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Biomedical subjects

H Kodama

Publications and source records attributed to H Kodama.

At least 325 records · Page 18Linked to original sources
PubMed1994

In vivo binding characteristics of carbamazepine and carbamazepine 10, 11-epoxide to serum proteins in monotherapy adult patients.

The in vivo serum protein binding characteristics of carbamazepine and carbamazepine 10, 11-epoxide, which was the main metabolite of carbamazepine in plasma, were assessed in sera from 30 adult patients with epilepsy on carbamazepine monotherapy. The binding characteristics of each compound were analyzed according to the two-site binding model. Association constants to the high-affinity binding site on alpha 1-acid glycoprotein (AAG) were 0.053 l/mumol for carbamazepine and 0.013 l/mumol for carbamazepine 10, 11-epoxide. The maximum binding capacities for drug-AAG binding were 49.2 mumol/l for carbamazepine and 48.1 mumol/l for carbamazepine-10, 11-epoxide. The products of the association constant and binding capacity for the lower-affinity site (i.e., the linear component of albumin binding site) were 1.273 for carbamazepine and 0.525 for carbamazepine 10, 11-epoxide. Within the total concentration range of each compound investigated, the contribution of drug-AAG binding to the total serum binding was relatively larger than that of drug-albumin binding.

Adolescent↗
PubMed1994

Enhancement of gastric mucosal blood flow by beta-3 adrenergic agonists prevents indomethacin-induced antral ulcer in the rat.

Indomethacin (32 mg/kg s.c.) produced mainly antral ulcers in refed rats but almost exclusively corpus erosions in fasted rats. Subcutaneous doses of a nonselective beta (isoproterenol), a selective beta-2 (salbutamol) and selective beta-3 adrenergic agonists CBRL35135, (R*,R*)-(+/-)-methyl 4-[2-[2-hydroxy-2-(3-chlorophenyl)ethylamino]propyl] phenoxyacetate hydrobromide; CL316,243, disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxy-ethyl]- amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate; SR58611A, ethyl[(7S)-7-[(2R)-(2(3-chlorophenyl)-2-hydroxyethylamino]5,6,7, 8-tetrahydronaphthalen-2-yloxy]acetate hydrochloride) dose-dependently attenuated the antral ulcers, and their activities were in the order of BRL35135 (ED50 = 0.03 mg/kg) > CL316,243 (ED50 = 0.04 mg/kg) > SR58611A (ED50 = 0.2 mg/kg) > isoproterenol (ED50 = 0.4 mg/kg) > salbutamol (ED50 = 6 mg/kg). Whereas only isoproterenol, salbutamol and BRL35135 significantly attenuated the corpus erosions and reduced gastric acid secretion in pylorus-ligated rats. In in vitro, all the beta agonists enhanced the beating rate of guinea pig atria (beta-1 action) and inhibited spontaneous contractions of rat uterus (beta-2 action) and colon (beta-3 action). There was found a statistically significant correlation between the IC50 values of the drugs on the colon and ED50 values on the indomethacin-induced antral ulcers (r = 0.97). In addition, the beta agonists excepting salbutamol increased antral gastric mucosal blood flow in rats anesthetized with halothane, and the activities were arranged in the potency order of inhibiting colon motility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1994

The differential roles of sympathetic nerve activity in the pathogenesis of antral and corpus lesions induced by indomethacin in rats.

A s.c. dose (32 mg/kg) of indomethacin induced antral ulcers and corpus erosions in refed rats, but almost exclusively corpus erosions in fasted rats. In the refed rats the antral ulcers were not affected by a preganglionic splanchnicectomy, but were significantly attenuated by 6-hydroxydopamine (80 mg/kg i.p.), prazosin (32 mg/kg p.o.), yohimbine (32 mg/kg p.o.) or streptozotocin (80 mg/kg i.v.), whereas the corpus erosions were exaggerated by the latter three treatments. Blood analysis revealed that refeeding of fasted rats caused instant increases in plasma glucose and insulin levels and a subsequent gradual increase in plasma norepinephrine (NE). These plasma parameter changes were hardly affected by an indomethacin treatment. The NE response to refeeding was reversed by 6-hydroxydopamine which minimally affected the glucose and insulin responses. Splanchnicectomy changed none of these responses, although it almost completely depleted plasma epinephrine levels. The NE response was enhanced by yohimbine and prazosin, and the insulin response was enhanced by the former. Streptozotocin abolished the insulin response and reversed the NE response. It is concluded that hyperinsulinemia in response to refeeding induces NE release and results in an activation of alpha-1 and/or alpha-2 adrenergic receptors which plays a permissive role in the indomethacin-induced antral ulcer formation. Conversely, this series of events may play a protective role against the corpus erosion formation.

