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Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 505 records · Page 28Linked to original sources

Normalization of reproductive function in germfree mice following bacterial contamination.

The capacity for reproduction in germfree mice remain inferior to their conventional counterparts even after improvement of feed and other such rearing conditions. The authors provide evidence of increased reproductive capacity in germfree mice following association with bacteria. Estrous cycles were normalized in female mice accidentally contaminated with bacteria, and in mice given fecal suspensions of the accidentally contaminated mice per os. Significant rises were seen in their copulation and implantation rates, reaching levels comparable to values in conventional mice. In male mice, bacterial contamination induced significant increase in sperm motility. Bacteria were identified in the feces of the contaminated mice, and reproductive capacity was examined in mice associated with the identified bacteria. As a result, normalization of the estrous cycle, and rises in copulation and implantation rates were noted in B. distasonis and C. perfringens di-associated mice. Values from B. subtilis mono-associated mice were comparable to those in germfree mice. These results from our accidental contamination indicate that B. distasonis and C. perfringens are capable of normalizing estrous cycles in female germfree mice, and in increasing their reproductive capacity by raising their rates of copulation and implantation.

Animals↗

[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (1). Single-dose intravenous toxicity studies in rats and dogs].

Single-dose toxicity studies of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, were conducted in Sprague-Dawley (SD) rats and beagle dogs. The rats of both sexes were administered ONO-5046.Na intravenously at a single dose of 150, 300 or 450 mg/kg. The male dogs were also given ONO-5046.Na at a single dose of 75 or 150 mg/kg. In the rat study, hypoactivity, bradypnea and paleness of limbs and pinna were observed at doses of 300 mg/kg and above. In particular, one of six female rats in the 450 mg/kg group showed clonic convulsion and died. In surviving animals, those signs disappeared within 3 hr after administration. No effect on body weight gain was seen in either group. Necropsy findings showed a slight foamy fluid in the bronchus, hemorrhage at the right knee joint muscle, tendon and lung in a dead animal. In the dog study, no effects on clinical signs, body weight, food consumption and blood biochemistry were seen in any animals of the 75 and 150 mg/kg groups. It is concluded that the approximate lethal doses are 450 mg/kg in rats and 150 mg/kg and above in dogs.

Alanine Transaminase↗

[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

A 4-week repeated dose toxicity study with 4-week recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control and saline control), 18.75, 37.5, 75 or 150 mg/kg. ONO-5046.Na did not affect signs, body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights, necropsy or histopathology at any dose. These results indicate that the NOAEL of (ONO-5046.Na in rats is 150 mg/kg/day for both sexes in this study.

Animals↗

[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (3). 4-week repeated dose intravenous toxicity study in dogs with 4-week recovery test].

4-week repeated dose toxicity study with 4-week recovery test of sodium N-[2-[4-(2, 2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in beagle dogs. The dogs of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 7.5, 15 or 30 mg/kg. In the 15 mg/kg female group and the 30 mg/kg male and female groups, transient hypoactivity and ataxic gait were observed. It is considered that these symptoms were attributed to the pharmacological effect of ONO-5046.Na. Also, in the 30 mg/kg male and female groups, erythrocyte, hematocrit and hemoglobin were decreased. In the 30 mg/kg male group, lung weight was increased. However, histopathological examination revealed there were no changes in any organs including the lungs. There were no treatment-related changes in body weights, food consumption, ophthalmology, occult blood in feces, urinalysis, blood chemistry, electrocardiography, blood pressure, temperature, pulse rate, hepatic and renal function or necropsy. These results indicate that the NOAEL of ONO-5046.Na in dogs in 15 mg/kg/day for both sexes in this study.

Animals↗

[Toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (4). 6-month repeated dose intravenous toxicity study in rats with 1-month recovery test].

A 6-month repeated dose toxicity study with 1-month recovery test of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. The rats of both sexes were administered ONO-5046.Na intravenously at a daily dose of 0 (vehicle control), 18.75, 37.5 or 75 mg/kg. ONO-5046.Na did not affect clinical signs, body weight, food consumption, opthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology at any dose. These results indicate that the NOAEL of ONO-5046.Na in rats is 75 mg/kg/day for both sexes in this study.

