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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 37 records · Page 2Linked to original sources

High frequency of QPY allele and linkage disequilibrium of granzyme-B in Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis.

Mediation of Epstein-Barr virus (EBV)-specific cytotoxicity in T lymphocyte via the perforin/granzyme pathway has been demonstrated; therefore, a study involving cytolytic molecules was essential for the clarification of hemophagocytic lymphohistiocytosis (HLH) pathogenesis. This investigation, which analysed the frequency of three allelic mutations of granzyme-B (55Q/R, 95P/A and 247Y/H) in patients with EBV-HLH and infectious mononucleosis, identified the high prevalence of the QPY haplotype in EBV-HLH patients in comparison with healthy controls. A > G polymorphism was also detected in intron 5; furthermore, nearly complete linkage disequilibrium was observed among these polymorphisms. The recessive role of the QPY haplotype of granzyme-B might be responsible for the pathogenesis of EBV-HLH. Cytotoxicity and DNA fragmentation of cytotoxic T lymphocytes did not differ among patients characterized by the QPY/QPY, RAH/RAH and QPY/RAH genotypes. This finding suggested that DNA fragmentation in target cells is mediated not only by granzyme-B but also by other molecules, including other granzymes or Fas.

Genetic Predisposition to Disease↗

Spontaneous extraskeletal osteosarcomas of the subcutis in Djungarian hamsters (Phodopus sungorus): report of two cases.

Spontaneous subcutaneous extraskeletal osteosarcoma was diagnosed in the subcutaneous tissue of two Djungarian hamsters. Histologically, the tumour was characterized by multiple nests of osseous and cartilaginous components within a proliferation of pleomorphic cells. No abnormality was observed in any skeletal bones and no change suggesting tumorous growth was observed in any other sites. This is the first report of extraskeletal osteosarcomas in Djungarian hamsters.

Animals↗

Implications of plasma concentrations of adiponectin in patients with coronary artery disease.

OBJECTIVE: To investigate whether concentrations of plasma adiponectin constitute a significant coronary risk factor, with particular focus on the relation between plasma concentrations of adiponectin and the development of acute coronary syndrome (ACS). SUBJECTS AND METHODS: Plasma concentrations of adiponectin were measured in 123 patients with coronary artery disease (CAD) and in 17 control participants. Patients were divided into three groups according to condition type: acute myocardial infarction (AMI) group (n = 59), unstable angina pectoris (UAP) group (n = 28), and stable angina pectoris (SAP) group (n = 36). RESULTS: Plasma concentrations of adiponectin correlated negatively with body mass index (r = -0.18, p < 0.05), serum triglyceride (r = -0.25, p < 0.01), and fasting glucose concentrations (r = -0.21, p < 0.05), but correlated positively with age (r = 0.26, p < 0.01), high density lipoprotein cholesterol concentrations (r = 0.35, p < 0.01), and low density lipoprotein particle size (r = 0.37, p < 0.01). Plasma concentrations of adiponectin in patients with ACS, in both the AMI and UAP groups, were significantly lower than those in patients with SAP and in the control group (ACS, 6.5 (3.0) microg/ml; SAP, 11.3 (5.9) micro g/ml; control 12.8 (4.3) microg/ml; p < 0.01). Additionally, plasma concentrations of adiponectin in patients with CAD (7.9 (4.6) microg/ml, p < 0.01) were significantly lower than in the control group. There were, however, no significant differences between patients with SAP and the control group (p = 0.36). Multiple logistic regression analysis showed that smoking, fasting glucose concentration, and low log adiponectin concentration correlated independently with the development of an ACS. CONCLUSIONS: The findings suggest that measurement of plasma concentrations of adiponectin may be of use for assessing the risk of CAD and may be related to the development of ACS.

Adiponectin↗

[Diplopia and blepharoptosis associated with orbital emphysema following thoracotomy with lung cancer; report of a case].

