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Biomedical subjects

M Nakamaru

Publications and source records attributed to M Nakamaru.

At least 19 recordsLinked to original sources
PubMed2001

Protective effect of a synthetic analog of prostaglandin E(1) on the small intestinal damage induced by the administration of methotrexate to rats.

Antitumor drugs like methotrexate cause damage to the small intestine, resulting in malabsorption. The present study evaluated this damage by determining the small intestinal absorption of 3-O-methyl-D-glucose (3-OMG) and a poorly absorbable marker, fluorescein isothiocyanate-labeled dextran (FD-4; average molecular mass, 4.4 KDa) using the in vitro everted intestine and in situ intestinal loop techniques. Methotrexate (15 mg/kg body weight) was orally administered to rats once daily for 5 days. A synthetic analog of prostaglandin E(1), OP-1206 (17S,20-dimethyl-trans-Delta(2)-prostaglandin E(1); 0.5 microg/kg body weight) was orally administered to rats twice a day for 5 days. The absorption clearance of FD-4 via the small intestine of the methotrexate-treated rats increased marked, but that of the methotrexate- and OP-1206-treated rats was significantly lower than that of the rats treated only with methotrexate. The absorption clearance of [(3)H]-3-OMG via the small intestine of the methotrexate-treated rats fell markedly, but that of the methotrexate- and OP-1206-treated rats was significantly greater than that of the rats treated only with methotrexate. The changes in AUC values of FD-4 and [(3)H]-3-OMG obtained from in situ intestinal loop experiment showed the same trends as those seen in the absorption clearance from the in vitro everted intestine experiment. These results show that OP-1206 alleviates the methotrexate-induced damage to the small intestine of rats.

3-O-Methylglucose↗
PubMed2000

Competition by allelopathy proceeds in traveling waves: colicin-immune strain aids colicin-sensitive strain.

Producing toxic chemicals to suppress both the growth and survivorship of local competitors is called allelopathy; some strains of the bacteria Escherichia coli produce a toxin (named colicin) which may kill colicin-sensitive neighbors while they themselves are immune. In a previous paper, the competitive outcome between colicin-producing and colicin-sensitive strains was shown to differ between a spatially structured and a completely mixed population. In this paper, we analyze the role of a third, "colicin-immune," strain, which does not produce colicin but is immune to it. Without spatial structure, the colicin-immune strain suppresses the colicin-producing strain and enables the colicin-sensitive strain to win. In a spatially structured population, modeled as a reaction-diffusion system, we examine the speed of boundaries between areas dominated by different strains in traveling waves and the events after the collision of two such boundaries. The colicin-immune strain passes through the area dominated by the colicin-sensitive strain and drives the colicin-producing strain to extinction. Subsequently the colicin-sensitive strain occupies the whole population.

Alleles↗
PubMed2000

Role of Pararectal Retroperitoneal Approach in Abdominal Aortic Aneurysm Repair.

To evaluate the appropriate use of the pararectal retroperitoneal approach (RPA) in abdominal aortic aneurysm (AAA) repair, we retrospectively compared the RPA with the transperitoneal approach (TPA). Fifty-four patients in whom the RPA was used and 92 who had the TPA were included in the study. The mean operating time was 286 minutes with the RPA and 252 minutes with the TPA. Intraoperative blood transfusions were necessary in 9.3% of patients who had the RPA and 16.2% who had the TPA. As assessed by computerized tomographic scanning, the mean size of the postoperative retroperitoneal hematoma was 440 mL in the RPA group and 180 mL in the TPA group. Ileus resolved a mean of 3 days postoperatively in the RPA group and 5 days postoperatively in the TPA group. The mean length of postoperative hospitalization was 21 days in the RPA group and 23 days in the TPA group. Prolonged postoperative ileus occurred in no patients in the RPA group and in three patients in the TPA group. None of the differences in outcomes between the groups were significant. Our findings indicate that, in carefully selected patients, the pararectal RPA is suitable for AAA repair.

Journal Article↗
PubMed2000

Acute eosinophilic myocarditis in a young woman.

