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Biomedical subjects

H Goto

Publications and source records attributed to H Goto.

At least 19 recordsLinked to original sources

Cloning and nucleotide sequence of the cDNA encoding human erythrocyte-specific AMP deaminase.

The nucleotide sequence of cDNA encoding human erythrocyte AMP deaminase has been determined by screening of human spleen cDNA library and by utilizing polymerase chain reaction (PCR) techniques. The 3.7 kb cDNA contains an open reading frame of 2301 bp which encodes 767 amino acids chain resulting in 89 kDa protein. The polyadenylation consensus signal (5'-AATAAA) located at 1212 bp 3' downstream from the stop codon. The homologies to human and rat muscle-specific AMP deaminases showed 64.1% and 65.2% identities, respectively, at the nucleotide level in the area of open reading frame, and 60.2% and 59.8% similarities at the deduced amino acid level.

AMP Deaminase

A novel Arg-Gly-Asp containing peptide specific for platelet aggregation and its effect on tumor metastasis: a possible mechanism of RGD peptide-mediated inhibition of tumor metastasis.

A novel cyclic tetrapeptide containing L-arginine-glycine-L-aspartic acid-L-phenylglycine (cyclo-RGDPhg) was synthesized and found to be a potent inhibitor of platelet aggregation induced by highly metastatic murine squamous cell carcinoma (SCCVII) cells (IC50 = 3.3 microM) as well as ADP (1.5 microM). This cyclic peptide, however, showed similar or less inhibitory activities on adhesion of SCCVII cells to fibronectin, vitronectin and type IV collagen as compared with those of parent linear tetrapeptide, RGDS. These results show that cyclo-RGDPhg peptide is a highly specific antagonist for gpIIb/IIIa on platelets. Moreover, this peptide failed to suppress pulmonary metastasis of SCCVII cells in an experimental metastasis model. These results indicate that RGD peptide-mediated inhibition of tumor metastasis is attributed to the suppression of cell adhesion but not platelet aggregation. These also suggest that platelet aggregation is not an essential step during blood circulation of tumor cells for the completion of metastasis.

Animals

A single receptor identical with that from intestine/T47D cells mediates the action of 1,25-dihydroxyvitamin D-3 in HL-60 cells.

Two anti-vitamin D receptor monoclonal antibodies binding to two different epitopes immunoprecipitate 100% of the HL-60 1,25-dihydroxyvitamin D-3 binding activity, while another monoclonal antibody specific for the porcine receptor precipitates none. Using a rat receptor cDNA probe, a single mRNA species of 4.6 kb was detected by Northern analysis of HL-60 mRNA. Using a cDNA probe from the cloned rat receptor, 10(7) recombinants from a lambda gt11 cDNA library constructed from mRNA isolated from HL-60 cells was screened yielding two positive clones. These clones had sequences identical with the known human receptor sequence from intestinal/T47D sources. Using PCR technology, the entire sequence of the HL-60 1,25-dihydroxyvitamin D-3 receptor was determined. This sequence was found identical with that reported for the human intestinal/T47D cDNA encoding the vitamin D receptor except for a single base. The substitution of this particular base does not alter the amino acid sequence however. Thus, the same receptor likely operates in differentiation and calcium transport functions.

Amino Acid Sequence

Age-associated decreases in prostaglandin contents in human gastric mucosa.

This study was designed to clarify effects of ageing on human gastric mucosal prostaglandin (PG) contents. Forty examinees were divided into 5 age groups of 8 persons each, as follows: age under 40, age 40-49, age 50-59, age 60-69, and age over 70. PG contents in human gastric mucosa were measured by microcolumn high performance liquid chromatography (HPLC) with helium/cadmium laser induced fluorescence detection using biopsy samples obtained by endoscopy. The contents of 6-keto-PGF1 alpha, PGF2 alpha, PGE2, and PGD2 in the under 40 group were 638 +/- 39, 97 +/- 16, 468 +/- 68, 497 +/- 86 (pg/mg tissue), respectively. No significant differences in PG contents among groups aged under 70 were observed. In contrast, significantly low PG contents in the over 70 group were observed, i.e., the contents of 6-keto-PGF1 alpha, PGF2 alpha, PGE2, and PGD2 were 311 +/- 58, 36 +/- 8, 196 +/- 48, 171 +/- 40, respectively, and their contents were significantly lower than those in other age groups. In conclusion, gastric mucosal PG contents decrease significantly in over 70 years-old and this might be a contributing factor in the pathogenesis of gastric ulcers in elderly people.

