Biomedical subjects

T Mikami

Publications and source records attributed to T Mikami.

At least 433 records · Page 24Linked to original sources

PubMed1993

Use of B95a cells for isolation of canine distemper virus from clinical cases.

Canine distemper virus (CDV) was readily isolated at high rate with marked cytopathic effect (CPE) in B95a cells, a marmoset lymphoid cell line, from the peripheral blood leukocytes, cerebrospinal fluid cells and brain of dogs. Difference in type of CPE, i.e. syncytium type and round-cell one, among the virus isolates indicate the presence of heterogeneity of virus populations in prevalent CDV. Thus, this cell system is expected to be useful for ecological studies on CDV in the field.

Animals↗

PubMed1993

Biological nature of feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) was first isolated in 1986 from a cat with an acquired immunodeficiency syndrome (AIDS)-like disease. This virus has many characteristics in common with human immunodeficiency virus which is an etiological agent of AIDS in human and is classified as a member of the lentivirus genus of the retrovirus family. Since the discovery of FIV, many researchers have studied the virus extensively from clinical, biological, and genetic aspects. In this review, the biological nature of FIV is summarized in four sections, i.e., morphological and biochemical properties of FIV biological properties of FIV, immunological aspects of FIV infection, and clinical aspects of FIV infection. This review includes some recent, unpublished data from our and other groups.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Nucleotide sequence of the glycoprotein C (gC) homologous gene of Marek's disease virus (MDV) serotype 2 and comparison of gC homologous genes among three serotypes of MDV.

The sequence analysis of the genomic region of Marek's disease virus (MDV) serotype 2 (MDV2) which had homology with the gene encoding MDV serotype 1 (MDV1) homologue of glycoprotein C (gC) of herpes simplex virus revealed that there was a single open reading frame (ORF) capable of encoding 479 amino acids. The predicted protein from this ORF had strong hydrophobic regions in both the amino and carboxyl termini and several potential N-linked glycosylation sites, as seen in those from the ORFs of MDV1 and MDV serotype 3 (MDV3 = herpesvirus of turkeys (HVT)) gC homologues. By northern-blot analysis using a DNA fragment located in the MDV2 gC homologue ORF as a probe, 3.6 and 1.9 kb RNA transcripts were identified in MDV2-infected cells. When the alignment of amino acid sequences of the gC homologous genes of three MDV serotypes were compared, the homology between MDV1 and MDV2 and that between MDV1 and HVT showed about 76% identity, whereas that between MDV2 and HVT was about 70% identity. These results suggested a possibility that the evolutionary distance between MDV1 and MDV2 and between MDV1 and HVT is shorter than that between MDV2 and HVT.

Amino Acid Sequence↗

PubMed1993

Analysis and distribution of etoposide in rat brain tumor model: intracarotid versus intracarotid with angiotensin II-induced hypertension.

The brain tissue distribution of etoposide has been investigated in 9L gliosarcoma-bearing rats with or without hypertension induced by angiotensin II (AT II). The rat brain tumor models were divided into the following two groups according to etoposide administration route: intracarotid injection (IC) group and intracarotid injection with hypertension induced by AT II (IHIC) group. Ten mg/kg of etoposide was given, and 30 min and 2, 4, 8, and 24 hr later the rats were sacrificed. The drug concentrations in the serum, tumor, and normal brain tissue were analyzed by high-pressure liquid chromatography. The etoposide concentration in the serum, tumor, and normal brain tissue peaked at 30 min in both groups. The serum concentration was similar between the two groups. The etoposide concentration in the tumor was at least 2.2 times higher in the IHIC group than in the IC group at 30 min and 2 hr. The area under drug concentration curve (AUC) in the tumor in the IHIC group was about 2.2 times higher than that in the IC group. The etoposide concentration in the normal brain on the drug injection side changed only slightly from 0.5 hr to 4 hr and was about 3 times higher in the IHIC group than in the IC group. The etoposide concentration in the contralateral normal brain was very low in both groups at 30 min and disappeared thereafter. Intracarotid injection of anticancer drugs with AT II-induced hypertension further increases the drug concentration and AUC in the tumor compared with intracarotid injection alone and can be useful in treatment of malignant brain tumors.

Angiotensin II↗

PubMed1993

Metabolism of beta-muricholic acid in the hamster and prairie dog.