Animals↗
PubMed1994

[The treatments of manic-depressive psychosis].

There are a number of types of treatment for manic-depressive psychosis, including pharmacotherapy, psychotherapy, electroconvulsive therapy and continuous sleep treatment. The most generally used therapy for mania is pharmacotherapy, including the use of lithium and major tranquilizers. With regard to depression, the choice of treatment from among pharmacotherapy, psychotherapy and physiotherapy must be made on a case by case basis. In some cases, we have chosen electroconvulsive therapy, continuous sleep treatment or other forms of therapy. On admission, it is difficult to obtain the patient's consent for treatment, when he lacks insight about his condition. In this paper, we describe the choice of treatments, requirements for admission, and management of the structure of treatment.

Antidepressive Agents↗
PubMed1994

[Clinical results of breast conservation therapy; a radiotherapeutical viewpoint].

Between November 1987 and March 1993, 244 breasts in 243 patients underwent breast conserving therapy at Kyoto University Hospital. Clinically, there were 159 stage I and 85 stage II tumors. Pathological staging showed 216 stage I, 24 stage II, and 4 stage III tumors. All except 10 tumors were invasive ductal carcinomas. Eleven tumors were margin--positive by histopathological examinations. As surgical treatment, quadrantectomy or wide excision with complete axillary dissection was performed. Radiation therapy consisted of 50 Gy delivered to the whole breast by opposed tangential fields over 5 weeks using 60Co gamma rays. For patients with a positive margin, boost electron irradiation was given to a total of 10 Gy. We used the CT simulator for individualized optimization of the tangential fields. Prompt and accurate determination of the tangential portals was possible by using the simulator to determine various parameters, including beam angle and the head rotation angle. During follow-up for 2-66 months (median, 20 months), unrelated death occurred in 2 patients and distant metastases developed in 5 patients (bone 4, lung 1). However, neither local recurrence nor symptomatic radiation pneumonitis has occurred. The cumulative survival rate and the disease--free survival rate at five years were 95.2% and 91.8%, respectively. These promising clinical results of breast conservation therapy encourage further clinical trials.

Breast Neoplasms↗
PubMed1994

[Effect of lithium, carbamazepine, and setiptiline on diacylglycerol in rat brain ex vivo].

The effect of lithium on diacylglycerol (DAG), which is an intracellular second messenger, was compared with those of carbamazepine and setiptiline ex vivo through phosphatidylinositol turnover (PI response). Consequently, (1) PI response cycling by stimulation of norepinephrine participated in the alpha 1 receptor. (2) DAG accumulation in rat brain exhibited a biphasic pattern. (3) Lithium elevated DAG accumulation at 30 seconds after stimulation by norepinephrine. (4) Carbamazepine did not affect DAG accumulation. (5) Setiptiline decreased DAG accumulation at 30 minutes after stimulation by norepinephrine.

Animals↗
PubMed1994

Non-invasive ultrasonic urination sensor for ambulatory patient support.

It is estimated that, in Japan, several million people suffer from urinary incontinence caused by, e.g., cerebrovascular disease, abdominal operations, spinal-cord damage, etc. Urinary incontinence is said to be a 'hidden' disease. When no adequate treatment is given, a serious situation may arise for both patients and their family. A non-invasive and unconstrained ultrasonic sensor has been designed enabling patients to discretely manage urination. The major problem of the sensor is how to maintain a proper irradiation angle to obtain an anteroposterior bladder diameter which corresponds to the actual bladder volume. Many types of ultrasonic probe holders have been tested and promising results have been obtained. The most practical, but as yet experimental, method is a four-element ultrasonic sensor, embedded in a flat probe.

