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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 361 records · Page 20Linked to original sources

Local cerebral blood flow and CO2 reactivity during prostaglandin E1-induced hypotension in patients undergoing cerebral aneurysm surgery.

The effects of prostaglandin E1 (PGE1) on local cerebral blood flow and CO2 reactivity were studied in 30 patients undergoing cerebral aneurysm surgery in eight of whom the aneurysm had not ruptured and was an incidental finding. The aneurysms were clipped at various intervals depending upon clinical conditions. Blood flow on the open brain surface was measured with a thermal gradient blood flow-meter. Hypotension was initially induced with 0.1 microgram kg-1 min-1 of PGE1 and subsequently adjusted to maintain the mean arterial blood pressure at about 70 mmHg. Local cerebral blood flow and CO2 reactivity were studied during and after PGE1 administration. Both were preserved, but CO2 reactivity values were lower in patients in whom the aneurysm had ruptured than in those in whom it had not ruptured. PGE1 may be an appropriate drug with which to induce hypotension during cerebral aneurysm surgery because cerebral blood flow and CO2 reactivity is preserved.

Adult

[A clinical study of transfer of cefminox and piperacillin into pulmonary tissue].

Serum concentrations of cefminox (CMNX) and piperacillin (PIPC) and their transfer into pulmonary tissue during surgery were serially studied following 1-hour intravenous instillation of 1 g of CMNX or PIPC immediately before thoracotomy, and the following results were obtained. Maximum serum concentrations of CMNX and PIPC were observed 1 hour after the commencement of administration, and their levels gradually decreased thereafter. The mean peak level of CMNX was 72.21 micrograms/ml, and T 1/2 was 1.62 hours. The mean peak level of PIPC was 43.26 micrograms/ml, and T 1/2 was 1.54 hours. In the pulmonary tissue, mean concentrations of CMNX in the normal pulmonary (alveolar) tissue were 28.80, 26.50 and 17.80 micrograms/g at 2.5, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 19.6, 18.40 and 20.53 micrograms/g, respectively. The mean concentrations of PIPC in the normal pulmonary (alveolar) tissue were 18.97, 7.34 and 5.0 micrograms/g at 2, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 7.2, 9.20 and less than 0.2 micrograms/g, respectively. PIPC also showed favorable transfer into the hilar lymph node tissue and obstructive pneumonitic lesions. The transfer of both drugs into pulmonary tissue suggests that both drugs are useful for the treatment of respiratory infectious diseases and the prevention of postoperative infections.

Adult

Transfer of beta-lactam preparations created in Japan to lung tissue and the drug selection for chemotherapy of respiratory tract infections.

Intraoperative transfer of eight beta-lactam preparations to lung tissues was investigated by one-gram one-hour intravenous drip infusion immediately prior to operation. The Japanese drugs used were piperacillin, cefotiam, ceftizoxime, cefuzonam, latamoxef, flomoxef, cefotetan and cefbuperazone. The serum peak level was highest with cefotetan, 104.1 micrograms/ml, followed by cefbuperazone, latamoxef, ceftizoxime, cefotiam, piperacillin, flomoxef and cefuzonam, in decreasing order. Except for cefuzonam, there was a correlation between the serum peak level and the human serum protein binding rate (r = 0.89). There was a correlation (r = 0.98) between the Cmax of normal lung tissue (alveoli) level and the serum peak level (Cmax), but no correlation between the former and the human serum protein binding rate. The tumour level was lower than that in normal lung tissue (alveoli), but the tissue level at the obstructive pneumonia area was higher. The Cmax of bronchiolar tissue level was highest with cefuzonam, followed by latamoxef. There was no correlation between the Cmax of bronchiolar tissue level and the serum peak level, human serum protein binding rate or the Cmax of lung tissue (alveoli) level. It is therefore presumed that the drug level in tissue of the acute pneumonia area can be determined from the serum peak level of the respective drug. An appropriate drug for chemotherapy may be selected from beta-lactam preparations which are effective against main causative organisms in acute respiratory tract infections. Cefuzonam and latamoxef are especially useful for chemotherapy in patients with acute bronchiolitis.

Adult

Early cancer of the gastric remnant--with special emphasis on the importance of follow-up of gastrectomized patients.