The metabolism of beta-muricholic acid was investigated in the prairie dog and the hamster. Intravenous infusion into bile fistula hamsters showed that beta-muricholic acid was extracted by the liver and secreted into the bile (> 85% in 1 h). Hepatic extraction of this compound and cholic acid in the prairie dog was not as rapid as in the hamster. In the bile of the prairie dog, most (93%) of the administered beta-muricholic acid was present as the taurine conjugate. In the hamster, 28% of infused beta-muricholic acid was secreted in unconjugated form, 43% as the taurine conjugate, and 22% as the glycine conjugate. In both species, the administered compound underwent little biotransformation. After intraduodenal injection of [6 alpha-3H]-labeled beta-muricholic acid into bile fistula hamsters, the bile acid was rapidly secreted into the bile; more than 80% of the administered radioactivity was recovered in 3 h. In the prairie dog, biliary recovery after intraduodenal administration of either beta-muricholic acid (43% in 3 h) or cholic acid (22% in 3 h) was slower than in the hamster. After intragastric administration, more than 80% of beta-muricholic acid was recovered unchanged in feces of both animal species.

Animals↗

PubMed1993

Metabolism and choleretic activity of homochenodeoxycholic acid in the hamster.

The hepatic metabolism and the choleretic effect of homochenodeoxycholic acid, the C25 homologue of chenodeoxycholic acid, were investigated in the hamster. After intravenous administration of 3H-labeled homochenodeoxycholic acid into biliary fistula hamsters, more than 80% of the radioactivity was recovered in bile in 4 h. A relatively small proportion of homochenodeoxycholic acid was present in bile as the taurine (22%) or glycine (4%) conjugate. However, more than 70% of the administered compound was biotransformed into C23 bile acids. The major C23 metabolites in bile were norchenodeoxycholic acid (17%), tauronorchenodeoxycholic acid (33%), and a trihydroxy norbile acid (identified as 3 alpha, 5 beta, 7 alpha-trihydroxy-24-nor-5 beta-cholan-23-oic acid, 19%). Small amounts (< 5%) of sulfate(s) and glucuronide(s) were also detected. Homochenodeoxycholic acid, when infused intravenously into the hamster, produced a striking choleresis. The increase in bile flow after infusion of this compound was 6- to 7-times that induced by chenodeoxycholic acid. The apparent choleretic activity of homochenodeoxycholic acid, 181 microliters/mumol, was much greater than that of chenodeoxycholic acid, 11 microliters/mumol. In conclusion, homochenodeoxycholic acid induced a hypercholeresis of the same order of magnitude as norchenodeoxycholic acid, presumably because considerable proportions of this compound were degraded to the hypercholeretic norchenodeoxycholic acid via beta-oxidation in the liver.

Animals↗

PubMed1993

[Doppler ultrasound in the diagnosis of atherosclerosis].

Atherosclerosis causes various types of flow disturbances within the affected arteries. Recent advances in the Doppler imaging technique have made possible evaluation of the temporal and spatial flow characteristics in the different portions of the arterial system, such as aorta, coronary, carotid and peripheral arteries. In the diagnosis of dissecting aneurysm of the aorta, transesophageal Doppler color flow imaging is quite useful to detect the site of entry, which is essential information for surgery. Intracoronary flow velocity can be accurately measured by intravascular Doppler technique. The recent introduction of a Doppler-tipped angioplasty guide wire makes it possible to measure the phasic flow deep within a coronary artery. The flow velocity measurement using a duplex system enables us to quantify the stenotic severity in carotid and peripheral arteries, and the Doppler color flow imaging, which has become available recently, also facilitates the demonstration and grading of atheromatous lesions in these arteries.

Aortic Dissection↗

PubMed1993

Bile acid sulfonates alter cholesterol gallstone incidence in hamsters.

The prevention of cholesterol gallstone formation by three bile acid analogs, sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24- sulfonate, sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,6 alpha-dihydroxy-5 beta-cholane-24-sulfonate, was examined in a hamster model of cholesterol cholelithiasis. Sodium taurochenodeoxycholate, sodium tauroursodeoxycholate and sodium taurohyodeoxycholate were studied simultaneously for comparison. Gallstones and cholesterol crystals were induced in 14 of 15 hamsters fed a bile acid-free, semipurified lithogenic diet containing 0.3% cholesterol and 4% butterfat for 6 wk. The addition of 0.1% sodium taurochenodeoxycholate and sodium tauroursodeoxycholate to the lithogenic diet had little effect on the formation of gallstones or biliary cholesterol crystals. In contrast, sodium 3 alpha,7 alpha-hydroxy-5 beta-cholane-24- sulfonate and sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate, when fed at the same dose, prevented cholesterol gallstone formation significantly. Sodium taurohyodeoxycholate and sodium 3 alpha,6 alpha-dihydroxy-5 beta-cholane- 24-sulfonate inhibited cholesterol gallstone formation effectively. The cholesterol saturation index of bile was greater than 1.00 in all groups, with the exception of the group fed sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate. Liver and serum cholesterol levels tended to be lower in most of the groups that were fed bile acids. This effect was most pronounced in the animals receiving sodium taurohyodeoxycholate. At the end of the experiment, the administered sulfonate analogs were detected in gallbladder bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Metabolism of sulfonate analogs of ursodeoxycholic acid and their effects on biliary bile acid composition in hamsters.

