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Biomedical subjects

K Sugimoto

Publications and source records attributed to K Sugimoto.

At least 397 records · Page 22Linked to original sources

Effects of anti-CD44 monoclonal antibody on adhesion of erythroid leukemic cells (ELM-I-1) to hematopoietic supportive cells (MS-5): CD44, but not hyaluronate-mediated, cell-cell adhesion.

Cocultivation of erythroid leukemic cells (ELM-I-1) with hemopoietic supportive cells (MS-5) resulted in a specific adhesion of ELM-I-1 cells to MS-5 cells. This phenomenon was designated as rosette formation. After induction of differentiation of ELM-I-1 cells, rosette formation was reduced, and no rosette formation was observed between erythrocytes and MS-5 cells. Studies on anti-adhesion molecule antibody treatment have revealed that CD44 plays a key role in rosette formation. Expression of CD44 on (the membrane of) ELM-I-1 cells was reduced after differentiation, and no CD44 expression was detected on erythrocytes. CD44 was also expressed on MS-5. Hyaluronate is known as the ligand of CD44, but neither hyaluronidase treatment nor addition of excess hyaluronate to the assay system affected rosette formation. These data indicate that hyaluronate is not responsible for rosette formation. Anti-CD44 antibody (KM81), which recognized the hyaluronate binding site of CD44, inhibited rosette formation. But other monoclonal antibodies against different epitopes except for the hyaluronate binding site, even those against CD44's hyaluronate binding site, did not inhibit rosette formation. Thus, rosette formation between MS-5 cells and ELM-I-1 cells is mediated by CD44 but not by the hyaluronate binding site of CD44.

Animals↗

Pharmacokinetics and pharmacodynamics of the alpha 1-adrenergic antagonist bunazosin retard in hypertensives.

The pharmacokinetics and pharmacodynamics of an alpha 1-blocker a sustained release formulation of bunazosin (Detantol R, E1015, 4-amino-2-(4-butyrylhexahydro-1H-1,4-diazepin-1-yl)-6,7- dimethoxyquinazoline hydrochloride, CAS 52712-76-2), were investigated in hypertensive patients with normal renal function (NRF) and those with impaired renal function (IRF). The subjects were hospitalized and placed on a constant sodium diet (NaCl 7 g/day) throughout the study. A 6 mg dose of bunazosin was administered orally once a day for 8 days. Measurement of blood pressure (BP) and sampling of blood and urine specimens were made on the first and last days of treatment. A significant decrease in both systolic and diastolic BP was observed after consecutive dosing of bunazosin compared to baseline values over 24 h in the NRF and for 8 h in the IRF. There were no significant differences in plasma profiles of bunazosin in both groups after single and consecutive dosing. The pharmakokinetic parameters of bunazosin in the NRF and IRF groups did not differ after the single and the consecutive dosing, except for plasma peak levels (Cmax) which were significantly higher in the IRF than those in the NRF. There were, however, neither prolongation of apparent elimination half-life (t1/2), nor increase in Cmax, nor area under the plasma concentration-time curve (AUC0-24) after consecutive dosing in both groups. Cumulative urinary excretion rates of bunazosin were less than 1.1% of dose in both groups, and those did not differ significantly between the NRF and IRF groups in both single and consecutive studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-1 Receptor Antagonists↗

Effect of an angiotensin receptor antagonist, TCV-116, on sympathetic nerve activity in patients with essential hypertension.

The effects of an angiotensin II receptor (AT1) antagonist on sympathetic nervous responses to a mental arithmetic task and a cold pressor test were investigated using a placebo-controlled, single-blind design in 8 patients with essential hypertension (53 +/- 3 years). All patients received a placebo for 2 weeks (placebo run-in period), after which the control group (P; n = 4) continued to receive the placebo, while the experimental group (TCV; n = 4) received TCV-116 at 4 mg/day for 4 weeks (treatment period). After basal measurements were carried out, an arithmetic task and a cold pressor test were conducted on the last day of each period. Blood pressure (BP), heart rate (HR) and electrocardiogram (ECG) were continuously monitored. Muscle sympathetic nerve activity (MSNA) was assessed by determining the burst rate of the mean voltage neurogram obtained from the tibial nerve. Sympathovagal balance was also assessed, by determining the area ratio of the low frequency (LF: 0.05-0.15 Hz) to high frequency bands (HF: 0.16-0.5 Hz) of a power spectral analysis of HR variability (maximum entropy method). During the placebo run-in period, there were no significant differences in basal BP, HR, LF/HF or MSNA between the two groups. During the treatment period, basal mean BP in the TCV group was significantly lower (p < 0.05) than that in the P group, but there were no significant differences in basal HR, LF/HF or MSNA between the two groups. Although the arithmetic stress significantly increased BP, HR and LF/HF in both groups, MSNA was not significantly altered in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗

Mechanically assisted intraoperative peritoneal lavage for generalized peritonitis as a result of perforation of the upper part of the gastrointestinal tract.

