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Biomedical subjects

N Kubo

Publications and source records attributed to N Kubo.

At least 37 records · Page 2Linked to original sources

Helicobacter pylori infection and coronary heart disease in Japanese patients.

Although several independent studies have claimed a link between Helicobacter pylori infection and coronary heart disease (CHD), this association has not been established conclusively. The aim was to determine whether an association between H. pylori infection and CHD can be demonstrated in Japanese patients. Three-hundred and four patients who underwent consecutive coronary arteriography were investigated. Ninety-four patients had single-vessel coronary stenosis and 112 had multi-vessel stenosis. The remaining 98 patients had no significant stenosis in any coronary arteries. H. pylori infection was diagnosed serologically and the association between infection and CHD was estimated by the odds ratio. The serum pepsinogen (PG) I-II ratio was used to estimate the degree of gastric atrophy. Seropositivity for H. pylori was significantly higher in the patients with CHD (67%) than in the controls (50%; p = 0.006). The odds ratio for CHD after having H. pylori infection was estimated as 1.35 (95% confidence interval 1.03-1.78; p = 0.028), after adjustment for the common risk factors of CHD in a logistic regression analysis. The association between CHD and H. pylori infection was more significant among patients without any history of diabetes or smoking. The PG I-II ratio in H. pylori-positive patients was significantly higher in the multi-vessel group (3.46) than in the control or single-vessel group (2.86, p = 0.030; 2.78, p = 0.008; respectively). H. pylori infection was shown to be an independent risk factor for CHD in Japanese patients, especially among those who did not have a history of diabetes or smoking. These data imply that the association between H. pylori infection and CHD is clinically relevant.

Adult↗

Effect of gamma-irradiation and bone marrow transplantation on atherosclerosis in LDL receptor-deficient mice.

Bone marrow transplantation (BMT) is commonly used to study the participation of bone marrow-derived cells in atherosclerosis. To determine the effect of this methodology on lesions, 16 male low density lipoprotein (LDL) receptor knockout (LDLr-/-) mice were reconstituted with bone marrow from syngeneic LDLr-/- mice after 10 Gy gamma-irradiation and compared with 12 male LDLr-/- littermates that did not undergo BMT (no-BMT group). Mice were fed a high fat diet (HFD) for 16 weeks to induce atherosclerosis. Sixteen additional LDLr-/- mice underwent BMT, and 12 male LDLr-/- mice that did not undergo BMT were fed a chow diet for 56 weeks. Thoracic aorta lesion areas were smaller in BMT mice than in no-BMT mice fed the HFD (P<0.0001). In contrast, aortic root lesion areas were greater in the BMT mice fed the HFD (P<0.0001) as well as in those fed the chow diet (P=0.0001). Abdominal aorta free cholesterol and cholesteryl ester mass were minimal in all groups studied. Aortic root lesions from all no-BMT mice were densely collagenous and encapsulated by a cellular cap, whereas lesions in the BMT mice contained lipid cores and minimal collagen staining. Although the reason for these differences in lesion size and composition remains unresolved, this study suggests that multiple parameters of lesion formation should be examined to assess atherosclerosis.

Animals↗

Vasospastic total occlusion at the left main tract in a single coronary artery.

A 64-year-old man was admitted to hospital under the suspicion of unstable angina pectoris. Coronary angiography showed that he has a single coronary artery originating from the right coronary artery (RCA) without significant fixed stenosis. Acetylcholine was superselectively infused into the left main coronary artery (LMCA), and confirmed the coronary vasospastic occlusion associated with chest pain and elevation of the ST-segment in the precordial leads. This is the first report of the induction of a totally occlusive spasm of the LMCA of a patient with a RCA type single coronary artery, and this case suggests that spasm of the aberrant coronary artery is a potential mechanism for sudden death in patients with a single coronary artery.

