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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 703 records · Page 39Linked to original sources

Preliminary report on teratogenic effects of zonisamide in the offspring of treated women with epilepsy.

PURPOSE: We wished to assess the risk of teratogenicity of zonisamide (ZNS) in humans. METHODS: Pregnant epileptic women treated with ZNS and their offspring were prospectively monitored from June 1989 to December 1994. The outcome of pregnancy and status of neonates were examined based on the same standardized protocol. RESULTS: Twenty-six offspring exposed to ZNS with or without other antiepileptic drugs (AEDs) were studied. Malformations were detected in 2 offspring (7.7%) exposed to ZNS polypharmacy. Anencephaly was detected in one case at 16 weeks of gestation (case 1, artificial abortion), and atrial septal defect was detected in another case at 37 weeks of gestation (case 2, delivery by cesarean section). Serum concentrations of ZNS during the first trimester of pregnancy were 6.1 micrograms/ml in case 1 and 6.3 micrograms/ml in case 2; in both cases, the levels were below the therapeutic concentration range of ZNS. CONCLUSIONS: Teratogenic effects of ZNS were not clearly defined from these results since malformations were detected in two polypharmacy cases but not in four monopharmacy cases. The present data do not indicate that the risk of ZNS teratogenicity is greater than that of other conventional AEDs. However, such risk cannot be neglected even at therapeutic dosages or concentrations of ZNS, especially in patients receiving poly-pharmacy.

Abnormalities, Drug-Induced↗

Immunocytochemical study of nerve fibers containing substance P in the junctional epithelium of rats.

Nerve fibers with substance P-like immunoreactivity (SP-IR) in the junctional epithelium (JE) of 32-42-d-old rats were examined by both light and electron microscopy using the avidin-biotin-peroxidase complex method. The density of nerve fibers with SP-IR was highest in the middle portion of the JE; however, a few fibers were localized in the coronal portion of the JE and close to the enamel surface. Also, rich innervation was found especially in the basal cell layer of the JE. Unmyelinated axons with SP-IR in the connective tissue underlying the JE were enveloped by Schwann cells but lost their Schwann cell sheath almost completely in the JE. The axons often formed varicosities with SP-IR as terminals in various areas of the JE. The terminals contained numerous large granular vesicles, small clear vesicles and a few mitochondria, and were surrounded by the cytoplasmic processes of the junctional epithelial cells. These terminals were sometimes located close to neutrophils in the JE; the minimum gap distance between the terminals and the processes of junctional epithelial cells or neutrophils was about 20 nm. A few terminals with SP-IR came close to the enamel surface, and the minimal distance between the terminals and the enamel surface was about 5 microns. SP-IR in the nerve terminals in the JE fixed with 0.1% or 0.25% glutaraldehyde was distributed diffusely in the axoplasm or was confined to the granular vesicles. These findings show that substance P is contained in the large granular vesicles in the nerve terminals, and suggest that these terminals may function as modulators of junctional epithelial cells and neutrophils.

Animals↗

Preparation of poly(D,L-lactide) and copoly(lactide-glycolide) microspheres of uniform size.

In an attempt to prepare monodisperse poly(D,L-lactide) and copoly(lactide-glycolide) microspheres, a novel emulsification technique (membrane emulsification) was employed and the preparation conditions which might affect the monodispersity were evaluated. With this technique nearly monodisperse poly(D,L-lactide) and copoly(lactide-glycolide) microspheres were successfully prepared and their sizes were controllable only by making use of microporous glass membranes of different pore sizes. However, in the present system of emulsion (methylene chloride/water) the surfactant used was limited to ionic ones and the amount of polymers available for the formation of microspheres was inevitably too small in concentration to entrap sufficient amounts of drug. As for the drug release, the effect of particle size was not appreciable but the method of solvent removal gave a great influence; the solvent extraction method showed a more drug-sustaining effect than did the solvent evaporation method. The present results suggest the possibility of making drug-loaded and biodegradable monodisperse microspheres.

Biocompatible Materials↗

Sleeve superior segmentectomy of the right lower lobe for endobronchial neurinoma. Report of a case.

A 30-year-old woman was found to have an obstructive intrapulmonary tumor at the right intermediate bronchus which caused atelectases of both right middle and lower lobes. The diagnosis of endobronchial neurinoma was made by bronchofiberscopic biopsy. Since the tumor was benign, we considered an operative procedure which would enable both complete resection of the tumor and preservation of the pulmonary function. By utilizing the techniques of sleeve superior segmentectomy of the right lower lobe and telescoping bronchial anastomosis, both objectives were achieved.

