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Biomedical subjects

N Kajiwara

Publications and source records attributed to N Kajiwara.

At least 37 records · Page 2Linked to original sources
PubMed1996

Vertical transmission to embryo and fetus in maternal infection with rat virus (RV).

The influence of maternal rat virus (RV) infection on rat embryogenesis and fetus was examined by viral reisolation, immunostaining and PCR analysis. Vertical transmission caused by the UT-1 strain of RV depended on the stage of gestation when maternal infection occurred. When females were infected at the pre-mating point, the number of fetuses was smaller than that normally obtained, possibly due to infection at the stage of the hatched blastocyst, but almost all of the fetuses obtained were free from infection and developed normally. The incidence of transplacental infection was the highest when pregnant females were infected in the middle of the gestation stage, and some of the fetuses died. In pregnant females which were infected late in the gestation stage, all fetuses developed normally. Some of them were infected transplacentally and harbored the infectious virus. Much attention should be paid to performing reliable rederivation of RV-infected rat colonies by hysterectomy and embryo transfer.

Animals↗
PubMed1995

Changes in the E/A ratio induced by handgrip-exercise are related to changes in the plasma atrial natriuretic peptide level, but not to changes in brain natriuretic peptide in mild essential hypertension.

We investigated the relationship between changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and changes in cardiac function during mild exercise in patients with mild hypertension. The handgrip test (HGT) was performed by 21 untreated, mildly hypertensive patients, mean age 45 +/- 5 years. M-mode and pulse Doppler echocardiograms were recorded before and during HGT. In 7 patients (Group A), diastolic function, which was determined by the peak early velocity and peak atrial velocity (E/A) ratio using Doppler echocardiography was attenuated during HGT (1.19 +/- 0.21 TO 1.04 +/- 0.16, p < 0.05). There was no change in diastolic function in the remaining 14 patients, left atrial diameter, cardiac index, ejection fraction, plasma renin activity, plasma norepinephrine, blood pressure, nor heart rate were different between the two groups. While ANP was increased in Group A during HGT (from 41.0 +/- 18.2 to 54.0 +/- 24.1 pg/ml, p < 0.05) it was unchanged in Group B (36.8 +/- 16.3 to 33.5 +/- 11.9 pg/ml). BNP did not change in either Group (Group A: 2.9 +/- 3.1 to 3.0 +/- 3.4 pg/ml, Group B: 2.6 +/- 1.6 to 3.6 +/- 4.8 pg/ml). The percent change in ANP during HGT did not correlate with the percent change in BNP. Thus, the impairment of cardiac functional reserve appeared to influence ANP excretion in patients with mild hypertension.

Adult↗
PubMed1995

[Staged bilateral upper lobectomy of pathologically different synchronous double primary cancer].

A case of double primary lung cancer was reported, one of which was peripheral type of adenocarcinoma of the right lung and the other was central type of squamous cell carcinoma of the left. A 66-year-old male was referred to our hospital on Nov. 2 1991, because a coin lesion at the right S1 was pointed out on chest X-ray. On bronchoscopy, a nodular tumor at the orifice of the left B3 was unexpectedly found. Biopsy of the left B3 tumor and washing cytology of the right B1 led to a diagnosis of left moderately differentiated squamous cell carcinoma (clinical T1N0 M0) and right adenocarcinoma (clinical T1N0M0). A right upper lobectomy was first performed with R2 lymph node dissection on Nov. 25 1991. Post-operatively, it was confirmed that the lesion was histologically poorly differentiated adenocarcinoma of the right S1, and the pathological stage was T2N0M0. Two weeks after the operation, chemotherapy of CDDP, VDS and MMC was given because of suspicion of rapid metastasis to the left hilar lymph nodes. Left upper lobectomy with R2 dissection was performed 7 weeks after the initial operation. Pathological findings showed squamous cell carcinoma originating from B3 with inflammatory lymphadenopathy and pathological evaluation was T1N0M0. He was discharged after an uneventful course of 3 weeks after the second operation. There are many reports that limited operations are recommended for each lesion in double primary lung cancer to reserve the pulmonary function. However, limited interventions cause frequently local metastasis, especially in peripheral type adenocarcinoma more than 3 cm in diameter and central type squamous cell carcinoma with lymph node metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

The efficacy of monatepil, a new calcium antagonist, in the treatment of essential hypertension.

