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Biomedical subjects

T Koizumi

Publications and source records attributed to T Koizumi.

At least 109 records · Page 6Linked to original sources
PubMed1999

Psychiatric disorders among Japanese children.

OBJECTIVE: To generate current data on the prevalence of psychiatric disorders among Japanese children, using DSM-III-R criteria. METHOD: As part of an ongoing longitudinal study in a Japanese community sample, 114 mother-child dyads were interviewed when the children were approximately 8 years old. DSM-III-R disorders of the children were diagnosed through the administration of a structured diagnostic instrument, the parent and child versions of the Child Assessment Schedule, to both the children and their mothers. RESULTS: The prevalence rate for any diagnosis was 49.1%, which is similar to that of U.S. children and adolescents. CONCLUSION: The Child Assessment Schedule is an appropriate scale for assessing the psychopathology of Japanese children, which is as prevalent as in a U.S. sample.

Adolescent↗
PubMed1999

Influence of plasma dialysate from normal and renal dysfunction rats on the electroencephalogram and gamma-aminobutyric acid A receptor complex modulation of thiopental.

We have previously reported that brain sensitivity to thiopental with respect to electroencephalogram (EEG) is enhanced in uranyl acetate pretreated renal dysfunction rats. The results were attributed to pharmacodynamic factors. In this study, in vivo EEG and in vitro binding studies for gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex were performed to investigate the mechanism of the enhanced effect of thiopental. The receptor binding properties in the brain membrane from normal and renal dysfunction rats were examined using [3H]tertbutylbicycloorthobenzoate (TBOB), [3H]flunitrazepam and [3H]muscimol. The effect of plasma dialysate from normal (ND) and renal dysfunction rats (RDD) on the thiopental induced EEG and receptor binding were also examined to confirm the role of endogenous compounds. The intrinsic receptor binding characteristics of various sites and their allosteric interaction with thiopental was similar in membrane preparations from normal and renal dysfunction rats. However, RDD, when compared to ND, enhanced the EEG induced by thiopental. At the receptor level, RDD significantly enhanced the thiopental induced inhibition of TBOB. No difference was found between the influence of ND and RDD on the interaction between thiopental and flunitrazepam or muscimol binding. These results showed that the thiopental induced allosteric inhibition of TBOB binding was potentiated by some endogenous compounds in RDD and suggests that this action might be the mechanism, at least in part, for the increased sensitivity of thiopental in renal dysfunction rats.

Animals↗
PubMed1999

Simultaneous transport and metabolism of nicotinic acid derivatives in hairless mouse skin.

In vitro simultaneous transport and metabolism of three ester prodrugs of nicotinic acid (NA), methyl nicotinate (MN), ethyl nicotinate (EN) and butyl nicotinate (BN) were studied using excised skin from hairless mouse. Hydrolysis studies of these esters with and without skin homogenate were also done at 37 degrees C. Both the ester and NA were detected in all receiver solutions in permeation studies, and no chemical hydrolysis of the esters was found, indicating that the esters were hydrolyzed during the skin permeation process. The total (ester+NA) flux from a saturated solution of ester prodrugs was higher than that of NA and was highest for MN, followed by EN and BN, whereas the total permeability coefficient of ester prodrugs increased from MN to BN. A difference in the NA/total flux ratio was found among these prodrugs; thus, esterase activity was also dependent on the alkyl chain length of the esters. The total flux from each ester solution increased linearly with the donor concentration. NA flux from MN and EN solutions increased with an increase in the donor concentration and reached a plateau at the high concentration range, suggesting that metabolic saturation occurred. NA fluxes at the plateau were similar among ester prodrugs and corresponded to the Vmax estimated from the hydrolysis experiment. The order of donor concentration at which NA reached a plateau also corresponded to the order of Km. It was confirmed that a difference in alkyl chain length of the ester prodrugs affected not only permeability but also metabolism in the skin permeation process.

Alkylation↗
PubMed1999

Effect of dosage form on stereoisomeric inversion of ibuprofen in volunteers.

