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Biomedical subjects

M Miyashita

Publications and source records attributed to M Miyashita.

At least 19 recordsLinked to original sources

Synthesis and antiulcer activity of N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with a potent mucosal protective activity.

As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal protective activities. A QSAR study showed that the most favorable N-substituents were electron-donating straight-chain alkyl groups of short length such as ethyl group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were selected as candidates for further study.

Animals

Determination and validity of critical velocity as an index of swimming performance in the competitive swimmer.

The purpose of this investigation was to test whether the concept of critical power used in previous studies could be applied to the field of competitive swimming as critical swimming velocity (vcrit). The vcrit, defined as the swimming velocity over a very long period of time without exhaustion, was expressed as the slope of a straight line between swimming distance (dlim) at each speed (with six predetermined speeds) and the duration (tlim). Nine trained college swimmers underwent tests in a swimming flume to measure vcrit at those velocities until the onset of fatigue. A regression analysis of dlim on tlim calculated for each swimmer showed linear relationships (r2 greater than 0.998, P less than 0.01), and the slope coefficient signifying vcrit ranged from 1.062 to 1.262 m.s-1 with a mean of 1.166 (SD 0.052) m.s-1. Maximal oxygen consumption (VO2max), oxygen consumption (VO2) at anaerobic threshold, and the swimming also velocity at the onset of blood lactate accumulation (vOBLA) were also determined during the incremental swimming test. The vcrit showed significant positive correlations with VO2 at anaerobic threshold (r = 0.818, P less than 0.01), vOBLA (r = 0.949, P less than 0.01) and mean velocity of 400 m freestyle (r = 0.864, P less than 0.01). These data suggested that vcrit could be adopted as an index of endurance performance in competitive swimmers.

Adolescent

Cardiovascular reflexes during sustained handgrip exercise: role of muscle fibre composition, potassium and lactate.

Six healthy men performed sustained static handgrip exercise for 2 min at 40% maximal voluntary contraction followed by a 6-min recovery period. Heart rate (fc), arterial blood pressures, and forearm blood flow were measured during rest, exercise, and recovery. Potassium ([K+]) and lactate concentrations in blood from a deep forearm vein were analysed at rest and during recovery. Mean arterial pressure (MAP) and fc declined immediately after exercise and had returned to control levels about 2 min into recovery. The time course of the changes in MAP observed during recovery closely paralleled the changes in [K+] (r = 0.800, P < 0.01), whereas the lactate concentration remained elevated throughout the recovery period. The close relationship between MAP and [K+] was also confirmed by experiments in which a 3-min arterial occlusion period was applied during recovery to the exercised arm by an upper arm cuff. The arterial occlusion affected MAP while fc recovered at almost the same rate as in the control experiment. Muscle biopsies were taken from the brachioradialis muscle and analysed for fibre composition and capillary supply. The MAP at the end of static contraction and the [K+] appearing in the effluent blood immediately after contraction were positively correlated to the relative content of fast twitch (% FT) fibres (r = 0.886 for MAP vs % FT fibres, P < 0.05 and r = 0.878 for [K+] vs % FT fibres, P < 0.05). Capillary to fibre ratio showed an inverse correlation to % FT fibres (r = -0.979, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cutaneous T-cell lymphoma associated with granular lymphocytic leukemia in its terminal stage.

A 79-year-old woman had cutaneous T cell lymphoma. After a long clinical course, numerous tumors and an enormous increase in peripheral granular lymphocytes without lymphadenopathy developed suddenly. Surface markers and DNA analysis of the tumor cells from her skin and peripheral blood and electron microscopic examination suggested that granular lymphocytic leukemia had developed in the terminal stage of cutaneous T cell lymphoma. To our knowledge this association has not been reported previously.

Acute Disease

Simple in vivo bioassay without radioisotopes for recombinant human erythropoietins.

A simple in vivo bioassay suitable for routine testing of quality control of recombinant human erythropoietin (rHuEPO) analogues was developed. The assay took four days, normal mice were used and radioactive compounds were not needed. EPO activity was measured by the increased number of some part of reticulocytes which increased specifically and dose-dependently by the injection of rHuEPO. They were considered to be mostly immature reticulocytes and were counted as the residual particles from blood cells after treatment with a hemolysing reagent. These particles could be counted by conventional automated microcell counters. The assay procedure was simple and easy. The sensitivity, reliability and reproducibility of this method were acceptable for routine in vivo bioassay of rHuEPOs. This method was economical, and can be used instead of the existing bioassays for rHuEPOs.

