Biomedical subjects

Y Yoshikawa

Publications and source records attributed to Y Yoshikawa.

At least 109 records · Page 6Linked to original sources

PubMed1999

Pharmacokinetic interactions between HIV-protease inhibitors in rats.

The interactions of four HIV-protease inhibitors, ritonavir (RIT), saquinavir (SAQ), indinavir (IND) and nelfinavir (NEL), were examined by in vitro metabolic studies using rat liver microsomal fractions. The substrate concentrations employed were 0.75 approximately 12 microM, and the inhibitor concentrations were 2.5 approximately 60 microM. The metabolic clearance rates of SAQ, NEL and IND as determined by V(max)/K(m) were 170.9+/-10.9, 126.0+/-4.4 and 73.0+/-2.0 microL/min/mg protein, respectively. RIT was a potent inhibitor of the other three protease inhibitors, and the inhibition constants (K(i)) were 1.64 microM for SAQ, 0.95 microM for IND and 1. 01 microM for NEL. NEL was the second strongest inhibitor with a K(i) for NEL inhibition of IND metabolism of 2.14 microM. IND was the third strongest inhibitor with K(i)s of 2.76 microM for inhibition of NEL and 3.55 microM for inhibition of SAQ. As SAQ has the highest metabolic clearance rate, the K(i) for the SAQ inhibition of IND metabolism was high, 9.50 microM. Based on these in vitro results, drug interactions between NEL and IND or RIT were studied after oral administration to rats where the dose of each drug was 20 mg/kg. The C(max) and AUC of NEL were increased 3.6- and 8.5-fold by the co-administration with RIT. However, in contrast to co-administration of NEL and RIT, the effect of IND on the pharmacokinetics of NEL was negligible and the t(1/2) of NEL was not significantly increased by IND. Therefore, the combination of NEL and IND is recommended as a combination therapy for AIDS patients.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Pharmacokinetics of cisplatin in analbuminemic rats.

The effect of protein binding on the pharmacokinetics of cisplatin (cis-diamminedichloroplatinum (II); CDDP) has been studied in analbuminemic rats, which genetically lack albumins, in comparison with normal rats. CDDP was reported to highly bind to serum components, and the major binder was thought to be an albumin. However, there were no significant differences in the serum disappearance profiles of platinum after intravenous (iv) bolus injection of CDDP to analbuminemic rats as compared with normal rats. The total body clearance, Cl(tot), of platinum in normal rats was 48.7+/-22.0 mL h(-1) (5 mg kg(-1)), 55.9+/-4.04 mL h(-1) (10 mg kg(-1)) and 49.0+/-3.57 mL h(-1) (20 mg kg(-1)), whereas Cl(tot) in analbuminemic rats was 52.0+/-8.48 mL h(-1) (5 mg kg(-1)), 62.9+/-10. 8 mL h(-1) (10 mg kg(-1)) and 62.8+/-6.81 mL h(-1) (20 mg kg(-1)). The serum blood urea nitrogen (BUN) and creatinine levels at 6 h after iv injection were higher in both groups of rats who received CDDP than those of pre-dose level. However, there were no significant differences in the renal function tests between analbuminemic rats and normal rats. The binding of CDDP to the serum samples obtained from analbuminemic rats and normal rats was measured by a centrifuging filtration method. The binding percentages were 68.0+/-5.9% (2.0 microg mL(-1)), 56.8+/-4.1% (5.0 microg mL(-1)) and 64.6+/-4.4% (10.0 microg mL(-1)) in analbuminemic rats and 52.9+/-3.5% (2.0 microg mL(-1)), 52.2+/-3.4% (5.0 microg mL(-1)), 56.9+/-1.9% (10.0 microg mL(-1)) in normal rats. Higher binding percentages were obtained in analbuminemic rats than in normal rats. In vitro binding studies under the two incubation conditions (5 min and 2 h) showed that the binding percentages of CDDP to serum proteins were 59.2+/-3.2% (5 min) and 72.3+/-6.5% (2 h) for albumin, 42.3+/-1.9% (5 min) and 39.5+/-2.5% (2 h) for alpha(1)-acid glycoprotein (AAG) and 51.7+/-5.3% (5 min) and 49. 2+/-1.9% (2 h) for gamma-globulin. From these studies, it was elucidated that albumin is not the major ligand in the rat serum and that other proteins also have important roles in the pharmacokinetics of CDDP.