BACKGROUND: The efficiency of intraoperative peritoneal lavage (IOPL) and peritoneal drainage in patients with generalized peritonitis remains controversial. The benefit of large volume IOPL, using a newly designed device, and of peritoneal drainage were evaluated in 101 patients with generalized peritonitis. STUDY DESIGN: Patients were divided into two groups, one treated by mechanically assisted IOPL (group 1), and the other treated by manual IOPL (group 2). They were further divided into two groups, one undergoing drainage (DR group) and the other undergoing no drainage (ND group). Based on data in the progress notes, patients in these groups were compared with each other with respect to disease process, volume of IOPL fluid, incidence of infectious complications, and other prognostic factors. RESULTS: In group 1, the incidence of infectious complications was significantly lower than in group 2 (10.8 versus 62.9 percent, p < 0.01). Patients who underwent operative treatment 12 hours or more after onset of peritonitis had a lower incidence of infection following high volume IOPL (greater than or equal to 30 L) compared with those patients who underwent low volume IOPL. The incidence of infectious complications was significantly higher in the DR group (32.8 versus 12.9 percent). CONCLUSIONS: A large volume of saline (greater than or equal to 30 L) was needed for IOPL. The new device for IOPL proved to be very successful and efficient. When IOPL was successful, it seemed that peritoneal drainage did not provide any additional benefits to the treatment of generalized peritonitis.

Adolescent↗

[Clinical evaluation of dynamic MRI in the re-diagnosis of therapeutic effect and recurrence after transcatheter arterial embolization for hepatocellular carcinoma].

We evaluated re-diagnostic ability of dynamic MRI as compared with T2 weighted image in the diagnosis of primary therapeutic effect and tumor recurrence after transcatheter arterial embolization (TAE) for hepatocellular carcinoma. Thirty-four nodules in 30 patients with hepatocellular carcinoma were estimated based on operative and angiographic findings. According to the time when dynamic MRI was taken, nodules were classified as a short-term observation group consisting of 15 nodules obtained within a month after TAE, or as a long-term observation group consisting of 19 nodules obtained over a month after TAE. In the short-term observation group, sensitivity, specificity, accuracy was 89%, 100%, 93% on dynamic MRI and 78%, 67%, 73% on T2WI, respectively. In the long-term observation group, these were 94%, 100%, 95% on dynamic MRI and 100%, 33%, 89% on T2WI and 94%, 67%, 89% on Lipiodol-CT, respectively. In both groups, dynamic MRI was superior in accuracy. Conclusively, we consider that dynamic MRI is a most accurate diagnostic method that should be added to routine MRI after TAE. Especially in the case diagnosed positive on T2WI, the usefulness of dynamic MRI should be emphasized to determine the schedule of the therapy, because the cases that were false positive on T2WI were accurately diagnosed on dynamic MRI.

Aged↗

[Surgical indication for unruptured cerebral aneurysm in patients with ischemic cerebrovascular disease].

A series of 44 cases is presented of patients who received surgical treatment for unruptured aneurysms in the anterior circulation, and which were associated with ischemic cerebrovascular disease (CVD). The age of patients varied from 34 to 76 (mean 62.8) years old. The associated ischemic CVD was transient ischemic attack (TIA) in ten, minor completed stroke in 23, and major completed stroke in 11 cases. Thirty five patients recovered fully. However, there were three deaths due to new cerebral infarction or delayed intracranial hemorrhage within 30 days after surgery (mortality 6.8%). Transient morbidity occurred in four patients (9.1%), and permanent morbidity in two patients (4.5%). In six cases, new ischemic events occurred after the surgery. In contrast, all 40 patients whose unruptured aneurysms were not associated with CVD fully recovered from the surgery they underwent. The authors indicate three risk factors which might lead to complication; diabetes mellitus, aneurysms located in the middle cerebral artery, and those larger than 6mm in diameter. Another three life-threatening factors are; elderly patients (> 65 year-old), male, aneurysms larger than 7mm in diameter. Direct surgery for unruptured aneurysms in ischemic CVD patients should be considered in cases free of risk factors indicated above. Eight cases in this series had extracranial carotid artery stenosis on the same side as the aneurysm. Carotid endoarterectomy (CEA) was performed prior to aneurysmal clipping in six patients, and their postoperative courses were excellent. In two patients, clipping was performed prior to CEA, and transient morbidity occurred in one of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A case of pulmonary eosinophilic granuloma with extrapulmonary involvement treated effectively with steroid hormone].