Animals

In vivo biological activities of recombinant human erythropoietin analogues produced by CHO cells, BHK cells and C127 cells.

The in vivo biological activity of four pharmaceutical preparations of recombinant human erythropoietin was compared. Two of the erythropoietins were produced by Chinese hamster ovary cells, CHO-K1, and the others were produced by mouse mammary cells, C127, and baby hamster kidney cells, BHK-21. The activities of the analogues were estimated by a simple cell counting method with conventional automated microcell counters. The amounts of these analogues gave straight logarithmic dose-response curves when plotted against the count of particles resistant to hemolysing reagent, which particles were mostly immature reticulocytes. The lines from the four analogues were parallel to each other. The relative activities of these analogues were 1.02, 1.19 and 1.21 when one of the analogues was arbitrarily used as the standard. These differences in the extent of the activity were not significant. Thus, the four recombinant human erythropoietin analogues, produced by four different mammalian cell lines, expressed the same biological potencies in vivo corresponding to their units, and the units used up to now by the manufacturers are equivalent. These results also draw the conclusion that the new simple in vivo bioassay can replace the existing accepted assay methods.

Animals

A simple method for determining critical speed as swimming fatigue threshold in competitive swimming.

The purpose of this investigation was to determine whether the concept of the critical power could be applied to competitive swimming by using critical swimming speed (CS) as determined both in the swimming flume (CS-flume) and in the normal swimming pool (CS-pool) and whether CS could be utilized as a practical index for assessing a swimmer's endurance performance. CS defined as the swimming speed which could be theoretically maintained continuously without exhaustion was expressed as the slope of a regression line between swimming distance (D) and its duration (T) obtained at various swimming speeds. Eight highly trained swimmers were instructed to swim until onset of fatigue at four predetermined swimming speed levels in the swimming flume and at maximal effort over four different swimming distances in the swimming pool. In the results of CS-flume and CS-pool, the regression relations between D and T were expressed in the general form, D = a+b x T, with r2 being higher than 0.998 (p less than 0.01), respectively. These results both from the flume and the pool indicated extremely good linearity. Furthermore, maximal oxygen uptake (VO2max) during the incremental exercise test, swimming speed corresponding 4 mM of blood lactate concentration (V-OBLA) and mean velocity in the 400 m freestyle (V-400) were measured on each subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

A mathematical model for the self-organization of orientation columns in visual cortex.

The visual cortex contains regular arrangements of neurons responding to specific types of visual stimulation, such as ocular dominance columns and orientation columns. These columnar structures can be considered as the functional architecture for early visual information processing. The model of activity-dependent self-organization reported here demonstrates that both response properties of neurons to visual stimulation and the related columnar organization can be reproduced based on the competition between ON- and OFF-center inputs. Furthermore, the relationships between anatomical neural organization and its physiological response properties are clarified. This model also predicts new columnar organization linking the symmetry of receptive fields, which has never been examined. A hypercolumn, composed of orientation columns and symmetry columns, is suggested to serve as a basis for the representation of visual information.

Animals

Developmental changes in gastric mucus gel thickness: responsiveness to 16,16-dimethyl prostaglandin E2 and mucosal protection in the rat.

The gastric mucosa of newborn rats is sensitive to the damaging effects of acid and ethanol. We measured gastric mucus gel thickness in newborn, suckling, and weaned rats by inversion microscopic observation. The thickness in newborn rats was 52.2 +/- 6.7 microns and increased with age, reaching 96.8 +/- 5.6 microns in 8-wk-old rats (p less than 0.001). Oral administration of 16,16-dimethyl prostaglandin E2 at concentrations of 10 and 100 micrograms/kg body weight increased mucus thickness in 8-wk-old rats but had no effect in 1-wk-old rats. We also assessed the effect of 16,16-dimethyl prostaglandin E2 on the prevention of gastric mucosal damage induced by ethanol. Oral 16,16-dimethyl prostaglandin E2 reduced damage in 8-wk-old rats, but there was no effect in 1-wk-old rats. These data suggest that the susceptibility of newborn rats to gastric mucosal injury may be related to the relative thinness of the gastric mucus gel layer and the failure of prostaglandins to increase the mucus gel layer thickness.

16,16-Dimethylprostaglandin E2

Enterovesical fistula caused by inflammatory bowel diseases.