Animals↗

[Nutritional intake by the oldest elderly Japanese. Tokyo Centenarian Study 6].

Rapid demographic aging has made caring for the elderly an increasingly important social issue in Japan. To study current conditions of the oldest elderly citizens, we investigated the dietary practices of centenarians in the Tokyo metropolitan area. First, we compared the food intake of centenarians with that of octogenarians. Next, to identify dietary trends, we investigated whether food intake by centenarians had changed significantly between 1981 and 1995. Nutritional intake by the centenarians and octogenarians in 1995 was about 60% and 75% that of the control, respectively. However, the nutritional intake of well nourished centenarians was similar to that of the octogenarians. Cognitive function and daily activity have an influence on nutritional intake. The centenarians were similar to the control subjects in their consumption of dairy products, sweets, and fruit. However, their intake of cereals, meat, fish, and fatty oils was loss than 60% that of the control, which indicates their preference for soft and sugary foods. The pattern of dietary practices of centenarians in 1981 was similar. Although the total food intake of centenarians amounted to 60% of the control in 1995 energy intake per kilogram of body weight averaged over 30 kcal. As to dietary trends, centenarians in 1981 are more cereals, eggs, algae products, and legumes than did their 1995 counterparts. This finding seems to reflect a generational difference in dietary habits.

Activities of Daily Living↗

[Circadian rhythmicity of heart rates in centenarians].

Holter electrocardiography was used to study the circadian rhythm of heart rate in 50 centenarians living in Tokyo and in Aichi prefecture. As a control group, 50 healthy subjects aged under 65 years old underwent medical check-ups including Holter electrocardiography at Keio Health Consulting Center. Harmonic analysis was used to approximate the 24-h time-series data on the RR intervals to a summation of three cosine waves with 24-h, 12-h and 8-h periods. The power of each period was adjusted for the goodness of the curve-fit, and the powers of the centenarians were compared with those of the controls. Then all the subjects were classified by k-means cluster analysis into k groups based on the power of the period, and patterns of heart rate rhythms were then identified. The power of the 24-h period in centenarians (32.7 +/- 16.0%) was significantly lower than that in controls (45.8 +/- 17.8%). Although there were no significant differences in the powers of the 12-h and 8-h periods, the power of the 8-h period in centenarians (7.0 +/- 8.4%) was slightly higher than that in controls (4.2 +/- 3.3%). Advances or delays in acrophase (acrophasal shift) were more common in centenarians than in controls. Five patterns of heart rate rhythms were identified: 24-h period dominant (n = 58). 24-h + 12-h period (n = 15), 12-h period dominant (n = 7), 8-h period augmented (n = 7), and low curve-fitting (n = 13). Both the 8-h period augmented pattern and the low curve-fitting pattern were more common in centenarians than in controls. Both the 24-h period dominant pattern and the 24-h + 12-h period pattern were less common in centenarians than in controls. These data indicate that the circadian rhythm of heart rate changes with aging.

Activities of Daily Living↗

Possible common origin of alpha-fetoprotein- and human chorionic gonadotropin--secreting cells in intracranial germ cell tumor. Case report.

A primary intracranial germ cell tumor in a 16-year-old boy secreted both alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). The tumor, located in the right thalamus, contained germinomatous, trophoblastic, and endodermal sinus components. To identify AFP- and HCG-secreting cells, germ cells from the surgical specimen were cultured in vitro. These cultured cells secreted AFP and HCG for 10 weeks, and immunohistochemical studies showed that some of the cells secreted both AFP and HCG. These findings suggest that multipotential germ cells migrate to the encephalic region and may become germ cell tumors containing various types of tissue.

Adolescent↗

[Carbon monoxide concentrations during low flow anesthesia].

