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Biomedical subjects

Y Kodama

Publications and source records attributed to Y Kodama.

At least 127 records · Page 7Linked to original sources

Role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors in rat preosteoblastic RCT-1 cells.

Retinoic acid induces differentiation of preosteoblastic cells. We have demonstrated that osteoblastic differentiation and down-regulation of transforming growth factor (TGF)-beta receptors requires the interaction of type I collagen with alpha 2 beta 1 integrin (J Biol Chem 271: 3938-3944, 1996). The purpose of this study was to clarify the role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors using preosteoblastic RCT-1 cells. Retinoic acid enhanced the expression of alkaline phosphatase and type I collagen, and reduced TGF-beta receptors in these cells. Inhibiting collagen synthesis abolished these changes. Because TGF-beta inhibits osteoblastic differentiation, the changes described here may contribute to the osteoblastic differentiation by retinoic acid.

Alkaline Phosphatase↗

PF1092A, B and C, new nonsteroidal progesterone receptor ligands produced by Penicillium oblatum. II. Physico-chemical properties and structure elucidation.

The structures of PF1092A (1), B (2) and C (3), new nonsteroidal progesterone receptor ligands produced by Penicillium oblatum, were elucidated by spectroscopic analyses. These compounds possess an eremophilane-type sesquiterpene carbon skeleton and differ only in that 1 and 2 are different monoacetates of 3. The absolute configurations of 1-3 were determined by single crystal X-ray diffraction analysis of the 4-bromobenzoyl ester of PF1092A and by measuring the optical rotations of the acetylation products of these compounds.

Furans↗

[A case of infected subdural hematoma complicating chronic subdural hematoma in a healthy adult man].

The authors report a case of so-called "infected subdural hematoma" as a complication of chronic subdural hematoma. The patient was a 55-year-old man who had sustained a small laceration of the forehead in a traffic accident on March 29, 1995. No fractures were detected on skull roentgenograms, and general and neurological examinations failed to reveal any abnormal findings. In early August 1995, the patient began to experience headaches, and on August 5 he developed a fever of 38 degrees C. On August 8 he suffered a left motor seizure and was admitted to our hospital. Laboratory studies revealed a peripheral leukocyte count of 10,800/mm3 and a C-reactive protein level of 18.1 mg/dl. Computed tomography scans showed a thick right fronto-parietal subdural low density mass and a thin left frontal subdural low density mass. An emergency operation was performed via a single right fronto-parietal burr hole. A chronic subdural hematoma containing slightly yellowish, bloody, purulent fluid was found beneath an outer membrane. The hematoma was irrigated with physiological saline containing antibiotics, and a drain was inserted into the subdural space. A subdural membrane was also present on the left but it contained no pus. Aggressive antibiotic therapy was performed, and the patient was discharged without any neurological deficit. Histologically the membrane was determined to be the outer membrane of a typical chronic subdural hematoma. Enterococcus faecalis, which has rarely been reported to cause infection of the central nervous system, was detected in a bacterial culture of the pus. Systemic investigation showed no evidence of otorhinologic or other focal infection. The above clinical findings suggested that hematogenous seeding of a chronic subdural hematoma had occurred in this patient. Subdural empyema arising from hematogenous seeding to a pre-existing subdural hematoma by an infection is very rare, but this type of complication must be kept in mind not only in the elderly, infants, and compromised hosts, but in patients without complications as well.

Chronic Disease↗

Correlation of susceptibility and resistance of twenty-five bacterial strains by analysis of MIC database of cephalosporins and oxacephalosporins.

MIC database of 1,407 cephalosporins and oxacephalosporins was utilized to characterize 25 bacterial strains including Gram-positive and Gram-negative bacteria. MIC values were converted to activity rank indices, and distribution patterns of these indices were compared among the bacterial strains. Salmonella enteritidis. No. 11 was the most susceptible bacterium, and the activity against this strain was ascribed to the binding of beta-lactams to the PBPs without any significant barrier to the approach of beta-lactams. Twenty-one strains were assumed to have similar types of PBPs to those of S. enteritidis No. 11 in the binding profile to beta-lactams. Comparison of the scatter diagrams of the activity rank indices revealed two different types of resistances arising from beta-lactamases (9 strains) and outer membrane permeability and/or active efflux (15 strains). The resistance factor arising from beta-lactamase was affected by the nature of the C-3 substituents of beta-lactams.

