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Biomedical subjects

Y Kitano

Publications and source records attributed to Y Kitano.

At least 127 records · Page 7Linked to original sources

General pharmacological profile of the new cognition-enhancing agent nefiracetam.

The general pharmacological properties of a novel cognition-enhancing agent, nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) were investigated, and the following results were obtained. 1. Central nervous system: Nefiracetam showed depressant activities (such as ataxia) on general behavior (mice), and inhibited spontaneous locomotor activity, rota-rod and traction performances (mice) and polysynaptic potential of the spinal reflex (rats), and potentiated pentobarbital anesthesia (mice). The drug inhibited electroshock-induced seizure at relatively low doses, but did not affect chemoshock-induced seizure (mice). Nefiracetam failed to show analgesic activity in the tail pinch test, but inhibited the acetic acid-induced writhing syndrome (mice). An inhibitory pattern in the electroencephalogram was observed (cats). Nefiracetam had little or no effect on body temperature (rats). 2. Respiratory and cardiovascular systems: Nefiracetam induced transient decreases in blood pressure, left ventricular pressure and LV dp/dt max at higher doses (dogs). 3. Autonomic nervous system: Nefiracetam had no influence on pupil size (rabbits). The drug induced no significant effect on the pressor response to norepinephrine or depressor response to acetylcholine, but inhibited the contractile response of the nictitating membrane to preganglionic cervical sympathetic nerve stimulation at the highest dose (dogs). 4. Gastrointestinal system: Nefiracetam inhibited gastrointestinal propulsion (mice), gastric emptying rate and gastric secretion (rats) at higher doses. Nefiracetam produced no apparent damage in the gastric mucosa, and had no effect on bile secretion (rats). 5. Isolated smooth muscle: Nefiracetam had no effect on the resting tonus of isolated ileum, whereas it inhibited the contractile response to acetylcholine, histamine, serotonin, nicotine and BaCl2 at higher concentrations (guinea pigs). Nefiracetam had no effect on the resting tonus or the serotonin-induced contraction of stomach fundus (rats). The drug had no effect on the resting tonus or the norepinephrine-induced contraction of vas deferens, but tended to inhibit the contraction induced by nerve stimulation (guinea pigs). Nefiracetam had little or no effect on the resting tonus or oxytocin-induced contraction of virgin uterus, or on spontaneous contraction of pregnant uterus (rats). Nefiracetam did not affect the resting tonus of trachea, whereas it inhibited isoproterenol-induced relaxation at the highest concentration (guinea pigs). Nefiracetam had no chronotropic effect in isolated atria, but showed a slight negative inotropic effect at the highest concentration (guinea pigs). 6. Miscellaneous: Nefiracetam slightly decreased urinary volume, whereas it did not affect urinary electrolyte excretion (rats).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Long-term ciclosporin treatment in children with steroid-dependent nephrotic syndrome.

We report the effect of 18-month ciclosporin (CS) treatment in 19 children with steroid-dependent frequently relapsing nephrotic syndrome. CS was started at 3-5 mg/kg per day after remission with steroid therapy, was adjusted to maintain a trough blood level of between 200 and 600 ng/ml and was administered for 6 months (high-dose CS). Then, the dosage of CS was decreased and 2.5 mg/kg per day was administered for the subsequent 12 months (low-dose CS). Only 2 patients had relapses during the initial 6 months of CS therapy. Eight patients had infrequent relapses, 4 had frequent relapses and 7 had no relapses during the 12 months of low-dose CS. Not only did continuation of CS at a lower dosage decrease the relapse rate, it also reduced steroid toxicity, allowed increased growth in 16 of the 19 patients and also decreased obesity scores in 12 of these patients. All of the side-effects that occurred during the 18-month period of CS treatment were reversible and none was serious enough to necessitate discontinuation of therapy. Our 18-month CS treatment was helpful in preventing relapses and reducing steroid toxicity in children with steroid-dependent frequently relapsing nephrotic syndrome.

Adolescent↗

Giant thymolipoma in a child.