6-Ketoprostaglandin F1 alpha

tsBN75 and tsBN423, temperature-sensitive x-linked mutants of the BHK21 cell line, can be complemented by the ubiquitin-activating enzyme E1 cDNA.

tsBN75 and tsBN423 are independently isolated temperature-sensitive (ts) mutants of the BHK21 cell line for cell growth. Both tsBN75 and tsBN423 belong to the same complementation group and show G2 block at the nonpermissive temperature. Both were efficiently transformed to ts+ cells with the mouse and human cDNA encoding the ubiquitin-activating enzyme, E1. While no transformants of tsBN423 cells had a DNA content greater than the parental 2C, several ts+ transformants of tsBN75 cells acquired a multiploid DNA content. These data thus demonstrate the function of the human and mouse E1 cDNAs and further suggest that E1 functions in more than one step in cell cycle progression.

Animals

Molecular analysis of five independent Japanese mutant genes responsible for hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency.

Five independent mutations in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene were identified in a partially HPRT deficient patient with gout and in four Lesch-Nyhan patients. Using the polymerase chain reaction (PCR) technique coupled with direct sequencing, the nucleotide sequences of the entire HPRT coding region amplified from the cDNA and also of each exon amplified form the genomic DNA were analyzed. Three independent point mutations in the coding region were detected in the partially HPRT deficient patient (Case 1) and in two Lesch-Nyhan patients (Case 2 and 3), resulting in single amino acid substitutions. The family study of Case 3, utilizing a PvuII restriction site created in the mutant gene, indicated that the mother was a heterozygote, and a sister and a fetal brother had inherited the normal HPRT gene from the mother. In two other mutants causing Lesch-Nyhan syndrome, a portion of the HPRT gene was deleted, and RNA splicing was missing in both mutants. A 4-bp deletion at the 5' end of exon 4 resulted in formation of three different types of abnormal mRNA (Case 4). The other mutant (Case 5) produced abnormal mRNA including 26 bp of intron 8 instead of the deleted 58 bp at the 5' end of exon 9, because of a 74-bp deletion from intron 8 to exon 9.

Amino Acid Sequence

Accessory bile duct draining into the stomach: case report and review.

Accessory bile duct with ectopic drainage into the gastrointestinal tract is an extremely rare congenital anomaly, and only 55 cases have been reported in the literature. We present another case of accessory bile duct draining into the stomach. Barium meal study of the stomach first revealed the accessory bile duct, and the diagnosis was confirmed by gastrofiberscopy, ultrasonography, hepatobiliary scintigraphy, computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP).

Adult

Hepatocellular carcinoma with extrahepatic primary neoplasms.

We experienced seven cases of hepatocellular carcinoma (HCC) with extrahepatic primary malignant neoplasms (PMNs), which accounted for 7.5% of 93 HCC cases in our department during a 5.5-year investigation period. No common characteristics of the seven patients with extrahepatic PMNs in terms of age, sex, computed tomographic (CT) features of hepatocellular carcinoma, or presence of liver cirrhosis were evident. One of the seven cases had triple PMNs. Extrahepatic PMNs were found in various organs: stomach, colon, kidney, lung, larynx, and esophagus. Attention to extrahepatic organs should be undertaken in the management of HCC. Two patients in hepatic coma died 4 and 6 months after the diagnosis of HCC due to the advanced HCC, and accompanying extrahepatic malignancies were not the primary cause of death.

Adult

Acute pulmonary toxicity of inhaled beta-1,3-glucan and endotoxin.

The number of inflammatory cells was studied in lung walls and airways after inhalation of endotoxin or beta-1,3-glucan. In the water unsoluble form, beta-1,3-glucan caused a delayed response in terms of a decrease in macrophages and lymphocytes in the lung wall, 1 to 7 days after exposure but no invasion of neutrophils into the airways. When solubilized in 0.02 N NaOH, the cell response was the same as that observed after exposure to endotoxin.

Administration, Inhalation

Arterial baroreflex attenuation during and after continuous propofol infusion.