Adult↗

Elevated amylase is related to the development of respiratory failure in organophosphate poisoning.

1. A retrospective study of organophosphate (OP) poisoning in the intensive care unit was performed to analyze the incidence of respiratory failure. 2. The patients were treated initially with gastrointestinal decontamination including gastric lavage and the administration of activated charcoal with cathartic. Further management included intravenous pralidoxim and atropine and ventilatory support. 3. Of the 32 OP poisoning patients, 16 patients developed respiratory failure and received ventilatory support. 4. An increase in plasma amylase above the normal range on the day of admission was related to the development of respiratory failure. 5. In OP poisoning, the elevation of amylase level was predictive of the subsequent respiratory failure.

Adult↗

Thalamic tremor: case reports and implications of the tremor-generating mechanism.

We report two patients with unilateral resting and postural tremor of the upper limb as a delayed manifestation of thalamic stroke. Neuroradiologic examination showed a lesion in the posterolateral thalamic region in both patients, but with no obvious involvement of the brainstem, the cerebellum, or the cerebellar outflow tract to the thalamic ventrolateral nucleus.

Adult↗

Function of posterior HoxD genes in the morphogenesis of the anal sphincter.

Vertebrate 5'-located HoxD genes are expressed in the most caudal part of the digestive tract and their potential functions during gut development have been assessed by gene disruptions. We have inserted reporter lacZ sequences within the Hoxd-12 gene and analysed the morphology of the gut in these mice as well as in Hoxd-13 mutant animals. When homozygous, both mutations induce an important disorganization of the anorectal region. In particular, severe alterations of the smooth muscle layers of the rectum led to defective morphogenesis of the internal anal sphincter. Similarly, Hoxd-12 and Hoxd-13 functionally overlap during digit development. The function of these genes in the morphogenesis of the digestive system as well as their functional evolution are discussed.

Anal Canal↗

Selective expression of mutated p53 in human cells immortalized with either 4-nitroquinoline 1-oxide or 60Co gamma rays.

Many studies on in vitro transformation of human cells indicate that the cells must be immortalized before they can be neoplastically transformed, indicating that immortalization is a critical step in multistep neoplastic transformation of human cells. We immortalized three human cell lines by repeated treatment with either 60Co gamma rays or a chemical carcinogen, 4-nitroquinoline 1-oxide, and found that all three immortalized cell lines have mutations in the tumor suppressor gene, p53. Direct sequencing of the reverse-transcribed mRNA and immunoprecipitation of p53 protein revealed that mutant p53 is selectively expressed in all the immortalized cell lines, whereas the genomic fragments of the immortalized cells contain wild-type and mutated p53 alleles. Although the mutated p53 is selectively expressed in the immortalized cells, expression of the wild-type p53 was induced by treatment of the cells with a hypomethylating reagent, 5-azacytidine, indicating that the wild-type p53 allele might be inactivated by hypermethylation of DNA. Actually, the entire genomic locus including the promoter region of p53 is hypermethylated in all the immortalized cell lines. Expression and phosphorylation of Rb was normal in these three cell lines. Thus, inactivation of both wild type p53 alleles and selective expression of mutated p53 seem to be key factors in the immortalization of human fibroblasts.

4-Nitroquinoline-1-oxide↗

Amino acid sequences and ribosome-inactivating activities of karasurin-B and karasurin-C.

Complete amino acid sequences of karasurin-B and karasurin-C purified from root tubers of Trichosanthes kirilowii Maxim.var.japonica Kitamura (Cucurbitaceae) were determined. Karasurin-B consist of 247 amino acid residues with a calculated molecular weight of 27,214 Da and karasurin-C of 249 amino acid residues with a calculated molecular weight of 27,401 Da. Their amino acid sequences are quite similar to that of karasurin-A, a major basic protein from the same root tubers, but the pI values are slightly different among them. All karasurins strongly inhibited in vitro translation in the rabbit reticulocyte system. The amino acid sequences of karasurins were compared with those of the ribosome-inactivating proteins (RIPs) from nine different species by UPGMA method, and the RIPs fro Cucurbitaceae plants phylogenetically formed one cluster clearly distinguishable from those of other origin.

Abortifacient Agents, Nonsteroidal↗

Combination effects of alpha-cyclodextrin and xanthan gum on rectal absorption and metabolism of morphine from hollow-type suppositories in rabbits.