A multicenter, open-label trial in Japan examined the efficacy, safety, and optimal dose of monatepil (AJ-2615) as monotherapy and in combination therapy with angiotensin-converting enzyme (ACE) inhibitors or beta-blockers. Patients with essential hypertension who had never been treated or had been refractory to conventional antihypertensive agents were enrolled in the trial. During a 4-week control period patients assigned to monotherapy received placebo and those assigned to combination therapy received an ACE inhibitor or beta-blocker and placebo. Patients with systolic blood pressure (BP) > or = 160 mm Hg and diastolic BP > or = 95 mm Hg at the end of the control period were enrolled in the study. The initial dose of monatepil was 30 mg/day in monotherapy and 15 mg/day in combination therapy; the daily dose was titrated to 60 mg/day according to the antihypertensive response. The treatment period was 8 to 12 weeks. Blood pressure decreased from 168 +/- 8/100 +/- 6 to 142 +/- 9/85 +/- 7 mm Hg (SD) with monatepil monotherapy, from 171 +/- 11/102 +/- 6 to 141 +/- 9/84 +/- 6 mm Hg in combination with ACE inhibitors, and from 175 +/- 13/102 +/- 7 to 153 +/- 21/91 +/- 9 mm Hg in combination with beta-blockers (P < .001). When patients in whom mean BP decreased by > or = 13 mm Hg were defined as responders, the response rate was 80.4%, 78.1%, and 51.6% in the respective groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1994

Comparison of manual and computer-assisted automatic measurements of wall thickness of the left ventricle in two-dimensional echocardiography.

To investigate the clinical applicability of automatic analysis of wall thickness in two-dimensional echocardiography, computer-assisted and conventional manual methods were compared in 26 cases. An echo threshold was automatically set in short-axis echo images through a discriminatory variance analysis of the signal-to-noise ratio. A fixed standard was determined inside the left ventricle using the circle window method, which we developed previously. Two abrupt echo reflections were selected as candidate points for the borders, and an outward search was conducted in all directions from a fixed standard to separately delineate the endocardial and epicardial interfaces. Interpolation using a spline function was applied to these points to complete the border lines. Differentiation was also used to eliminate the anterior and posterior papillary muscles. Significant correlations of r = 0.98 were found between the computer and manual assessments of the epicardial and endocardial intraluminal ventricular areas (p < 0.01). A correlation of r = 0.87 was also obtained for myocardial wall thickness as determined by the 2 methods (p < 0.01). Variability of the reproducibility using the computer method was 0.22% for the epicardial area and 0.64% for the endocardial area. These results confirm that computer-aided automatic measurement of wall thickness is clinically applicable to two-dimensional echocardiography.

Adult↗
PubMed1994

Thrombolytic therapy for acute myocardial infarction-effects, problems and strategies.

The effects and problems of coronary thrombolysis (CT) were investigated in 652 patients with initial acute myocardial infraction (AMI). Nosocomial mortality obtained by matching factors which determined prognosis was significantly lower in patients treated by CT (8.3%) than in those who did not undergo CT (18.1%). Regardless of whether the treatment was intracoronary arterial (ICT) or intravenous (IVCT), the primary cause of the decreased mortality was reperfusion of the coronary artery responsible for infarction (mortality 6.1% in the reperfused group vs 21.5% in the ineffective group). CT therapy improved left ventricular ejection fraction (LVEF), the nosocomial mortality rate, and regional wall motion at the site of infarction in cases that were reperfused less than 3 h, 3-6 h, and even 6 or more hours after the therapy. The long-term prognosis was significantly better in the reperfused group than in the ineffective group for 5 years and 7 months after therapy. However, CT was accompanied by both (1) poor prognosis in the ineffective group; and (2) unfavorable effects on the prognosis and on the daily life of patients with severe stenosis even after treatment. Accordingly, supplemental ICT and rescue PTCA (strategy (A)) were performed to treat the first problem, and deferred PTCA (strategy (B)) was conducted to treat the second problem in 80 patients with initial AMI. As a result, strategy (A) increased the coronary reperfusion rate to 94.3%, and strategies (A) and (B) together decreased the nosocomial mortality rate of 8.5% to 3.8%, and reduced the risk of death by 55.3%.

Humans↗
PubMed1993

Chimeric renin-angiotensin system demonstrates sustained increase in blood pressure of transgenic mice carrying both human renin and human angiotensinogen genes.

