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Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 163 records · Page 9Linked to original sources
PubMed1994

Cloning, nucleotide sequence and expression of a hemolysin gene of Clostridium septicum.

A genomic library of Clostridium septicum NCTC547 strain was made in Escherichia coli by means of lambda gt10. The DNA insert of a hemolysin-positive (Hly+) lambda-clone was transferred into pUC19. The resulting plasmid, pCS21, confers a Hly+ phenotype on E. coli. Crude lysates of E. coli (pCS21) possessed a strong lytic activity on human erythrocytes and also a lethal effect on mice, characteristic of an alpha toxin. Nucleotide sequence analysis revealed that the insert DNA (5.2 kb) in pCS21 included at least one open reading frame of 1380 bp. The coding frame for hemolysin was predicted to be 1329 bp in size and to encode a protein of 49.8 kDa. It coincided with the molecular mass (48 kDa) of the alpha toxin secreted by C. septicum. Taken together, the data indicated that plasmid pCS21 indeed encoded an alpha toxin gene of C. septicum.

Amino Acid Sequence↗
PubMed1994

Dose-dependent plasma clearance of human epidermal growth factor in rats.

Exogenously administered human epidermal growth factor (hEGF) shows a marked dose-dependent plasma disposition in rats. In the present study, total plasma clearance (CLtotal) of hEGF was examined from the viewpoint of hepatic blood flow and accessible EGF receptors in a dosing range of hEGF from 30 to 1000 micrograms/kg. In rats in which down-regulation of EGF receptors caused a reduction in their number (50% below the normal level) (group 1), the CLtotal of hEGF was decreased only at a medium dose (100 micrograms/kg) compared to those in normal rats. In rats in which hepatic intoxication with carbon tetrachloride caused 50% reduction of both EGF receptor number and hepatic blood flow (group 2), CLtotal was decreased at low and medium hEGF doses. The decrease at a low hEGF dose was proportional to the decrease in the hepatic blood flow. In rats with reduced hepatic blood flow caused by hypothermia (group 3), CLtotal was decreased at all hEGF doses examined, and the decrease at a low hEGF dose (50 micrograms/kg) was proportional to the hepatic blood flow. The decreases of CLtotal at a medium hEGF dose in groups 1, 2 and 3 were well accounted for by the decrease of hepatic blood flow and/or EGF receptor number in a well-stirred model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Hepatitis C virus genotypes are not responsible for development of serious liver disease.

Although hepatitis C virus (HCV) is known to have at least four kinds of genotypes, no clear relationship has yet been established between the genotype and the severity of liver disease. Therefore, we determined HCV genotypes in sera of 251 Japanese patients with type C chronic liver disease, using polymerase chain reactions with six independent primers. One set of primers and a probe derived from 5'-noncoding region of HC-J1 was supposed to detect all four genotypes, while the other five were devised to detect each of the genotypes. Among the patients, the major genotype was type II (69%) and the second most common was type III (18%). Type IV was found in 7%, while none had type I genotype. There was no significant difference in the distribution of any genotype among different stages of liver disease, although the ratio of type II to type III tended to be higher in the group of cirrhosis and hepatocellular carcinoma than in the chronic hepatitis group (5.5 vs 3.0). The amounts of HCV RNA were significantly greater in patients with type II (P < 0.001) compared with those with types III and IV. However, HCV concentrations of each genotype were not associated with the disease status. These results suggest that HCV genotypes are unlikely to be responsible for the development of more serious liver disease.

Adult↗
PubMed1994

Pharmacokinetic analysis of the absorption enhancing action of decanoic acid and its derivatives in rats.

The enhancing action of decanoic acid (C10) and its derivatives on mucosal absorption of phenolsulfonphthalein (PSP) in the jejunum or colon was analyzed using pharmacokinetics in rats. After administration of a solution containing PSP and an enhancer [C10, 2-hydroxydecanoic acid (2-OHC10), or 3-hydroxydecanoic acid (3-OHC10)] into the jejunal or colonic loop, the amounts of PSP and enhancer remaining in the loop and/or plasma PSP concentration were determined periodically. 2-OHC10 exhibited a greater absorption enhancing potency than C10, while 3-OHC10 was less effective. Disappearance of residual PSP from the loop ceased after complete absorption of the enhancer. The enhancer-induced disappearance rate constant of PSP correlated well with the product of the enhancer disappearance rate and its capacity to sequester calcium ions. In conclusion, the enhancement of PSP mucosal absorption by C10 and its derivatives is consistent with a pharmacokinetic model, assuming that the enhanced membrane permeability of PSP depends on the enhancer disappearance kinetics from the loop and its calcium ion sequestration capacity.