The first stage of eosinophilic myocarditis is called the necrotizing phase. This stage of eosinophilic myocarditis of unknown cause is often fulminant and rapidly fatal, occurring predominantly in males. Here, we report a case of eosinophilic myocarditis in the acute necrotizing phase occurred without known cause in a 23-year-old Japanese female. Severe diffuse hypokinesis of the left ventricular wall motion (ejection fraction 19.3%), significant concentric edematous thickening of the left ventricular wall (20.1 mm in diastole) and a moderate amount of pericardial effusion (10 mm wide echo free space posteriorly) were revealed by echocardiography. Eosinophils were observed and degranulated eosinophilic cationic proteins were stained with antibody against eosinophilic cationic proteins (EG2) in the myocardial specimens obtained by myocardial biopsy. In spite of its severity, the disease resolved promptly with steroid therapy.

Acute Disease↗
PubMed1999

Surgical strategy for abdominal aortic aneurysm with concurrent symptomatic malignancy.

In an attempt to improve the guidelines for concurrent management of concomitant abdominal aortic aneurysm (AAA) and symptomatic malignancy, a retrospective study was undertaken. A total of 186 AAA repairs were performed electively, and 25 patients (13.4%) had concurrent symptomatic malignancy from April 1986 to March 1997. Fourteen patients underwent a one-stage operation, including five abdominoperineal rectal resections, four subtotal gastrectomies, three total gastrectomies, and two right hemicolectomies. Eleven others underwent a two-stage operation, including four with total gastrectomy and left hemicolectomy followed by AAA repair, as well as two with right hemicolectomy and one with left hemicolectomy prior to AAA repair. There were no operative deaths or severe postoperative complications. Of the 25 patients, 22 (88.0%) are still alive during follow-up ranging from 8 months to 11 years. Our surgical approach to both lesions is as follows: (1) Using the transperitoneal approach alone, subtotal gastrectomy and abdominoperineal rectal resection can be safely done simultaneously. (2) Although total gastrectomy can also be performed concurrently, the approach used for each lesion is separate. (3) Colorectal resection is generally done separately. However, a one-stage operation can be performed using the thromboexclusion procedure for AAA repair in patients with right-sided colonic cancer or a temporary transverse colostomy for left-sided colorectal cancer.

Aged↗
PubMed1999

Celiomesenteric anomaly with concurrent aneurysm.

We describe a rare case of a celiomesenteric anomaly with concurrent aneurysm. The patient, a 53-year-old man, had no abdominal pain or discomfort. The presence of a celiac artery aneurysm was suspected on the basis of the results of abdominal computerized tomographic scanning and echo ultrasound scanning performed because of proteinuria. Intra-arterial digital subtraction angiographic results showed the anomaly and aneurysm. Because of the risk of rupture of the aneurysm, the lesion was repaired surgically, with the placement of an interpositional prosthetic graft. We found no previous reports of celiomesenteric anomaly with concurrent aneurysm repaired with prosthetic graft.

Aneurysm↗
PubMed1999

Role of dipyridamole myocardial scintigraphy in abdominal aortic aneurysm repair.

BACKGROUND: We evaluated the usefulness of preoperative dipyridamole myocardial scintigraphy (DMS) under low-level exercise in predicting postoperative cardiac problems in patients undergoing elective abdominal aortic aneurysm (AAA) repair. METHODS EXPERIMENTAL DESIGN: retrospective comparison of patients who did and did not undergo the investigation preoperatively. SETTING: at the Keio University Hospital and the Kawasaki City Hospital. PATIENTS: eighty-five patients who had abdominal aortic aneurysm repair consecutively from 1986 to 1990 without undergoing dipyridamole myocardial scintigraphy preoperatively were compared with 118 patients who underwent the repair consecutively from 1991 to 1997 after having had preoperative scintigraphy. MEASUREMENTS: postoperative occurrences of myocardial infarction and angina pectoris in the two groups of patients were compared statistically. RESULTS: In the group not having scintigraphy, cardiac events occurred in 12 patients (14.1%) after repair. Ten patients had a myocardial infarction; six died within 30 days of operation and four died after the 31st postoperative day. The other two patients had angina pectoris; both survived. In the group having scintigraphy, there were no postoperative cardiac events (p<0.001). Seventeen patients had positive results on preoperative scintigraphy. Seven of them had undergone coronary artery bypass grafting and five coronary angioplasty before the repair. In the five other patients, scintigraphy, was found to have yielded false positive results. CONCLUSIONS: Dypiridamole myocardial scintigraphy is an accurate predictor of postoperative myocardial infarction and angina pectoris in patients being evaluated for elective abdominal aortic aneurysm repair and should be used routinely.