BACKGROUND: Orbital emphysema is a common complication of trauma and fracture of orbital bones. However, subcutaneous emphysema also can rarely lead to orbital emphysema. We reported the clinical and radiological findings in a patient with diplopia and blepharoptosis following thoracotomy for lung cancer. CASE: A 76-year-old man had undergone left inferior lobectomy and ND 2 a in October 2002, based on the clinical diagnosis of stage IB lung squamous cell carcinoma. He presented with diplopia and blepharoptosis several days following thoracotomy. Chest X-ray demonstrated extensive subcutaneous emphysema, and physical examination also revealed diffuse subcutaneous emphysema including face and palpebrae. Head computed tomography (CT) revealed subcutaneous emphysema in the infratemporal fossa bilaterally. His diplopia and blepharoptosis gradually resolved, and he was discharged with no visual complaints on the fourteenth postoperative day. CONCLUSIONS: Subcutaneous emphysema can lead to diplopia and orbital emphysema in the absence of orbital trauma. Early surgical intervention for air leakage is highly recommended to avoid both the orbital emphysema and the visual complications in the event that subcutaneous emphysema should get to including face or palpebrae.

Aged↗

[A clinical evaluation of the practical reliability in video-assisted thoracic surgery for right primary lung cancer].

Recently, lobectomy by video-assisted thoracic surgery (VATS lobectomy: VL) has been widely applied to peripheral lung cancer because of its less invasive approach compared to standard thoracotomy (ST). However, the appropriate approach in VL still remains to be solved. The aim of this study was to evaluate the practical reliability of our technical devices in VL for right primary lung cancer. For the VATS procedures, a mini-thoracotomy measuring about 6-7 cm was made in the fourth or fifth intercostal space (ICS) under the auscultatory triangle without rib resection. Two access holes 12 mm in size were also made in the fourth ICS at the anterior axillary line and in the seventh ICS at the posterior axillary line, respectively. These access holes were used for insertion of thoracoscope, endoscopic stapler or retracting instrument according to operative procedure. After stapling of the vessels and bronchus, the resected pulmonary lobe was removed from the thorax using a plastic retrieval bag. The present study showed the technical feasibility of this unique thoracoscopic approach in the standard lobectomy with systematic nodal dissection for right lung cancer.

Aged↗

In-situ visualization and quantification of mineralization of cultured osteogenetic cells.

An osteoblastic cell line (HOS cells) produces a prominent osteoid matrix with mineralization. Fibroblasts, on the other hand, do not exhibit this mineralization. To evaluate the degree of mineralization, we added calcein to the culture medium and then observed the culture wells by using an image analyzer. The calcein uptake into the cell/matrix layer was detected in the HOS cells but not in the fibroblasts. The calcein uptake was also quantified in situ by using an image analyzer, which revealed high levels in the HOS cells, which correlated well with the calcium content of the mineralized matrix. Rat marrow cells were also cultured in media containing calcein, fetal bovine serum, beta-glycerophosphate, L-ascorbic acid 2-phosphate, and with or without dexamethasone. With the dexamethasone, the cells exhibited osteogenic differentiation that resulted in mineralized matrix formation after about 10 days. The matrix formation coincided with the appearance of calcein uptake into the cell/matrix layer, with the amount of calcein uptake increasing with time. By contrast, the culture without the dexamethasone did not exhibit matrix formation and the calcein uptake was negligible. In the case of both HOS cell and rat marrow cell cultures in vitro, calcein did not affect expressions of their alkaline phosphatase activity or osteocalcin production. Furthermore, histologic observation revealed that rat marrow cells subcultured with calcein could show osteogenic ability after in vivo implantation. These results suggest that the current method of detecting calcein uptake in a culture allows the monitoring of the osteogenic capacity of cultured cells, as well as the measurement of the amount of mineralization produced by the osteogenic cells. Given that osteogenic cultured cells/mineralized matrices are used in bone reconstruction surgery, the in situ monitoring method is invaluable in that it allows us to evaluate the osteogenic capacity of in vitro constructs.

Alkaline Phosphatase↗

A subchronic toxicity study of shea nut color in Wistar rats.

Shea nut color, obtained from nuts of the shea tree (Butyrospermum parkii), is used as a food-coloring agent. Flavonoid pigments are considered to be the responsible constituents. As there have been no reports of toxicological evaluation, a 13-week subchronic toxicity study was performed in Wistar Hannover rats at dose levels of 0 (control), 0.07, 0.31, 1.25 and 5% in powdered basal diet. The average of daily shea nut color intake was 51.3, 226.1, 986.8 and 3775.5 mg/kg/day for males and 56.4, 272.9, 1166.7 and 4387.7 mg/kg/day for females, respectively. During the administration period, daily observation of clinical signs and weekly measurement of body weights and food consumption were performed. After the end of the treatment, hematology, serum biochemistry, organ weight and histopathological examinations were conducted. No significant toxicological changes were observed in any parameters in this study. Hence, the no adverse effect dose of shea nut color was estimated to be greater than 5.0% for both sexes (3775.5 mg/kg/day for males and 4387.7 mg/kg/day for females).