Animals↗

PubMed1999

Effects of SIVmac infection on peripheral blood CD4+CD8+ T lymphocytes in cynomolgus macaques.

We have previously reported that CD4+CD8+ double-positive (DP) T cells with a resting memory phenotype exist in a substantial proportion of peripheral blood lymphocytes of adult cynomolgus macaques. In this study, we examined the effects of simian immunodeficiency virus of macaque (SIVmac) infection on DP T cells. In vitro, SIVmac239 nef-open (239) and its nef-deletion mutant replicated well in both CD4+CD8- and DP T cells. However, when the macaques were infected with 239, DP, but not CD4+CD8-, T cells were transiently increased in parallel with cell activation and viral replication, followed by depletion within 1 month postinfection. Interestingly, the nef gene was required for depletion but not for the increase and activation of DP T cells. These data suggest that the pathogenic SIV infection may downmodulate production and/or blood circulation of DP T cells by a Nef function-related mechanism(s) different from that for the depletion of CD4+CD8- T cells.

Animals↗

PubMed1999

Coexisting extraadrenal pheochromocytoma and von Meyenberg complexes: report of a case.

We herein report on a 62-year-old man who developed extraadrenal pheochromocytoma and von Meyenberg complexes of the liver (bile duct microhamartoma). The patient identified preoperatively as having a paraaortic mass which was subsequently diagnosed to be a pheochromocytoma. During the operation, small multiple nodules were unexpectedly recognized in the liver. Some of the liver nodules were resected by a wedge biopsy, and then were pathologically identified to be von Meyenberg complexes. This may be the first reported case of the coexistence of pheochromocytoma and von Meyenberg complexes. It is therefore necessary for surgeons to be aware of von Meyenberg complexes in the differential diagnosis of multiple liver metastases in malignant disease.

Abdominal Neoplasms↗

PubMed1999

Positive bladder cooling reflex in patients with bladder outlet obstruction due to benign prostatic hyperplasia.

The bladder cooling reflex was evaluated in patients with bladder outlet obstruction to study the effect of obstruction on the afferent neural function of the bladder, especially on the C-afferents. The bladder cooling test was performed by infusion of 0 degree C saline into the bladder with simultaneous detrusor pressure measurement in 104 patients with bladder outlet obstruction due to benign prostatic hyperplasia. In 49 patients (47%) a positive cooling reflex was observed. This was defined as a rise in the detrusor pressure following cold saline instillation exceeding 15 cmH2O (range 15-130 cmH2O, mean 60.6 cmH2O; positive group). In the remainder of cases the pressure rise ranged from 0 to 12 cmH2O (mean 6.1 cmH2O; negative group). Bladder outlet obstruction may cause some alteration in the afferent neural function of the bladder, in particular of the C-afferent fibers.

Aged↗

PubMed1999

Prognostic value of pressure-flow study in surgical treatment of benign prostatic obstruction.