The metabolism of sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate was studied in hamsters. In bile fistula animals these sulfonate analogs of ursodeoxycholic acid were absorbed mainly from the terminal ileum and secreted rapidly into the bile without biotransformation or conjugation. After oral administration, the sulfonate analogs were excreted in the feces at the same rate as chenodeoxycholic acid and its metabolic products. The intestinal microorganisms transformed chenodeoxycholic acid largely into lithocholic acid; the sulfonate analogs were completely resistant to biotransformation. After a 2-week feeding period, the sulfonate analogs of ursodeoxycholic acid accounted for 24.0% and 16.9% of total biliary bile acids. These sulfonates did not affect the proportions of the natural bile acids in the bile, and the ratio of glycine-conjugated bile acids to taurine-conjugated bile acids was not altered by feeding the sulfonates. In contrast, when ursodeoxycholic acid was fed, the proportions of the natural bile acids and the glycine/taurine ratio were changed. These results suggest that the sulfonate analogs had no profound effect on endogenous bile acid metabolism and did not cause a depletion of the hepatic taurine pool during enterohepatic circulation. The sulfonates had no effect on intestinal cholesterol absorption and serum cholesterol levels.

Animals↗

PubMed1993

[Exercise test to predict postoperative complications in patients with impairment of pulmonary function].

We studied the prediction of postoperative complications in patients whose predicted postoperative FEV1.0% and/or %VC were below fifty. Preoperative exercise tests were performed in 88 cases mainly old patients of age or with impaired pulmonary function; 57 were lobectomies, 10 were bilobectomies and 21 were pneumonectomies. Predicted postoperative FEV1.0% and/or %VC were below fifty in 29 cases consisting of 12 lobectomies, one bilobectomy and 16 pneumonectomies. Among these 29 patients, thirteen suffered postoperative complications (A group) and sixteen did not (B group). All five cases of operative death (death within 30 days after operation) were included in the A group. The prediction of postoperative complications in cases of which pred. postope, FEV1.0% and %VC were fifty or over (C group) was also studied. The results were as follows; (1) The percentage of complications among A and B groups was higher than that among C group but no statistical difference could be found. (2) In the A group, the number of pred. postope. FEV1.0% and/or %VC had little correlation to complications. (3) Statistical differences between A and B group were found in submax VO2 (p < 0.05), VO2/VE at AT (p < 0.001) and VCO2/VE at submaximal exercise (p < 0.001). (4) Cardiac output ratio of maximal exercise to rest had marked correlation to complications (p < 0.001) in C group but had no correlation in the A and B groups. (5) The three items of A and B groups, submax VO2 < 500 ml/min/m2, VO2/VE at AT < 40 ml/l and submax VCO2/VE < 25 ml/l, showed high correlation to operative death (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Study on three patients with malignant glioma showing tumor reduction during maintenance therapy with MCNU].

Tumor regression occurred in three of 19 patients (15.8%) with malignant glioma during maintenance therapy using MCNU. In two patients, the tumor reduced 5 and 8 months after the initial treatment, respectively. In the remaining patient, though the maintenance therapy was interrupted for a while and consequently the tumor size increased, readministration of MCNU reduced the tumor size two months later. Therefore, since the antitumor activity of MCNU against malignant glioma seems to require a certain time depending on the case, it is recommended that MCNU be given as maintenance therapy for at least half a year.

Adult↗

PubMed1992

Defective biliary excretion of epinephrine metabolites in mutant (TR-) rats: relation to the pathogenesis of black liver in the Dubin-Johnson syndrome and Corriedale sheep with an analogous excretory defect.