Enterovesical fistula caused by inflammatory bowel diseases is a rare disorder. Two male patients with recurrent cystitis had sigmoid colon diverticulitis causing enterovesical fistula. One female patient with Crohn's disease developed enterovesical fistula with abdominal and urinary symptoms. In each patient, a barium enema revealed causative bowel diseases. The precise diagnosis of enterovesical fistula was made either by cystography or cystoscopy. One-stage resection of the inflamed bowel with fistula and affected the bladder wall was proved to be an effective treatment for these three patients, while a long term follow up is specifically necessary in the patient with Crohn's disease.

Adult

Validity of critical velocity as swimming fatigue threshold in the competitive swimmer.

The purpose of this investigation was to determine whether the critical velocity (CV) as the swimming speed which can be theoretically maintained for a very long time without exhaustion could be applied to estimate the swimmer's endurance performance. CV was based on the concept of critical power originality established by Monod and Scherrer (1965) and extended by Moritani et al. (1981), and expressed as the slope of a regression line between swimming distance (D) at each velocity and its sustained time (T). Seventeen highly trained swimmers were instructed to swim the four different swimming distances (50 m, 100 m, 200 m and 400 m) at maximal effort using the swimming pool. In the results of CV, the regression relations between D and T were expressed in the general form, D = a + bxT, with r2 showing higher than 0.997 (p less than 0.001). These results indicate extremely good lineality. Furthermore, VO2max during incremental exercise test, swimming speed corresponding 4 mM of blood lactate concentration (V-OBLA) and mean velocity in the 200 m and 400 m freestyle (V-200 and V-400) were measured on nine subjects. Significant correlations were found between CV and V-OBLA (r = 0.862, p less than 0.01), CV and V-200 (r = 0.781, p less than 0.01), CV and V-400 (r = 0.999, p less than 0.001), V-OBLA and V-400 (r = 0.869, p less than 0.01) and V-200 and V-400 (r = 0.776, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Competitive Behavior

Localized proliferative effect of preadipocytes on cultured human epidermal keratinocytes.

The effect of preadipocytes (ST 13) on cultured normal human epidermal keratinocytes (NHEK) was investigated. The growth of NHEK was accelerated with co-cultured ST 13 cells. This stimulative effect must have been localized around viable ST 13 cells, because neither the medium nor the surface conditioned by ST 13 or the ST 13 cell fragments showed any promotion of NHEK growth, and NHEK showed a compact, paving-like arrangement only when they were attached directly to ST 13 cells. It became clear that these compactly arranged keratinocytes have an active proliferative ability, since their nuclei showed a marked uptake of 5-bromodeoxyuridine (BrdU) and they were positively stained with anticytokeratin 37, a monoclonal antibody against the basal epidermis. Under electron microscopy, ST 13 preadipocytes were closely connected with NHEK. These results, together with those of previous reports, suggest that the localized proliferative effect of ST 13 cells on NHEK is due to cell-to-cell contact.

Adipose Tissue

[A case of hydropneumothorax].

A 19-year-old girl was admitted because of fever, cough and suddenly occurred chest pain. One month earlier she had experienced a fever and cough, then she had felt sudden chest pain 2 weeks prior to the admission. A chest X-ray showed left pneumothorax and massive pleural effusion. A diagnosis of hydropneumothorax was made. In spite of the chest tube drainage, reexpansion of the lung was unsatisfactory. Thoracotomy and decortication of the lung resulted in good reexpansion. Histological finding revealed pleuritis due to bacterial peribronchial infection, which resulted in hydropneumothorax, namely an abscess ruptured to the pleural cavity.

Adult

The ventilatory threshold gives maximal lactate steady state.

The purpose of this study was to examine whether the ventilatory threshold (Thv) would give the maximal lactate steady state ([la]ss, max), which was defined as the highest work rate (W) attained by a subject without a progressive increase in blood lactate concentration [la]b at constant intensity exercise. Firstly, 8 healthy men repeated ramp-work tests (20 W.min-1) on an electrically braked cycle ergometer on different days. During the tests, alveolar gas exchange was measured breath-by-breath, and the W at Thv (WThv) was determined. The results of two-way ANOVA showed that the coefficient of variation of a single WThv determination was 2.6%. Secondly, 13 men performed 30-min exercise at WThv (Thv trial) and at 4.9% above WThv (Thv + trial), which corresponded to the 95% confidence interval of the single determination. The [la]b was measured at 15 and 30 min from the onset of exercise. The [la]b at 15 min (3.15 mmol.l-1, SEM 0.14) and at 30 min (2.95 mmol.l-1, SEM 0.18) were not significantly different in Thv trial. However, the [la]b of Thv + trial significantly increased (P less than 0.05) from 15 min (3.62 mmol.l-1, SEM 0.36) to 30 min (3.91 mmol.l-1, SEM 0.40). These results indicate that Thv gives the [la]ss, max, at which one can perform sustained exercise without continuous [la]b accumulation.