Animals↗
PubMed1994

Decanoic acid induced enhancement of rectal absorption of hydrophilic compounds in rats.

The enhancing effect of decanoic acid (C10) on the rectal absorption of phenolsulfonphtalein (PSP) was analyzed with a pharmacokinetic model. The transfer index of PSP from the rectal lumen to the epithelial layer in the presence of C10 was proportional to the product of the C10 disappearance rate from the rectal lumen and its calcium ion sequestration capacity. The enhancement of rectal PSP absorption by different doses of C10 was also predictable by using a permeability index, Pa, of PSP, which was defined as a proportionality constant relating transfer index and the product value described above. The Pa values of various hydrophilic compounds with different molecular weights were also estimated from their rectal bioavailability in the presence of C10. A linear relationship was observed between Pa values and reciprocal values of the square root of individual molecular weight. These findings suggest that the Pa index is related to the permeant's diffusion coefficient through paracellular aqueous openings formed by C10.

Animals↗
PubMed1994

Pharmacokinetics of the garlic compound S-allylcysteine.

The pharmacokinetic behavior of S-allylcysteine (SAC), one of the biologically active transformation products from garlic, was investigated after oral administration to rats, mice, and dogs. SAC was rapidly and easily absorbed in the gastrointestinal tract and distributed mainly in plasma, liver, and kidney. The bioavailability was 98.2, 103.0, and 87.2% in rats, mice, and dogs, respectively. SAC was mainly excreted into urine in the N-acetyl form in rats; however, mice excreted both SAC and the N-acetyl form. The half-life of SAC was longer in dogs than in rats and mice.

Animals↗
PubMed1994

Invasive ductal carcinoma with a predominant intraductal component arising in a fibroadenoma of the breast.

A rare case of invasive ductal carcinoma with a predominant intraductal component arising within a fibroadenoma of the breast in a 42 year old Japanese female was investigated by light microscopy. The patient, who had a well-defined, rubbery breast tumor measuring 2.0 x 3.0 cm, had undergone a tumorectomy 21 months after she noticed the tumor. Histologically, the fundamental architecture of the tumor showed an intracanalicular-type of fibroadenoma, but extensive proliferation of atypical cells was noticed in the lumen of the ducts. Tumor cells in the canaliculi had characteristics of ductal carcinoma, such as solid, comedo and cribriform patterns. As most of the ducts were occupied by carcinoma cells with several foci of microinvasion in the stroma of the fibroadenoma, it was diagnosed as invasive ductal carcinoma with a predominant intraductal component arising within a fibroadenoma. This coexistence of in situ proliferation and invasive lesions of carcinoma within a fibroadenoma suggest the origin of the carcinoma to have been in the epithelial component of the fibroadenoma. In addition, this study clarifies the fact that carcinoma cells may proliferate and spread along the lumen of pre-existing ducts of the fibroadenoma and speculates that the duct system of the fibroadenoma has complete continuity.

Adult↗
PubMed1994

Scanning electron microscopy of elastic system fibers in the articular disc of the rat mandibular joint.

Elastic system fibers (ESFs), i.e., microfibrils (putative oxytalan fibers), elaunin and elastic (true elastin) fibers, in the rat mandibular joint were studied mainly using scanning electron microscopy (SEM) and light microscopy (LM) with the aid of image processing. The present quantitative analysis using LM showed that the articular disc and capsule, which are the sites that receive physical compressive force during mastication, contained more ESFs than the articular cartilage of the mandibular joint. In addition, oxytalan fibers were the principal ESFs in all the articular components (capsule, articular disc, supraossous layer of articular surfaces and articular cartilage). Subsequently, ESFs in the articular disc, which contained more thick ESFs, were closely examined by SEM using both collagen- and elastin-digestion methods. SEM showed networks of microfibrils beneath the articular surfaces (superior and inferior layers) in the thin central portion of the articular disc; the principal microfibrils ran at nearly right angles to the collagen fibers. The microfibrils were cemented with amorphous elastin, thickened and shifted towards interconnecting oblique fibers and many main ESF trunks, which were oriented in the direction of the layered wavy collagen fibers and parallel to the direction of applied force, to sustain the mechanical force. From the superior and inferior layers, the main ESFs shifted towards the middle portion of the disc, transitional zone (synovial osteochondral junction) and the other articular components, showing no specific directivity. Transmission mission electron microscopy revealed that the thick main ESFs in the elastic network were elaunin fibers. The present study indicated that ESFs unite, branch and therefore construct an extensive and complicated protective stretchable network, which is interposed with the less tensible collagen network in the mandibular articular disc.