Dubin-Johnson patients, mutant Corriedale sheep and TR- and EHBR mutant rats have recessively inherited defective bile canalicular secretion of many nonbile acid organic anions. The human and ovine mutants have black livers and lysosomal pigment accumulation. The livers in TR- and EHBR mutant rats are not black, and sparse lysosomal pigment accumulation is seen. Previously, we postulated that the unidentified pigment in the Dubin-Johnson syndrome results from the accumulation of tyrosine, phenylalanine and tryptophan metabolites, such as metanephrine, which are normally secreted in bile as organic anions. We tested this hypothesis in TR- rats. 3H-epinephrine was injected intravenously; control rats secreted 2.80% +/- 0.52% of the injected dose in bile as compared with 0.19% +/- 0.07% in TR- rats. From 82% to 90% of biliary radioactivity was due to polar conjugates in control rats and mutant rats. TR- rats retained more of the injected dose in the liver, particularly in lysosomes, and secreted more in urine than did control rats. After feeding control and TR- rats for 4 mo with a rat chow diet supplemented with 4% tyrosine, tryptophan and phenylalanine, the liver did not become grossly black; however, histological and electron microscopic study revealed dense lysosomal pigment accumulation in TR- rats. Intraportal injection of metanephrine resulted in the appearance of black liver in TR- rats that persisted for at least 2 hr and was not associated with pigment accumulation by light or electron microscopic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effect of intracarotid infusion of etoposide with angiotensin II-induced hypertension on the blood-brain barrier and the brain tissue.

This study investigated the effects of the intracarotid infusion of etoposide in combination with angiotensin II (AT II)-induced hypertension on the blood-brain barrier (BBB) and brain tissue in rats. Eighty rats were divided into five groups: Group 1, intravenous infusion of AT II to increase arterial blood pressure; Group 2, intracarotid infusion of etoposide at 22.5 mg/m2 for 10 minutes; Group 3, intracarotid infusion of etoposide at 75.0 mg/m2 for 10 minutes; Group 4, intracarotid infusion of etoposide at 75.0 mg/m2 for 20 minutes; Group 5, intracarotid infusion of etoposide at 75.0 mg/m2 for 10 minutes with AT II-induced hypertension. Evans blue staining of the brain was used as a monitor of BBB disruption. Mean arterial blood pressure over the experimental period in Group 1 increased from 86.3 +/- 1.3 mmHg (mean +/- SEM) to 139.0 +/- 2.4 mmHg, and Group 5 from 85.9 +/- 1.8 mmHg to 137.3 +/- 2.4 mmHg. None of the animals in Group 1 and 2 showed any obvious neurological change, while all the animals in Group 3, 4 and 5 exhibited diminished activity as their sole neurological change throughout the course of the experiment. Slight evidence of BBB disruption was seen in only 25% of the animals in Group 1. Significant BBB disruption was found in the animals in Group 2, 3, 4 and 5. No histological change was observed in any animal in Group 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Interleukin-6 is antiproliferative to a mouse hybridoma cell line and promotive for its antibody productivity.

Monoclonal antibody production by hybridoma cells at moderately slowed growth states would be favorable for commercial scale production since cells can devote their resources to performing the differentiated function, immunoglobulin production. We found that a purified recombinant human interleukin-6, which had been reported to support or stimulate proliferation of B cell hybridoma/plasmacytoma cells, suppressed growth of a hybridoma cell line in serum-free medium. In the presence of the interleukin, the growth-suppressed cells were viable for remarkably long periods in batch culture, and after removal of the interleukin from the culture medium, they started to proliferate at their normal growth rate. As the concentration of the interleukin increased in the culture, the growth rate decreased and the specific antibody productivity (antibody production rate per cell) increased to 5-fold of control at 10 U ml-1 (2 ng ml-1) of the interleukin.

Animals↗

PubMed1992

Penetration of etoposide into human malignant brain tumors after intravenous and oral administration.

Penetration of etoposide into the cerebrospinal fluid, brain tumor, and brain tissue after intravenous administration was investigated in patients presenting with malignant brain tumors. A relatively low dose (55-65 mg/m2) was used to compare intravenous with oral administration. High-performance liquid chromatography with fluorescence detection was used to evaluate drug levels. Plasma and cerebrospinal fluid levels of etoposide after oral administration (50-150 mg/day) were also studied so as to determine the adequate oral dose for the treatment of malignant brain tumors. The peak plasma concentration after intravenous administration ranged from 7.01 to 10.47 micrograms/ml, varying in proportion to the injected dose, whereas that after oral administration was lower, namely, 1.44-4.99 micrograms/ml, and was unstable when the oral dose was 150 mg daily. The peak cerebrospinal fluid level following either intravenous or oral administration was much lower than the plasma concentration and was influenced by the peak plasma level and the sampling site. The etoposide concentration in cerebrospinal fluid taken from the subarachnoid space and ventricle of patients displaying no tumor invasion and of those presenting with meningeal carcinomatosis and in cerebrospinal fluid taken from the dead space after tumor resection was 0.7% +/- 0.5%, 3.4% +/- 1.0%, and 7.2% +/- 8.5%, respectively, of the plasma concentration. Serial oral administration did not result in the accumulation of etoposide in cerebrospinal fluid. The tumor concentration (1.04-4.80 micrograms/g) was 14.0% +/- 2.9% of the plasma level after intravenous administration, was related to the injected dose, and was approximately twice the concentration detected in the brain tissue. Therefore, a relatively low dose of etoposide injected intravenously penetrates the brain tumor at an efficacious concentration. Our results indicate than an oral dose of 100 mg etoposide be given for malignant brain tumors, as limited penetration of the drug into the intracranial region was observed.