Animals↗

Preoperative blood pressure and catecholamines related to hypothermia during general anesthesia.

BACKGROUND: We previously demonstrated that preoperative blood pressure values affect intraoperative hypothermia during general anesthesia. We hypothesized that increased catecholamine secretion could be responsible for the relationship between preoperative blood pressure and hypothermia. METHODS: To evaluate the effect of preoperative systolic blood pressure (SBP) and plasma catecholamine levels on core temperature during general anesthesia, 40 male patients who were scheduled for open abdominal surgery were allocated to two groups: those whose preoperative SBP was 140 mmHg or greater (high SBP group, n = 20), and those whose SBP was less than 140 mmHg (normal SBP group, n = 20). Anesthesia was maintained with 0.4% isoflurane and opioids. RESULTS: The average age, height, and weight of the patients in the two groups did not differ. Preoperative SBP, mean blood pressure, diastolic blood pressure and heart rate in the high SBP group were significantly higher than those in the normal SBP group. Plasma norepinephrine concentrations in the high SBP group were significantly greater than those in the normal SBP group before and 1 h after the induction of anesthesia. Tympanic membrane temperatures in the normal SBP group started to decline further just after the induction of anesthesia, more so than that in the high SBP group. The vasoconstriction threshold in the normal SBP group was significantly lower than that in the high SBP group. CONCLUSION: These results suggest that the higher levels of preoperative catecholamine secretion contributed to the lesser degree of intraoperative hypothermia observed in the high SBP group.

Abdomen↗

The vasoconstriction threshold is increased in obese patients during general anaesthesia.

BACKGROUND: In anaesthetized patients, body temperature decreases often, but overweight patients become less hypothermic. Obesity in itself protects body heat, and thermoregulatory reflexes may maintain normothermia in obese patients. We tested the hypothesis that even slight obesity increases the vasoconstriction threshold. METHODS: Twenty male patients aged 30-65 years scheduled for open abdominal surgery were allocated to two groups: body fat >/=25% (obese group, n = 10), or <25% (normal weight group, n = 10). Anaesthesia was maintained with 0.4% isoflurane and opioid. The thermoregulatory vasoconstriction threshold was defined by the tympanic membrane temperature at which the skin temperature gradient equalled 0 degrees C. Plasma adrenaline, noradrenaline and leptin were measured. RESULTS: Age, height, heart rate and blood pressure did not differ between the two groups of patients. In the obese group the vasoconstriction threshold was higher than that in the normal weight group: 36.0 +/- 0.1 vs. 35.5 +/- 0.2 degrees C. Consequently, after 4 h of anaesthesia, the core temperature was highest in the obese patients: 36.4 +/- 0.1 vs. 35.5 +/- 0.2 degrees C. CONCLUSIONS: These results suggest that core temperature is maintained in obese patients because their vasoconstriction threshold to a low environmental temperature is high.

Adult↗

Aseptic meningitis during combined continuous spinal and epidural analgesia.

Continuous spinal analgesia (CSA) offers considerable advantages: (1) it requires 10% of the local anesthetic; (2) it may be instituted after patient positioning, thus minimizing the potential for cardiovascular instability; and (3) with low doses of dilute short-acting local anesthetic, the recovery period is shortened (1). Continuous spinal analgesia has been used for various procedures such as surgery and cancer pain control. However, CSA has not gained wide popularity because of its possible complications, such as headache, nerve injury, infection and accidental removal or migration of the catheter. Although real possibilities, these complications have been rarely documented. We describe an episode of aseptic meningitis during combined CSA and EA.

Abdominal Pain↗

Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid malignant tumors.