Angina Pectoris, Variant↗

Helical computer assisted tomography in pulmonary hypertension complicating left-to-right shunts--correlation with pulmonary hemodynamics.

The present study analyzed the helical computer-assisted tomography (CAT) findings in 30 patients with pulmonary hypertension (PH) associated with left-to-right shunts; specifically, ventricular septal defect, 23; atrioventricular septal defect, 6; patent ductus arteriosus, 1. Eight patients had 21 trisomy. Age ranged from 1 to 18 (mean, 4.1) months, and body weight ranged from 2.6 to 10.7 (mean, 4.9) kg. In all patients, the chest CAT revealed patchy areas of high and low attenuation (mosaic pattern) and regional atelectasis in the lung fields. The volume of low attenuated lesions and of atelectasis, and the total lung volume were derived from integration of areas measured on the CAT image. The ratios of low attenuated lesion/total lung volume (Lo), volume of atelectasis/ total lung volume (Ate) and low attenuated lesion and volume of atelectasis/total lung volume (Lo&Ate) were compared with hemodynamic parameters measured at cardiac catheterization. The pulmonary to systemic resistance ratio correlated with Lo (r=0.61, p<0.01) and Lo&Ate (r=0.69, p<0.01), whereas the pulmonary vascular resistance correlated with Ate (r=0.53, p<0.01). Lo, Ate and Lo&Ate in the chest CAT are reliable parameters that can be used to estimate pulmonary vascular resistance in patients with PH associated with left-to-right shunts.

Cardiac Catheterization↗

Transient ventricular wall thickening in acute myocarditis: a serial echocardiographic and histopathologic study.

The present study was designed to determine whether the wall thickening seen in acute myocarditis is caused by interstitial edema. The study group comprised 25 patients (idiopathic myocarditis, 17; eosinophilic myocarditis, 8) in whom acute myocarditis was diagnosed histologically and who underwent echocardiography and endomyocardial biopsy during both the acute and convalescent phases. The following echocardiographic parameters were measured: interventricular septum and left ventricular posterior wall thickness, left ventricular end-diastolic dimension, and left ventricular ejection fraction. Based on the myocardial biopsy specimens, the degree of interstitial edema was classified into 3 grades [(-), 1(+), 2(+)] and the transverse diameter of cardiac myocytes was measured using light microscopy. The thickness of both the interventricular septum and left ventricular wall decreased from 14.3+/-3.7 mm and 13.3+/-2.4 mm in the acute phase to 9.7+/-1.7 mm (p<0.001) and 10.2+/-1.7 mm (p<0.0001), respectively, in the convalescent phase. Edema was present in 22 patients (88.0%) in the acute phase, but in the convalescent phase, edema was present in only 7 patients (28.0%), indicating a significant reduction in the degree of edema (p<0.0001). Cardiac myocyte diameter did not differ significantly between the acute (13.6+/-1.1 microm) and convalescent (13.8+/-1.8 microm) phases.

Acute Disease↗

[Apical ballooning by transient left ventricular dysfunction (so-called "ampulla" cardiomyopathy) associated with therapy for acute pulmonary thromboembolism: a case report].

An 86-year-old-woman presented with apical ballooning left ventricular dysfunction associated with therapy for acute pulmonary thromboembolism. She was referred to our hospital for advanced treatment for her shock state due to acute pulmonary embolism with normal left ventricular(LV) function. Her condition was stabilized using a percutaneous cardiopulmonary support system. Suction embolectomy was successfully carried out after pulmonary arteriography. After the therapy, echocardiography revealed apical ballooning and hyperkinesis of the base(LV ejection fraction = 28%), although coronary arteriography showed no fixed stenosis. LV wall motion significantly improved on day 3(LV ejection fraction = 45%). Pulmonary embolism relapsed on day 5 in spite of anticoagulation treatment. She died of multiple organ failure on day 9. Autopsy findings indicated no sign of myocardial infarction or myocarditis, patchy appearance of myocardial contraction band necrosis and few migrated lymphocytes. The mechanism for the flow mis-matched LV dysfunction remains unknown. The probable explanations include non-ischemic stress such as catecholamine or neurogenic stress, and possibly ischemic stress or ischemia/reperfusion injury.