Bacteria↗

[Magnetic resonance imaging of Kernohan's notch in chronic subdural hematoma].

Compression of the crus cerebri against the free edge of the tentorium contralateral to a supratentorial mass, the so-called Kernohan's notch, can be a cause of false localizing sign. Kernohan's notch has been thoroughly studied clinically and pathologically, but not radiographically. The authors describe a case of left chronic subdural hematoma, which resulted in left hemiparesis caused by Kernohan's notch. Injury to the contralateral cerebral peduncle was clearly shown by magnetic resonance imaging (MRI) performed in the postoperative period. A 43-year-old man was transferred to our hospital in deep coma with dilated pupils, unreactive to light. Computed tomography (CT) scans obtained on admission revealed a left chronic subdural hematoma and a midline shift to the right. After drainage and irrigation of the left chronic subdural hematoma through a single burr hole, his clinical condition improved gradually. But 1 month after the operation, mild left hemiparesis still persisted. MRI T2-weighted images demonstrated an abnormally increased signal area in the right cerebral peduncle. T1-weighted coronal images showed the anatomical relationship between the hypointense lesion in the right cerebral peduncle and tentorial edge. Three-dimensional-MRI (3D-MRI) clearly demonstrated the surface image of Kernohan's notch. We emphasize the utility of 3D-MRI for detecting evidence of brain stem injury, such as Kerno han's notch.

Adult↗

5-Hydroxytryptamine1B and alpha 2 adrenaline receptors in the brain of rats prenatally treated with methylazoxymethanol.

Methylazoxymethanol (MAM)-induced cerebral hypoplasia resulted in a significant increase in concentrations of 5-hydroxytryptamine (5-HT, serotonin) and norepinephrine in the frontal cortex, suggesting that these monoaminergic neurons were compressed due to smaller brain volumes. The serotonergic and noradrenergic presynaptic autoreceptors in rat brain are thought to be 5-HT1B receptors and alpha 2-adrenoceptors, respectively. If so, prenatal MAM treatment should increase the density of 5-HT1B and adrenaline alpha 2 receptors in the brain via the compression of noradrenergic and serotonergic axon terminals in the brains of rats with MAM-induced microencephaly. However, neither the densities nor the affinities of 5-HT1B and adrenaline alpha 2 receptors were changed in the MAM rats, suggesting that these presynaptic autoreceptors comprise only a small percentage of the total receptor population. Most 5-HT1B and adrenaline alpha 2 receptors were localized post-synaptically.

Alkylating Agents↗

Correlation of susceptibility and resistance of twenty-five bacterial strains by analysis of MIC database of cephalosporins and oxacephalosporins

MIC database of 1,407 cephalosporins and oxacephalosporins was utilized to characterize 25 bacterial strains including Gram-positive and Gram-negative bacteria. MIC values were converted to activity rank indices, and distribution patterns of these indices were compared among the bacterial strains. Salmonella enteritidis No. 11 was the most susceptible bacterium, and the activity against this strain was ascribed to the binding of beta-lactams to the PBPs without any significant barrier to the approach of beta-lactams. Twenty-one strains were assumed to have similar types of PBPs to those of S. enteritidis No. 11 in the binding profile to beta-lactams. Comparison of the scatter diagrams of the activity rank indices revealed two different types of resistances arising from beta-lactamases (9 strains) and outer membrane permeability and/or active efflux (15 strains). The resistance factor arising from beta-lactamase was affected by the nature of the C-3 substituents of beta-lactams.

Journal Article↗

Different pathways of inhibitory effects of wortmannin on exocytosis are revealed by video-enhanced light microscope.