The prognostic value of pressure-flow study (P-FS) in the surgical treatment of bladder outlet obstruction (BOO) was retrospectively studied in patients with benign prostatic hyperplasia. In 74 patients who underwent surgical treatment for BOO, P-FS and free uroflowmetry were performed pre- and postoperatively. On P-FS, obstruction and detrusor contractility were analyzed according to the Schäfer nomogram. The patients were classified into the following 3 groups according to their preoperative P-FS: group A consisted of 39 patients with normal detrusors and obstruction (obstruction grade 3-6); group B consisted of 13 patients with weak detrusors and obstruction; and group C included 22 patients with weak or very weak detrusors combined with minimal obstruction, if any (obstruction grade 0-2). Postoperatively, the detrusor pressure at maximal flow rate and obstruction grades on P-FS improved significantly in groups A and B but not in group C. The rate of improvement was most prominent in group A, followed by groups B and C. On free uroflowmetry, however, a significant improvement occurred in all three groups with respect to maximal flow rate, average flow rate, and postvoid residue. Moreover, the rate did not differ among the three groups except for the maximal flow rate as determined between groups A and C. Although good detrusor contractility and evident obstruction on analysis of P-FS will guarantee the best surgical outcome, subjects with weak detrusors and minimal obstruction will also have a good outcome by the relief of BOO. In the weak detrusor, P-FS may be limited in diagnosing obstruction and have a low prognostic value, and such patients should not necessarily be excluded from surgical indications.

Aged↗

PubMed1999

A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria.

Alkaptonuria is a rare autosomal recessive disorder characterized by homogentisic aciduria, ochronosis, and arthritis. Although a deficiency of homogentisic acid 1,2-dioxygenase has recently been confirmed at the molecular level, no effective treatment regimen has yet been developed for this disorder. In the present study, 2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of p-hydroxyphenylpyruvate dioxygenase (which catalyzes the formation of homogentisic acid from p-hydroxyphenylpyruvic acid) was adopted as a possible therapeutic agent for alkaptonuria. NTBC dose-dependently reduced the urinary output of homogentisic acid in a murine model of alkaptonuria that had been created with ethylnitrosourea. These findings suggest that NTBC may be the first potent pharmacotherapeutic agent for alkaptonuria.

4-Hydroxyphenylpyruvate Dioxygenase↗

PubMed1999

A clonal culture assay for human cord blood lymphohematopoietic progenitors.

We describe a two-step clonal culture assay system for human lymphohematopoietic progenitors present in umbilical cord blood which are capable of differentiation along both myeloid and B-lymphoid lineages. Human cord blood CD34+ cells were plated in methylcellulose in the presence of stem cell factor (SCF), granulocyte-colony stimulating factor (G-CSF), interleukin (IL)-7, and the murine stroma cell line, MS-5. The growing primary colonies were individually examined for their potentials to differentiate along both myeloid and B-lymphoid lineages by reculturing aliquots of the primary colonies in methylcellulose culture containing IL-3, G-CSF and erythropoietin (Epo), and on a monolayer of MS-5 in the presence of SCF and G-CSF. Approximately 10-15% of the primary colonies generated various combinations of myeloid cells and CD19+ sIgM+ cells. Subsequent studies using micromanipulated single CD34+ cells unequivocally demonstrated the clonal origin of the lymphohematopoietic progenitors. This culture system should prove valuable for elucidation of the mechanisms regulating early stages of human lymphohematopoiesis.

Animals↗

PubMed1999

Ventricular outflow tracts after Kawashima intraventricular rerouting for double outlet right ventricle with subpulmonary ventricular septal defect.

