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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 397 records · Page 22Linked to original sources

Effects of HL-004, a novel ACAT inhibitor, on cholesterol accumulation and removal in cultured smooth muscle cells from stroke-prone spontaneously hypertensive rats (SHRSP).

The cholesterol metabolism of cultured smooth muscle cells (SMC) from the thoracic aorta of SMC from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) was compared. SMC from SHRSP had a higher acylCoA:cholesterol acyltransferase (ACAT) activity and accumulated more cholesterol than those from WKY. By using SMC from SHRSP, the effects of a novel ACAT inhibitor, HL-004, on the accumulation and removal of cholesterol were investigated. HL-004 inhibited microsomal ACAT activity from rabbit liver, intestine, aorta, and cultured SMC of SHRSP with 50% inhibition (IC50) values of 2.2, 1.7, 7.9, and 20 nM, respectively. HL-004 suppressed the accumulation of the intracellular cholesteryl ester (CE), but did not affect the intracellular free cholesterol (FC) content. Removal of cholesterol from the lipid-loaded SMC was accelerated by HL-004. These effects of HL-004 on cholesterol levels showed a good parallel to ACAT inhibition. It would thus appear that the suppression of cholesterol accumulation and the removal of cholesterol in SMC by HL-004 can be attributed to its ACAT inhibition in the cell, which reduces the content of intracellular CE.

Acetanilides↗

Straying phenomenon of migrating LHRH neurons and highly polysialylated NCAM in the chick embryo.

The present study on unilaterally incompletely placodectomized chick embryos revealed that arrival of migrating LHRH neurons into the forebrain area is dependent on the presence of a central projection of the olfactory nerve. When a fragment of the lateral and medial olfactory epithelium was spared the damage, a small number of LHRH-ir cells were found to migrate into the forebrain along a thin NCAM-H-expressing fiber bundle of the olfactory nerve. In embryos with large lesions which destroyed the lateral olfactory epithelium, the poorly developed NCAM-H-positive olfactory nerve fibers were arrested where they meet the NCAM-positive medial nasal branch of the ophthalmic nerve and frequently fused with this branch fiber bundle. In these embryos, no LHRH-ir cells were detected in the forebrain area. They were deviated from their regular migratory course to the NCAM-H-positive medial nasal branch fiber bundle. This straying phenomenon indicates that some structural support is apparently needed for the migration of LHRH-ir cells, but their migratory route is not completely programmed in their precursor cells in the olfactory placode. In cultures of placodal tissues, the coexistence of migrating LHRH-ir cells with NCAM-H-expressing neural elements was always confirmed. It is suggested therefore that not only the structural support for the migration but also the interaction between LHRH-ir cells and NCAM-H-expressing neural elements is a prerequisite for successful LHRH neuronal migration.

Animals↗

The effects of tibial tunnel placement and roofplasty on reconstructed anterior cruciate ligament knees.

Seventy-five anterior cruciate ligament (ACL) reconstructions augmented with the Kennedy Ligament Augmentation Device were evaluated according to classification of tibial drill-hole position on the basis of the anatomic landmarks of the ACL by two-dimensional radiographic imaging of the fully extended knee. The effects of roofplasty to avoid graft impingement were also assessed. The tibial drill-hole position was classified in relation to the medial intercondylar tubercle on anterior-posterior (AP) view, and in relation to Blumensaat's line (B-line) on lateral view. Arthroscopic evaluation of the ACL and incidence of chronic synovitis as well as Lysholm knee score, manual knee tests, knee extension and flexion angles, and knee tester measurements were performed. The results indicated that the knee joints in which the tibial drill hole was positioned laterally from the medial intercondylar tubercle or in which the tibial drill hole was positioned anteriorly to the B-line showed a tendency to develop more postoperative chronic synovitis. The knees in which the tibial drill hole was positioned anteriorly to the B-line also showed larger AP laxity. There was no difference between the non-roofplasty and roofplasty groups.

Adult↗

Healing after removal of benign cysts and tumors of the jaws. A radiologic appraisal.

A retrospective review of the radiographic findings after removal of benign jaw cysts (n = 31) and ameloblastomas (n = 24) was carried out. The radiographic features of the site margins and interior contents were classified into four categories. In most patients radiographic changes were detected between 1 and 4 months after removal of the lesion, and complete bone healing was found 4 months or more after surgery. Radiographic changes included "spiculed" or "trabecular" contents within the interior of the surgical site. The fourth month was found to be the optimum time for follow-up radiographic examination for the early detection of residual lesions. In nine (53%) of the patients who had ameloblastoma, recurrent lesions were noted within or at the periphery of the original surgical sites 6 to 10 years after the initial tumor removal.

Adult↗

Factors influencing gelation time of tissue conditioners.

To investigate the effects of the composition and structure on the gelation of tissue conditioners, we measured gelation time with an oscillating rheometer. Also, the plasticizer factor was determined using linear multiple regression equations with the dependent variable of gelation time and the independent variables of molecular weight, molar volume, solubility parameter and viscosity of plasticizers. The results obtained were (i) gelation time decreased as the average particle size of poly-ethyl-methacrylate was decreased and its weight average molecular weight increased; (ii) gelation time decreased as ethanol content in the liquid increased. It varied depending on the type of plasticizer; (iii) it was suggested that gelation time was explained by linear multiple regression equations with independent variable of molar volume, solubility parameter and viscosity of plasticizer. In particular, the most influential factor was suggested to be molar volume.

Ethanol↗

Stroke-prone SHR and arteriolipidosis-prone SHR as models for atherosclerosis: their mechanisms and application for nutritional and pharmacological studies.