Adult↗
PubMed1994

[Thoracotomy for patients with bronchial asthma].

We discussed the perioperative management in three patients with bronchial asthma who underwent thoracotomy. The management was as follows: 1. theophylline and steroid agents were preoperatively given till wheezing disappeared, 2. just before surgery, theophylline or beta-stimulator and steroid agents were given, 3. during surgery, aminophylline and steroid agents were given and bronchodilative anesthetics were inhaled, 4. steroid agents were postoperatively applied sufficiently so that signs due to bronchial asthma don't appear. Preoperative respiratory conditions improved with disappearance or decrease of wheezing, and resection of giant bulla and lobectomies with radical mediastinal lymph node dissection were safely possible with no evidence of the side effects due to steroid administration. The perioperative sufficient suppression of airway-tract hyperactivity is very important for thoracotomy in patients with bronchial asthma.

Adult↗
PubMed1993

Characterization of inhibitory activities and binding mode of synthetic 6'-modified methyl N-acetyl-beta-lactosaminide toward rat liver CMP-D-Neu5Ac: D-galactoside-(2-->6)-alpha-D-sialyltransferase.

6'-Deoxy (12), 6'-thio (13), and 6'-O-tetrahydropyranosyl (14) analogues of methyl N-acetyl-beta-lactosaminide (3), were synthesized from lactose. NOE experiments proved that they adopt the same conformation as that of 3. Inhibition studies using these synthetic analogues, including the disulfide dimer 15, toward (2-->6)-alpha-sialytransferase (EC 2.4.99.1) revealed that the 6'-deoxy analogue 12 had remarkable inhibitory activity as the first acceptor-analogue inhibitor for this enzyme. It is noteworthy that the disulfide 15 also behaves as an inhibitor. The results indicated that chemical modification at the 6'-position of 3 did not cause much decrease in the binding affinity to the sialytransferase. Further, a novel possibility that the acceptor and the acceptor-analogue inhibitor can bind simultaneously to the sialytransferase was proposed based on the inhibition studies with 12 and CMP.

Amino Sugars↗
PubMed1993

Central nervous system involvement of adult T-cell leukemia-lymphoma with multinucleated giant cells in the brain, skin, and kidney.

BACKGROUND: A case of central nervous system (CNS) involvement in a patient with adult T-cell leukemia-lymphoma (ATLL) with multinucleated giant cells (MNGC) is presented. METHODS: A 48-year-old woman with human T-lymphotropic virus type I (HTLV-I) antibody titer had multiple focal brain symptoms and skin eruptions without lymphadenopathy, hepatosplenomegaly, or increased abnormal lymphocytes in the peripheral blood. No spastic paraparesis of the lower limbs was found. The encephalopathy was progressive, and she died 5 months later despite repeated intrathecal administration of methotrexate, cytosine arabinoside, and prednisolone and monthly systemic chemotherapy with doxorubicin, cyclophosphamide, vincristine, and prednisolone. RESULTS: Postmortem examinations identified unusual ATLL lesions composed of marked infiltrations of atypical mononuclear cells and bizarre MNGC with histiocytic granulomatous reactions in the leptomeninges, brain tissues along the Virchow-Robin spaces, skin, and kidney. Immunohistochemical stains confirmed the T-cell nature of such mononuclear cells and partially T-cell and partially macrophage nature of the MNGC, although no evidence of HTLV-I expression was found. CONCLUSIONS: ATLL presenting with CNS symptoms is rare. It was assumed that the direct cytopathic effects of HTLV-I were responsible for the formation of the MNGC after considering the similarity with MNGC in encephalopathy caused by the human immunodeficiency virus.

Brain↗
PubMed1993

In vivo determinations of carbamazepine and carbamazepine-10, 11-epoxide binding parameters to serum proteins in monotherapy patients.