Pharmacokinetics of morphine and its glucuronides in plasma were studied after rectal administration of hollow-type oleaginous suppositories containing kneading mixtures of morphine hydrochloride, alpha-cyclodextrin, and/or xanthan gum in rabbits. In combination with xanthan gum, alpha-cyclodextrin reduced the first-pass metabolism of morphine in the rectal mucosa and by the liver and improved the apparent rectal bioavailability of the opioid about 4 fold. In vitro permeation studies using an isolated rectal mucosal preparation of rabbits revealed that alpha-cyclodextrin increased the transepithelial conductance and facilitated the transport of morphine through the rectal mucosa. Furthermore, alpha-cyclodextrin facilitated its own mucosal permeation and reduced the glucuronidation of morphine during the passage through the rectal mucosa, probably through restricting the formation of a catalytic complex of morphine with glucuronyltransferases, rather than because of the enzyme saturation. The present data suggest that alpha-cyclodextrin in combination with xanthan gum is particularly effective in improving the rectal bioavailability of morphine from hollow-type suppositories.

Analgesics, Opioid↗

Is pre-intervention intravascular ultrasound necessary in evaluating target lesion calcification in patients undergoing transcatheter therapy?

To identify a subset of patients with a high probability of extensive calcification for further intravascular ultrasound (IVUS) examination, the frequency and extent of target lesion calcification as assessed by IVUS and its correlations with age, gender and risk factors as well as the value of angiography in identifying ultrasound calcification were analyzed in 88 patients undergoing balloon angioplasty for significant coronary atherosclerotic stenosis. The extent of calcification was semi-quantitatively graded as 0: no calcification; +: calcification arc < 90 degrees; ++: calcification arc from 90 degrees to 180 degrees; : calcification arc > 180 degrees. The distribution pattern of calcification was classified as superficial, deep or mixed. The results indicate: (1) the frequency of target lesion calcification was 38.6%, of which 52.9% showed a superficial pattern and 56.0% had a calcification arc < 90 degrees; and (2) only age was significantly associated with target lesion calcification in all of the patients. The frequency of calcification was remarkably higher in patients > or = 60 years old than in patients < or = 60 years old (61.9% vs 17.4%, p < 0.001); (3) among patients less than 60 years old, those with calcification had a higher average number of risk factors than those without; and (4) the total sensitivity of angiography in identifying ultrasound calcification was 43.6%, with a significantly higher sensitivity for calcification arc > 180 degrees and mixed pattern. In conclusion, pre-intervention IVUS may be necessary in patients > or = 60 years old and in those < 60 years old with more than two risk factors in selecting devices to optimize interventional strategies.

Age Factors↗

Increased conversion ratio of tryptophan to niacin by the administration of clofibrate, a hypolipidemic drug, to rats.

The effect of clofibrate, a hypolipidemic drug and also known as a peroxisomal proliferator, on the conversion ratio of tryptophan to niacin was investigated by using rats. The rats were fed with a nicotinic acid-free, 20% casein diet (control group) or the same diet + 0.25% clofibrate group) for 19 days. The conversion ratio gradually increased with increasing number of days. Around day 8, the ratio was about 10-times higher in the clofibrate group than in the control group, and the value remained almost constant after that day. The content of liver total nicotinamide was higher in the clofibrate group than in the control group. Among the enzymes involved in the conversion of tryptophan to niacin, the aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) activity, which is critical in the conversion, was lower in the clofibrate group than in the control group. As the change in ACMSDase activity took several days, there is a possibility that clofibrate decreased the biosynthesis of ACMSDase protein and/or mRNA. To learn whether the increase in the conversion ratio by clofibrate would be nutritionally meaningful or not, the growth-promoting activity of clofibrate was determined by using weanling rats fed with a nicotinic acid-free, tryptophan-limiting diet (basal diet). As a result, the body weight gain was higher in the clofibrate group than in the basal group. This result shows that clofibrate enhanced the conversion ratio without any side-effects under the conditions used and supports again the claim that the activity of ACMSDase exerts a critical influence on the tryptophan-NAD conversion.

Animals↗

Effects of feeding tryptophan-limiting diets on the conversion ratio of tryptophan to niacin in rats.