Thymolipoma, a rare benign mediastinal tumor, was found in a 6-year-old boy. Computed tomography scans, magnetic resonance imaging, and angiography of internal thoracic artery confirmed the diagnosis before surgery.

Adipose Tissue↗

Comprehensive planning of operative strategy for separation of ischiopagus tripus twins with particular reference to quality of life.

A 27-year-old mother was diagnosed by prenatal ultrasonography as having triplets at gestational age 32 weeks. Following cesarean section at 37 weeks, a pair of female babies were noted for the first time to be joined by a common pelvis with three lower limbs. They had separate upper gastrointestinal tracts, which joined in the distal ileum, leading to a common colon, rectum, and a single anus. Each twin had a functioning kidney, with a single ureter leading to a common bladder. A common urethra originating from the bladder neck ran into the urogenital sinus of one baby. Prior to the surgical separation, placement of four tissue expanders and 20 pneumoperitoneums were performed, in order to stretch the parietes for easier approximation of the wound edges. At 13 months of age, separation was performed, requiring 17 hours. The skin and musculature from the conjoined third leg was used as a fillet for abdominal wall closure in each patient. One infant was given the distal half of the colon and an entire anus with a temporary jejunostomy, and the right half of the bladder with the urethra. The other infant was given the proximal half of the colon with a permanent colostomy, and the left half of the bladder with permanent cystostomy using appendiceal pedicle graft (Mitrofanoff's procedure). This is the 10th case of surgical separation in ischiopagus tripus twins reported in the literature, and the seventh successful separation with both patients alive.

Female↗

Suppression of cytotoxic T-lymphocyte activity during human pregnancy.

We have investigated alterations in Epstein-Barr virus antigen specific cytotoxic T-lymphocyte (EBV-CTL) activity during human pregnancy. EBV-CTL activity was determined by a modified EBV induced B-cell focus regression assay and was expressed in terms of a regression index (IR50), i.e. the initial cell concentration required to achieve a 50%-incidence of regression in EBV-infected cell culture. Increased values of IR50 indicate the suppression of EBV-CTL activity. In 113 human female T-cell leukemia type-I (HTLV-I) non-carriers, the IR50 values (mean +/- S.E.) in non-pregnant, pregnant (the first trimester, second trimester and third trimester of pregnancy) and puerperal women were 10.6 +/- 1.4, 16.1 +/- 1.1 (20.1 +/- 2.0, 14.8 +/- 2.0, 14.6 +/- 1.6), and 12.1 +/- 1.9 respectively. Among HTLV-I carriers, the IR50 values (mean +/- S.E.) were likewise 34.6 +/- 8.0, 87.4 +/- 5.2 (101.7 +/- 6.3, 88.3 +/- 8.4 and 79.5 +/- 9.2) and 39.2 +/- 7.1 respectively. This data demonstrate: 1) EBV-CTL activity was suppressed during pregnancy (P < 0.05), especially in the first trimester (P = 0.0003). 2). In HTLV-I carriers, this suppression was shown in the first trimester (P = 0.0002), in the second trimester (P = 0.0002) and in the third trimester of pregnancy (P = 0.0014) and 3). One month after delivery, this suppression had returned to the non-pregnant level in both HTLV-I non-carriers and HTLV-I carriers. Pregnancy therefore has a suppressive effect on antigen specific cytotoxic T-lymphocyte activity and this effect is amplified in HTLV-I carriers.

Adult↗

Expression of basement membrane components in skin equivalents--influence of dermal fibroblasts.

We have made a skin equivalent constructed of fibroblasts embedded in a type I collagen, with an overlying stratified keratinocyte epithelium to examine formation of the basement membrane. We assessed the influence of the existence and species of fibroblasts in the collagen gel. Cultured human keratinocytes were well attached to the dermal equivalent. Plating efficiency was not clearly different among several types of gel. On the control and mouse fibroblast gel, sheet formation was delayed and epithelial stratification on the human fibroblast gel was more remarkable than on the control gel. On the human fibroblast gel, we observed the expression of basement membrane components (bulbous phemphigoid antigen, laminin, type IV collagen and fibronectin) between the sheet of cultured keratinocytes and the human fibroblast gel earlier than those on the control gel and mouse fibroblast gel. Type VIII collagen was not observed in any of the models at 4 weeks.