Elevated carbon monoxide (CO) concentrations have been reported during general anesthesia using inhaled anesthetics. In order to assess the safety of low flow anesthesia, we examined CO concentrations in anesthesia circuit during low flow anesthesia. Thirty patients were randomly divided into two groups. Anesthesia was induced with intravenous thiopental 5 mg.kg-1 and maintained with oxygen 2 l.min-1, nitrous oxide 4 l.min-1 and isoflurane (group H) or oxygen 0.5 l.min-1, nitrous oxide 0.5 l.min-1 and isoflurane (group L). The concentrations of CO in exhaust gas of anesthetic gas monitor were examined by CO sensor (XC-341, Shinkosumosudenki, Tokyo) and COHb was analyzed. The concentrations of CO in group L were significantly higher than in group H. The highest value, however, was 30 ppm. The COHb levels were slightly higher in group L, but the highest value was 2.1%. We consider that these results show no clinical risk and low flow isoflurane anesthesia may be performed safely. Measuring the CO concentrations is helpful for the safety of low flow anesthesia.

Aged↗

Considerations for surgical treatment of patients with upper lumbar disc herniations.

Nine patients treated by surgery for upper lumbar disc herniations were reviewed. Of nine patients with upper lumbar disc herniations at the L1-L2 or L2-L3 level, five were treated by anterior procedures, whereas four underwent posterior procedures. Four of the five patients on whom anterior procedures were performed underwent additional spinal instrumentation using the Kaneda device and Z-plate system. Clinical symptoms improved in all nine patients. Confirmation of the type and level of disc herniation and increased thoracolumbar kyphosis must be taken into consideration when the optimal surgical procedure and spinal instrumentation method are selected.

Adult↗

[Pitfalls and their solution in MIDCAB].

Between July 1996 and September 1997, 11 patients underwent coronary artery bypass starting with left anterior small thoracotomy. All patients were evaluated with Electron Beam Computed Tomography (EBCT) preoperatively. Two patients out of 11 required conversion to sternotomy due to inadequate length of left internal mammary artery (LIMA) graft. One patient had a graft occlusion and underwent reoperation, when a graft avulsion was identified. Distance between LIMA and LAD by EBCT highly predicted needs of procedure modification to obtain additional length of graft. We demonstrated anterior pericardiopexy as an additional technique for protecting LIMA graft from abnormal tension. We conclude that it is crucial to harvest adequate length of LIMA in MIDCAB and anterior pericardiopexy may be useful to prevent a graft avulsion.

Aged↗

[Bronchodilator aerosol propellant interferes with an photoacoustic spectrophotometer respiratory gas analyzer].

A patient with bronchial asthma was scheduled for an operation under nitrous oxide-isoflurane anesthesia. We monitored isoflurane concentrations continuously using an anesthetic gas analyzer (BK 1304). Upon puffing procaterol hydrochloride aerosol for 4 times, the analyzer showed a rapid increase in end-tidal isoflurane concentration. The BK 1304 uses infrared photoacoustic spectrophotometry and it is susceptible to interferences caused by Freon propellants in bronchodilator aerosols. We should take care in monitoring inhalational anesthetics when using aerosols containing Freon propellants.

Aerosols↗

[Carbon monoxide in the expiratory gas during laparoscopic surgery].

One of the complications of laparoscopic surgery is carbon monoxide (CO) production under the use of electrocautery. We experienced a case in which high levels of CO were detected in the expiratory gas. An 80-year old, 33 kg female was scheduled for laparoscopic nephrectomy. Anesthesia was induced with thiopental and vecuronium and maintained with nitrous oxide 60% in oxygen and isoflurane. The concentrations of CO in the anesthetic circuit were examined with CO sensor (XC-341, Shinkosumosudenshi, Tokyo). The CO concentrations were not detected at the start of operation. About 140 minutes after carbon dioxide pneumoperitoneum, the CO concentration increased up to 170 ppm accompanying a high Paco level. The high concentrations, however, decreased immediately after ending of pneumoperitoneum. The HbCO levels were unchanged. Subcutaneous emphysema was noted at the end of surgery. This is because CO is more absorbable in the subcutaneous tissue than in the peritoneal cavity. We consider that CO was absorbed in subcutaneous emohysema during pneumoperitoneum and exhausted in the expiratory gas. When subcutaneous emphysema occurred during laparoscopic surgery, we should be aware of absorption of CO.

Aged↗

[In vitro study on intrathecal application of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant tumor].