A 21-year-old female was admitted to Tamono City Hospital with chief complaint of dyspnea due to spontaneous pneumothorax. The patient was transferred to our clinic for further examination of abnormal chest X-ray findings together with skin lesions and other symptoms of polyuria, amenorrhea and narrowed visual fields. Histochemical and electron microscopic examination of lung tissue obtained by open lung biopsy led to the diagnosis of eosinophilic granuloma. Furthermore, enhanced computed tomography and magnetic resonance images showed the existence of an intracranial tumor in the supra-hypophyseal region which was interpreted as the cause of hormonal and visual disturbances. Because of dyspnea and enlargement of intracranial tumor, treatment with steroid hormone was commerced followed by tapering of the dose. Chest X-ray findings and skin lesions improved markedly and the intracranial tumor regressed significantly with this steroid therapy, indicating that the intracranial tumor represented involvement with eosinophilic granuloma.

Adult↗

[Clinical evaluation on renal pelvic and ureteral tumors].

We report 82 patients with renal pelvic and ureteral tumors admitted to Kyoto Prefectural University of Medicine, Kyoto Second Red Cross Hospital and Shakai-Hoken Kyoto Hospital between January, 1981 and December, 1991. Sixty two were males and 24 were females, and they were between 47 and 93 years old (average: 68.2 years). The tumor occurred on the right side in 34 patients, on the left side in 51 patients and on both sides in one patient. There were 43 renal pelvic tumors, 37 ureteral tumors and 6 renal pelvic with ureteral tumors. The most frequent symptom was macrohematuria, which was seen in 54 patients (62.8%). Urinary cytology was performed in 76 patients and a positive result was obtained in 44 patients (57.9%). We performed surgical treatment on 71 patients. The most frequently adopted method was total nephroureterectomy with partial cystectomy which was performed on 51 patients (71.8%). Of the 73 specimens diagnosed histopathologically, 71 specimens were transitional cell carcinoma (TCC), one was a squamous cell carcinoma (SCC) and one was a mixed type of TCC and adenocarcinoma. As to grading, 6 specimens were G1, 28 G2, 38 G3 and one GX. As to staging, 8 specimens were pTa, 17 pT1, 21 pT2, 18 pT3, 8 pT4 and one pTX. The overall survival rate (by Kaplan-Meier's method) at 3 and 5 years was 47.0% and 39.5%, respectively. The patients with high grade tumors and those who had ureter preservation, the survival rate was lower than in the other patients.

Aged↗

[Clinical evaluation of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy for advanced urothelial cancer].

M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy was performed on 27 patients with advanced urothelial cancer. The patients included 20 with bladder cancer, 4 with upper urinary tract cancer and 3 with both lesions. Complete response (CR) was observed in 2 (7.4 +/- 9.9%) patients and partial response (PR) in 10 (37.0 +/- 18.2%) patients after the treatment, i.e., the overall objective response rate was 44.4 +/- 18.7%. The rate of relapse or recurrence in the patients with CR and PR was 100% and 90.0%, respectively. The mean duration of the response was 18.5 +/- 13.4 months and 10.7 +/- 10.9 months for CR and PR, respectively. The overall survival rate after one year was 30.2%. Bone marrow suppression was the most serious side effect. The white blood cell count became below 1,000/microliters in 10 patients (36.7%). Among them, 4 patients suffered from sepsis. In conclusion, M-VAC chemotherapy was effective for induction therapy against advanced urothelial cancer, although the effective duration was short. Further maintenance therapy should be established.

Adult↗

Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia.

The p53 gene is currently thought to be a tumor suppressor gene, and its alterations have been suggested to be involved in the pathogenesis of several human malignancies, including some leukemias and lymphomas. We present here evidence for the possible involvement of p53 gene mutations in the myelodysplastic syndrome (MDS), although the incidence is relatively low. Forty-four patients with MDS and six patients with overt leukemias that developed from MDS were studied for p53 gene alterations using reverse transcriptase-polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Three patients with MDS (2 RAEB and 1 RAEB in T) had missense point mutations in the conserved regions of the p53 coding sequence. Furthermore, expression of the wild-type p53 mRNA was not detected in these three patients. The probable absence of normal p53 function in the three cases studied here suggests that alterations in the p53 gene may occasionally play a role in MDS. These three MDS patients with p53 gene mutations and an MDS-derived erythroleukemia cell line that we had previously reported to carry a p53 gene mutation showed no N-ras gene mutations, suggesting heterogeneity in the oncogenic mechanism of MDS.

Amino Acid Sequence↗

Convenient plasmid for extrachromosomal DNA recombination in mouse cells.