Adult

Hierarchical regulation of interleukin production: induction of interleukin 6 (IL-6) production from bone marrow cells and marrow stromal cells by interleukin 3 (IL-3).

IL-3 stimulated the production of IL-6 from a bone marrow-adherent cell population, macrophages and from hemopoietic supportive stromal cell lines. It also induced IL-6 production from a stem cell-enriched population of bone marrow cells which did not produce IL-6 without stimulation. In contrast, stimulation with IL-6 of all the cell populations studied in the present experiments did not induce IL-3 production. These results indicate a hierarchical network in the regulation of interleukin production, and existence of a positive feedback mechanism; IL-3 induces IL-6 production which in turn stimulates stem cells into cycle and induces stem cells to respond to IL-3.

Animals

Effects of enriched lactate solution (ELS) for resuscitation after burn injury.

Full skin thickness burns covering 35 per cent of the total body surface of rabbits were followed by measurements of Na-K ATPase and arterial blood gas analyses, before and after the burn injury. Studies of the effects of intravenous fluids with different compositions showed that the active transport of the cell membrane was depressed in vivo immediately after a burn injury, mainly due to acidosis. This phenomenon was not completely corrected by the Baxter formula which uses conventional lactated Ringer's solution. However, an improvement was observed in those groups given the 'Enriched Lactate Solution' (ELS) containing large quantities of lactate as the base source. These results suggest that ELS, which positively corrected acidosis in accordance with its concentration, is very effective and more appropriate than the conventional lactated Ringer's solution for early burn resuscitation.

Acidosis

Detection of direct mutagenicity of cigarette smoke condensate in mammalian cells.

Mutagenicity of cigarette smoke condensate (CSC) and the acidic, basic and neutral fractions of CSC was examined in the AL hybrid cell, a Chinese hamster ovary cell containing one human chromosome 11. Since the human chromosome 11 is not necessary for survival of the AL cells, mutations involving large deletions and chromosomal loss by non-dysjunction are non-lethal events that are detectable by loss of human cell surface antigens (a1, a2 and a3) encoded by genes on chromosome 11p (a1 and a3) and 11q (a2) through an antibody-complement lysis assay. Exposure of AL cells to CSC without exogenous metabolic activation caused a dose-dependent cytotoxicity and mutagenicity. Mutagenicity also increased with time of incubation up to 3 h with a maximum of 300 a1- mutants/10(5) survivors (250% above background; P less than 0.0005) after incubation with 100 micrograms/ml CSC. Cytotoxicity and mutagenicity of CSC were inversely proportional to cell density. Fifty percent lethal doses for the acidic, basic and neutral fractions of CSC after 3 h of incubation were 30, 100 and 240 micrograms/ml respectively, and the acidic fraction at a concentration of 25 micrograms/ml induced 350 a1- mutants/10(5) survivors (230% above background; P less than 0.0005); the basic and neutral fractions were less mutagenic. These results indicate that CSC and fractions of CSC can directly produce a spectrum of mutations, through both deletional and non-dysjunctional mechanisms of a kind known to lead to inactivation of tumor suppressor genes.

Animals

A case of cutaneous metastases of gastric carcinoma showing peculiar clinical features.

A 52-year-old male patient presented with multiple cutaneous nodules on the face, trunk, and upper extremities. Examination of a skin biopsy specimen disclosed numerous signet ring cells throughout the dermis. Histopathologic examination of the stomach, along with gastroscopy, revealed that the cutaneous metastases were of gastric origin. The metastatic skin lesion on the shoulder and the back of the patient grew relatively rapidly, showing an erysipelas-like lesion followed by prominently large tumor masses. The clinical appearance seen in our case is thought to be rare. Radiotherapy and chemotherapy appeared to be effective in reducing some tumors and the swelling on the anterior of the neck, and in prolonging life.

Adenocarcinoma