Seven patients with early cancer of the gastric remnant (group 1) and nine with gastric remnant cancer which developed after surgery for early gastric cancer (group 2), were studied clinicopathologically. The findings can be summarized as follows: In group 1, the majority of cases were classified as type I by gross type. Most lesions were in the posterior wall of the remnant stomach. All lesions were differentiated carcinomas. In group 2, of the nine early gastric tumors resected at the initial surgery, six were present at site A and three at site M. The gross type of the tumor was varied. Six patients underwent a Billroth II, and two a Billroth I, resection. The findings at the second operation (for gastric remnant cancer) showed that five lesions were located in the gastric stump or anastomosed region and four in the posterior or anterior wall of the remnant stomach. Histologically, the lesions included four undifferentiated and five differentiated carcinomas. Of the nine lesions involving the gastric remnant, only two were at an early stage, the remaining seven being at an advanced stage. The outcome was extremely poor in this group. Many of the patients died of carcinomatous peritonitis. In summary, a large percentage of the patients of group 1 had a type I lesion in the remnant stomach. In group 2, more than half of the lesions were located in the gastric stump or at the site of the anastomosis, and the majority of the lesions were at an advanced stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

[A case of acute renal failure due to left contracted kidney, complicated by right renal infarction].

A 46-year-old woman, who had been treated with anti-arrhythmic drugs and digitalis for mitral stenosis and paroxysmal atrial fibrillation, suddenly developed severe abdominal pain and nausea. There was tenderness around right CVA. BUN and serum-creatinine were elevated, 57 mg/dl and 4.5 mg/dl respectively. She was in acute renal failure (ARF). WBC, GOT, GPT, LDH were also elevated. Abdominal ultrasonography showed normal-size right kidney (12 cm) and atrophic left kidney (8.5 cm). Selective right renal angiography revealed right renal arterial embolism, suggesting that ARF developed from right renal infarction complicated by left atrophic kidney. Renal scintigram using 99mTc-DTPA indicated non-function type left kidney. Because of the high risk of surgery, she received anticoagulant therapy. Fifteen days later, BUN and serum-creatinine returned to 14mg/dl, 2.2mg/dl, respectively.

Acute Kidney Injury

Age-dependent induction of thymic lymphomas by N-propyl-N-nitrosourea in the F344/DuCrj rat.

N-Propyl-N-nitrosourea (PNU) is one of the most potent thymic-lymphomagenic agents in rats. Our previous experiments strongly suggested that leukemogenic viruses were not the cause of thymic lymphomas in rats and that target cells of PNU exist in the thymus but not in the bone marrow. On the other hand, the role of retrovirus in lymphomagenesis is undeniable in mice. Therefore, chemically induced rat thymic lymphoma provides a good model to analyse lymphomagenesis without viral implications. In the present experiment 1, we investigated the relationship between the age of animal at commencement of PNU treatment and the incidence of thymic lymphomas. Incidences of thymic lymphomas were 100, 100, 80 and 18, and average latent periods were 15.1, 18.7, 25.4 and 27.3 weeks after the start of PNU-treatment, in 5-, 10-, 20- and 40-week-old groups, respectively. In experiment 2, rats were sacrificed postnatally at 5, 10, 20, 30 and 40 weeks each, and thymus weight, number of thymocytes in the thymus, frequency of mitosis, and percentage of OX-7 (Thy 1.1), OX-8 (CD8), or W3/25 (CD4) positive cells, were examined cytologically. Thymus weight, number of cells in the thymus and mitotic index were maximum at 10 weeks old, and thereafter decreased gradually. No marked changes were observed in the ratio of each cell-surface marker positive cell. These results indicate that induction of thymic lymphomas by PNU is very closely related with the total number of mitotic cells in the thymus. Thus, chemical induction of rat thymic lymphoma reflects an age-dependent function of the thymus.

Age Factors

[Role of psychological factors as a determinant of the hypercapnic ventilatory response and dyspnea sensation].