Administration, Oral↗

PubMed1992

Identification and nucleotide sequence of a gene in feline herpesvirus type 1 homologous to the herpes simplex virus gene encoding the glycoprotein B.

The nucleotide sequence of the glycoprotein B (gB) homologous gene of feline herpesvirus type 1 (FHV-1) was determined. The gene was found to be located within a 9.6 kbp SalI fragment by Southern-blot hybridization with a probe derived from the herpes simplex virus type 1 (HSV-1) gB DNA sequence. Furthermore, the predominant portion of the coding sequences was mapped to a 1.9 kbp Hin cII-EcoRI and its flanking 2.7 kbp Eco RI-Eco RI subfragments in the 9.6 kbp SalI fragment. The entire nucleotide sequence revealed that the FHV-1 gB homologous gene is capable of encoding a polypeptide of 948 amino acids. The predicted precursor polypeptide derived from this open reading frame could have a calculated M(r) of 106 kDa in unglycosylated form and contains ten potential N-linked glycosylation sites and a probable internal proteolytic cleavage site. By Northern-blot analysis using portions of the open reading frame as a probe, 3.9 and 3.3 kb RNA transcripts were identified in FHV-1 infected cells. The alignment of the amino acid sequence of the FHV-1 gB homologue with those of 14 other herpesviruses revealed that 10 cysteine residues were completely conserved. Meanwhile, when evolutionary trees were generated among these herpesvirus gB counterparts, the FHV-1 gB homologous nucleotide sequence seems to be closely related to equine herpesvirus type 4 and its amino acid sequence to pseudorabies virus.

Amino Acid Sequence↗

PubMed1992

Replicative difference in early-passage feline brain cells among feline immunodeficiency virus isolates.

The susceptibility of early-passage feline brain cells and Crandell feline kidney (CRFK) cells to infection with three isolates of feline immunodeficiency virus (FIV) was investigated. The Petaluma strain of FIV could well infect both the feline brain cells and CRFK cells. The KYO-1 strain could well infect the feline brain cells but the replication in CRFK cells was demonstrated only by coculturing fresh feline T-lymphoblastoid cells with the infected cells. On the other hand, the TM1 strain could infect the feline brain cells but not CRFK cells. Moreover, the replicative ability of the TM1 strain in the feline brain cells was much less than the KYO-1 and Petaluma strains. These results indicate that biological differences can be detected among the FIV isolates.

Animals↗

PubMed1992

Heterogeneity of feline herpesvirus type 1 strains.

Heterogeneity of 9 feline herpesvirus type 1 (FHV-1) strains consisting of the prototype C27 strain, one French isolate, six Japanese isolates, and the attenuated vaccine F2 strain was examined by biological, immunological, and molecular biological methods. No significant difference was observed in virus growth and antigenic properties among the strains in Crandell feline kidney cell cultures. Hemagglutination activity was also detected in all extracts of cells infected with each strain. However, in immunoblot analysis, a virus-structural immunogenic protein with an M(r) of 36 kDa was lacking in 2 strains, one of which was the vaccine F2 strain, whereas the other immunogenic proteins including three kinds of major glycoproteins were detected in all strains without differences in electrophoretic mobilities. Furthermore, when restriction endonuclease analysis was performed to examine the genomic heterogeneity of strains, the cleavage patterns with the enzyme MluI showed a genomic heterogeneity between wild and vaccine strains. In contrast, only a slight variation in the sizes of some fragments was shown with most of the 7 other enzymes used. These results indicated that the lack of the 36 kDa protein and the MluI cleavage pattern could be used as markers of the vaccine F2 strain. The specific markers are important not only to control the quality of the vaccine but also to evaluate the vaccine immunity in FHV-1 infection in cats.

Animals↗