Adolescent↗

Cutaneous eruptions induced by granulocyte colony-stimulating factor in two cases of acute myelogenous leukemia.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induced cutaneous eruptions in two cases of acute myelogenous leukemia. In both cases, the eruptions appeared during rhG-CSF therapy for neutropenia induced by the remission-induction chemotherapy and disappeared rapidly after the discontinuance of rhG-CSF therapy. Histopathology of those eruptions revealed dermal cell infiltrations consisting of some neutrophils and atypical cells. It was interesting that, although there were no leukemic cells in the peripheral blood or bone marrow, eruptions containing many leukemic cells appeared. The mechanism of the appearance of these eruptions was unclear, but it was considered that a few leukemic cells might have responded to rhG-CSF and proliferated in the skin.

Adult↗

Immunohistologic localization of ras p21 in normal, hyperplastic, and neoplastic epidermis.

BACKGROUND: Ras p21, a ras oncogene product, plays an important role in tumorigenesis, proliferation, and differentiation in various tissues and cells. METHODS: Using a monoclonal antibody raised against ras p21 (RASK 4), localization of ras p21 in normal epidermis and involved epidermis of various skin diseases was examined immunohistologically. RESULTS: Ras p21 was not present in basal cells of normal epidermis or basaloid cells of basal cell epithelioma but was found almost evenly in the cytoplasm of squamous cells and granular cells. This suggests that ras p21 is concerned with differentiation of epidermal cells. The mode of distribution of ras p21 differed from one cell to another in epidermal cells that turned to malignancy. The distribution was uneven and irregular in the tumorous region on the whole. CONCLUSIONS: This result might possibly represent abnormal differentiation of epidermal cells that turned to malignancy, deviating from the regular mode of the distribution of ras p21, which is necessary for normal differentiation.

Epidermis↗

Synthesis, structure and antitumor activity of a new water-soluble platinum complex, (1R,2R-cyclohexanediamine-N,N')[2-hydroxy-4-oxo-2-pentenoato(2-)-O2] platinum(II).

The reaction of dihydroxo(1R,2R-cyclohexanediamine)platinum(II) with 2,4-dioxopentanoic acid gave a water-soluble complex, (1R,2R-cyclohexanediamine-N,N')[2-hydroxy-4-oxo-2-pentenoato (2-)-O2] platinum(II). The structure of the complex was determined by X-ray crystal analysis. The data indicated a chelation of the acetylacetonato part of 2,4-dioxo-pentanoic acid to platinum(II). The complex showed moderate antitumor activity against murine leukemia L1210 in mice (T/C = 195% at a dose of 200 mg/kg) and high activity against cisplatin-resistant L1210 leukemia (T/C = 275% at a dose of 25 mg/kg).

Animals↗

[Central effects of iohexol and iopamidol, non-ionic contrast media].

Central effects of intravenously (i.v.)-administered iohexol were compared with those of iopamidol in a series of tests. Mannitol was used as a reference. As assayed by the primary screening test based on Irwin's method, i.v. administration of mannitol resulted in a score of 0 in ddY mice and a score of 0.6 in ICR mice in the startle response. These results were not different from the data of both iohexol and iopamidol. Iopamidol at a dose of 1750 mgI/kg produced an inhibitory effect on the spontaneous locomotor activity. Iohexol at a dose of 7000 mgI/kg potentiated the duration of thiopental-induced narcosis. Hypothermia was caused by high doses of both iohexol and iopamidol. Electric stimulus increased the mortality of mice pretreated with high doses of iohexol and iopamidol. Both drugs had no notable activities in the anticonvulsant, electroencephalic, muscle relaxant and antinociceptive tests. These results indicate that both iohexol and iopamidol do not necessarily possess a similar pharmacological action. Judging from the LD50 of approximately 15000 mgI/kg for both drugs, they seem unlikely to have a specific pharmacological action on the central nervous system.

Animals↗

Clinical application of low reactive level laser therapy (LLLT) for atopic dermatitis.