Exocytosis of secretory granules, including histamine, in rat basophilic leukemia (RBL-2H3) cells, which exhibit Ca(2+)-dependent secretion of granules when stimulated with antigen or Ca(2+)-ionophore (A23187), was observed under a video-enhanced light microscope. Exocytotic events of individual granules including fusion, extrusion, and membrane retrieval were visualized in individual cells stimulated with antigen or A23187. Exocytosis of granules stimulated with A23187 showed two peaks in its time courses. The earlier one of the peaks was inhibited by wortmannin ( > 100 nM), as an inhibitor of myosin light chain kinase (MLCK), and the other was not. Exocytosis by antigen-stimulation, however, showed only one peak, which was inhibited by low concentration of wortmannin ( < 50 nM) as an inhibitor of phosphatidylinositol 3-kinase (PI3-kinase). These results indicate that quantitative analysis of exocytosis visualized by video-enhanced light microscope reveals two different pathways, through P13-kinase and MLCK, of inhibitory effects on exocytosis by wortmannin in RBL-2H3 cells.

Androstadienes↗

Habitual and genetic factors that affect urinary background levels of biomarkers for organic solvent exposure.

Urinary hippuric acid, phenol, and o-cresol, which are biomarkers for toluene, benzene, and phenol exposures, are usually present in a significant amount in urine collected from subjects who have not been occupationally exposed to the organic solvents. With the improvement of working environments, the urinary concentrations of the biomarkers have become lower and closer to the levels of urine from unexposed subjects. It is very useful to clarify the background levels of these biomarkers and the factors which effect the background levels of the biomarkers in order to make effective use of biological monitoring under low level exposure. In the present study, the effects of life habits and the genetic polymorphisms of the metabolizing enzymes on the background levels of urinary hippuric acid, phenol and o- and p-cresol were clarified, using 351 males (means age: 38.6, range: 19-71) who were not occupationally exposed to hazardous chemical materials. Their life habits, smoking, alcohol consumption, and dietary habits were examined by means of a questionnaire. The genotypes of five metabolizing enzymes, that is, low Km aldehyde dehydrogenase (ALDH2), polymorphic N-acetyl transferase (NAT2), cytochrome P-4501A1 (CYP1A1), cytochrome P-4502E1 (CYP2E1), and glutathione-S-transferase mu (GSTM1) were determined form peripheral blood samples. The urinary hippuric acid and creatinine were analyzed by HPLC and urinary phenol, o-, p- and m-cresol were determined by GC/MS. Recoveries and the coefficients of variance of phenol, o-cresol, and p-cresol ranged from 92.7 to 107.8% and 1.3% to 6.7%, respectively. Linear relationships between the concentrations of phenol, o- and p-cresol, and their peak area ratios were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗

Rapid induction of more malignant tumors by various genotoxic carcinogens in transgenic mice harboring a human prototype c-Ha-ras gene than in control non-transgenic mice.

In this study, we investigated the carcinogenic response of transgenic mice carrying the human prototype c-Ha-ras gene, namely Tg rasH2/CB6F1 mice, to various genotoxic carcinogens and compared it with that of control non-transgenic CB6F1 mice (non-Tg mice). The present studies were conducted as the first step in the evaluation of the Tg rasH2/CB6F1 mouse as a model for the rapid carcinogenicity testing system. Short-term (< or = 6 months) rapid carcinogenicity tests of various genotoxic carcinogens, 4-nitroquinoline-1-oxide, cyclophosphamide, N,N-diethylnitrosamine, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and methylazoxymethanol, revealed that Tg rasH2/CB6F1 mice are more susceptible to these genotoxic carcinogens than control non-Tg mice. Tg rasH2/CB6F1 mice developed tumors more rapidly compared with non-Tg mice. Malignant tumors were observed only in the carcinogen-treated Tg rasH2/CB6F1 mice, but not in non-Tg mice treated with the same carcinogens. Each carcinogen induced tumors in corresponding target tissues of the Tg rasH2/CB6F1 mice. Only a very few lung adenomas but no other tumors were seen as spontaneous tumors during the 6 months of carcinogenicity tests. These results demonstrate that more rapid onset and higher incidence of more malignant tumors can be expected with high probability after treatment with various genotoxic carcinogens in the Tg rasH2/CB6F1 mice than in control non-Tg mice. The Tg rasH2/CB6F1 mouse seems to be a promising candidate as an animal model for the development of a rapid carcinogenicity testing system.