Aged↗
PubMed1998

Score-dependent fertility model for the evolution of cooperation in a lattice.

The evolution of cooperation is studied in a lattice-structured population, in which each individual plays the iterated Prisoner's Dilemma game with its neighbors. The population includes Tit-for-Tat (TFT, a cooperative strategy) and All Defect (AD, a selfish strategy) distributed over the lattice points. An individual dies randomly, and the vacant site is filled immediately by a copy of one of the neighbors in which the probability of colonization success by a particular neighbor is proportional to its score accumulated in the game. This "score-dependent fertility model" (or fertility model) behaves very differently from score-dependent viability model (viability model) studied in a previous paper. The model on a one-dimensional lattice is a analysed by invasion probability analysis, pair-edge method mean-field approximation, pair approximation, and computer simulation. Results are: (1) TFT players come to form tight clusters. When the probability of iteration w is large, initially rare TFT can invade and spread in a population dominated by AD, unlike in the complete mixing model. The condition for the increase of TFT is accurately predicted by all the techniques except mean-field approximation; (2) fertility model is much more favorable for the spread of TFT than the corresponding viability model, because spiteful killing of neighbors is favored in the viability model but not in the fertility model; (3) eight lattice games on two-dimensional lattice with different assumptions are examined. Cooperation and defects can coexist in the models of deterministic state change but not in the models of stochastic state change.

Biological Evolution↗
PubMed1998

Evaluation of damaged small intestine of mouse following methotrexate administration.

PURPOSE: Methotrexate (MTX) treatment causes damage to the small intestine, resulting in malabsorption and diarrhea. The active and passive transport capacities of the small intestine are decreased by the treatment. The purpose of this study was to evaluate the damage to the small intestine of mice caused by MTX administration by examining the permeability of the paracellular pathway of the small intestinal epithelium. METHODS: MTX was administered orally to male ddY mice once daily for 1-6 days. The permeability of the small intestine to the nonabsorbable markers phenol red (PR) and fluorescein isothiocyanate (FITC) dextrans was examined using everted segments of the intestine. RESULTS: PR and FITC dextran permeation through the small intestine increased significantly in parallel with changes in body weight of the mice, wet weight of the small intestine and chemical composition of the small intestinal epithelium. CONCLUSIONS: In addition to changes in permeation through the transcellular pathway reported previously, this study revealed that MTX treatment disorders the paracellular barrier function of the small intestinal epithelium, resulting in increased permeation of nonabsorbable markers via the paracellular pathway of the small intestinal mucosa. The present approach to the examination of the barrier function of the intestinal epithelium could be of great use in evaluating the damage to the small intestine and malabsorption.

Administration, Oral↗
PubMed1998

Docosahexaenoic acid exhibits a potent protection of small intestine from methotrexate-induced damage in mice.

Oral administration of methotrexate (MTX) to mice causes the damage of small intestine. The permeability of poorly absorbable compound fluorescein isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) through the small intestine was studied in vitro using everted segments of the small intestine. The permeability of FITC-dextran increased remarkably in the MTX-treated mice and oral administration of docosahexaenoic acid ethyl ester (DHA) protected the small intestine from the increase in the small intestinal permeability induced by the MTX treatment. The MTX treatment decreased retinol concentration in plasma of mice and the coadministration of DHA maintained its concentration to the level of control mice. The present study showed that DHA protected the small intestine of mice from the MTX-induced damage.

Animals↗
PubMed1998

[Assessment of ischemic heart disease by dipyridamole stress electrocardiographic gated myocardial single photon emission computed tomography with technetium-99m tetrofosmin].