Animals↗
PubMed1994

[Genomic changes in the E2/NS1 region of HCV before and after IFN therapy in relation to clinical course].

To estimate the relationship between genomic change in the E2/NS1 region and clinical feature, we made a pairwise comparison in the nucleotide and deduced amino acid sequences for multiple recombinant clones of the E2/NS1 region, which derived from blood samples taken from four patients (three treated by IFN) at different stages. Sequence heterogeneities among the clones were generally high but they appeared to be significantly lowered after cessation of therapy. Our results showed, through IFN therapy, a few clones were selected and survived, although many clones disappeared. After discontinuation of the drug, three patients became carrier state, normal ALT levels with viremia. Evolution of defective viruses was seen in most of the cases. These features of HCV genome suggest that the virus could circulate as an extremely heterogeneous population including defective virus, and that this heterogeneity lend itself to selection pressures including interferon therapy and host immune response.

Aged↗
PubMed1994

Dual-energy computed tomographic diagnosis of pulmonary nodules.

Dual-energy computed tomography (CT) was used to study apparently noncalcified pulmonary nodules in 19 patients. We obtained both high- and low-voltage images during one CT scan study using a special CT apparatus, and four of 11 benign lesions were diagnosed as benign by measurement of the CT number. Moreover, this particular CT apparatus was useful in judging the presence or absence of calcification in pulmonary nodules.

Aged↗
PubMed1994

[Effect of lentinan for advanced prostate carcinoma].

A prospective, randomized multi-center study was conducted to assess the clinical effectiveness of Lentinan, an immunomodulatory agent, in the metastatic prostate cancer. Of seventy-five patients enrolled from July 1987 to June 1992, 69 were eligible. All patients received hormonal therapy and chemotherapy using Tegafur p.o. at a dose of 400-800 mg/day. While 33 patients received Lentinan i.m. for at least three months, the other 36 did not. The dose of Lentinan was 2 mg weekly for inpatients and 4 mg every other week for outpatients. The mean age of treated and control patients was 70 (range; 53-83) and 71 (range; 50-86), respectively. The 50% survival length of treated and control patients was 48 and 35 months, respectively. The five-year survival rate of treated patients was 43% according to the Kaplan-Meier method, while that of control patients was 29% (p < 0.05). We conclude that Lentinan is effective in metastatic prostate cancer when incorporated into hormonochemotherapy.

Aged↗
PubMed1994

Ultrasonographic abdominal screening of atomic bomb-exposed subjects.

Abdominal ultrasonographic screening for cancer was performed in 6,001 Hiroshima and Nagasaki A-bomb exposed and comparison subjects, all members of the Adult Health Study of the Radiation Effects Research Foundation, formerly the Atomic Bomb Casualty Commission. This study yielded 20 cancers, including 7 hepatocellular, 3 gastric, 3 renal and 2 urinary bladder cancers; one cancer each of the ovary, pancreas, colon and ureter; and one cancer metastatic to the liver, whose primary was unknown. Seventeen of these 20 subjects manifested no symptoms or signs of their disease. A variety of additional tumors, unproven and probably benign, including uterine myomata, and other abnormalities were also detected. Abdominal ultrasonographic screening greatly assisted in the detection of cancers, most of which neither the patients nor their physicians were aware. In this screened fixed population sample the cancer detection rate was 0.33%, exceeding any such rates previously reported in the medical literature.

Abdominal Neoplasms↗
PubMed1993

Isolation and amino acid sequence of the 30S ribosomal protein S19 from Mycobacterium bovis BCG.

The 30S ribosomal proteins from Mycobacterium bovis BCG were separated by reverse phase-high performance liquid chromatography (RP-HPLC). The isolated proteins were analyzed by SDS-PAGE, blotted on PVDF-membranes and subjected to sequence analyses using a gas-phase sequencer to correlate them to those of the well studied Escherichia coli and Bacillus stearothermophilus ribosomes. Moreover, the internal amino acid sequence of one ribosomal protein, MboS19, which is homologous to E. coli ribosomal protein S19 (EcoS19) and B. stearothermophilus ribosomal protein S19 (BstS19), was further analyzed by sequencing its internal peptides and two segments from the N- and C-termini of the protein were selected to deduce the sequence of two oligonucleotide primers which were used in a polymerase chain reaction. Using the amplified DNA fragment thus obtained as a hybridization probe, the gene encoding protein S19 was identified and cloned. Sequence analysis of the DNA fragment, together with peptide sequence analysis could determine the complete amino acid sequence of MboS19. This sequence proved to be 64% and 71% identical to those of the corresponding S19 proteins from the eubacteria E. coli, and B. stearothermophilus, respectively; 33% of the residues of MboS19 were identical to those in the archaebacterial ribosomal protein HmaS19.