4-Nitroquinoline-1-oxide↗

Evaluation of unbound serum carbamazepine and carbamazepine-10,11-epoxide concentration prediction methods in polytherapy adult patients with epilepsy.

We retrospectively evaluated the ability of equations with in vivo population binding parameters of our previous study (Method 1) or an average unbound fraction of 0.25 of Pynnönen (Method 2) to predict the unbound serum carbamazepine (CBZ) concentration in 35 serum samples from 18 adult patients with epilepsy receiving polytherapy. In 9 serum samples from 6 patients, the ability of equations for unbound serum carbamazepine-10,11-epoxide (CBZ-E) concentration prediction was also determined in predictive performance with in vivo population binding parameters of our previous study (Method A) or an average unbound fraction of 0.5 of Pynnönen (Method B). Mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) were calculated for each method, and these values served as a measure of prediction bias and precision. Method 1 shows a bias to underpredict unbound serum CBZ. The MAE and RMSE were smaller in Method 2 (MAE = 0.454 &mgr;m/L, RMSE = 0.597 &mgr;m/L) than Method 1 (MAE = 0.597 &mgr;m/L, RMSE = 0.721 &mgr;m/L). Method 2 is superior to Method 1 in accuracy and precision. The effects of antiepileptic comedications on predictive performance of Methods 1 and 2 were determined in each group of serum samples with (n = 18, Group 1) or without (n = 17, Group 2) valproic acid (VPA) comedication. The results obtained by Method 1 show a bias to underprediction in Group 1 and no bias to over- or underprediction in Group 2. Results obtained by Method 2 show no bias to over- or underprediction in Groups 1 and 2. The effects of VPA comedication on predictive performance of unbound serum CBZ are relatively larger in Method 1 than Method 2. There was a weak but significant positive relationship between age and unbound serum CBZ fraction by simple regression analysis (n = 35, r = 0.368, p = 0.0297). The determined coefficient indicated that only about 14% of variations in unbound serum CBZ fraction can be explained by age, however. In each of Groups 1 and 2, no significant relationship was observed between age and unbound serum CBZ fraction. The effects of age on predictive performance of unbound serum CBZ are relatively small in patients receiving polytherapy. For unbound CBZ-E prediction, each of Methods A and B has no bias to over- or underprediction. The MAE was larger in Method B (MAE = 0.311 &mgr;m/L) than Method A (MAE = 0.233 &mgr;m/L). The differences in RMSE were small between Methods A (RMSE = 0.349 &mgr;m/L) and B (RMSE = 0.333 &mgr;m/L), however. Each of Methods A and B may have similar accuracy and precision.

Journal Article↗

Clearance of phenytoin and valproic acid is affected by a small body weight reduction in an epileptic obese patient: a case study.

The interaction between clearance of phenytoin, valproic acid, phenobarbital and carbamazepine, and changes in body weight was determined in a 19-year-old obese woman with epilepsy (body weight 93 kg, BMI 36.3 kg/m2). The patient, who was given daily oral doses of 100 mg phenobarbital, 350 mg phenytoin, 800 mg valproic acid and 800 mg carbamazepine over 5 months was hospitalized for obesity treatment. The daily dosage of each drug was held constant during treatment of the obesity. Blood samples were taken five times. Weight reduction was 7 kg (7.5%) over 46 days. Estimation of the pharmacokinetic parameters in each drug was performed by Higuchi's Bayesian program, PEDA Pearson's correlation coefficient (r) between clearance and body weight was calculated for each drug. High positive correlations were found between clearance and body weight for phenytoin (r = 0.800) and valproic acid (r = 0.785), but not for phenobarbital (r = -0.227) and carbamazepine (r = 0.152). Clearance of phenytoin and valproic acid may be potentially affected by small changes in body weight.