We examined, in 38 healthy adult subjects (male 15, female 23), the relationship between psychological background as assessed by manifest anxiety scale test and Yatabe-Guillford test, and the hypercapnic ventilatory response (HCVR), which was tested twice with and without inspiratory resistive loading (17 cmH2O/L/sec). In addition, we attempted to evaluate the possible role of psychological factors in dyspnea sensation felt during HCVR, which was simultaneously assessed by visual analogue scaling (VAS). The slope value of HCVR was positively correlated with the social extraversion score in the male group (r = 0.55, p less than 0.05) only when the test was conducted without resistive loading. In the female group, it was positively correlated with emotional instability in both conditions (r = 0.46, p less than 0.05) without resistive loading and r = 0.47, p less than 0.05 with resistive loading). With respect to dyspnea sensation, manifest anxiety score alone had a positive correlation with VAS score evaluated in relation to ventilation only in the male group (r = 0.61, p less than 0.05). From these findings, we conclude that psychological factors may play a role as a determinant of HCVR, regardless of the presence of inspiratory resistive loading, as well as a determinant of the sensation of dyspnea during HCVR.

Adult

[Thermal regulation disturbance in severely handicapped patients--the second report].

Thirty-three severely handicapped patients were investigated on body temperature regulation by rectal temperature monitoring and hypophyseal hormonal function. The lowest body temperature in the day in the cases with handicaps of prenatal onset tended to be lower than that of peri or postnatal onset. This finding suggests that different causes make regulation disturbance of body temperature in handicapped children. On the other hand, low urine osmolarity in the morning and irregular menstruation were recorded suggesting hypothalamic dysfunction in poor regulation cases.

Body Temperature Regulation

[A successful allogeneic bone marrow transplantation for acute promyelocytic leukemia with anthracycline-induced cardiomyopathy at relapse].

A 14-year-old girl with acute promyelocytic leukemia (APL) developed cardiomyopathy following chemotherapy for remission induction and subsequent consolidation consisting of cumulative doses of 644 mg/m2 of daunorubicin and 31 mg/m2 of mitoxantrone. Six months after the first complete remission, when relapse of APL was recognized an allogeneic bone marrow transplantation (BMT) from her HLA-identical brother was performed. A preconditioning regimen, consisting of cytarabine (Ara-C, 2 g/m2/day x 3 days and 4 g/m2/day x 3 days), total body irradiation (TBI, 1200 cGy) and etoposide (VP-16, 50 mg/kg) caused moderate gastrointestinal symptoms and transient hemorrhagic cystitis, but did not worsen her cardiac function. Both continuous intravenous administration of heparin to control DIC and continuous low dose dopamine infusion to prevent cardiac failure achieved their purpose. The patient is leukemia-free and has no symptoms related to cardiomyopathy at the eight month after BMT. A preconditioning regimen (Ara-C, TBI and VP-16) appeared to be suitable for BMT to a patient with anthracycline-induced cardiomyopathy.

Adolescent

[Effect of aging on control of breathing].

In an attempt of elucidate the effect of aging on control of breathing, we measured hypercapnic ventilatory responses (HCVR) under three different conditions in 14 elderly volunteers (mean age: 69 yrs) and in young control subjects (29 yrs). There was no significant difference in the slope value (S) of HCVR between the two groups when the test was conducted under hyperoxic conditions. However, under hypoxic conditions, the "S" was significantly increased only in the young subjects, but not so in the elderly. When an resistive load (17 cmH2O/L-sec) was added to an inspiratory line, the "S" was not changed as a result of augmented P0.1 response in the young subjects, while the "S" was significantly decreased without any increase in P0.1 response in the elderly. The dyspnea score at the end-tidal PCO2 of 50 Torr, which was evaluated by visual analogue scale, was consistently higher in the elderly than in the young under any conditions. These results suggest that hypoxic-hypercapnic interaction on ventilation and load compensation reflex to inspiratory resistive loading are impired in the elderly subjects and that these are not associated with bluntness of respiratory sensation.

Adult

Specificity of heme for hemopoietic recovery from AZT toxicity.