Simultaneous assessment of stress perfusion and rest function is possible with gated single photon emission computed tomography (SPECT) using stress injected technetium-99m (99mTc) tetrofosmin (TF). The feasibility of dipyridamole stress electrocardiographic gated myocardial SPECT (GSPECT) with TF was examined as an alternative to conventional stress/rest imaging. Fifty-one patients underwent stress GSPECT. 740 MBq of TF was administered 3 min after dipyridamole infusion. GSPECT acquisition was performed one hour after the injection. Additional rest SPECT was performed on another day only in patients with abnormal perfusion on stress images. Perfusion and thickening were analyzed visually on 17 segments of the left ventricle. Percentage of wall thickening (%WT) was also calculated in 17 segments of the polar map. Thirty-two of 51 patients (63%) had normal stress perfusion and normal rest thickening. Nineteen of 51 patients (37%) had abnormal perfusion on stress images. Among 157 abnormal perfusion segments of the 19 patients, 139 segments (89%) had thickening and the rest (11%) had no thickening. %WT was higher in the reversible segments with or without thickening. There was better agreement for the identification of normal segments and the presence of reversibility between stress GSPECT and the conventional stress/rest study in patients without previous myocardial infarction than in those with previous myocardial infarction (89% vs 79%). These results suggest that stress GSPECT may substitute for conventional stress/rest perfusion study in patients without previous myocardial infarction, allowing shorter examination time and lower cost. However, stress GSPECT does not replace the need for rest perfusion study in patients with previous myocardial infarction, because of underestimation of viability, but %WT may eliminate this underestimation.

Aged↗
PubMed1997

The evolution of cooperation in a lattice-structured population.

The evolution of cooperation among unrelated individuals is studied in a lattice-structured habitat, where individuals interact locally only with their neighbors. The initial population includes Tit-for-Tat (abbreviated as TFT, indicating a cooperative strategy) and All Defect (AD, a selfish strategy) distributed randomly over the lattice points. Each individual plays the iterated Prisoner's Dilemma game with its nearest neighbors, and its total pay-off determines its instantaneous mortality. After the death of an individual, the site is replaced immediately by a copy of a randomly chosen neighbor. Mathematical analyses based on mean-field approximation, pair approximation, and computer simulation are applied. Models on one and two-dimensional regular square lattices are examined and compared with the complete mixing model. Results are: (1) In the one-dimensional model, TFT players come to form tight clusters. As the probability of iteration w increases, TFTs become more likely to spread. The condition for TFT to increase is predicted accurately by pair approximation but not by mean-field approximation. (2) If w is sufficiently large, TFT can invade and spread in an AD population, which is impossible in the complete mixing model where AD is always ESS. This is also confirmed by the invasion probability analysis. (3) The two-dimensional lattice model behaves somewhat in between the one-dimensional model and the complete mixing model. (4) The spatial structure modifies the condition for the evolution of cooperation in two different ways: it facilitates the evolution of cooperation due to spontaneously formed positive correlation between neighbors, but it also inhibits cooperation because of the advantage of being spiteful by killing neighbors and then replacing them.

Animals↗
PubMed1997

Plasma angiotensinogen concentrations in obese patients.

A close relationship between obesity and hypertension has been recognized, and plasma angiotensinogen concentrations (p-AGT) have been reported to correlate with blood pressure (BP). However, little is known about AGT in obese patients with hypertension. To define the role of AGT in obese hypertension, we measured p-AGT in obese patients. The subjects were 42 obese patients diagnosed on the basis of a body mass index (BMI) of more than 25 kg/m2, and 21 sex- and age-matched nonobese patients, whose BMI was less than 25 kg/m2. The hypertensive patients had not previously received antihypertensive drugs. P-AGT (P < .05) and mean BP (P < .0001) was increased in the obese patients as compared with the nonobese patients. Positive correlations were observed between BMI and p-AGT, mean BP and p-AGT, and BMI and mean BP (all P < .05). However, after adjustment for blood pressure, p-AGT was not different between groups, and after adjustment a positive correlation remained only between BMI and mean BP. These results suggested the possible involvement of increased p-AGT in hypertension in obese patients, although this may be a secondary change to hypertension or obesity.

Adult↗
PubMed1997

Tissue angiotensinogen gene expression induced by lipopolysaccharide in hypertensive rats.