Aged↗

[Responses to a questionnaire on laboratory examinations performed by graduates of Jichi Medical School in rural practice].

Graduates from Jichi Medical School are obligated to work at rural clinics or hospitals, where most of them are the only medical doctor in the house. Our need to continuously improve medical education, including the learning that takes place in the clinical setting, requires us to understand how these graduates actually use laboratory examinations and what examinations they find most important in their practice. We designed a questionnaire to address these questions. Three hundred sixty-eight graduate physicians working at clinics or hospitals in both rural or urban areas were asked to complete the questionnaire, providing information on the size of their institution, the laboratory equipment and examinations that they have direct access to, and what examinations they find most important. Two hundred seventy-eight (75.5%) of the 368 recipients responded. More than seventy percent of the respondents reported that their institutions had electrocardiographs, abdominal and cardiac ultrasonographs, urinalysis test paper, and portable blood glucose meters; and more than half of them reported having used these instruments without assistance in emergency situations and outside of ordinary office hours. Moreover, a majority of the respondents said that they considered it important that a physician is able to use these instruments without the help of other staff members. These responses clearly show the importance and usefulness of covering examination techniques and the principles of laboratory medicine in medical education.

Attitude of Health Personnel↗

[Intracranial capillary hemangioma: a case report].

Capillary hemangiomas are the most common tumor of the neck and head in children. Intracranial capillary hemangioma without generalized neuro-cutaneous hemangiomatosis is extremely rare, with only one report in the literature. We report a case of intracranial capillary hemangioma originating from the temporal base. An 8-year-old boy presented with a severe headache and nausea. A CT scan showed a low-density area in the left temporal lobe and an iso-density mass at the temporal base. This mass was enhanced by contrast medium. The mass lesion appeared as an iso-intensity area on T1-weighted MR images and as a high-intensity area on T2-weighted MR images, and the mass was enhanced almost uniformly by gadoliniumdiethylene triaminepenta-acetic acid. Cerebral angiography showed abnormal staining fed by the anterior temporal artery. An operation was performed, and all of the tumor with the dura attached was removed. The histological diagnosis was capillary hemangioma. The tumor consisted of a proliferation of capillary vessels lined by a single layer of endothelial cells. In this paper, we review the clinical features, neuro-imaging findings and proposed etiology of capillary hemangioma.

Brain Neoplasms↗

Development of antibody against epitope of lipoprotein(a) modified by oxidation: evaluation of new enzyme-linked immunosorbent assay for oxidized lipoprotein(a).

BACKGROUND: Recently, the biological effects of oxidized lipoprotein(a) [Lp(a)] have been reported to be more potent than Lp(a), the arteriosclerosis-relevant lipoprotein. Thus, investigations with oxidized Lp(a) are expected to provide viewpoints different from the conventional ones based on Lp(a). METHODS AND RESULTS: An anti-Lp(a) monoclonal antibody (161E2) was produced against synthetic peptide antigen (Arg-Asn-Pro-Asp-Val-Ala-Pro). This epitope was characterized as having various properties because its external exposure was induced as a result of oxidative modification. Using 161E2 antibody, we developed a new enzyme-linked immunosorbent assay to measure Lp(a) modified by oxidative stress. The present data demonstrated that oxidized Lp(a) that contains the epitope of 161E2 antibody was present in the serum of humans. Therefore, we used this new enzyme-linked immunosorbent assay to evaluate the role of oxidized Lp(a) in patients with hypertension, which induces oxidative stress. Interestingly, hypertensive patients with complications showed a significantly higher level of oxidized Lp(a) in serum than did normotensive subjects (P:<0.01), whereas there was no significant difference in native Lp(a) between normotensive and hypertensive subjects. Importantly, positive immunostaining with 161E2 monoclonal antibody was found in the human arteriosclerotic tissue. CONCLUSIONS: We developed a new antibody against an epitope in Lp(a) as a result of oxidation treatment but not in native Lp(a). The present data demonstrated in vivo the presence of oxidized Lp(a) in the atherosclerotic tissue and its elevation in hypertensive patients. The presence of oxidized Lp(a) may be important in understanding the role of Lp(a) in cardiovascular disease.