OBJECTIVE: To determine whether or not the ventricular outflow tracts can be efficiently constructed in patients with double outlet right ventricle with subpulmonary ventricular septal defect by the Kawashima intraventricular rerouting in which the morphologically right ventricular outlet is divided into two, one for the systemic and the other for the pulmonary circulations. METHODS: The intraventricular rerouting procedure was carried out in nine patients with this particular malformation. Age at repair ranged from 35 days to 3 years old. The distance between the attachments of the tricuspid and the pulmonary valves was 10 mm or greater in all except one patient in whom the measured value was 3 mm. Resecting subaortic musculature appropriately, a tailored patch, either oval-shaped (in seven) or heart-shaped (in two), was placed to construct an unobstructed channel for the left ventricular outflow tract with its diameter greater than that of the anticipated normal aortic orifice at the time of repair. For an unobstructed channel to the pulmonary arteries, enlargement of the right ventricular outflow tract was carried out using a patch in six. RESULTS: All patients survived the operative procedure. On postoperative catheterization, mean pulmonary arterial pressure was 15 +/- 8 mmHg, and cardiac index was calculated as 3.3 +/- 0.6 l/min per m2. It proved that the constructed left ventricular outflow tract can become larger in the longer term. Pressure gradient across the left ventricular outflow tract was greater than 20 mmHg in two patients in the intermediate term. One of these two underwent reoperation for the obstruction 10 years after the initial repair. It was suspected that use of a heart-shaped internal conduit, which seems to result from inadequate conal resection, was one of the possible causes of such obstruction in the longer term. Pressure gradient of 47 mmHg was seen across the right ventricular outflow tract in one patient, although this patient has undergone no reoperation. Enlargement of the right ventricular outflow tract could minimize postoperative obstruction for the pulmonary pathway. CONCLUSIONS: The intraventricular rerouting remains one of the attractive surgical options for repair in this particular setting, in terms of successful construction of the ventricular outflow tracts.

Child, Preschool↗

PubMed1999

Accumulation of MAC387+ macrophages in paracortical areas of lymph nodes in rhesus monkeys acutely infected with simian immunodeficiency virus.

We investigated the histological features of lymph nodes, focusing on monocytes/macrophages, in rhesus monkeys (Macaca mulatta) acutely infected with simian immunodeficiency virus (SIV). In monkeys infected with a pathogenic SIV, SIVmac239, MAC387(+) newly blood-derived macrophages markedly increased in number at paracortical areas at 11 to 14 days postinoculation, concomitant with the peak of the primary SIV antigenemia. The MAC387(+) macrophages densely gathered around high endothelial venules and formed cell clusters with CD3(+) T lymphocytes, tingible body macrophages, and plasmacytoid monocytes. In the cell clusters, CD3(+) T lymphocytes which closely adhered to the MAC387(+) macrophages enlarged in size, suggesting a histological manifestation of T-lymphocyte activation by macrophages. By 54 days postinoculation, when SIV antigenemia became undetectable, the MAC387(+) macrophages decreased in number and the cell cluster disappeared from paracortical areas. In contrast, the monkeys infected with a nef-deleted mutant of SIVmac239 showed lower levels of SIV antigenemia and lower numbers of MAC387(+) macrophages in paracortical areas than those infected with SIVmac239. These results indicate that MAC387(+) macrophages accumulate in paracortical areas for the period of the intense primary SIV antigenemia and may play an important role in activating naive T lymphocytes.

Animals↗

PubMed1999

Analysis of a simple biodegradation process for the removal of volatile organic chemicals from wastewater based on a gas stripping principle.

A simple biodegradation system consisting of an air stripping tank and a bioreactor was proposed for the treatment of volatile organic chemicals in wastewater. Toluene was used as a model of volatile organic chemicals. An aqueous solution of toluene and a basic mineral medium were placed in the air stripping tank and bioreactor, respectively. Toluene was stripped by supplying compressed air into the stripping tank through a sparger, and the stripped toluene was degraded by Pseudomonas putida mt-2 (ATCC 33015) in the bioreactor under aerobic conditions. The effect of the air stripping rate on bacterial growth was examined. A quantitative relationship was found between the air flow rate in the air stripping tank (Qa) and the stripping rate constant. During cultivation, the bacterial cells grew by utilizing toluene as the sole carbon source, and reached their maximum cell concentration (Xm) at the stationary phase. Xm showed a gradual decrease with increase in Qa from 1.8 to 7.2 l/h, indicating a decrease in the rate of toluene degradation with increasing Qa. The Xm at Qa=1.8 l/h was the highest among the experiments under different values of Qa, which was almost twice that at Qa=7.2 l/h. Mathematical analysis taking the growth kinetics and mass transfer of toluene into consideration satisfactorily explained the system performance.

Journal Article↗

PubMed1999

An African green monkey lacking peripheral CD4 lymphocytes that retains helper T cell activity and coexists with SIVagm.