The reduction of arterial blood pressure produced by propofol may be, in part, attributable to impaired baroreflex integrity. The purpose of this study was to investigate arterial baroreflex sensitivity during and after continuous propofol infusion. In urethane anaesthetized rabbits, left renal sympathetic nerves were exposed and placed on a bipolar silver electrode to record renal sympathetic nerve activity (RSNA). Mean arterial pressure (MAP) via a femoral artery and heart rate (HR) by electrocardiogram were continuously recorded. The rabbits were divided into two groups of eight each: Group 1, propofol 5 mg.kg-1 bolus followed by infusion 0.5 mg.kg-1 x min-1; Group 2, propofol 2 mg.kg-1 bolus followed by 0.2 mg.kg-1 x min-1. Phenylephrine pressor and sodium nitroprusside (SNP) depressor tests were carried out before propofol was started (control), at 15 and 30 min during 30 min infusion, and at 15, 30 and 60 min after its discontinuation. The change of RSNA was plotted with respect to every 5 mmHg increment and decrement of MAP to construct sympathetic baroreflex sigmoid curves, and to evaluate baroreflex sensitivity. The baroreflex sensitivity was also evaluated by calculating the ratio of maximum increase of RSNA or HR to SNP-induced maximum decrease of MAP (delta RSNA/delta MAP, delta HR/delta MAP). Despite the same decreases or increases in MAP, RSNA was attenuated after 15 and 30 min of propofol infusion in both groups compared with control (P < 0.05). Decreased delta RSNA/delta MAP gradually returned to the control level 60 min after discontinuation of propofol in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Characterization of the stage(s) in the virus replication cycle at which the host-cell specificity of the feline parvovirus subgroup is regulated in canine cells.

Feline panleukopenia virus (FPLV), mink enteritis virus (MEV), and canine parvovirus (CPV) are classified as a host-range variants. They show different host-range specificity in vivo and host-cell specificity in vitro. For instance, FPLV and MEV cannot grow or can grow only inefficiently in canine cell lines such as MDCK and the canine fibroma cell line A72. Here we have studied the mechanism(s) by which the different cell tropism is mediated in vitro. When FPLV or MEV was inoculated to A72 cells, viral DNA replicated slightly, few viral-antigen-positive cells were detected, and the culture fluid contained the threshold level of infectivity. On the other hand, when an infectious molecular clone of MEV (pMEV) was introduced into A72 cells, viral DNA replicated efficiently, and the culture fluid of pMEV-transfected cells contained much higher infectivities than that of MEV-infected cells. In spite of the restrictive growth in A72 cells, MEV could bind to A72 cells as efficiently as CPV. No detectable viral RNA was produced in MEV-infected A72 cells. In contrast, efficient viral transcription occurred in pMEV-transfected A72 cells. These results suggest that the restrictive infections of MEV and FPLV in A72 cells are not mediated by the attachment of the virus to the cells or by the events occurring after the viral transcription. It appears to be caused by the stage(s) in the virus replication cycle, which exists between a postadsorptional step required for virus penetration and the initiation of viral transcription.

Aleutian Mink Disease Virus

Correlation between increased susceptibility to primary Toxoplasma gondii infection and depressed production of gamma interferon in pregnant mice.

To explore a possible mechanism of pregnancy-associated suppression of T cell-mediated immunity to Toxoplasma gondii, acquired resistance and gamma interferone (IFN-gamma) production in pregnant mice were compared with those in virgin mice after infection with the S-273 strain of this protozoan parasite. The 50% lethal dose of this strain was less than 200 tachyzoites for pregnant mice and 2,800 organisms for virgin controls. Toxoplasma-induced production of both IFN-alpha and IFN-gamma in the bloodstream of pregnant mice was significantly depressed as compared with that in virgin controls. The administration of recombinant murine IFN-gamma (rMuIFN-gamma) resulted in a significant decrease of mortality and parasitic growth in the organs of pregnant mice infected with a lethal dose of S-273 strain tachyzoites. Thus, the impairment of T cell-mediated immune responses was evident in pregnant mice from the impaired IFN-gamma-generating capacity and poor survival rate after primary infection with Toxoplasma. When mice with chronic Toxoplasma infection were injected with specific antigen, the resultant production of IFN-gamma was also significantly suppressed during pregnancy. However, there was no direct correlation between the serum levels of IFN-gamma and susceptibility to reinfection, since the mortality rate of chronically infected pregnant mice after the challenge with the high virulent RH strain was not significantly higher than that of virgin controls.

Animals

Mechanism and prevention of chronic colonic inflammation with trinitrobenzene sulfonic acid in rats.

