturater nodes in 8 patients (57%), hypogastric nodes, in 6 patients (43%), external iliac nodes in 6 patients (43%), common iliac nodes in 4 patients (29%) and presacral nodes in 2 patients (14%). We confirmed that radical retropubic prostatectomy is effective treatment for locally confined prostate cancer and removal of obturater, hypogastric lymph nodes and the internal chain of external iliac lymph nodes is important in detecting metastases.

Aged↗

PubMed1995

[Indication of neobladder replacement in patients undergoing radical cystectomy for bladder cancer].

Neobladder replacement has become an important procedure in the patient undergoing radical cystectomy for invasive bladder cancer. It yields postoperatively excellent quality of life in these patients. The indications of the patients selection have not been established, since long-term clinical results have not been presented and some issues such as urethral recurrence of the original disease, growth of the cancer from the neobladder made of the gastrointestinal tract and influences arising from orthotopic micturition are still unclear. We reviewed the reports describing neobladder replacement in the patients undergoing cystectomy for the bladder cancer. At present the criteria of patients selection described by most authors can be summarized as follows, (1) male patients, (2) patients having an available gastrointestinal tract for reconstructing the neobladder, (3) patients having a good renal function and liver function and could tolerate for the surgery and (4) patients with no evidence of disease in their urethra and prostate (direct invasion of the disease). As to carcinoma in situ within the bladder, some authors included their indication and the others contraindication.

Cystectomy↗

PubMed1995

Adenovirus surveillance, 1982-1993, Japan. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

The Infectious Agents Surveillance Center, the National Institute of Health, Japan, received 17,265 reports from 1982 to 1993 on cases from whom adenovirus was isolated or detected; 85% from 57 public health institutes and the other 15% from two national hospitals and two commercial diagnostic laboratories. The followings were found. Three major diseases caused by adenovirus were upper respiratory tract infection, gastroenteritis, and conjunctivitis. Patients of upper respiratory tract infection numbered 6,837 (40% of all patients due to adenovirus), the identified serotypes being in order of frequency types 3, 2, 1, and 5. Those of gastroenteritis numbered 1,636 (9.5%). From 40% of the gastroenteritis patients, adenovirus was detected by electron microscopy or immunochemical methods without cultivation. From the remaining 60%, virus was isolated in tissue culture; the serotypes of the isolates resembled those causing upper respiratory tract infection. Patients of conjunctivitis numbered 3,437 (20%), the frequency being in order of types 3, 4, 8, 37, and 19. Conjunctivitis due to types 3 and 4 prevailed every summer; type 3 was isolated often from children with pharyngo-conjunctival fever and the other four types were mostly from adults with epidemic keratoconjunctivitis. Type 3 had a unique feature not seen in other types: it was most frequently isolated, causing upper respiratory tract infection, gastroenteritis, conjunctivitis, and pharyngo-conjunctival fever. Reports on isolation of type 7, which has been reported to cause severe pneumonia in many other countries, were as few as 28 (0.2%).

Adenoviridae Infections↗

PubMed1995

Processing of hepatitis C virus precursor polyprotein.

To elucidate the possible involvement of hepatitis C virus protein in the development of hepatocellular carcinoma. viral proteins produced from the largest open reading frame of the viral genome were analyzed. The function of each protein in virus replication was also examined. Virus proteins are produced by proteolytic cleavage by cellular and virus encoded proteinases. One of the viral proteins is a phosphoprotein, and the degree of phosphorylation is regulated by another viral protein. This regulation of phosphorylation may play an important role in modulating the proliferation of virus-infected cells.

Genome, Viral↗

PubMed1994

Long-term depression requiring tACPD-receptor activation and NMDA-receptor blockade.

In slices from the rat visual cortex, application of the metabotropic glutamate receptor (mGluR) agonist trans-1-aminocyclo-pentane-1,3-dicarboxylic acid (tACPD), whether combined with tetanization or not, produced only a reversible depression but not long-term depression (LTD) of synaptic transmission. In the presence of both tACPD and the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoate, tetanization induced LTD. These findings suggest requirement of tACPD-sensitive mGluR subtypes for inducing a form of LTD in the visual cortex.

Animals↗

PubMed1994

Modulation of KC/gro protein (interleukin-8 related protein in rodents) release from hepatocytes by biologically active mediators.

Modulation of the release of KC/gro protein (a chemoattractant for neutrophils; IL-8 related protein in rodents) from isolated hepatocytes after stimulation with biologically active mediators was investigated. The release of KC/gro protein from hepatocytes of control rats was enhanced by stimulation with lipopolysaccharide, IL-1 beta or TNF-alpha in a dose-dependent manner, but was not enhanced by IL-6. In contrast, although spontaneous release of KC/gro protein from the hepatocytes of chronically ethanol-fed rats was markedly enhanced as compared with control rats, the relative increase by stimulation with lipopolysaccharide, IL-1 beta or TNF-alpha was significantly smaller than in controls. These findings suggest that the regulation of hepatocyte KC/gro protein production might be disturbed in chronically ethanol-fed rats.