The toxicity of azidothymidine (AZT) was studied on normal human bone marrow hemopoietic colony growth as determined by assays of CFU-E, BFU-E, and CFU-GM. The potential sparing effect of hemin and heme analogues on AZT-suppressed bone marrow was also investigated. AZT at a lower concentration (0.1 mumol/L) inhibited CFU-E by 68%, BFU-E by 84%, and CFU-GM by 59%. AZT at a higher concentration (1.0 mumol/L) inhibited CFU-E by 88%, BFU-E by 90%, and CFU-GM by 69%. Addition of hemin (10 mumol/L) to cultures containing AZT (0.1 mumol/L) increased CFU-E growth by 279%, BFU-E by 282%, and CFU-GM by 72%. A similar concentration of heme analogues did not have an enhancing effect; in contrast, zinc protoporphyrin (ZnPP) was inhibitory to bone marrow progenitors CFU-E, BFU-E, and CFU-GM. In addition, no enhancement of colony growth was obtained when progenitor cells were cultured in the presence of 10(-2)-10(-5) M iron. These results demonstrate that exogenous hemin has a specific beneficial effect on human bone marrow hematopoietic progenitor cells which is not seen with iron or other metalloporphyrins. Furthermore, this beneficial effect includes a reversal of the cytotoxic effect of AZT on bone marrow progenitors.

Cell Division

Effect of erythroid differentiation factor on megakaryocytic differentiation of L8057, a murine megakaryoblastic leukemia cell line.

To assess the potent effect of erythroid differentiation factor (EDF) on megakaryocytopoiesis, effect of EDF on megakaryocytic differentiation of L8057, a murine megakaryoblastic cell line, was examined. EDF potentiated AchE induction of L8057 in a dose dependent manner. The potency of EDF on megakaryocytic differentiation is comparable to that on erythroid differentiation reported previously. The present results suggest that EDF may play a regulatory role in megakaryocytopoiesis as well as in erythropoiesis.

Acetylcholinesterase

A unique vacuolar processing enzyme responsible for conversion of several proprotein precursors into the mature forms.

Proprotein precursors of vacuolar components are transported from the endoplasmic reticulum into vacuoles, where they are proteolytically processed into their mature forms. However, the processing mechanism in plant vacuoles is very obscure. Characterization of a purified processing enzyme is required to determine whether a single enzyme is responsible for processing many vacuolar proteins with a large variability of molecular structure. If this is true, how can it recognize the numerous varieties of processing sites? We have now purified a processing enzyme (Mr = 37,000) from castor bean seeds. Our results show that the purified enzyme can process 3 different proproteins isolated from either the endoplasmic reticulum or transport vesicles in cotyledon cells to produce the mature forms of these proteins which are found at different suborganellar locations in the vacuole: the 2S protein found in the soluble matrix, the 11S globulin found in the insoluble crystalloid and the 51 kDa protein associated with the membrane. Thus a single vacuolar processing enzyme is capable of converting several proprotein precursors into their respective mature forms.

Amino Acid Sequence

Metabolism of 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(R)-HETE) in corneal tissues: formation of novel metabolites.

12(R)-Hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], a cytochrome P450 arachidonate metabolite, is metabolized by corneal tissues via three distinct metabolic pathways: beta-oxidation, omega-hydroxylation, and keto-reduction. The major metabolite released from the intact rabbit corneal epithelium or cultured cells was identified by mass spectrometric analysis as 8-hydroxy-4,6,10-hexadecatrienoic acid, the tetranor metabolite derived following two steps of beta-oxidation from the carboxy terminus. The beta-oxidation pathway was expressed in both microsomes and mitochondria isolated from bovine corneal epithelium and was dependent on the addition of oxidizing equivalents. The major metabolite of 12(R)-HETE in subcellular fractions of bovine corneal epithelial cells was a dihydro compound, 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE). This derivative is presumably formed by an oxidation of the hydroxyl group followed by two keto-reduction steps, since its formation was accompanied by the appearance of a keto metabolite identified as 12-oxo-5,8,14-eicosatrienoic acid. The omega-hydroxylation, in contrast to other cell types, was a minor route for 12(R)-HETE metabolism in these tissues. Since 12(R)-HETE has been implicated as a modulator of Na(+)-K(+)-ATPase activity and its related functions in ocular tissues, these findings raise the possibility that the newly described metabolites may be involved in regulating corneal functions. In addition, the presence of a keto reductase in the cornea may be of great importance following injury since 12(R)-HETrE resulting from 12(R)-HETE by this activity is a potent ocular proinflammatory compound.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid