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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 343 records · Page 19Linked to original sources

Antihypertensive effect of repeatedly administered YM358, an angiotensin AT1-receptor antagonist, in stroke-prone spontaneously hypertensive rats.

YM358 2,7-diethyl-5-[[2'-(1H-tetrazole-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[ 1,5-b][1,2,4]-triazole potassium salt), a novel nonpeptide angiotensin AT1-receptor antagonist, was administered daily for 4 weeks to 24-week-old stroke-prone spontaneously hypertensive rats (SHRSP). Its effects on systolic, mean and diastolic arterial pressure (SAP, MAP and DAP), heart rate and locomotor activity were investigated by using radiotelemetry. A clear diurnal variation in blood pressure, heart rate and locomotor activity was observed in synchrony with the light cycle. YM358 at a daily oral dose of 10 or 30 mg/kg produced a reduction of blood pressure in a dose-dependent manner. Although a mild attenuation of the antihypertensive effect of YM358 was observed during the early stage of therapy, YM358 at 30 mg/kg per day produced a significant and consistent decrease in 24-hr MAP and DAP, and it prevented the further development of hypertension. YM358 did not affect either heart rate or locomotor activity or their diurnal variations. After the discontinuation of therapy with YM358, the blood pressure recovered promptly to the control level while there was no sign of a rebound increase in blood pressure. These results suggest that YM358 may be potentially useful for the treatment of hypertension.

Angiotensin Receptor Antagonists↗

Lack of mutations of preproparathyroid hormone gene in three kindreds with familial isolated hypoparathyroidism.

The mutations of the preproparathyroid hormone (preproPTH) gene have been reported to cause some cases of familial isolated hypoparathyroidism (FIH). We investigated the preproPTH gene of five affected subjects of three Japanese kindreds with FIH. The mode of inheritance in FIH of two families was thought to be autosomal dominant, and the FIH of the other was probably inherited in an autosomal recessive manner. Exons 1, 2 and 3 of the preproPTH gene and its exon-intron boundaries were analyzed with either polymerase chain reaction and single strand conformational polymorphism, or direct sequencing of the amplified DNA. We did not detect any mutations in the amplified regions of the preproPTH gene, but an A to G transition in intron 1 was identified in all of the affected subjects. Among them, four were heterozygote, and the other was homozygote. This transition was considered to be a polymorphism, which was the same as reported previously. These results indicate that the preproPTH gene abnormalities are not responsible for FIH in these families. Further studies are required to elucidate whether genes coding for other molecules, such as calcium-sensing receptor, are involved in FIH.

Base Sequence↗

Malignant lymphoma induction in rabbits by oral inoculation of crude virus fraction prepared from Ts-B6 cells (cynomolgus B-lymphoblastoid cells harboring Epstein-Barr virus-related simian herpesvirus).

Malignant lymphoma was induced in Japanese (JWY), New Zealand (NZY) and Dutch (DUY) white rabbits by oral spray of cell-free pellets of culture fluid (crude virus fraction) of Ts-B6 cells (cynomolgus monkey B-lymphoblastoid cells harboring Epstein Barr virus-related simian herpesvirus or Cyno-EBV). Nine of 11 inoculated rabbits developed malignant lymphomas within 42-160 days after oral inoculation (JWY, 2/3; NZY, 5/6; DUY, 2/2). In contrast, none of the control rabbits inoculated in the same fashion with B95-8 (EBV-producing marmoset cell line) cell-free pellets developed malignant lymphoma. Most rabbits showed increased anti-VCA IgG and anti-EA-DR IgG antibody titers after inoculation by oral spray of Ts-B6 cell-free pellets. EBV-encoded RNA-1 was revealed in the tumor cells by in situ hybridization. EBV DNA was detected in the rabbit peripheral blood leukocytes (PBL) by polymerase chain reaction; the earliest positive result was obtained only two days after oral inoculation. These data suggest that orally administered Cyno-EBV in Ts-B6 cells infects PBL and then induces malignant lymphoma in rabbits. The availability of this animal model promises to clarify the role of EBV in human lymphoma and provides a means for studying prophylactic and therapeutic regimens.

Administration, Oral↗

Effect of polydextrose on absorption of triglyceride and cholesterol in mesenteric lymph-fistula rats.

In most experimental designs, the inhibitory effect of water-soluble dietary fibers on lipid absorption is evaluated by the decrease in plasma lipid concentration or the increase in fecal lipid output. The aim of this study was to evaluate the acute effect of a water-soluble polysaccharide, polydextrose, on lipid transport to the mesenteric lymph using lymph-fistula rats. The mesenteric lymph duct of rats was cannulated, and an infusion tube was introduced into the duodenum. After recovery, a lipid emulsion containing radioactive triolein and cholesteryl oleate was infused into the duodenum for 8 hr. The tested group was infused with the lipid emulsion containing 5% or 10% polydextrose as dietary fiber. Samples from the lymph-fistula were collected, and the luminal contents and mucosa were collected at the end of infusion. Lymph flow in the mesenteric lymph decreased in the polydextrose group after the infusion. The amounts of both triglyceride and cholesterol remaining in the lumen were greater in the polydextrose group, due to decreased transport of lipid into the lymph. These effects were dose dependent in the 5% and 10% polydextrose groups. The results of this study indicate that polydextrose retarded the transport of triolein and cholesterol into the mesenteric lymph.

Animals↗

Angiogenesis inhibitor TNP-470 suppresses tumorigenesis in rat urinary bladder.

PURPOSE: The efficacy of the anti-angiogenic factor TNP-470, an analogue of fumagillin, in controlling the development of bladder tumors was investigated. MATERIALS AND METHODS: The anti-angiogenic activity of TNP-470 was evaluated in vitro by its capacity to suppress the growth and migration of bovine capillary endothelial cells. To investigate its effect in vivo on the development of tumors, we instilled 0.5 microgram of TNP-470 dissolved in rat urine into heterotopically transplanted rat urinary bladders in which carcinogenesis had been initiated by N-methyl-N-nitrosourea. RESULTS: In vitro, TNP-470 selectively inhibited the growth and migration of endothelial cells. Instillation of TNP-470 shortly after treatment with carcinogen reduced the tumor incidence significantly (p < 0.05) as compared with that in control animals receiving urine only. CONCLUSIONS: TNP-470 suppresses the development of bladder tumors when the treatment is started at an early stage of neoplasia. It may be useful in preventing recurrences or new growth of bladder tumors.

Animals↗

Evaluation of acute ischemic mitral regurgitation following cardiopulmonary bypass assessed by biplane transesophageal echocardiography.

The aim of this study was to evaluate pathogenesis and outcome of acute ischemic mitral regurgitation (MR) in patients undergoing coronary artery bypass grafting (CABG) using biplane transesophageal echocardiography (TEE). Biplane TEE was continuously monitored in a total of 96 patients who were scheduled for elective CABG surgery. Of 96 patients, 10 with no MR at stages 1 (after anesthetic induction but before skin incision) and 2 (after cardiopulmonary bypass [CPB] and decannulation) were excluded. In the remaining 86 patients with MR between stages 1 and 2, 45 (group A) had an increase in MR, and 41 (group B) had a decrease in MR. An increase in MR at stage 2 in group A was associated with a significant increase in annular diameter (p < 0.05), and pulmonary capillary wedge pressure (p < 0.01) compared with stage 1. A significant decrease in the left ventricular end-diastolic area (p < 0.01), end-systolic area (p < 0.05) and the mean wall motion abnormality score (WMA score) (p < 0.001) was observed at stage 2 compared with stage 1 in group B. In 16 of 17 patients (94%) with an increased WMA score in group A, a regional wall motion abnormality (RWMA) was detected in the right coronary artery (RCA) and/or left circumflex coronary artery (LCX) areas. In 7 patients in group A, MR increased continuously until stage 3 (after sternal closure) despite treatment. In 2 of these 7 patients, pulmonary venous systolic flow (PVSF) decreased during stage 2 and persisted to stage 3. The post operative course of these 2 patients was complicated with atrial fibrillation (AF). The increase in annular diameter and worsening in RWMA in RCA and/or LCX areas are associated with acute ischemic MR following CPB. The majority of acute ischemic MR cases were resolved by pharmacological intervention. Post operative AF was noted in 2 patients with acute ischemic MR associated with persistently decreased PVSF following CPB despite treatment.

Acute Disease↗

[Difference of blood cell counts with reference blood cell counters in different makers: Part II].

This is the second report of evaluation on the difference of blood cell counting among different automated blood cell counters in Japan. We tested reference blood cell counters of 6 different companies: Coulter, Sysmex, Bayer-Sankyo, Nihon Kohden, Horiba and Dainabot. Forty ml of whole blood were taken from 3 healthy persons and EDTA-2K anticoagulated blood samples (Sample 1, 2 and 3) were sent to each company to determine blood cell counts with a reference automated counter. As a result, the following items showed more than 10% difference among makers: RBC between Dainabot and Horiba in Sample 3, hematocrit values between Coulter and Dainabot in Sample 2, WBC between Nihon Kohden and each of three makers (Sysmex, Horiba and Dainabot) in all 3 samples and that between Bayer-Sankyo and each of two makers (Sysmex and Horiba) in Sample 3 and platelet count between Dainabot and each of 3 makers (Bayer-Sankyo, Nihon Kohden and Horiba) in all 3 samples. The following items showed difference between 5 and 10%: MCV between Coulter and each of two makers (Bayer-Sankyo and Horiba), WBC between each of two makers (Coulter and Nihon Kohden) and each of other 4 makers, and platelet count between each of two makers (Nihon Kohden and Horiba) and each of 3 makers (Coulter, Sysmex and Bayer-Sankyo). Recently Japanese Committee for Clinical Laboratory Standards proposed minimum clinical allowance of blood cell count as follows: hemoglobin 3%, RBC 4%, MCV 4%, WBC 7% and platelet count 10%. It is suggested that all of the items showing the difference more than above allowance among makers should be improved for clinical use to have good external quality control in blood cell counting by automated instruments.

Blood Cell Count↗

[A case of malignant syndrome triggered by the use of haloperidol and chrorpromazine].

Malignant syndrome is a disease characterized by high fever, extrapyramidal syndrome and dysautonomia recognized during or at the time of stopping administration of antipsychotic medication and it is the most severe and lethal side effect of antipsychotic medication. In the present case, triggered by the use of haloperidol and chrorpromazine, lisp of the tongue, trembling of both hands, perspiration on the hands and legs and other symptoms appeared. Later, difficulty of breathing, trembling of whole body and massive perspiration appeared, and disturbance of autonomic nervous system such as mydriasis and perspiration occurred. By blood analysis, CPK showed a high value of 518 U.l-1 and malignant syndrome was suspected. After i.v. administration of dantololene 20 mg, the perspiration was and the trembling were reduced. With this improvement of symptoms the patient was released from the hospital after about one month. These care suggests that a fundamental knowledge of antipsychotic agents must be acquired and attentive care be given when such drugs are administered.

Adult↗

Does lateral lymph node dissection improve survival in rectal carcinoma? Examination of node metastases by the clearing method.

BACKGROUND: The treatment of rectal carcinoma by lateral lymph node dissection has risks and benefits. Therefore, we investigated the therapeutic efficacy of lateral lymph node dissection. STUDY DESIGN: We studied 198 patients with rectal carcinoma who underwent lateral lymph node dissection. Metastases to the lymph nodes were examined by the clearing method. The incidence of urinary and male sexual dysfunction was determined by measuring the residual urine volume and individual interview 1 year after operation. RESULTS: The rate of metastasis to lateral lymph nodes was 11.1 percent, and metastasis to the lateral lymph nodes occurred more frequently with lower rectal carcinoma classified as pT3 or pT4 in the TNM system. The rate of local recurrence was 12.5 percent and the 5-year survival rate after curative resection was 70.1 percent. The 5-year survival rate in patients with metastasis to the lateral lymph nodes was 25.1 percent, and this rate was significantly lower than the 5-year survival rate of 74.3 percent in patients without metastasis to the lateral lymph nodes. Urinary dysfunction was observed in 67.5 percent of patients, and male sexual dysfunction was found in 97.4 percent of men younger than 60 years of age with prior sexual ability. CONCLUSIONS: The prognosis for patients with metastasis to the lateral lymph nodes is poor, and the improvement in survival rate from lateral lymph node dissection is minimal.

Female↗

Evaluation of combined therapy with chemoembolization and ethanol injection for advanced hepatocellular carcinoma.

To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection therapy (PEIT) for advanced hepatocellular carcinoma, we studied the effectiveness of TACE therapy combined with PEIT (50 cases) and TACE alone (50 cases). In both groups, patients had multiple lesions, or a single lesion with a diameter exceeding 2 cm or with vascular invasion (stages II, III, and IV in the tumor staging classification of the Liver Cancer Study Group of Japan). The clinical features in the two groups were comparable. The cumulative survival rates with TACE-PEIT were 95.0% for 1 year, 72.5% for 2 years, and 50.0% for 3 years, whereas the rates with TACE alone were 92.5% for 1 year, 57.5% for 2 years, and 20.0% for 3 years. The survival rate in the TACE-PEIT group was significantly higher than that in the TACE alone group. Moreover, the survival rate of patients with stage II or III disease in the TACE-PEIT group was significantly better than that in the TACE alone group, and the survival rate of patients with Child's classification B or C in the TACE-PEIT group was significantly higher than that in the TACE alone group. Multivariate analysis using Cox's proportional hazard regression model showed that the most significant prognostic factors in the TACE-PEIT group were tumor embolus in the portal vein and the number of tumors. These results suggest the effectiveness of combining TACE and PEIT for the treatment of advanced hepatocellular carcinoma.

Antibiotics, Antineoplastic↗

[Effects of bilateral lung volume reduction surgery in a patient with severe pulmonary emphysema].

A 61-year-old man suffering from severe pulmonary emphysema underwent lung volume reduction surgery on both upper lobes. By one year after surgery functional residual capacity had decreased by 2.5 L and FEV1 had increased by a factor of 2.4. Diaphragm excursion, as assessed by dynamic magnetic resonance imaging, had increased and ventilation and pulmonary gas exchange had improved. Performance on a 6-minute-walk test and exercise tolerance measured on a bicycle ergometer improved, and both peak VE and VO2 increased. Before surgery, pulmonary artery pressure Ppa and pulmonary capillary wedge pressure Pewp during exercise were abnormally high, but 6 months after the operation the increases in Ppa and Pcwp during exercise were markedly reduced.

Chronic Disease↗

Lymph node metastases detected in the mesorectum distal to carcinoma of the rectum by the clearing method: justification of total mesorectal excision.

BACKGROUND: Total mesorectal excision effectively reduces the local recurrence rate of carcinoma of the rectum. This study was undertaken to clarify the rationale for total mesorectal excision. STUDY DESIGN: We retrospectively reviewed the records of 198 patients who underwent resection of a carcinoma of the rectum. The presence of nodal metastases in the mesorectum distal to the primary tumor was examined by the clearing method. RESULTS: The metastatic rate in the distal mesorectum was 20.2 percent. The metastatic rates according to the extent and site of the tumor were as follows: pT1, 0 percent; pT2, 0 percent; pT3, 21.9 percent; pT4, 50 percent; rectosigmoid, 10 percent; upper rectum, 26.3 percent; and lower rectum, 19.2 percent. The longest distal spread from the primary tumor to the metastatic node was 2 cm in carcinoma of the rectosigmoid, 4 cm in carcinoma of the upper rectum, and 3 cm in carcinoma of the lower rectum. CONCLUSIONS: Total mesorectal excision is required for patients with T3 and T4 tumors in the lower rectum, and excision of all mesorectal tissue down to at least 5 cm below the tumor is required for patients with T3 and T4 tumors in the upper rectum.

Humans↗

Mammalian occludin in epithelial cells: its expression and subcellular distribution.