Amino Acid Sequence↗
PubMed1993

Long-term carriage of hepatitis C virus with normal aminotransferase after interferon treatment in patients with chronic hepatitis C.

Studies were undertaken to investigate whether interferon therapy could induce hepatitis C virus (HCV) carriage with normal serum alanine aminotransferase (ALT) values using an assay that combined reverse transcription and polymerase chain reaction. The subjects studied were 53 patients with chronic active hepatitis C who received interferon (alpha, 33 cases; beta, 20 cases) therapy. All were seropositive for HCV RNA prior to therapy. In all 22 complete responders, whose ALT levels fell to normal during therapy and for at least 24 weeks after therapy, HCV RNA became persistently negative except in two cases. The two had sustained viremia on treatment and for 1.0-1.5 years of follow-up, although their biochemical tests were normal. In 15 patients with a transient response in whom the disease recurred when interferon was stopped, HCV RNA was undetectable in 80% of the cases at the end of therapy, but the virus reappeared with subsequent elevation of ALT in all patients. However, 3 patients in this group had normal enzyme levels with viremia for 2.1-2.8 years of follow-up after acute deterioration of illness. In 16 patients who did not respond to interferon, HCV RNA was persistently positive during and after therapy. These findings suggest that interferon therapy induces a long-term carrier state of HCV infection with normal ALT levels in some patients.

Adult↗
PubMed1993

Effect of absorption promoters on subcutaneous absorption of human epidermal growth factor in rats.

Subcutaneous administration of human epidermal growth factor (hEGF) to rats gave a significantly smaller value of area under the curve (AUC) of concentration in plasma of immunoreactive hEGF versus time than intravenous administration, probably because the slow entry rate into the blood circulation and consequently the enzymic degradation of hEGF at the injection site. In the present study, absorption promoters such as sodium caprate, N-acylamino acids, disodium ethylenediamine-tetraacetate (EDTA), and sodium glycocholate were used because they were expected to inhibit the enzymic degradation of hEGF at the injection site and to facilitate the entry of hEGF into the blood circulation. Coadministration of an absorption promoter with hEGF significantly increased the entry rate and AUC value of immunoreactive hEGF compared with the case without the absorption promoter. The enzymic degradation of hEGF in the supernatant of the rat subcutaneous tissue homogenates and in the buffer solution containing leucine aminopeptidase or protease was markedly inhibited by the presence of the absorption promoters except EDTA. On the other hand, only EDTA increased the initial entry rate of FITC-dextran (M(r), 4000), which is not metabolized at the injection site, although all absorption promoters including EDTA markedly increased the extravasation of Evans blue. Thus, the increased subcutaneous bioavailability of hEGF in the presence of absorption promoters (except EDTA) was mainly attributed to the inhibitory effect of absorption promoters against the enzymic degradation of hEGF at the subcutaneous tissues.

Adjuvants, Pharmaceutic↗
PubMed1993

Comparison of envelope and precore/core variants of hepatitis B virus (HBV) during chronic HBV infection.

We analyzed entire pre-C/C and pre-S/S coding genes of hepatitis B virus (HBV) in serial serum samples from four chronic HBV carriers with 4-5 years of follow-up. Two patients with chronic active hepatitis became seronegative for HB e antigen (HBeAg), but the hepatitis did not subside, while the other two were persistent asymptomatic carriers with normal aminotransferase values. DNAs amplified by PCR were cloned and sequenced (subtype adr). After HBeAg became negative, one patient had 96-183 bp deletions in 4/6 clones for C gene. In addition, both patients had 129-183 bp deletions in 3/6 and 2/5 clones for pre-S1 gene, respectively. Divergence rate of deduced amino acid for both pre-C/C and pre-S/S regions from the adr subtype was significantly higher in patients with chronic hepatitis than in asymptomatic carriers. Furthermore, the divergence rate for pre-S/S region was usually greater in asymptomatic carriers as well as chronic hepatitis patients compared with that for pre-C/C region. However, no significant difference was found in the rate of amino acid divergence for the entire HBV genes between the serial samples in all patients studied here. These results suggest that active hepatitis induces variation of HBV gene and defective virus is often selected along with the disappearance of HBeAg. In addition, the fact that patients with active liver disease possess greater numbers of mutant clones than asymptomatic carriers suggests that viral mutants are being immune-selected.

Adult↗