Natural infection with simian immunodeficiency virus (SIV) is known to occur in the African green monkey (AGM). The actual onset of the disease has not been recognized in SIVagm infected AGM, and the precise reason for such apathogenicity in the AGM remains unclear. We reported previously that AGM peripheral CD4 lymphocytes underwent a peculiar differentiation from CD4+ to CD4- cells after in vitro activation, and we inferred that the AGM does not fall into a fatal immunodeficient state because of the generation of CD4- helper T cells in vivo. To evaluate this possibility, we examined the relationship between CD4 expression and helper T cell activity in the naturally infected AGM. We identified a healthy monkey almost lacking CD4 T cells in the periphery. This AGM showed no signs and symptoms of immunodeficiency and retained a helper T cell activity in antibody production comparable to those of CD4+ AGMs. In addition, SIVagm could be isolated from CD8+ lymphocytes in the CD4- AGM. These observations suggest that a unique host-virus adaptation has developed in the AGM, and may be helpful in explaining the fundamental reason for the apathogenicity occurring in this monkey.

Amino Acid Sequence↗

PubMed1999

Folding transition of long duplex DNA from mammalian cells.

Conformational change in individual giant DNAs from pig liver is studied by use of fluorescence microscopy. With the addition of spermidine (a trivalent amine), each DNA chains undergo abrupt transition from an elongated coiled state into a folded compact state. It is found that the all-or-none characteristics in the folding transition for the mammalian DNA is similar to that in phage DNAs.

Animals↗

PubMed1999

Localization of immunoreactive testosterone and 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase in cynomolgus monkey (Macaca fascicularis) testes during postnatal development.

The age-related expression of testosterone and 3beta-HSD in the testes of cynomolgus monkeys was detected using light-microscopic immunocytochemistry. Intense deposits of immunoreactive testosterone were labeled in parts of Leydig cells in neonatal, late infantile, pubertal, and adult testes, and only a few Leydig cells in early infantile testes. The immunoreactive 3beta-HSD was labeled in parts of Leydig cells and in all Sertoli cells in neonatal, late infantile, pubertal, and adult testes, whereas only a few Leydig cells, but no Sertoli cells, were labeled in early infantile testes. The fluctuations of testosterone and 3beta-HSD expression in testes correlated well with those already observed plasma testosterone levels during postnatal development in cynomolgus monkeys.

3-Hydroxysteroid Dehydrogenases↗

PubMed1999

A dissolution test for a pressure-controlled colon delivery capsule: rotating beads method.

The rotating beads method is a new in-vitro dissolution test proposed for drugs formulated as pressure-controlled colon delivery capsules (PCDCs). The apparatus consisted of a glass vessel (500 mL) containing 4-mm (i.d.) glass beads (5000, 10000 or 15000) and dissolution medium (0-067 M phosphate buffer, pH 7; 25, 50 or 100 mL) containing polyvinyl alcohol (PVA; 5, 10 or 20 w/v%) to simulate the viscosity of the colon. The vessel was rotated at 5, 10 or 25 rev min(-1) and the temperature was maintained at 37 degrees C. Fluorescein was used as a model drug to explore the optimized conditions under which differences in the drug dissolution rate are detected between colon delivery systems. Fluorescein was formulated in four types of colon delivery systems. One was a tablet coated with an enteric polymer, Eudragit S-100, and the other three were PCDCs prepared with different thicknesses of ethylcellulose coating membrane (type I, II, III). The dissolution behaviour of fluorescein from the PCDC formulation was significantly different from that of the Eudragit S-100-coated tablets, when the dissolution conditions were as follows: rotation speed, 10 rev min(-1); bead number, 10000; dissolution medium, 50mL with 10% PVA. This dissolution method was applied to acetaminophen sustained-release tablets and two other drugs having low solubility in the colon, tegafur and 5-aminosalicylic acid. Similarly, significant differences in the dissolution rates of drugs from the PCDC formulation and the enteric tablet were detected. There was good correlation between the in-vitro dissolution rates and in-vivo absorption rates using T50 (the time for half of the amount of drug to be released from the preparation) and Cmax/Tmax (enteric tablet) or Cmax/(Tmax-Ti) (PCDC), where Ti is the first appearance time in the systemic circulation. The rotating beads method is a valuable technique for evaluating the dissolution rate of drugs formulated in PCDC.