1. The role of prostanoids in experimental colitis with trinitrobenzene sulfonic acid (TNBS) in rats was investigated. The effects of cyclosporine A (CsA) on the development of experimental colitis were also examined. 2. Five kinds of prostanoids were detected in rat colonic tissue by high performance liquid chromatography. These were 6-keto-prostaglandin (PG) F1 alpha, PGF2 alpha, PGE2, PGD2 and thromboxane B2. 3. In TNBS-induced experimental colitis, all prostanoid concentrations except PGD2 increased, although the time courses differed from each other. 4. Medication with indomethacin markedly reduced prostanoid concentrations in TNBS-induced colitis. However, indomethacin did not show any effect on damage scores. 5. Cyclosporine A reduced damage scores 14 days after TNBS treatment, and the protective effects were observed, whereas CsA did not affect colonic tissue prostanoid concentrations. 6. Prostanoids might be produced secondarily in the genesis of TNBS-induced colitis, although they may attenuate the inflammatory response. It was also suggested that CsA was likely to have therapeutic effects on experimental colitis by inhibiting the immune reaction with TNBS, which induced the chronic inflammation.

Animals

[Single-dose treatment of tosufloxacin (TFLX) for acute uncomplicated cystitis].

The effectiveness of a single 300-mg dose of tosufloxacin and of 3-day treatment with tosufloxacin (300 mg daily) were compared in a prospective trial in order to clarify the cost-effectiveness of tosufloxacin for acute uncomplicated cystitis. Fifty female patients (25 patients of each group) with acute uncomplicated cystitis received one of these treatment regimens, and the clinical data and follow-up culture results were analyzed. The effectiveness rates of single-dose treatment and 3-day treatment after 3 days were 100% and 96%, respectively. The recurrence rates of single-dose treatment and 3-day treatment after 14 or 28 days were 0% (0/13 patients) and 15% (2/13 patients), respectively. There was no significant difference in the effectiveness rate and the recurrence rate between these two groups, statistically. All isolated strains were eliminated in both regimens. From these results, it is suggested that single-dose treatment of tosufloxacin is effective enough for acute uncomplicated cystitis.

4-Quinolones

Effects of histamine H2-receptor antagonists and a proton pump inhibitor on the mucosal hydroxyproline content of ethanol-HCl-induced gastric lesions in rats.

We evaluated the effects of different antisecretory agents (H2-receptor antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH-HCl). The lesion indices showed the highest value 30 min after administration of EtOH-HCl and a significantly decreased value 15 h later. The mucosal hydroxyproline concentration was significantly increased 30 min after EtOH-HCl administration, reached a maximum 6 h later and subsequently decreased as time passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not reduce the lesion indices in less than 24 h and suppressed the increase in mucosal hydroxyproline concentrations significantly compared with the control group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal hydroxyproline concentrations. These facts suggest that H2-receptor antagonists might delay the healing of EtOH-HCl-induced gastric lesions through the suppression of collagen regeneration under the condition of exclusion of gastric acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles

Effect of duodenal mucosal blood flow on duodenal alkaline secretion in rats.

To investigate the role of duodenal mucosal blood flow (DMBF) in the regulation of duodenal alkaline secretion (DAS), both parameters were measured before and after the administration of various drugs in rats. The DMBF was determined using an electrolytically generated hydrogen gas clearance technique, and the DAS was measured by the perfusion method. The administration of dulcerozine, a potent duodenal ulcerogenic agent, at a dose of 250 mg/kg and serotonin at a dose of 20 mg/kg, which produces duodenal ulcerations with an acid load, decreased both DMBF and DAS. On the other hand, the administration of secretin at a dose of 10 U/kg increased both parameters. There were parallel changes in DMBF and DAS. It is concluded, therefore, that DAS may be regulated by DMBF and that both parameters may be involved in the defense mechanism of duodenal mucosa.

Alkalies

Effects of interleukin-3 and interleukin-6 on peripheral blood cells from multiple myeloma patients and their clinical significance.

The effects of interleukin-3 (IL-3) and interleukin-6 (IL-6) on nonadherent mononuclear cells (NMC) from the peripheral blood of 28 patients with multiple myeloma (MM), 3 patients with monoclonal gammopathy of undetermined significance (MGUS), and 3 normal controls were investigated. In 15 of 27 evaluable patients with MM, monoclonal-cytoplasmic-immunoglobulin (cIg)-positive plasma cells appeared from the T-cell-depleted NMC after 10 days of culture in the presence of IL-3 and IL-6. These changes were not observed in the T cell fraction of myeloma blood or in the T-cell-depleted NMC obtained from cases of MGUS or from normal controls. The percentage of cIg-positive plasmacytoid cells after 10 days of culture was significantly higher in the presence of both IL-3 and IL-6 than with each interleukin alone or the control medium. Furthermore, these changes were often observed in untreated patients. These findings suggest that myeloma precursor cells exist in the peripheral blood of MM patients, especially at diagnosis, and differentiate into cIg-positive cells in the presence of IL-3 and IL-6. This assay may be useful in discriminating the early stage of myeloma from MGUS.

Antigens, CD