A reaction between enzyme renin and its only natural substrate angiotensinogen is the initial and rate-limiting step for producing a potent vasoconstrictor angiotensin II as the final product of the renin-angiotensin system, a contributory factor in the pathogenesis of hypertension. In order to assess the role of the interaction of human renin with human angiotensinogen in the development of high blood pressure, we have constructed the chimeric renin-angiotensin cascade in mice comprising both human renin and human angiotensinogen as well as the endogenous angiotensin-converting enzyme and angiotensin II receptor by cross-mating separate lines of transgenic mice carrying either the human renin or human angiotensinogen genes. Although each single gene carrier did not develop hypertension despite the observed normal tissue-specific expression of the transgenes, dual gene strains exhibited a chronically sustained increase in blood pressure. Administration of a human renin-specific inhibitor (ES-8891) was effective in reducing the elevated blood pressure only against the cross-mated hybrid mice, but treatment of an angiotensin-converting enzyme inhibitor (captopril) and a selective antagonist (DuP 753) directed at the angiotensin II receptor decreased the basal level of blood pressure even in single gene carriers as well as in dual gene mice. These results clearly demonstrated that the sustained increase in blood pressure of the hybrid mice was initiated by the interaction between the products of the two human genes.

Angiotensin I↗
PubMed1993

Nipradilol inhibits rat mesangial cell mitogenesis through the activation of soluble guanylate cyclase.

Nipradilol is a beta-adrenoreceptor blocking agent, whose structure contains an NO2 group. Thus, it is possible that it modulates the function of glomerular mesangial cells through the activation of soluble guanylate cyclase. To prove this hypothesis, we examined the effect of nipradilol on soluble guanylate cyclase, intracellular cyclic guanosine monophosphate (cGMP) accumulation, and the mitogenesis of cultured rat glomerular mesangial cells. Nipradilol increased intracellular cGMP accumulation in a dose-dependent manner through the activation of soluble guanylate cyclase. Furthermore, nipradilol inhibited the incorporation of [3H]thymidine into the mesangial cells stimulated by 2.5% fetal bovine serum in a dose-dependent manner. These results indicate that nipradilol may modulate mesangial cell function through an increase in intracellular cGMP resulting from the activation of soluble guanylate cyclase.

Adrenergic beta-Antagonists↗
PubMed1993

Differential modulation of mitogenic and metabolic actions of insulin-like growth factor I in rat glomerular mesangial cells in high glucose culture.

In order to explore the possible contribution of insulin-like growth factor I to the development of diabetic nephropathy, the effect of glucose on the mitogenic and metabolic actions of insulin-like growth factor I in cultured rat glomerular mesangial cells was examined. The stimulation of [3H]-thymidine incorporation by insulin-like growth factor I in the cells exposed to high concentrations (55 mmol/l) of glucose (4.6 +/- 1.3 fold stimulation) was significantly suppressed as compared with that in the cells cultured in 11 mmol/l glucose (17.5 +/- 0.8 fold). In contrast, [3H]-amino-isobutylic acid uptake into the mesangial cells was significantly enhanced by glucose (2.03 +/- 0.03 nmol.mg protein-1. 15 min-1 at 55 mmol/l glucose vs 0.59 +/- 0.01 at 11 mmol/l glucose), while 2-deoxyglucose uptake remained unchanged. [125I]-insulin-like growth factor I binding was slightly but significantly increased in the cells exposed to high concentrations of glucose. Thus, glucose may modulate the mitogenic and metabolic actions of insulin-like growth factor I differently in cultured mesangial cells probably at the post-insulin-like growth factor I receptor level. These results may indicate that the differential modulation of the actions of insulin-like growth factor I by glucose could result in the increase in amino acid uptake and decrease in the cell proliferation in the mesangial cells, possibly leading to enhanced mesangial matrix synthesis with a relatively small increase in mesangial cell volume as seen in diabetic nephropathy.

Aminoisobutyric Acids↗
PubMed1993

Neurotropism of mouse-adapted haemagglutinating encephalomyelitis virus.

The propagation of a mouse-adapted strain (67N) of haemagglutinating encephalomyelitis virus in infected mice and murine cells was examined by viral re-isolation and immunostaining. Viral propagation was strictly limited to the neurons and to an established line of neuroblastoma cells in in-vivo and in-vitro experiments. These results provide adequate evidence that this virus is neurotropic.

Animals↗
PubMed1993

Rat renin promoter activity in cultured cells and transgenic mice.

Renin, a key enzyme controlling blood pressure, is mainly synthesized in kidney. To characterize the rat renin promoter, we have constructed a reporter gene containing the 238-bp putative regulatory region linked to a bacterial chloramphenicol acetyltransferase (CAT), and analyzed its promoter activity by in vitro transfection and introduction of the CAT fusion gene into germline of mice. CAT activity was detected in transfected embryonic kidney-derived 293 cells, but not in HeLa cells derived from cervical carcinoma, showing that the putative promoter region of the rat renin gene directs transcription in a cell type-dependent manner. To examine whether the sequence was sufficient to regulate the expression of the CAT chimeric gene in mice, we generated seven transgenic mice carrying the reporter construct. Unexpectedly, the transgene was not expressed in any of the independent transgenic mice examined. These results suggest one possibility that an additional control region may be required for efficient expression of the rat renin promoter in developing mice.