Animals↗

Regulation of macrophage-specific gene expression by degenerated lipoproteins.

The effect of aggregated low-density lipoprotein (agLDL) on cell viability and macrophage-specific gene expression using human peripheral blood monocytes in culture was investigated. AgLDL suppressed activation-induced cell death of phorbol ester-treated macrophages. The inhibition of apoptosis was accompanied by downregulation of apoptosis-promoting proteases, including interleukin-1beta-converting enzyme (ICE) and CPP32 and upregulation of anti-apoptotic cytokine (interleukin-1beta (IL-1beta)). In contrast, macrophage-colony stimulating factor (M-CSF) enhanced cell death of lipid-bearing macrophages, suggesting that the anti-atherogenic action of M-CSF is at least in part mediated through apoptotic elimination of macrophages. Then, we attempted to isolate the genes specifically induced by agLDL in macrophages using a subtraction-based cloning strategy. One of the genes isolated, termed LIG (LDL-inducible gene), encodes a human homolog of E2 ubiquitin-conjugating enzyme. Ubiquitination of multiple intracellular proteins was observed in agLDL-treated macrophages, which coincided with upregulation of LIG. These results suggest that LIG acts as a direct mediator of foam cell formation through polyubiquitination and subsequent degradation of cellular proteins with apoptosis-inducing properties. The regulation of apoptosis by macrophage-specific gene expression may contribute to foam cell formation and atherosclerosis.

Apoptosis↗

A new dynamic myocardial phantom for the assessment of left ventricular function by gated single-photon emission tomography.

Gated myocardial perfusion single-photon emission tomography (SPET) has been used for the measurement of left ventricular (LV) function and validated by means of comparison with other imaging modalities. We have designed a new dynamic myocardial phantom in order to validate the LV function as assessed by the use of gated myocardial perfusion SPET. The phantom consists of two half-ellipsoids (an endocardial surface and an epicardial surface) and a thorax. The myocardial space is filled with a radioactive solution. The endocardial surface moves continuously towards and away from the epicardial surface in the longitudinal axis to vary the LV volume [143 ml at end-diastole (ED), 107 ml at end-systole (ES)] and thickness (apex 8 mm at ED and 26 mm at ES, midplane 8 mm). The mean values of wall motion (WM) for the apical midplane region and the basal midplane region were 5 mm and 2 mm, respectively. Gated myocardial SPET was performed during 8 and 16 intervals. These projection data sets were processed using a Butterworth filter with an order of 5 and a critical frequency of 0.34 cycles/cm. LV function was calculated using the quantitative gated SPET (QGS) algorithm. The LV function values estimated by gated SPET during 16 intervals [22% for ejection fraction (EF), 3.7 mm for WM of the apical midplane, 1.7 mm for WM of the basal midplane] closely resembled actual LV functions [25% for EF, 5 mm for WM of the apical midplane, 2 mm for WM of the basal midplane]. However, the estimated values during 8 intervals were smaller than those during 16 intervals (19% for EF, 3.3 mm for WM of the apical-midplane, 1.1 mm for WM of the basal-midplane). The estimated LV volumes closely correlated with the actual volumes (r=0.99 for 16 intervals, r=0.95 for 8 intervals). Utilizing this phantom, LV function estimated using gated myocardial SPET can be compared with actual values.