BACKGROUND: This phase I dose-escalating study investigated the tolerability and toxicity of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid tumors. Thirty-one patients were included. PATIENTS AND METHODS: Patients initially received a single oral dose of gefitinib followed by 10-14 days of observation. Oral gefitinib was subsequently administered on 14 consecutive days, every 28 days. Dose escalation was from 50 mg/day to a maximum of 925 mg/day or dose-limiting toxicity (DLT). RESULTS: Most adverse events were mild (grade 1/2); the most frequent were an acne-like rash and gastrointestinal effects. Two of six patients at 700 mg/day had DLT; no further dose escalation occurred. C(max) was reached within 3-7 h and exposure to gefitinib increased with dose. Mean terminal half-life following multiple dosing was 50.1 h (range 27.8-79.7 h). A partial response (duration 35-361 days) was observed in five of the 23 patients with non-small-cell lung cancer over a range of doses (225-700 mg/day), and seven patients with a range of tumors had disease stabilization (duration 40-127 days). CONCLUSIONS: In conclusion, gefitinib showed a favorable tolerability profile in Japanese patients. The safety profile, pharmacokinetic parameters and antitumor activity observed in our study are comparable to those observed in patients from the USA and Europe.

Administration, Oral↗

Assessment of myocardial viability using coronary zero flow pressure after successful angioplasty in patients with acute anterior myocardial infarction.

OBJECTIVES: To investigate the relation between coronary flow reserve (CFR), coronary zero flow pressure (Pzf), and residual myocardial viability in patients with acute myocardial infarction. DESIGNS: Prospective study. SETTING: Primary care hospital. PATIENTS: 27 consecutive patients with acute anterior myocardial infarction. MAIN OUTCOME MEASURES: F-fluorodeoxyglucose (FDG) positron emission tomography (PET) was used in 27 patients who underwent successful intervention within 12 hours of onset of a first acute anterior myocardial infarction. Within three days before discharge they had < 25% stenosis in the culprit lesion as determined by angiography 24 (3) days after acute myocardial infarction. Pzf and the slope index of the flow-pressure relation (SIFP) were calculated from the simultaneously recorded aortic pressure and coronary flow velocity signals at peak hyperaemia.%FDG was quantified by comparing FDG uptake in the infarct myocardium with FDG uptake in the normal myocardium. RESULTS: There was a correlation between %FDG and CFR, where y = -1.477x + 62.517, r = -0.072 (NS). There was also a correlation between %FDG and SIFP, where y = -0.975x + 60.542, r = -0.045 (NS), and a significant correlation between %FDG and Pzf, where y = -0.98x + 85.108, r = -0.696 (p < 0.001). CONCLUSIONS: CFR does not correlate with FDG-PET at the time of postreperfusion evaluation of residual myocardial viability. The parameter that correlates best with residual myocardial viability is Pzf and this may be a useful index for predicting patient prognosis.

Aged↗

[Conservative therapy for recurrent bronchial stump fistula occurred after surgery for lung cancer with cerebrovascular disease].

BACKGROUND: Although pyrothorax caused by bronchial stump fistula is 1 of the most severe respiratory complications frequently encountered after surgery for lung cancers, it is very difficult to prevent the development of pyrothorax. However, conservative treatment for bronchial stump fistula occurred after surgery for lung cancer was successfully performed in 1 of our elderly lung cancer patients with a history of cerebrovascular events. CASE: Patient was a 74-year-old man who developed cerebral infarction in October 2000, and was continuously undergoing rehabilitation for left hemiplegia. Chest computed tomography (CT) demonstrated a tumorous lesion in the right S6. Clinical diagnosis of stage IA squamous cell carcinoma was made. His performance status (PS) was degree IV, and he required complete assistance. In addition, since several abnormal florae were detected by preoperative examinations of sputum, the development of postoperative respiratory complications was suspected. In April 2001, thoracoscopy-assisted right inferior lobectomy and nodal dissection 1 (ND 1) were performed. Although the patient developed bronchial stump fistula on the 6th hospital day, it was successfully treated by conservative procedures after second surgery. CONCLUSION: Conservative therapy under nutritional management mainly consisting of central venous nutrition may be useful for some surgically treated lung cancer patients with bronchial stump fistula when they have mild inflammation and the reduction of pyrothorax cavity can be expected by re-expansion of the residual lobes of the lung.

Aged↗

Dose- and time-response studies of sodium o-phenylphenate urinary bladder carcinogenicity in rats.