There is now convincing evidence that various tissues express their own tissue renin-angiotensin system, which may be regulated independently of the systemic renin-angiotensin system. However, little information is available on the regulation of the tissue renin-angiotensin system. We investigated the regulation of tissue angiotensinogen gene expression with respect to the development of hypertension. We measured basal and lipopolysaccharide-stimulated plasma angiotensinogen concentrations by radioimmunoassay and examined the expression of tissue angiotensinogen by Northern blot analysis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 and 13 weeks of age. Basal plasma angiotensinogen concentration in SHR was comparable to that in WKY at 4 weeks of age and was significantly higher than that in WKY at 13 weeks of age. Lipopolysaccharide induced a significant increase in plasma angiotensinogen concentration in both WKY and SHR at 4 and 13 weeks of age. At 4 weeks of age, the basal levels of angiotensinogen mRNA in the liver, fat, adrenal, and aorta were higher in WKY than in SHR. At 13 weeks of age, the basal levels of angiotensinogen mRNA in the fat, adrenal, aorta, spleen, and kidney were higher in WKY than in SHR, while that in the liver did not differ significantly between the two strains. At 4 weeks of age, pretreatment with lipopolysaccharide increased the angiotensinogen mRNA levels in the liver, fat, adrenal, and aorta in both WKY and SHR. At 13 weeks of age, pretreatment with lipopolysaccharide increased the angiotensinogen mRNA levels in the liver, aorta, and adrenal; decreased those in the spleen; and had no effect in the kidney in both WKY and SHR. Interestingly, lipopolysaccharide increased the angiotensinogen mRNA level in fat only in SHR, with no effect in WKY, at 13 weeks of age. Lipopolysaccharide stimulated tumor necrosis factor-a mRNA expression in fat of WKY and SHR, and the increase in tumor necrosis factor-alpha mRNA level in SHR was significantly greater than that in WKY. Therefore, the increased tumor necrosis factor-alpha mRNA expression may be involved in the increased lipopolysaccharide-induced expression of angiotensinogen gene in fat of SHR at 13 weeks of age. These data suggest that the transcriptional and probably posttranscriptional regulation of angiotensinogen mRNA differs between SHR and WKY, that the regulation of angiotensinogen gene expression is tissue-specific, and that the altered expression of the angiotensinogen gene may be involved in the development of hypertension.

Angiotensinogen↗
PubMed1991

Angiotensin converting enzyme inhibitors suppress the vascular renin-angiotensin system of spontaneously hypertensive rats.

The effects of angiotensin converting enzyme (ACE) inhibitors on the release of angiotensin II (Ang II) from isolated mesenteric arteries of spontaneously hypertensive rats (SHRs) were examined. Delapril, enalapril, and captopril suppressed Ang II release in a dose-dependent manner. After oral treatment with delapril (10 mg/kg/day), enalapril (10 mg/kg/day), and captopril (50 mg/kg/day) for 1 week, the blood pressure of SHRs was significantly reduced in the three groups and 54%, 46%, and 36% decreases in basal Ang II release were observed, respectively, compared with control. However, low-dose captopril (10 mg/kg/day) had no effect on blood pressure or basal Ang II release. These results provide clear evidence that ACE inhibitors suppress vascular renin-angiotensin activity of SHRs, and the possible contribution of the tissue renin-angiotensin system to spontaneous hypertension is suggested.

Angiotensin II↗
PubMed1991

Converting enzyme inhibitors regressed cardiac hypertrophy and reduced tissue angiotensin II in spontaneously hypertensive rats.

To examine the role of the tissue renin-angiotensin system in left ventricular hypertrophy, converting enzyme inhibitors were administered orally to 12-week-old male spontaneously hypertensive rats (SHR) for 4 weeks, and cardiac tissue angiotensin II was measured. Treatment with enalapril (10 mg/kg per day) and trandolapril (1 mg/kg per day) lowered systolic blood pressure, left ventricular weight and left ventricular angiotensin II content. Plasma angiotensin II concentration was increased by the treatment with enalapril whereas trandolapril did not cause any change. There was significantly positive correlation between left ventricular weight and angiotensin II content. Because angiotensin II promotes cell proliferation, these results suggest that cardiac tissue angiotensin II, rather than circulating angiotensin II, may account for the pathophysiology of left ventricular hypertrophy in SHR.

Angiotensin II↗