Diastole↗

Transfer of the mitochondrial rps10 gene to the nucleus in rice: acquisition of the 5' untranslated region followed by gene duplication.

Mitochondrial ribosomal protein S10 (rps10) is encoded by the mitochondrial genome in potato and pea. Here we show that the rps10 gene is absent from the mitochondrial genome of rice and has been transferred to the nucleus. Cloning and transcriptional analysis show that there are two rps10 genes in the rice nuclear genome and that their transcripts differ in abundance. Western analysis detected the RPS10 protein in the soluble fraction of rice mitochondria, although neither RPS10 has any obvious N-terminal presequence for targeting to mitochondria. This result suggests that targeting information is present in the internal region of rice RPS10. Genomic sequence analysis indicated that each rps10 gene has an intron in the 5' untranslated region (5' UTR) and that these intron sequences are homologous to each other. This result strongly suggests that a duplication event occurred after transfer of the rps10 gene to the nucleus. The duplicated rps10 genes have since been translocated to different chromosomes, because the two rps10 genes were mapped on chromosomes 6 and 12 by RFLP analysis. Interestingly, the 5' UTR and the intron of the rice rps10 genes are homologous to sequences found in several rice genes with various functions, such as osk4, EF-1beta2 and RAG1, suggesting a common origin and a functional role for the 5' UTR. Acquisition of the 5' flanking region might have accelerated the activation of the mitochondrial rps10 gene which was transferred to the nuclear genome.

5' Untranslated Regions↗

Injury to the gastric mucosa and cellular dynamics in a rat model of duodenogastric reflux: the possible significance of gastrin induction and a heat shock protein.

Injury to the gastric mucosa caused by duodenogastric reflux (DGR) is often encountered after gastrectomy or truncal vagotomy (V) with pyloroplasty. This study was designed to investigate the histological features of the gastric mucosa under such conditions. A rat model of DGR and DGR+V was established and the thickness of the oxyntic mucosa was measured. Cellular dynamics in the presence of injury to the gastric mucosa caused by DGR were investigated by the immunohistochemical staining of bromodeoxyuridine (BrdU) and heat shock protein 70 (HSP70). The relationship between persistent hypergastrinemia and mucosal injury was also studied. Duodenogastric reflux activated the intracellular induction of HSP70 in our rat model of DGR. Hypergastrinemia was noted in the V group. Compared with values from the DGR group, the numbers of BrdU-labeled cells increased, the glandular proliferation zone expanded, and the thickness of the oxyntic mucosa was significantly higher in the DGR+V group. Compared with the DGR group, there was greater induction of HSP in the DGR+V group during the acute stage. This finding suggests that denervation of the gastric mucosa and hypergastrinemia after vagotomy may be associated with the expression of HSP.

Animals↗

Development of an inveterate gastroduodenal ulcer caused by antral G-cell hyperplasia of the stomach (pseudo-Zollinger-Ellison Syndrome): report of a case.

We describe herein the case of a 54-year-old Japanese woman in whom an inveterate peptic ulcer developed in association with pseudo-Zollinger-Ellison Syndrome (pseudo-ZES). The patient presented with weight loss and abdominal distension caused by antral and duodenal stenosis due to an inveterate peptic ulcer. Her serum gastrin level was very high; however, no evidence of a gastrinoma or carcinoid tumor was detected by preoperative examinations or surgery. A total gastrectomy and double-tract reconstruction was performed, and pathological examination revealed a gastric ulcer (UL-IV) with no histopathological evidence of a neoplasm. Immunohistochemical staining showed an obvious increase in the number of endocrine cells that were positive for chromogranin A, and marked G-cell hyperplasia was observed in the antral mucosa. Furthermore, the number of enterochromaffin-like cells was remarkably high. From the results of the immunohistochemical examination, the patient was diagnosed as having hypergastrinemia due to antral G-cell hyperplasia. Postoperatively, the patient's serum gastrin level fell rapidly to within the normal range, her nutritional status improved, and her weight increased by about 10 kg within 1 year.