Patients with atopic dermatitis (AD) were treated with diode low reactive level laser therapy (LLLT), and the following results were obtained. 1) Itchy sensation decreased in 79 of 112 cases (71%) after this therapy. 2) Skin eruptions improved in 69 of 112 cases (62%). 3) There were no side effects during and after LLLT. 4) Major histocompatibility complex (MHC) class II antigen and inter-cellular adhesion molecule (ICAM)-1 expression on epidermal cells decreased after the therapy. 5) The number of CD1 positive epidermal dendritic cells did not significantly change before and after LLLT.

Adolescent↗

Glomerular anionic sites in minimal change nephrotic syndrome and focal segmental glomerulosclerosis.

In order to examine the changes in charge of the glomerular basement membrane (GBM) in nephrotic syndrome, anionic sites in the GBM were studied quantitatively. Renal biopsy specimens were obtained from 5 children with minimal change nephrotic syndrome (MCNS) and 5 with nephrotic syndrome and focal segmental glomerulosclerosis (FSGS). Biopsy specimens obtained from 5 patients without proteinuria were also examined as controls. Anionic sites were stained with polyethyleneimine (PEI) as a cationic probe and were examined by electron microscopy. The number of PEI-labeled anionic sites in the lamina rara externa of the GBM was counted in the glomerular capillary region and in the paramesangial region separately. The number of anionic sites per 1000-nm GBM was 20.9 +/- 0.6 in the capillary and 21.2 +/- 0.7 in the paramesangium in controls. They were significantly decreased in MCNS (16.5 +/- 0.7 in the capillary and 16.9 +/- 0.5 in the paramesangium, p < 0.001) and in FSGS (16.7 +/- 0.7 in the capillary and 17.0 +/- 0.6 in the paramesangium, p < 0.001). The decrease of anionic sites suggests a defect in the charge-selective barrier in the lamina rara externa of the GBM in MCNS and FSGS, and this defect both in the capillary and in the paramesangium may be responsible for the proteinuria in these two conditions.

Anions↗

Effective reduction of plasma LDL levels by LDL apheresis in familial defective apolipoprotein B-100.

The clinical response to long-term reduction of the plasma LDL cholesterol concentration was studied in a man with severe coronary artery disease associated with familial defective apolipoprotein B-100 (FDB). Plasma exchange repeated at 2-week intervals, combined with lipid-lowering drugs, led to remission of angina and improved exercise test performance. A similar clinical response was achieved after LDL apheresis with dextran sulphate columns repeated once every 2 weeks in combination with drug treatment. The reduction in plasma LDL cholesterol level brought about by LDL apheresis was at least as marked in the FDB patient as in 5 patients with familial hypercholesterolaemia. We conclude that FDB patients with coronary artery disease may derive clinical benefit from prolonged reduction of their plasma cholesterol levels and that LDL containing apo B-100 in which arginine at position 3500 is replaced by glutamine is removed from plasma by dextran sulphate columns as efficiently as is normal LDL.

Apolipoprotein B-100↗

Advantages and pitfalls of amnion inversion repair for the treatment of large unruptured omphalocele: results of 22 cases.

This is a report of our experience with 22 cases of large unruptured omphaloceles treated by amnion inversion during the period 1973 through 1990. The method is characterized by three stages: (1) a silastic sheet is sutured directly to the skin around the amniotic membrane, under local anaesthesia, without dissection between the skin and the amnion; (2) the reduction of herniated viscera into the abdominal cavity is achieved by squeezing the sheeting using a specially modified stapler; and (3) the amniotic membrane is preserved intact, and inverted into the abdominal cavity at the time of abdominal wall closure. Of the 22 infants, 19 survived with satisfactory results. Two patients died of multiple associated anomalies, and the remaining patient died of sepsis arising at the time of the final abdominal closure. This procedure has proved to be effective and safe for high-risk patients with congenital heart diseases, anal atresia, tracheoesophageal fistula, or bronchial stenosis and prematurity. The practical aspects of the procedure, as well as its advantages and pitfalls, are illustrated.

Amnion↗