We investigated the effects of feeding various types of nicotinic acid-free, tryptophan-limiting diets on the conversion ratio of tryptophan to niacin in rats. Various tryptophan-limiting diets were made by adding zein, gelatin, glycine, threonine, methionine, or glycine + threonine + methionine to a nicotinic acid-free, 9% casein diet. When the rats were fed with the tryptophan-limiting diets, the conversion ratio of tryptophan to niacin was markedly decreased. However, the ratio recovered after the addition of tryptophan to the tryptophan-limiting diets. These results clearly prove that the conversion was lowest when the rats were fed with the tryptophan-limiting diets. Therefore, we think that the pellagragenic factor of corn is simply due to a low content of tryptophan, but the adverse effect is due to a low conversion ratio of tryptophan to niacin.

Amino Acids↗

In vivo inhibition of kynurenine aminotransferase activity by isonicotinic acid hydrazide in rats.

It is known that the anti-tuberculosis drug, isonicotinic acid hydrazide (INH), causes pellagra, a niacin deficiency syndrome, and peripheral neuritis in humans. We investigated the effects of INH on the metabolism of tryptophan to niacin in rats fed on a niacin-free diet. The activity of kynurenine aminotransferase was significantly inhibited by feeding a diet containing INH and by an injection of INH, and the urinary excretion of xanthurenic acid, the side-reaction product of the conversion pathway of tryptophan to niacin, was below the limit of detection. The inhibition of kynurenine aminotransferase and the resulting decreased formation of xanthurenic acid generally mean a higher conversion ratio of tryptophan to niacin. However, the conversion ratio was no different between the control and INH groups.

Animals↗

Rush immunotherapy with house dust extract in patients with mild extrinsic asthma.

Rush immunotherapy (RIT) with house dust extract was given to 15 patients with mild extrinsic or mixed asthma. Every patient was strongly positive for IgE on the radioimmunosorbent test and sensitive to house dust extract on the scratch skin test. Nine patients were positive on the bronchial provocation test to house dust extract and 6 could not be examined. All patients did not drop out and got to house dust extract solution 10(-1) within 1 week. The symptom-medication scores decreased significantly after RIT. During RIT 1 patient developed a mild asthmatic attack and 3 patients developed generalized skin reaction. Eight weeks later, the threshold for house dust-provoked bronchoconstriction increased in 9 patients, but did not in 3 patients. The blood eosinophil count and blood histamine level significantly decreased. We conclude that RIT is able to raise antigen concentrations for a short periods and effective but not risky for mild asthma.

Adolescent↗

Tracheal, circulatory, and respiratory responses to femoral nerve stimulation.

Tracheal, circulatory, and respiratory responses to electrical stimulation of the afferent nerve from the hindlimb were analyzed in decerebrate, paralyzed, and mechanically ventilated dogs. Tension of the tracheal smooth muscle (TSM), arterial blood pressure, and phrenic nerve activity (PNA) were measured during stimulation of the proximal end of the transected femoral nerve (FNS) with train pulses (duration; 0.5 ms, frequency; 40 Hz). With low intensity (e.g., 0.62 V) FNS, TSM exhibited relaxation, arterial pressure decreased, and neural respiratory output (NRO) was reduced (3 of 8 dogs) or unchanged (5 of 8 dogs). With increases in stimulus intensity, TSM always exhibited relaxation while arterial pressure and NRO exhibited excitatory responses almost at the same thresholds (approximately 5 V). The TSM relaxation and the excitatory NRO and arterial responses augmented with increases in stimulus intensity up to 16 times of threshold of the excitatory NRO response. TSM response was blocked by intravenous atropine but pressor response and phrenic response were not. The arterial response disappeared after administration of a ganglionic blocker. These findings suggest that TSM, arterial pressure, and PNA may be controlled by one neuronal mechanism during high intensity FNS, but that arterial pressure and PNA may be modified by another mechanism in an inhibitory direction when the stimulus intensity is low. This study suggested the existence of a neural mechanism which controls the airway and cardiorespiratory systems properly to execute exercise. Physiological significance of the responses to low intensity femoral nerve stimulation was uncertain.

Animals↗

Intraoperative radiation therapy and chemotherapy for huge choroid plexus carcinoma in an infant--case report.

A 2-month-old boy presented with a huge choroid plexus carcinoma in the left cerebral hemisphere. Almost total resection of the tumor was achieved, but a remnant abruptly enlarged 5 months later, requiring reoperation. After radical resection of the tumor, intraoperative radiation (10 Gy) was delivered. Postoperative chemotherapy was performed with methotrexate and vincristine, selected on the basis of in vitro chemosensitivity testing. No recurrence of the tumor was detected 18 months after the second operation. Radical surgery with these adjuvant therapies may be a good method to control this aggressive disease in infants.

Antineoplastic Agents↗