Diagnosis, Differential↗

Phase II trial of pre-irradiation KRN8602 (MX2) in malignant glioma patients.

KRN8602 (MX2) is a newly developed morpholino anthracycline that crosses the blood-brain barrier where it becomes distributed in brain tissue after intravenous administration. This morpholino anthracycline has been found to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo, We performed a phase II trial using KRN8602 as a single agent in malignant glioma patients who had not received prior adjuvant therapy. The 13 patients (5 glioblastomas, 7 anaplastic astrocytomas and 1 malignant oligodendroglioma) enrolled received at least 1 cycle of KRN8602 at 35 mg/m2/day in 3-4 week intervals by intravenous bolus. Ten of these patients could be evaluated for response, and 13 for toxicity. Three patients (1 glioblastoma and 2 anaplastic astrocytomas) demonstrated a complete response (3/10, 30%). Concerning side effects, myelosuppression was moderately severe, with 30.7% of patients developing grade 3 leukopenia. Severe nausea/vomiting was observed in 69% of the patients, however, cardiotoxicity was not observed. The results indicate that KRN8602 demonstrated modest activity against malignant glioma with relatively severe, but manageable toxicity. Further assessment of the efficacy and toxicity of KRN8602 against malignant glioma may be worthwhile.

Adult↗

A phase II study of nimustine hydrochloride, cisplatin, and etoposide combination chemotherapy for supratentorial malignant gliomas.

Twenty-eight patients who were previously treated by aggressive surgery and radiation and were diagnosed with supratentorial malignant gliomas received a combination of nimustine hydrochloride; 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), cisplatin and etoposide (ACE therapy) as primary treatment. Cisplatin and etoposide were given at doses of 20 and 60 mg/m2/day for 5 days, respectively, ACNU doses 80 mg/m2/day on the first day. Treatment was repeated at 4-week intervals for up to 3 cycles. Seventeen patients (60.7%) complained of nausea. Grade 3 or 4 hematological toxicity occurred in 11 patients (39.3%), and grade 3 or 4 renal toxicity occurred in 2 patients. The percentage of patients who showed complete or partial response was 28.6% (8/28). The median time of tumor progression was 40 weeks, and the median survival time was 146 weeks. There were some long-surviving patients who may have benefited from ACE combination. This study demonstrated the effects of ACE combination in patients with supratentorial malignant gliomas.

Adult↗

Comparison between segmental wall motion and wall thickening in patients with coronary artery disease using quantitative gated SPECT software.

This study was performed to evaluate regional wall motion (WM) and wall thickening (WT) using gated myocardial perfusion single photon emission computed tomography (SPECT) and to determine their similarity and disparity in patients with coronary artery disease (CAD). A total of 44 patients underwent 1 day stress/rest (MIBI) gated SPECT. Commercially available quantitative analysis of gated SPECT (QGS) software was used to generate 3D surface display and cine-mode SPECT display. Left ventricle was divided into nine segments to score WM and WT from 0 (no abnormality) to 4 (severe abnormality) by six independent observers. Finally a mean score was calculated for each segment from the scores of six observers. There was fairly good correlation between WM and WT of individual segments (r = 0.62, p < 0.0001). Concordance rate (IWM - WTI < 1) was 85%. A large difference between WM and WT (WM - WT > or = 2) was observed in 15 segments, including 12 segments with greater WM abnormalities and 3 segments with greater WT abnormalities (lateral and inferior walls). Greater WM abnormalities were most commonly observed in anteroseptal segments especially in post coronary artery bypass grafting (CABG) patients. In conclusion, WM and WT showed similarity on QGS studies. However, these two parameters may be determined separately in gated SPECT studies for comprehensive and robust evaluation of the functional status of myocardium. Analyses based on WM assessment alone may lead to erroneous results especially in septal regions.

Aged↗