Administration, Rectal↗

PubMed1999

Egg-eating behaviour in laboratory squirrel monkeys (Saimiri scuireus).

The present study aimed to clarify an individual character of squirrel monkey by analysing a complicated behaviour, the egg-eating behaviour series (ES), of laboratory-reared squirrel monkeys. Eight types of unit movements were observed in the ES: the initial taking of the egg by hand; rolling it between the fingers; sniffing it in its shell; biting it in its shell; pressing or rubbing it against a surface of the cage; opening or peeling it; eating it; or putting it down without eating. In the first experiment, the behaviour of 72 monkeys was recorded by direct observation or by a video camera, following which the sequences of the movement from a total of 378 ES were analysed. Three statistically significant ES were detected (Ta-Bi-Op/Pe-Ea, Ta-Ro-Bi-Op/Pe-Ea and Ta-Pr/Ru-Bi-Op/Pe-Ea). In the second experiment, eight squirrel monkeys were selected at random from the same group and 31 to 36 ES for each monkey were observed and analysed. These monkeys were classified into a pressing/rubbing (Pr/Ru) group and a no-Pr/Ru group. Pr/Ru appeared to have no relationship to the monkey's age or sex. Furthermore, the Pr/Ru group monkeys contained individuals always exhibiting Pr/Ru in their ES and others sometimes lacking Pr/Pu in their ES. In short, the monkeys could be divided into two groups (i.e., Pr/Ru and no-Pr/Ru) and they displayed their own individual characteristic ES. We concluded that the ES observed in this experiment suggest that the squirrel monkeys acquired individual characteristics in their ES in the laboratory environment.

Animals↗

PubMed1999

Effective delivery of a lipophilic 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG) into rat lymphoid tissues.

Lipophilic 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG) was evaluated for its improved lymph node delivery by comparison with the parental nucleoside (ddG) in vitro and in vivo. The in vitro studies with rat plasma, lymph node homogenate and stomach content indicated that 6-Cl-ddG converted to ddG more effectively in the lymph node homogenate and that 6-Cl-ddG was more stable than ddG in the stomach content. In an in vivo study, plasma and lymph nodes were collected from rats after a subcutaneous or oral administration of 6-Cl-ddG or ddG. With the subcutaneous administrations of the drugs, the area under the concentration time-curve (AUC) value in the plasma for converted ddG following a 6-Cl-ddG administration was less than half the value for ddG following a ddG administration but the converted ddG AUC values in the lymph nodes due to 6-Cl-ddG administration were 1.4- to 2.0-fold higher than the ddG AUC values due to ddG administration. Moreover, with the oral administrations, the converted ddG AUC value in plasma after a 6-Cl-ddG administration was 3-fold higher than ddG after a ddG administration, and high levels of converted ddG were detected in the lymph nodes, but no ddG was detected in the lymph node following ddG administration. These results suggest that lipophilic 6-Cl-ddG is a useful prodrug for delivering ddG into the lymph nodes by oral administration.

Administration, Oral↗

PubMed1999

Opportunistic Pneumocystis carinii infection in red-bellied tamarins (Saguinus labiatus).

P. carinii infection in red-bellied tamarins (Saguinus labiatus), born and maintained in a laboratory breeding colony, was examined by histopathologic examination postmortem. P. carinii cysts were detected in 6 of 10 red-bellied tamarins examined, by using Grocott's, toluidine blue O and immunostaining with avidin-biotin complex using antisera for rat-, simian-, and human-P. carinii. The results obtained from the present studies imply that P. carinii may be an important pathogen in this species.

Animals↗