Dose- and time-response studies of urinary bladder carcinogenesis due to orally administered sodium o-phenylphenate (OPP-Na) were performed using 5-week-old male Fischer 344 rats given diets containing 0 (control), 2500, 5000, 10,000, 15,000 or 20,000 ppm OPP-Na for 104 weeks and fed basal diets until 112 weeks (experiment 1). In addition, rats received diets containing 20,000 ppm OPP-Na for 0 (control), 12, 24, 52 or 104 weeks and were killed at week 112 (experiment 2). In experiment 1, the transitional cell carcinoma (TCC) was the major tumor type in the urinary bladder, and the dose-response curve was steep with many tumors occurring at the high doses of 15,000 and 20,000 ppm. The virtually safe dose at a risk level of 10(-6) for TCCs and papillomas was estimated to be 144 ppm by the Weibull model, a high value similar to that for sodium saccharin. In experiment 2, a few TCCs developed after 24 weeks of treatment, but the time-response curve was also steep with the majority of lesions occurring after longer exposure periods. Based on the observed steepness in dose- and time-responses, any implied cancer risk of OPP-Na at the low doses of interest to man must be considered to be very small.

Agrochemicals↗

A chronic toxicity study of josamycin in F344 rats.

The chronic toxicity of josamycin was examined in Fischer 344 (F344) rats. Groups of 10 males and 10 females were given the test compound in the diet at concentrations of 0 (control), 0.02, 0.1, 0.5 or 2.5% for 52 weeks. Daily intake of josamycin was 0, 10, 50, 260 and 1310 mg/kg body weight in males and 0, 10, 60, 290 and 1460 mg/kg body weight in females, respectively. Body weight gain was significantly (P<0.05) reduced in the male 2.5% group but no noticeable changes were found in food intake. In hematological examination, the platelet count was significantly (P<0.01) lower in the male groups given 0.02% or more of josamycin and in the 2.5% female group as compared with the control group values in a dose-dependent manner. In serum biochemical examination, blood urea nitrogen was significantly (P<0.05 and P<0.01, respectively) higher in males given 0.5 and 2.5% and total bilirubin was significantly (P<0.05) higher in females receiving 2.5% as compared with those of the control group. No death occurred at any dose levels during the dosing period. At necropsy, with the exception of cecal enlargement in the groups given more than 0.1% josamysin and a significant (P<0.01) increase in the relative liver weight of females in the 2.5% group, no particular findings related to the administration were observed. Histopathologically, the incidence and severity of liver bile duct proliferation in female 2.5% group were significantly (P<0.01) greater than those of the control group. Other histological changes found in the treated and control groups were similar to the spontaneous lesions in this strain of rats in terms of the incidence and severity. Interestingly, the josamycin treatment reduced the development of altered liver cell foci in females in a dose-dependent manner. Thus, it is concluded that, under the present experimental conditions, josamycin induces bile duct proliferation in female F344 rats at a high dose of 1460 mg/kg body weight. Based on the decrease of platelet count found in males given 10 mg/kg body weight or more, the no-observed-adverse-effect level (NOAEL) was estimated to be less than 10 mg/kg body weight.

Animals↗

Iron lactate induction of pancreatic and endometrial proliferative lesions and a lack of increased tumors in a 104-week carcinogenicity study in F344 rats.

Iron lactate has been used as a food additive for iron supplementation. The present study was conducted to determine whether it might have carcinogenic potential. A total of 150 male and 150 female Fischer 344 rats were divided into three groups and fed basal diet containing 0, 1 or 2% of iron lactate for 104 weeks. No iron lactate-induced tumors were observed in any groups, although the incidences of pancreatic acinar cell and endometrial gland hyperplasias were increased in males and females, respectively, in the 2% group. Thus our in vivo animal data indicate that iron lactate lacks carcinogenicity in male and female F344 rats. However, estrogenic effects might be concluded based on the data for endometrial lesions. In a second experiment, an estrogen responsive rat pituitary tumor cell line, MtT/Se, and a human breast cancer cell line, MCF-7, were therefore employed to examine the estrogenic potential of iron lactate with regard to receptor binding affinity and ERE-reporter gene activation. Results in both cases were negative. Further investigations are needed to elucidate the mechanisms of induction of pancreatic and endometrial proliferative lesions by iron lactate.

Animals↗