Animals↗
PubMed1993

Production of transgenic rats using pregnant and pseudopregnant rats prepared at a breeding farm.

We used pregnant and pseudopregnant Wistar-Imamichi rats, prepared at a breeding farm, for production of transgenic rats. The donor and recipient rats were transported to our facility for ova manipulation and embryo implantation, respectively. As a foreign gene, 1.9 kb of a hybrid gene was constructed with the rat renin promoter and chloramphenicol acetyltransferase-coding gene. Fertilized oocytes were collected from the donor and the foreign DNA was microinjected into the pronuclei of 539 oocytes by the method of Hochi. The manipulated oocytes were cultured to the 2-cell stage. One hundred seventeen 2-cell embryos were implanted in the recipient rats. Of 67 newborns, 55 rats grew up to be 3-week-old weanlings. Genomic DNA was extracted from the tail of these weanlings and examined by polymerase chain reaction analysis. Six transgenic rats were found to have been generated by the present method. In this way, transgenic rats were produced by an efficient combination of breeding farm utilization and laboratory research.

Animals↗
PubMed1993

[Quantitative cytochemical analysis of T1 breast cancer].

The authors attempted to estimate the relationship between three biological parameters (nuclear DNA content, PCNA (proliferating cell nuclear antigen)/cyclin, HER-2/neu oncoprotein) and lymph node metastasis. We evaluated 37 breast cancers which were less than 2 cm in maximum dimension. Quantitative analysis was performed using a CAS 200 Image Analysis System, after Feulgen staining and immunochemical staining using anti-PCNA/cyclin monoclonal antibody and anti-HER-2/neu oncoprotein polyclonal antibody. In lymph node-negative cases 20.0% were aneuploid, while in lymph node-positive cases 58.8% were aneuploid. A total of 20.0% lymph node-negative cases were in the high proliferation group, as opposed to 52.9% of lymph node-positive cases. This analysis revealed a significant relationship between cell proliferation and lymph node metastasis. Analysis of the expression of HER-2/neu oncoprotein revealed no significant relationship between overexpression of HER-2/neu oncoprotein and lymph node metastasis, but the expression of HER-2/neu oncoprotein was significantly related to a shorter relapse-free survival.

Breast Neoplasms↗
PubMed1993

[Effect of glucose on soluble guanylate cyclase in cultured rat mesangial cells].

The intracellular content of cyclic GMP (cGMP) is known to mediate the effects of various vasodilating substances on glomerular mesangial cells. However, little is known about the role of soluble guanylate cyclase (SGC) in these cells in diabetes. We, therefore, investigated the changes in SGC activity as well as the cGMP content in rat mesangial cells (MC) cultured under high glucose or hypertonic conditions. The following results were obtained. 1. Sodium nitroprusside (SNP) (10(-4) M, 10min.) increased cyclic GMP (cGMP) content in MC from 8.17 +/- 0.99 pmol/mg protein to 981.6 +/- 86.3. 2. SNP (10(-4) M) stimulated SGC activity from 38.3 +/- 10.8 pmol cGMP formed/mg protein/10 minutes to 74.4 +/- 5.2. 3. In the coincubation experiment with bovine aortic endothelial cells, bradykinin (10(-6) M, 10min.) increased cGMP content in MC from 6.24 +/- 1.35 to 348.3 +/- 45.3. However, 4. the activity of SGC and SNP-induced increase of cGMP were not influenced by culturing MC in high glucose or hypertonic media. Similarly, the cGMP increase in MC coincubated with BAEC under bradykinin stimulation was not altered by culturing under high glucose or hypertonic conditions. These data suggested that SGC may play an important role in the regulation of cGMP content in MC. However, this enzyme may not be involved in the increase of cGMP content in MC cultured under high glucose condition.

Animals↗
PubMed1993

Dependence of angiotensin production in transgenic mice carrying either the human renin or human angiotensinogen genes on species-specific kinetics of the renin-angiotensin system.

In order to study the functional role of the renin-angiotensin system in the control of blood pressure, projects were initiated using transgenic mice carrying either the human renin gene or the human angiotensinogen gene. To extend the usefulness of the transgenic model system of hypertension research, a two-tiered strategy for generation of transgenic mice with high blood pressure has been developed. This unique system allows the establishment of transgenic lines with a strict species specificity of the renin-angiotensinogen reaction exhibited by transgene products that are regulated in a tissue specific manner. In this report, the strategy concerning the "two-tiered method" is presented and evidence is provided the overproduction of angiotensin occurs only in the combined reaction with human renin and human angiotensinogen expressed in transgenic mice.

Amino Acid Sequence↗