Twelve healthy volunteers were given ibuprofen racemate in two different dosage forms, a suspension and a tablet. The plasma concentration-time profiles of S- and R-ibuprofen were determined and the R-ibuprofen inversion clearance was calculated. Although the area under the curve was almost the same in both the suspension and tablet studies, the inversion clearance was larger in the suspension study than in the tablet study (1.18+/-0.65 and 0.72+/-0.63 l/h, shown as the mean+/-S.D.). The Michaelis-Menten parameters for this inversion process were then determined in vitro with human liver microsomes (1.3+/-0.2 mM for Km and 3.1+/-0.3 nmol/min/mg protein for Vmax, shown as the mean+/-S.D.). These parameters indicated that the stereoisomeric inversion of R-ibuprofen in the liver was not likely to be saturated at the plasma concentrations measured in the volunteer study. The profile of the plasma concentration ratio between S-ibuprofen and R-ibuprofen revealed a difference in the early phase of these two studies. Therefore the inversion difference between those two studies probably resulted from the difference in the absorption phase of each dosage form. Our study demonstrated that R-ibuprofen inversion could be affected by alteration of dosage form.

Adult↗
PubMed1999

Influence of enzyme distribution and diffusion on permeation profile of prodrug through viable skin: theoretical aspects for several steady-state fluxes in two transport directions.

A physical modeling and theoretical simulation aspect for the simultaneous transport and metabolism of prodrug in viable skin were described to understand the influence of enzyme distribution and diffusion. The physical model was formulated assuming that the viable epidermis and dermis have distinct diffusional and metabolic characteristics and that the metabolic reaction in each layer follows a first-order kinetics. The differential equations were analytically solved, and the steady-state flux of prodrug into receiver and that of metabolite into receiver and donor and the total flux in forward (epidermis to dermis) and backward (dermis to epidermis) directions were derived. The flux of prodrug in the forward direction always equals that in the backward direction. The metabolite flux into receiver became transport direction-dependent when the diffusional characteristic of epidermis was different from that of dermis regardless of enzyme distribution. The metabolite flux into donor in the backward direction relative to that in the forward direction increased with increase of dermis/epidermis ratio of any parameters among metabolic rate constant, partition coefficient and diffusion coefficient of prodrug and metabolite. The difference of total flux between the 2 transport directions was caused by the difference in metabolic rate constant, partition coefficient and diffusion coefficient of prodrug between epidermis and dermis. The higher any parameters were for dermis, the higher was total flux in the backward direction.

Biological Transport↗
PubMed1999

Single dose pharmacokinetics and pharmacodynamics of oxazepam in normal and renal dysfunction rats.

The purpose of this work was to investigate the disposition characteristics and pharmacodynamics of a benzodiazepine, oxazepam, in renal dysfunction rats. For the in vivo experiment, normal and renal dysfunction rats were given 40 mg/kg of oxazepam as the bolus dose. A quantitative electroencephalographic (EEG) method was used as the surrogate measure of the pharmacological response. The oxazepam concentration in plasma and cerebrospinal fluid (CSF) was assayed by the HPLC method. The steady-state volume of distribution and clearance based on total and unbound plasma did not change in renal dysfunction rats. Amplitude changes in the EEG induced by oxazepam in normal and renal dysfunction rats were characterized by a log-concentration response model or sigmoidal Emax model. The pharmacodynamic parameters from these models were not altered in renal dysfunction. In in vitro binding studies for gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex, the oxazepam-induced effect was not potentiated by the plasma dialysate from renal dysfunction rats. Thus, it was suggested that the brain sensitivity to benzodiazepines was not altered in renal insufficiency.

Animals↗
PubMed1999

Application of a non-linear dispersion model to analysis of the renal handling of p-aminohippurate in isolated perfused rat kidney.

To analyze the renal handling of therapeutic compounds observed as a non-linear process with a diffusion phenomenon, we employed a non-linear dispersion model described with a partial differential equation and solved it by using the finite difference method with an implicit scheme in a model dependent analysis. In this study, the renal handling of p-aminohippurate (PAH) was investigated in isolated perfused rat kidney, in which a 50 microl bolus of injection solution containing [3H]PAH and [14C]inulin was administered rapidly into the renal artery. The venous outflows were then collected for 15 min with a fraction collector. The renal extraction ratio of PAH was decreased from 65% to 18% as the PAH concentration in the injection solution was increased from 2 microM to 10 mM. The PAH outflow profile changed as the extraction process became saturated. With the non-linear dispersion model, the Michaelis-Menten parameters for the PAH extraction process were estimated by a model fitting calculation. The calculated values were 0.83 micromol/min/kidney for Vmax and 89 microM for Km. It was demonstrated that the model dependent analysis with a non-linear dispersion model is a useful approach to characterize renal drug handling, and is probably applicable for examining other non-linear processes which involve a diffusion phenomenon.

Animals↗
PubMed1999

Pulmonary embolism due to right ventricular thrombus in a case of Behcet's disease.

Right ventricular thrombus is a very rare manifestation of cardiovascular Behcet's disease. A 25-year-old man was admitted to hospital due to cough and fever of unknown origin. He experienced repetitive pulmonary embolism due to a right ventricular thrombus, which was surgically removed. A diagnosis of Behcet's disease was made based on his clinical course and the histological findings of the right ventricular wall and the skin lesion. He was quickly relieved of his symptoms after warfarinization and cyclosporine therapy.

Adult↗
PubMed1999

Serial scintigraphic assessment of iodine-123 metaiodobenzylguanidine lung uptake in a patient with high-altitude pulmonary edema.

Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) can be considered an indicator of pulmonary endothelial cell function. Serial (123)I-MIBG images of the chest were acquired in a patient with high altitude pulmonary edema (HAPE). The initial evaluation was performed 7 days after admission. The lung to upper mediastinum ratios (LMRs) of (123)I-MIBG uptake were 1.33 (for the right lung) and 1.12 (for the left lung). The second examination of (123)I-MIBG lung uptake, which was performed 2 months later, showed LMRs of 1.39 (right lung) and 1.33 (left lung). We speculated that the decreased lung uptake of (123)I-MIBG at the early recovery stage could reflect an impairment in pulmonary endothelial cell metabolic function in the development of HAPE.

3-Iodobenzylguanidine↗
PubMed1999

Osmoregulation of vasopressin secretion in patients with the syndrome of inappropriate antidiuresis associated with central nervous system disorders.

To clarify the characteristics of vasopressin (AVP) secretion in patients with the syndrome of inappropriate antidiuresis (SIAD) related to central nervous system disorders, we examined the response of AVP secretion to osmotic stimulus by hypertonic saline infusion and analyzed the possible causative factors in six patients with SIAD associated with head trauma or cerebral infarction. Hyponatremia developed after head trauma in four patients and cerebral infarction in two patients. In all patients the clinical state and laboratory findings fulfilled the criteria for SIAD, which was supported by either nonsuppressible plasma AVP levels or effectiveness of treatments with water restriction, demeclocycline, nonpeptide V2 AVP antagonist or diphenylhydantoin. Although patterns of plasma AVP response to the osmotic stimulus varied, plasma AVP concentrations neither increased nor decreased to undetectable levels with a rise in plasma osmolality. In one patient, plasma AVP levels responded to increasing plasma osmolality when plasma osmolality normalized; in which the threshold and the sensitivity of osmostat were normal. In two other patients, AVP secretion responded to plasma osmolality after the treatment. The changes in AVP secretion were not due to nonosmotic stimuli for AVP release. In conclusion, this study shows that patients with SIAD and central nervous system disorders may have persistent AVP secretion with a loss of hypotonic suppression such as found in patients with adrenal insufficiency or depletional hyponatremia in central nervous system disorders, indicating that careful evaluation is necessary to determine the relationship between persistent AVP secretion and the pathogenesis of hyponatremic disorders.

Aged↗
PubMed1999

[Estimation of pulmonary hypertension in lung and valvular heart diseases by perfusion lung scintigraphy].

To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lung disease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09 +/- 1.28 for the normal subjects, 1.97 +/- 0.89 for the patients with lung disease, and 1.59 +/- 0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lung disease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (> 20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lung disease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lung disease and valvular heart disease.

Adult↗
PubMed1999

[Amyopathic dermatomyositis with interstitial pneumonia: effective treatment with cyclophosphamide pulse therapy].

A 42-year-old man was admitted to our hospital because of dyspnea on exertion, skin eruptions on the face and extremities, and interstitial shadows mainly in the lower fields of both lungs. Characteristic skin lesions and skin biopsy findings without muscle symptoms or elevated CPK resulted in a diagnosis of amyopathic dermatomyositis (ADM). Thoracoscopic lung biopsy specimens disclosed BOOP-type interstitial pneumonia. Oral prednisolone (PSL) was initiated at 60 mg/day and gradually tapered. However, because his respiratory symptoms and laboratory findings deteriorated, the patient underwent 5 courses of cyclophosphamide (CPA) pulse therapy. Following improvement of his subjective symptoms, arterial blood gas data, and respiratory functions, the patient was discharged and placed on oral PSL and CPA. CPA was discontinued 18 months later. The patient has continued to receive PSL (5 mg/day) and has been in good condition for 3 years. Though the prognosis for interstitial pneumonia associated with ADM is reported to be poor, our patient represented a rare case of BOOP-type interstitial pneumonia brought into remission by CPA pulse therapy.

Adult↗
PubMed1999

[Primary ciliary dyskinesia treated with living-donor lobar lung transplantation].

We report a case of primary ciliary dyskinesia in which a living-donor lobar lung transplant was performed. A 24-year-old woman with a diagnosis of primary ciliary dyskinesia and bronchiectasis was admitted to Shinshu University Hospital because of persistent dyspnea and pyrexia over a period of 4 months. Although she was given various antibiotics, neutrophilia, elevated plasma C-reactive protein (CRP) levels, and respiratory failure persisted. Chest roentgenograms and computed tomography disclosed severe bronchiectasis and diffuse infiltrative shadows in both lung fields. Pseudomonas aeruginosa was detected in a sputum culture. Although a variety of conventional therapies were administered, the patient's oxygenation progressively deteriorated. She was intubated and assisted by mechanical ventilation. The patient and her family proposed lung transplantation, and we concluded that a living-donor lobar lung transplant would be a suitable treatment for her disease. We transported the patient to Okayama University Hospital by helicopter 10 days after intubation. A living-donor lobar lung transplant was successfully performed with lung tissues donated by the patient's mother and sister for each transplant site.

Adult↗
PubMed1999

[ADOC regimen for unresectable advanced thymic cancer].

Between 1996 and 1998, we treated 6 patients with unresectable and advanced thymic cancer (stages IVa and IVb). All received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (i.v.) on day 1,0.6 mg/m2 of vincristine i.v. on day 3, and 700 mg/m2 of cyclophosphamide i.v. on day 4; ADOC regimen, respectively at 3-4 week intervals. Four patients obtained a partial response (PR) after ADOC chemotherapy and the overall clinical response rate was 67%. No life-threatening side effects were noted. In 2 patients, cisplatin plus VP-16 chemotherapy failed to demonstrate any benefits prior to the ADOC regimen. Radiotherapy was initiated after the achievement of PR in the other 2 patients. ADOC chemotherapy appears to be an effective treatment for thymic cancer.

Aged↗
PubMed1998

Antibodies specific for (6-4) DNA photoproducts: cloning, antibody modeling and construction of a single-chain Fv derivative.

We have investigated a series of four monoclonal antibodies that specifically recognize pyrimidine (6-4) pyrimidone photoproducts. One of these antibodies (64M4), bound all four possible pyrimidine-pyrimidone photoadducts with equal affinities whereas the others (64M2, 64M3 and 64M5) were selective for TC and TT sequences. In addition, 64M5 had the highest binding affinity for photodamaged DNA of the four [T. Mori et al., Photochem. Photobiol. 54 (1991) 225-232]. To help understand the differences between these antibodies, we have cloned and sequenced the variable region genes from all four. Comparing these sequences revealed that all four were highly similar to one another, although there were some differences in potential antigen-contact regions. To assess the influences of these sequence differences at the structural level, computer models were constructed for all four antibodies. Most of the sequence differences occurred in potential antigen contact regions, suggesting specific positions that might account for the observed differences in binding affinities and selectivities. A single-chain Fv derivative of 64M5 was therefore constructed and characterized to provide an experimental system in which structure-function relationships can be tested. This derivative could be isolated from Escherichia coli using two chromatographic steps and possessed the same binding specificity as the parent monoclonal antibody.

Amino Acid Sequence↗
PubMed1998

Mitogenic activity of endothelin on human cultured prostatic smooth muscle cells.

The effects of endothelins on human prostatic smooth-muscle cell growth were examined. Endothelin-1 and endothelin-3 induced a concentration-dependent increase in DNA synthesis and also promoted cell growth. Use of subtype selective antagonists BQ-123 ((cyclo(D-Trp-D-Asp(ONa)-Pro-D-Val-Leu); endothelin ET(A) receptor selective) and BQ-788 ((N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl Leu-D-Trp-(COOMe)-D-Nle-ONa); endothelin ET(B) receptor selective), indicated that mitogenic effects of endothelin were mediated through activation of both endothelin ET(A) and ET(B) receptors. The mitogenic effects of endothelin-1 and endothelin-3 were significantly inhibited by pretreatment of the cells with pertussis toxin. However, mitogenesis due to basic fibroblast growth factor was not affected. In conclusion, endothelin has mitogenic effects on human prostatic smooth muscle cells through activation of both endothelin ET(A) and ET(B) receptors via different signalling pathways from basic fibroblast growth factor. This may contribute to smooth muscle hyperplasia associated with benign prostatic hyperplasia.

Aged↗
PubMed1998

Development of unfavorable hepatoblastoma in children of very low birth weight: results of a surgical and pathologic review.

BACKGROUND: The incidence of hepatoblastoma in children of very low birth weight (< 1500 g) is increasing in Japan. The authors reviewed surgical and pathologic aspects of the tumor to clarify the characteristics of the patients. METHODS: Fifteen patients (9 boys and 6 girls) who were diagnosed between the ages of 6-77 months (median, 16 months) were identified from the data in the Japan Children's Cancer Registry and the data base of medical journals. The patients' birth weights ranged from 560-1380 g (median, 826 g) and the gestational age ranged from 23-33 weeks (median, 25 weeks). The medical records of all patients were reviewed and the patient's stage of disease according to the classification of the Japanese Society of Pediatric Surgeons, treatment, and outcome were analyzed. RESULTS: Ten tumors (67%) were classified as Stage II or IIIA and 5 (33%) were classified as Stage IIIB or IV. There was a significant correlation between the gestational age and tumor stage (correlation coefficient - 0.6851; P = 0.0048). The gestational age of the 5 patients with Stage IIIB or IV tumors was 23-25 weeks (median, 24 weeks), whereas it was 25-33 weeks (median, 27.5 weeks) for the 10 patients with Stage II or IIIA tumors (P = 0.0036). Birth weight ranged from 560-826 g (median, 734 g) in Stage IIIB and IV patients, which was significantly lower than that in Stage II and IIIA patients (range, 607-1380 g, median, 909 g; P = 0.0500). Complete tumor resection was achieved in 7 patients (47%). The actuarial 2-year survival of all patients was 0.42, and the 2-year survival of patients who underwent complete tumor resection was 0.69, which was significantly better than the 2-year survival of those who underwent incomplete resection (0.17; P = 0.0211). The 2-year survival of the patients with tumors of well differentiated histology was 0.60, which also was significantly better than the 2-year survival of those with tumors of poorly differentiated histology (0.19; P = 0.0453). CONCLUSIONS: These results indicate that children of very low birth weight (< 1500 g) are at high risk of developing advanced hepatoblastomas and that hepatoblastoma with unfavorable biologic behavior develops in children who are extremely premature at birth. These new findings suggest the presence of etiologic factors relevant to the patient's immaturity and the development of unfavorable hepatoblastoma.

Child↗