We constructed a convenient plasmid for DNA recombination assay. The plasmid, pMR1, contains a double prokaryotic terminator to decrease the background and two unique restriction enzyme sites on both sides of the double terminator to allow for easy construction. The assay is capable of selecting the bacterial cells containing recombined plasmid DNA on a selective plate containing ampicillin and chloramphenicol. We adapted pMR1 for V(D)J recombination and homologous recombination and detected both types of recombination in murine PreB cell line. As pMR1 has the double terminator, background on the selective plate decreases effectively and we select only the recombined clones. We consider the vector, pMR1, to be convenient for the analysis of homologous and non-homologous recombinations.

Abelson murine leukemia virus↗

Mapping of the human CENP-B gene to chromosome 20 and the CENP-C gene to chromosome 12 by a rapid cycle DNA amplification procedure.

By optimizing the primer-annealing temperature in a rapid air cycling procedure, two human DNA sequences encoding centromere proteins B and C (CENP-B and CENP-C) were specifically amplified without any detectable amplification of highly homologous rodent DNA sequences. Using a panel of rodent/human hybrid DNA, the genes for human CENP-B and CENP-C were conveniently mapped to chromosomes 20 and 12, respectively.

Animals↗

Dynamic changes in stress fiber expression in rat uterine vein endothelial cells associated with pregnancy.

En face endothelial preparations of rat uterine vein were stained with rhodamine-phalloidin to investigate the dynamics of stress fiber expression during pregnancy. In prepregnant animals, somewhat plump, spindle-like endothelial cells of the uterine vein had only a few short stress fibers. With the progress of pregnancy, however, many long stress fibers appeared within the elongated endothelial cells. Within 2 hr after delivery, these stress fibers became dramatically decreased in number as the cells reverted from an elongated to a plump shape and returned to the prepregnancy level by 14 days postpartum. The uterine vein showed a significant increase in length during pregnancy and quickly shortened after delivery. Thus, expression of stress fibers in endothelial cells of the uterine vein seems to be related to the tension loaded on this vessel during its elongation in parallel with the marked growth of the uterine body during pregnancy. This study shows that stress fibers are dynamic structures that may serve to maintain endothelial cell integrity during the exertion of tensile stress on the vessel wall.

Actins↗

Effect of cadmium on osteogenesis within diffusion chambers by bone marrow cells: biochemical evidence of decreased bone formation capacity.

The biological and biochemical effects of cadmium administration on bone marrow in rats were examined. When young adult rats were administered cadmium (Cd) repeatedly at a dose of 750 micrograms/kg body wt for up to 4 weeks, metallothionein mRNA was detected by a gene expression analysis in their bone marrow at 2 weeks after the first Cd administration, though the amounts were lower than those in liver. To determine the direct effect of cadmium on bone formation, the potential of Cd-treated bone marrow cells and demineralized bone matrix (DBM) to form bone and cartilage was assessed using a diffusion chamber (DC) in vivo, by histological examination, and by biochemical parameters such as alkaline phosphatase (ALP) activity, total calcium and phosphorus content, and the bone-specific vitamin K-dependent Gla-containing protein (BGP) content, relative to mineralization. Diffusion chambers were inoculated with DBM and bone marrow cells from either Cd-treated or nontreated rats (control) and were then implanted subcutaneously into syngeneic nontreated rats. The accumulation of BGP in DCs with Cd-treated bone marrow was significantly lower than that in control DCs. Unlike in control DC, a peak of ALP activity did not occur at 4 weeks postimplantation in DC implants inoculated with Cd-treated bone marrow; the ALP activity and calcium content in these implants were also significantly lower than those of the control bone marrow-containing chambers at the early stage of implantation. Histological examinations of chambers with Cd-treated marrow showed a decreased area of cartilage and bone foci compared with those in control chambers. These findings suggest that Cd administration inhibits the osteoblastic and chondroblastic differentiation pathway in bone marrow through direct effects on these cells.

Animals↗

Role of marginal stress fibers formed in the rat vascular endothelial cells.

Fluorescence cytochemistry using en face preparations of rat vascular endothelial cells (ECs) revealed the localization of actin, fibronectin (FN) and fibronectin receptor (FNR) along not only central stress fibers (SFs) but also the cell margins. Electron microscopy showed very close proximity between the topographical distribution of intracellular microfilament bundles and that of subendothelial FN in the EC margins. Therefore, these basal and marginal actin cables may be comparable to the well-established central SFs present in ECs. Formation of the central SFs was induced in ECs or mesothelial cells in response to tension, by which their cellular integrity seems to be effectively maintained. However, even when central SF formation was inhibited by cytochalasin D, the ECs with marginal SFs showed high resistance to mechanical tension, whereas mesenteric mesothelial cells having no such fibers easily lost their integrity. Thus, together with central SFs, the marginal SFs characteristic of rat vascular ECs may play an essential role in strengthening cell-matrix adhesion.

Actins↗