Occludin has been identified from chick liver as a novel integral membrane protein localizing at tight junctions, and the cDNA encoding its mammalian homologue was identified very recently (Ando-Akatsuka, Y., M. Saitou, T. Hirase, M. Kishi, A. Sakakibara, M. Itoh, S. Yonemura, M. Furuse, Sh. Tsukita, J. Cell Biol. 133, 43-47 (1996)). Here we describe the basic properties of mammalian occludin in epithelial cells at the DNA, RNA, and protein levels. The human occludin gene was mapped to chromosome band 5q13.1 by fluorescent in situ hybridization. Northern blotting identified several occludin mRNA bands, suggesting the possible expression of several alternatively spliced products. Occludin mRNA was detected in cultured epithelial cells, but not in cultured fibroblasts. The mRNA level was high in the testis, kidney, liver, lung, and brain, which reportedly bear well-developed tight junctions. We then produced monoclonal and polyclonal antibodies using recombinant mouse occludin as the antigen, which reacted not only with mouse, but also human, dog and pig occludin. These antibodies recognized several bands around 60 kDa in epithelial cells but not in fibroblasts. Immunofluorescence microscopy of various tissues revealed that the staining intensity of occludin correlated well with the number of tight junction strands in epithelial cells. By contrast, the staining of ZO-1, a well-characterized tight junction-associated protein, was not specific for tight junctions. Furthermore, the exclusive concentration of occludin at tight junctions in epithelial cells was confirmed by immunoreplica electron microscopy.

Animals↗

[Left hand clumsiness due to disturbance of kinesthesia after damage to the dorsal column of the high cervical cord].

We described a 48-year-old, right-handed woman who manifested left hand clumsiness after damage to the dorsal column of the high cervical cord due to probable multiple sclerosis. On February 29, 1996, she developed a weakness in the right limbs. Subsequently, she suffered numbness and clumsiness in the left limbs, even though muscle strength of the left limbs was preserved. Seventeen days later, she was referred to our hospital. A T2-weighted MRI after admission demonstrated high signal intensities in the left dorsal column and the right antero-lateral part of the cervical cord at the C1 to C3 vertebral level. Under the diagnosis of probable multiple sclerosis, steroid pulse therapy was applied twice and she gradually regained muscle strength in the right limbs and sensation in the left limbs. One month later, elemental sensations such as pain, touch, temperature, vibration, and position, as well as discriminative sensations such as localization sensation, two-point discrimination, barognosis, pinch-press discrimination, and graphesthesia in the left limbs returned to normal. However, her left hand remained clumsy, especially when she tried to manipulate objects. She also showed a great difficulty in sustaining a constant level of pinching force by the left thumb and index finger, and in localizing her right thumb placed in space with the left hand with her eyes closed. She stated herself that she could not sense at all how her left hand and fingers were moving. Somatosensory evoked potentials recorded from the right scalp showed that the NI was poorly organized and the patency of subsequent peaks was delayed. Transcranial magnetic stimulation revealed that the pyramidal tract from the right motor cortex to the left cervical cord was functionally intact. These observations lead us to conclude as follows: (1) the patient's left hand clumsiness is probably due to the disturbance of kinesthesia, which is crucial to activate temporo-spatial patterns of complex hand and finger movements as well as to maintain long sequences of simple motor execution without vision; and (2) kinesthesia is a specific sensation that is presumably conveyed by the dorsal columns and could be selectively affected by a cervical cord lesion.

Female↗

[Evaluation of atherosclerotic changes in the thoracic aorta using transesophageal and epiaorta echocardiographies in patients undergoing coronary artery bypass graft].

The aim of this study was to evaluate the atherosclerotic changes of the entire thoracic aorta using transesophageal echocardiography (TEE) as well as epiaorta echography (epiaorta echo) in CABG surgical patients and to evaluate specifically the use of epiaorta echo. A total of 230 consecutive patients were studied (201 TEE, and 29 both TEE and epiaorta echo examinations). Intra-aortic plaque was detected by 70.0 +/- 8.5 years, while that of 73 patients without plaque was 54.5 +/- 9.2 years. The difference was statistically significant (P < 0.001). The plaque was detected as solitary or diffused. By TEE, it was impossible to obtain images from the distal ascending aorta to the proximal aortic arch (blind zone). By epiaorta echo, clear images from the aortic valve annulus to the first 3 cm of proximal ascending aorta was difficult to obtain. However, the rest of the ascending aorta to the proximal arch was clearly imaged. Thus, when TEE demonstrates diffused plaque in the aortic annulus to the proximal ascending aorta, epiaorta echo should be used to examine the distal ascending aorta to the proximal arch.

Adult↗