Alcoholism↗

PubMed1994

Mechanism of gene activation by the Escherichia coli positive regulator, OmpR: a mutant defective in transcriptional activation.

The OmpR protein is an activator specific for the E. coli ompC and ompF genes. This protein functions in a phosphorylation-dependent manner through a presumed interaction with RNA polymerase. In this study we isolated OmpR mutants which were suggested to be defective for transcriptional activation, but not for DNA binding. Two such mutants, that we isolated, have a single amino acid alteration at positions 131 [P131S], and 179 [P179L], respectively, of OmpR, comprising 239 amino acids. These altered amino acids in OmpR may be implicated, directly or indirectly, in the presumed RNA polymerase/OmpR interaction that is important for transcriptional activation.

Bacterial Outer Membrane Proteins↗

PubMed1994

Genetic alterations of the putative envelope proteins encoding region of the hepatitis C virus in the progression to relapsed phase from acute hepatitis: humoral immune response to hypervariable region 1.

Hypervariable region I (HVRI) of the putative second envelope glycoprotein (gp70) of hepatitis C virus (HCV) undergoes sequential alterations at intervals of several months during the chronic phase of hepatitis. To evaluate the implications of sequence variability in HVRI of HCV, we investigated the sequence variability of the whole envelope-protein(gp35 and gp70)-coding regions of HCV genome derived from patient M in acute and relapsed phases (8-month interval) of hepatitis. From this analysis, we found that a Leu (position 405) in HVRI substituted to Pro, and that 4 additional substitutions could be detected in gp70 during the relapsed phase. Sequence-specific antibody against HVRI derived from patient M was first detected in the serum at 8 months after the onset of hepatitis, but no other specific antibodies against peptides containing amino-acid position(s) substituted in regions other than HVRI could be detected. Epitope mapping using the sequence of HVRI derived from the acute phase of hepatitis was also performed, and a B-cell epitope (positions 397 to 407) of 11 amino acids was identified. However, the Pro variant at position 405 did not display an escape pattern from the antibody produced at 8 months after the onset. In addition, we demonstrated the existence of important amino-acid residue positions which are recognized by the anti-HVRI antibody produced in patient M using introduction point mutations within HVRI.

Adult↗

PubMed1994

Immune complex independent activation of complement, C1s secreted from hamster embryo malignant fibroblasts, Nil2C2 in serum free culture medium.

Antibody independent activation of complement C1s was examined by immunoblot analysis using an antibody against a synthetic peptide of hamster C1s L chain. Approx. 50% of C1s secreted from hamster embryo malignant fibroblasts Nil2C2 was functionally active in its two-chain form in the serum free culture medium. In contrast, no active C1s was found in a culture medium of hamster embryo fibroblasts (HEF). Active C1s was detectable, however, in the culture medium after HEF became a cell line. The immune complex independent activation of C1s was also observed in rat cell lines but not in secondary rat embryo fibroblasts. C1s in a membrane fraction of Nil2C2 was a proenzyme form and was not activated by incubation of the membrane itself suggesting that C1s was activated after secretion. The activation of C1s was not inhibited by human C1 inhibitor (C1-INH), benzamidine or soy bean trypsin inhibitor (SBTI) but was inhibited by leupeptin, nitrophenyl guanidinobenzoate and DFP. Our results suggest that C1s is activated either by a serine proteinase(s) other than those reported to cleave C1s or by an activator which directly stimulates autoactivation of C1s.

Amino Acid Sequence↗

PubMed1994

A novel synthetic phyllolitorin analogue [desTrp3,Leu8]phyllolitorin inhibits scratching behavior induced by neuromedin C in rats.

[DesTrp3,Leu8]phyllolitorin (DTP) (pGlu-Leu-Ala-Val-Gly-Ser-Leu-Met-NH2) was synthesized as an analogue of phyllolitorins, a new member of bombesin family, and examined if it antagonized neuromedin C (NMC)-induced scratching. DTP inhibited dose-dependently the scratching behavior by NMC (1 microgram), whereas it did not alter any element of other grooming behaviors. DTP (6 micrograms) alone was found to be neither toxic nor active in inducing both scratching and grooming, which were comparable to vehicle alone. Assuming that the scratching behavior is commonly and specifically elicited by bombesin family peptides, DTP might be classified as a new type of bombesin antagonist.

Amino Acid Sequence↗

PubMed1994

Characterization of a plasmid-borne and constitutively expressed blaMOX-1 gene encoding AmpC-type beta-lactamase.