To evaluate the possible clinical intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for malignant brain tumors, its anti-tumor activity and neurotoxicity were compared with that of 5-fluorouracil (5-FU) and 5-fluorouridine (FUrd) in vitro. FdUrd showed good tumoricidal activity against cultured mouse 203 glioma cells and rat Walker 256 carcinoma cells as well as A172 human glioblastoma cells. Daoy human medulloblastoma cells and CADO-LC4 human lung cancer cells. It also showed less toxicity for primary cultures of neurons from C57/BL6 mouse and human embryo compared to 5-FU and FUrd. Thymidine phosphorylase (TPase) and thymidine kinase (TK), key enzymes for metabolism of 5-FU derivatives, were measured in cerebrospinal fluid (CSF). TPase or TK activity was detected in the CSF of hardly any patients with malignant brain tumors including meningeal carcinomatosis. These data indicated that the CSF is a favorable site for FdUrd chemotherapy, because the rate of conversion of FdUrd injected to 5-FU would be minimal. In conclusion, FdUrd may be potentially useful for intrathecal treatment of meningeal carcinomatosis.

Animals↗

[Use of a CO-oximeter for forensic diagnosis of hypothermia].

Blood samples were collected from the right and left atria separately in 9 cases of hypothermia and 18 cases of non-hypothermia during judicial and consented autopsy between March 1995 and December 1997. The oxyhemoglobin ratio (O2Hb), reduced hemoglobin ratio (RHb) and oxygen saturation (sO2) were measured by oximetric analysis. O2Hb, R-Hb and sO2 were significantly greater in the hypothermic group than the non-hypothermic group. We conclude that the diagnosis of hypothermia can be established in cases where O2Hb and sO2 in the left atrium exceed 80%, irrespective of values in the right atrium.

Adult↗

[In vivo study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) in meningeal dissemination of malignant tumor].

FdUrd was evaluated in vivo as a potential agent for intrathecal chemotherapy of meningeal carcinomatosis. Neurotoxicity was examined pathologically in normal mice after 4 consecutive intrathecal injections of FdUrd. Using mice models of meningeal carcinomatosis, antitumor activities were studied by evaluating survival time. Pathological examination showed none of the following abnormal findings: demyelination, degeneration and destruction of ependymal linings. FdUrd also had an effect on meningeal carcinomatosis of mice (203 glioma and MM46 transplantable ascitic mammary cancer). In causing FdUrd to exhibit its efficacy, it is necessary to take into consideration the balance between the activity of two key enzymes, thymidine phosphorylase (TPase) (anabolic enzyme) and thymidine kinase (TK) (metabolic enzyme), in tumor tissues as compared with their activity in normal tissues. TPase activity which results in conversion to 5-FU was much lower in malignant glioma and metastatic brain tumors compared with tumors in other extracranial organs. TPase activity in normal brain was much less than in normal tissues in extracranial organs and its activity in gray matter (cortex) was significantly lower than that in white matter. On the other hand, TK activity in malignant brain tumors was much less than that in extracranial organs, however, its activity in normal brain was almost equal to that in normal tissues in extracranial organs. These data obtained in vivo study showed FdUrd to be a possible agent for intrathecal chemotherapy.

Animals↗

Quantitative relationships among thaxtomin A production, potato scab severity, and fatty acid composition in Streptomyces.

Thaxtomin A production in culture, potato common scab severity (percentage of tuber surface infected or number of lesions per tuber), and fatty acid profiles were determined for 78 Streptomyces isolates. Only pathogenic Streptomyces spp. (n = 17) produced thaxtomin A in culture. Thaxtomin A production in culture (microgram/mL) was significantly positively correlated with the percentage of tuber surface infected (R = 0.60; p = 0.017) but not with the number of lesions per tuber (R = 0.37; p = 0.17). An increase of 1 microgram/mL in thaxtomin A production corresponded to an 11% increase in disease severity (percentage of tuber surface infected). The data indicate that quantitative information on the ability of a particular pathogen isolate or population to produce thaxtomin A may be critical to understanding and predicting the disease potential of that population. Using cluster analysis of fatty acid data, 94% of 67 unknown field isolates grouped with other field isolates having the same pathogenicity (plus or minus).

Bacterial Toxins↗