Adult↗

Comparison of two binding equations for prediction of the concentration of unbound valproic acid in the serum of adult epileptic polytherapy patients.

Because binding of valproic acid to plasma proteins affects the efficacy of the drug in the treatment of epilepsy (only the unbound fraction of the drug is effective) we have compared two methods which use different binding parameters to predict the in-vivo concentration of unbound valproic acid in serum. The study was performed on 46 serum samples from 29 polytherapy adult patients with epilepsy. Mean prediction error, mean absolute prediction error and root mean squared error were calculated for each method; these values served as a measure of prediction bias and precision. The mean absolute prediction errors and root mean squared errors for the two methods were similar in magnitude (Method 1, mean absolute prediction error = 10.0 microM, root mean squared error = 15.0 microM; Method 2, mean absolute prediction error = 10.3 microM, root mean squared error = 13.5 microM). Method 2 had a general tendency to over-predict unbound valproic acid; both methods had a tendency to over-prediction for total concentrations above 500 microM. Method 1 had a tendency to under-prediction at total concentrations below 250 microM. Within the total concentration range of valproic acid investigated, Method 1 was superior to Method 2 for prediction of unbound serum valproic acid. Our approach using Method 1 may be useful for prediction of unbound serum valproic acid concentration in patients with total valproic acid concentrations ranging from 250 to 500 microM; Method 2 may be useful for patients with total valproic acid below 500 microM. Our results suggest that there is wide and unpredictable variability in valproic acid binding to serum proteins among study populations.

Adolescent↗

Absence of mutations in parathyroid hormone (PTH)/PTH-related protein receptor complementary deoxyribonucleic acid in patients with pseudohypoparathyroidism type Ib.

To clarify the mechanism of resistance to PTH in patients with pseudohypoparathyroidism (PHP) type Ib, the complementary DNA (cDNA) for PTH/PTH-related protein (PTHrP) receptor was analyzed in skin fibroblasts from three patients with PHP Ib and compared with those from a patient with PHP Ia and a normal subject. We have divided the full coding region of PTH/PTHrP receptor cDNA into five parts and amplified the cDNA by reverse transcription-coupled PCR. There was no difference in the size of PCR products among these patients and the normal control. Single strand conformation polymorphism analysis of the PCR products also showed no aberrant bands in PHP Ib patients. Furthermore, no mutation in PTH/PTHrP receptor cDNA was found by direct sequencing of the PCR products from these patients. These results demonstrate that there is no mutation in PTH/PTHrP receptor cDNA from skin fibroblasts at least in the examined patients with PHP Ib. In addition, the expression of PTH/PTHrP receptor messenger ribonucleic acid was reduced in two patients but was increased in one patient with PHP Ib, suggesting that a reduction in PTH/PTHrP receptor expression cannot explain the resistance to PTH in all patients with PHP Ib. Elucidation of the pathogenesis of PHP Ib may require examination of tissue-specific abnormality in the PTH signal transduction system in the kidney.

Adolescent↗

Passage of chicken egg yolk antibody treated with hydroxypropyl methylcellulose phthalate in the gastrointestinal tract of calves.

Two types of chicken egg yolk antibody samples for oral passage trials in calves were prepared: (1) hydroxypropyl methylcellulose phthalate (HPMCP) antibody powder (HAP)--a powder produced by spray-drying a supernatant obtained after precipitation of lipids from egg yolk with HPMCP and (2) control antibody power (CAP)--a powder produced from an antibody solution with HPMCP. Antibody activity and pattern of distribution of both antibody preparations in the gastrointestinal tract of calves were compared by enzyme-linked immunosorbent assay. At 2 hr post administration, anti-K99 fimbrial antibodies from both the CAP and the HAP were detected in the abomasum of calves with titers of 1:128 and 1:256, respectively. However, at 4 hr, anti-K99 fimbrial titers of the CAP and the HAP were reduced to 1:2 and 1:64, respectively, due to digestion in the abomasum. These results indicated that the egg yolk antibody powder with HPMCP was more resistant against gastric juice in the stomach, thereby, ensuring a transfer of functional antibodies to the small intestine of calves after oral administration.

Abomasum↗

Indoor pollution from heating.

The concentrations of indoor pollutants generated from types of heaters were measured in a model room of 20m2 in area and 45m3 in capacity. We used six different heaters: three kerosene heaters of different types, town and propane gas heaters, and an electric heater. Three ventilation conditions were introduced into each experiment: non-ventilation, fan-on ventilation with closed door and fan-off ventilation with half-opened door. The results obtained by heating under non-ventilation condition were as follows: The concentrations of NO2 and CO2 were comparatively high and the values obtained from all the heaters except the electric heater exceeded the 1-hr Environmental Quality Standards, Japan (EQS NO2: 0.04-0.06 ppm) and the Building Sanitation Management Standards, Japan (BSMS CO2: 1,000 ppm), respectively. The CO concentration emitted from reflection kerosene and town gas heaters slightly exceeded the BSMS (10 ppm). The concentrations of suspended particulate matter and polynuclear aromatic hydrocarbons showed an increasing tendency during the use of kerosene-fueled heaters. Under two ventilating conditions, NOx concentration decreased to less than a third in comparison with non-ventilating condition.

Air Pollutants↗

[A case of cranial hypertrophic pachymeningitis with intracranial hemorrhage].

A case of cranial hypertrophic pachymeningitis of unknown etiology in a patient with 15-year history of headaches, cranial nerve palsies, and gait disturbance is reported. A 77-year-old woman was brought to our institute in a coma. CT revealed intracerebral hemorrhage in the right temporal lobe and thickening of the falx and tentorium. Fifteen years previously the patient had undergone CT scanning because of headaches, cranial nerve palsies, and progressive gait disturbance and a thickened tentorium, mild hydrocephalus and edematous change in the right temporal lobe had been reported. Since the etiology of her symptoms was unclear at the time, she did not receive adequate treatment. Her symptoms gradually progressed thereafter, and her visual acuity and hearing deteriorated. MR imaging in 1994 showed the thickened tentorium as a hypointense area with hyperintense edges on Gd-DTPA enhanced images. Angiography revealed narrowing of posterior portion of the superior sagittal sinus. The patient's condition rapidly deteriorated due to the intracranial hypertension and she subsequently died. Autopsy revealed a thickened tentorium with xanthochromic surface. This hypertrophic change was also seen in the dura mater of the posterior and middle cranial fossa. Microscopic examination of the thickened tentorium revealed extensive fibrous tissue with a chronic inflammatory infiltrate, predominantly of lymphocytes. No specific lesions were revealed by staining with hematoxylin-eosin, PAS, Gram's or Ziehl-Neelsen stains. The patient had no inflammatory or infectious diseases of other organs, and a diagnosis of idiopathic cranial hypertrophic pachymeningitis of unknown etiology was made. Considering the above findings, the thickened tentorium depicted as a hypointense area on the T1- and T2-weighted images and the Gd-enhanced edges of the tentorium are thought to be represent fibrous tissue and inflammatory regions, respectively.

Aged↗

[Adult-onset aqueductal stenosis caused by membranous occlusion in the aqueduct: a case report].

The authors report a case of adult-onset aqueductal stenosis caused by membranous occlusion of the aqueduct. The patient was a 35-year-old man, who suffered from progressive headache. On admission, computed tomography (CT) scan showed marked dilatations of the lateral and third ventricles. Midsagittal T1-weighted magnetic resonance imaging (MRI) scan showed a membranous occlusion at the lower end of the aqueduct, with dilatation of the proximal aqueduct and elevation of the tectum. Midsagittal cine-MRI demonstrated the cerebrospinal fluid flow in the aqueduct. The patient was diagnosed as having hydrocephalus resulting from membranous stenosis of the aqueduct by MRI. A ventriculo-peritoneal shunt operation was performed and his symptoms improved markedly. The membranous occlusion of the aqueduct is a rare cause of hydrocephalus. The etiology and therapy of aqueductal stenosis are discussed.

Adult↗