A 1954-bp DNA fragment containing the blaMOX-1 gene, identified on a large resident plasmid (pRMOX-1) of Klebsiella pneumoniae NU2936, was sequenced and an open reading frame (ORF) coding for a 390-amino-acid (aa) MOX-1 was found. The total deduced aa sequence of MOX-1 shared considerable homology with that of AmpC-type class C beta-lactamases of Gram- bacteria, especially of Pseudomonas aeruginosa PAO1 [51.3%; 63.8% at the nucleotide (nt) level]. However, the regulatory gene ampR and a 38-bp AmpR-binding region were not present upstream from blaMOX-1, although the expression of P. aeruginosa ampC is directly regulated by AmpR. Possible -35 and -10 regions, a Shine-Dalgarno (SD) sequence and terminators were identified which are peculiar to blaMOX-1. On the other hand, a sequence highly homologous (91.6%) to the region upstream from dhfrX in the In7 integron carried by plasmid pDGO100 was found upstream from blaMOX-1 at nt 1 to 488. No significant difference was detected between the promoter activities of blaMOX-1 in ampD- and ampD+ strains of Enterobacter cloacae, as measured by the chloramphenicol acetyltransferase (CAT) assay. These results clearly show that blaMOX-1 belongs to the group of ampC-related bla genes and that it is expressed constitutively, independently of transcriptional regulators such as AmpR, AmpG and AmpD. Homology analysis among AmpC enzymes or ampC genes implied that integration of the chromosomal ampC gene into a large resident plasmid, followed by transconjugation, was involved in the evolution of blaMOX-1.

Amino Acid Sequence↗

PubMed1994

Genetic alteration of the hepatitis C virus hypervariable region obtained from an asymptomatic carrier.

Hepatitis C virus (HCV) genome shows extensive sequence diversity at 2 hypervariable regions (HVR1 and HVR2) of the putative envelope glycoprotein (gp70). We recently reported that the amino-acid sequence of HVR1, but not of HVR2, underwent a striking mutation or mutated sequentially over a period of several months in patients with chronic hepatitis (CH). Here, we examined whether these genetic alterations in HVR1 occurred in an asymptomatic HCV carrier. The level of HCV RNA in serum was almost the same throughout the 4 time points sampled over 16 months. However, we found that the amino-acid sequence of the HCV HVR1 from this asymptomatic carrier altered with time, as seen in patients with CH. Alterations of amino acids in the HVR1 were correlated with persistent HCV infection rather than with clinical symptoms. Sequence heterogeneity of HVR1 was not correlated with alanine aminotransferase (ALT) values or liver histological findings. The necessity of clinical follow-up of HCV asymptomatic carriers is discussed.

Adult↗

PubMed1994

Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma.

We attempted to detect circulating hepatocellular carcinoma by demonstrating hepatocyte-associated mRNA in the nuclear cell component of peripheral blood using nested reverse transcription-polymerase chain reaction because of the extremely small number of tumor cells in the circulation. Albumin mRNA was demonstrated not only in the liver tissue (hepatocytes) and HepG2 cells but also in nuclear cells of the blood from normal healthy volunteers (neutrophils and lymphocytes) by reverse transcription-polymerase chain reaction. In contrast, alpha-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2 cells, but not in peripheral blood of normal healthy volunteers, indicating the possibility of using alpha-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lymphocytes. alpha-Fetoprotein mRNA in peripheral blood was detected in 17 of 33 cases of hepatocellular carcinoma (52%), 2 of 13 cases of cirrhosis (15%) and 2 of 17 cases of chronic hepatitis (12%). alpha-Fetoprotein mRNA was not demonstrated in 26 cases of normal healthy volunteers (0%). Among the patients with hepatocellular carcinoma, total volume of tumor tissue, maximum size of tumor and serum alpha-fetoprotein level were markedly increased in the patients with alpha-fetoprotein mRNA in blood. In addition, alpha-fetoprotein mRNA was detected in the blood of all 6 patients showing metastasis at extrahepatic organs (100%), in contrast to 11 of 27 cases without metastasis (41%). From these results, we conclude that the presence of alpha-fetoprotein mRNA in peripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma.

Adult↗

PubMed1994

Role of polymorphonuclear leukocytes in galactosamine hepatitis: mechanism of adherence to hepatic endothelial cells.

To investigate the role of polymorphonuclear leukocytes in galactosamine-induced hepatic injury, we injected rats intraperitoneally with antiserum against rat polymorphonuclear leukocytes to deplete circulating neutrophils, then administered galactosamine plus lipopolysaccharide. Polymorphonuclear leukocytes in the hepatic sinusoids were increased after administration of galactosamine plus lipopolysaccharide, whereas pretreatment with the antiserum decreased the number of circulating leukocytes and reduced the mortality and the severity of hepatic injury. Serum collected 1 hr after galactosamine/lipopolysaccharide treatment enhanced in vitro polymorphonuclear leukocyte adherence to hepatic endothelial cells and induced leukocyte superoxide production. Intercellular adhesion molecule-1 expression on hepatic endothelial cells was also enhanced after stimulation with the serum. Polymorphonuclear leukocyte adhesion was partially inhibited by an antibody against tumor necrosis factor-alpha but not by superoxide dismutase. These results suggest that polymorphonuclear leukocytes play an important role in galactosamine-induced hepatic injury and that the accumulation and activation of leukocytes, as well as the enhanced expression of adhesion molecules on hepatic endothelial cells, can be induced by biologically active mediators such as tumor necrosis factor-alpha. In addition, prostaglandins E1 and E2 lessened the enhanced adherence of polymorphonuclear leukocytes and thus contributed to protection against hepatic injury.

Alprostadil↗