The in vivo serum protein binding parameters of carbamazepine (CBZ) and carbamazepine-10, 11-epoxide (CBZ-E), which was the main metabolite of CBZ in plasma, were determined in sera from 27 patients on CBZ monotherapy. Based on the results by recent studies, the authors assumed that CBZ and CBZ-E binding to serum proteins were composed of specific binding sites on alpha 1-acid glycoprotein (AAG) and albumin. Therefore, the authors determined the binding parameters of each compound by specific binding equation for two proteins. Association constants for drug-AAG binding were .071 L/mumol for CBZ and .016 L/mumol for CBZ-E. Conversely, those for drug-albumin binding were .00052 L/mumol for CBZ and .00072 L/mumol for CBZ-E. Within the investigated total concentration ranges in each compound, the AAG binding contributes largely to the drug-serum protein interactions. Furthermore, our results indicate that the albumin binding contributes to the nonsaturable serum protein binding of these compounds in the therapeutic range.

Adolescent↗
PubMed1993

Transient recruitment of osteoclasts and expression of their function in osteopetrotic (op/op) mice by a single injection of macrophage colony-stimulating factor.

Severe deficiency of osteoclasts in op/op mice, caused by the absence of functional macrophage colony-stimulating factor (M-CSF), is cured by daily injections of purified recombinant human M-CSF (rhM-CSF). In this study, we found that a single injection of 5 micrograms rhM-CSF is enough for recruitment of osteoclasts in mutant mice. Osteoclast number increased during the period between 2 and 4 days after the single rhM-CSF injection. When YM175, a new derivative of bisphosphonate, was administered to the mice 4 days after rhM-CSF injection or later, osteoclasts disappeared by 3 days after YM175 administration. However, a significant number of osteoclasts were detected even at 3 days after YM175 administration when YM175 was administered 3 days after rhM-CSF injection or earlier. These results indicate that YM175 is cytotoxic only to functioning osteoclasts and that recruitment of osteoclasts is finished 4 days after a single rhM-CSF injection. The osteoclasts actively resorbed bone trabeculae for a prolonged period, demonstrating that M-CSF is not requisite for the functioning of mature osteoclasts.

Animals↗
PubMed1993

Identification of new cystathionine mono-oxo acids, S-(3-oxo-3-carboxy-n-propyl) cysteine and S-(2-oxo-2-carboxyethyl) homocysteine, in the urine of a patient with cystathioninuria.

Novel cystathionine mono-oxo acids, S-(3-oxo-3-carboxy-n-propyl) cysteine and S-(2-oxo-2-carboxyethyl) homocysteine, and cyclic amino acid, cystathionine ketimine, have been detected in the urine of a patient with cystathioninuria using liquid chromatography-mass spectrometry with an atmospheric pressure ionization interface system and an amino acid analyzer. To determine these cystathionine mono-oxo acids and cystathionine ketimine we took advantage of the selective absorbance at 380 nm of the phenylisothiocyanate-ketimine interaction product. The total concentrations of these compounds found in the urine samples of a cystathioninuric patient and six healthy subjects were respectively 3611.3 and 148.4 micrograms +/- 35.9/g of creatinine. The cystathioninuric patient excreted 20 times more cystathionine mono-oxo acids in the urine than healthy subjects.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

In vivo binding characteristics of carbamazepine and carbamazepine-10,11-epoxide to serum proteins in paediatric patients with epilepsy.

The in vivo serum protein binding characteristics of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) were assessed in sera from 23 paediatric patients on CBZ monotherapy. We assumed that CBZ and CBZ-E binding to serum proteins comprised specific binding sites on alpha 1-acid glycoprotein (AAG) and non-specific binding sites on serum albumin. Therefore, the binding characteristics of each compound were analysed according to specific and nonspecific binding equations. Association constants for drug-AAG binding were 0.096 l.mumol-1 for CBZ and 0.023 l.mumol-1 for CBZ-E. Within the concentration ranges investigated the specific binding of each compound contributes to the drug-serum protein interactions. Age did not show a significant correlation with the serum unbound fraction of each compound.

Adolescent↗