1. Peritoneal macrophages (Mphi) were harvested from non-stimulated 2 month old SHRSP and WKY, and incubated with acetyl LDL or [14C]-oleate-albumin complex to check total, free and esterified cholesterol (Cho) accumulation as well as acy coenzyme A-cholesterol acyltransferase (ACAT) activity and its activation by hyperlipidaemic serum. 2. Total and esterified Cho accumulation as well as ACAT activity were enhanced in Mphi from SHRSP compared with those from WKY. 3. To observe the dietary or pharmacological influence on atherogenesis, arteriolipidosis-prone SHR (ALR) were given a high fat cholesterol diet with 3% taurine or a Ca blocker (Nilvadipine, N; 30 mg/kg), both of which significantly decreased serum Cho level and clearly attenuated arterial fat deposition.

Animal Nutritional Physiological Phenomena↗

Interleukin-4 inhibits the production of interleukin-1 by adult T-cell leukemia cells.

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) produce high levels of interleukin-1 (IL-1), which is believed to play an important role in neutrophilia, elevation of C-reactive protein, osteolytic bone lesions, hypercalcemia, and fever in ATL. However, relatively little is known regarding the regulatory mechanism of IL-1 production in ATL. Interleukin-4 (IL-4) affects the monocytes- and neoplastic cells-mediated cytokine production. In this study, we investigated the effect of IL-4 on IL-1 alpha and IL-1 beta production by ATL cells in vitro. IL-4 was found to markedly inhibit the release of IL-1 alpha and IL-1 beta into the conditioned medium in a dose-dependent manner. Northern blot analysis of steady-state IL-1 mRNA demonstrated that IL-4 treatment of ATL cells resulted in a reduction of IL-1 mRNA. These results support the notion that ATL cells spontaneously produce IL-1 alpha and IL-1 beta; however, such production can be inhibited by the immunomodulating agent, IL-4. IL-4 may play an important regulatory role in the production of IL-1 in ATL.

Aged↗

Potassium depletion potentiates amphotericin-B-induced toxicity to renal tubules.

Hypokalemia and potassium depletion are frequent complications of amphotericin B therapy. Both ischemic and gentamicin-induced renal failure is potentiated by potassium depletion; it is, therefore, possible that amphotericin B nephrotoxicity is similarly influenced. This study evaluated whether the acute nephrotoxic response to amphotericin B is potassium sensitive. Potassium-depleted and control rats were subjected to an acute intravenous infusion of either amphotericin B (AmB-K; AmB, n = 10 in each) or its vehicle (V-K, V; n = 6 in each). Potassium-depleted rats had both lower urinary daily excretion and lower plasma levels of potassium than control animals (0.1 +/- 0.0 vs. 2.1 +/- 0.2 mEq/day, p < 0.001, and 3.8 +/- 0.2 vs. 1.9 +/- 0.1 mEq/l, p < 0.001, respectively). In AmB and AmB-K groups, there were equivalent falls in glomerular filtration rate and renal blood flow, and a rise in renal vascular resistance, compared with V and V-K. In contrast, the AmB-K group showed a higher urinary excretion of sodium (AmB-K vs. AmB: 2.9 +/- 0.7 vs. 1.1 +/- 0.3 microEq/min; p < 0.05) and fractional excretion of Na (AmB-K vs. AmB: 1.6 +/- 0.4 vs. 0.6 +/- 0.1%; p < 0.05) in comparison to the AmB group. Neither of these parameters changed in either amphotericin B or vehicle-treated groups. These results suggest that potassium depletion does not influence the acute renovascular effects of amphotericin B but potentiates its tubular toxicity. This may have clinical implications since hypokalemia and potassium depletion are frequent complications of amphotericin B therapy.

Amphotericin B↗

Facial nerve paralysis induced by herpes simplex virus in mice: an animal model of acute and transient facial paralysis.

We have been the first to succeed in producing an acute and transient facial paralysis simulating Bell's palsy, by inoculating herpes simplex virus into the auricles or tongues of mice. The KOS strain of the virus was injected into the auricle of 104 mice and the anterior two thirds of the tongue in 30 mice. Facial paralysis developed between 6 and 9 days after virus inoculation, continued for 3 to 7 days, and then recovered spontaneously. The animals were painlessly sacrificed between 6 and 20 days after inoculation for histopathologic and immunocytochemical study. Histopathologically, severe nerve swelling, inflammatory cell infiltration, and vacuolar degeneration were manifested in the affected facial nerve and nuclei. Herpes simplex virus antigens were also detected in the facial nerve, geniculate ganglion, and facial nerve nucleus. The pathophysiologic mechanisms of the facial paralysis are discussed in light of the histopathologic findings, in association with the causation of Bell's palsy.

Animals↗

Significance of increased neutrophils in patients with advanced colorectal cancer.

We examined the ratio of neutrophils to lymphocytes (N/L ratio) in the peripheral blood in patients with colorectal cancer. The ability to produce active oxygen and phagocytosis of neutrophils, G-CSF, sIL-2R and IAP (immunosuppressive acidic protein) were also measured. The N/L ratios were significantly higher in the advanced stages of cancer than in normal controls. The ability to produce active oxygen in the terminal stage was 33% lower than in the control group. The G-CSF levels had no relationship with the neutrophil counts. IAP levels increased with cancer stage, and were inversely related to the ability to produce active oxygen. The IAP levels correlated well with the sIL-2R levels and the N/L ratio. These findings suggest that the ability to produce active oxygen, N/L ratio and IAP reflect anticancer mechanisms and that they may be useful when considering treatment or prognosis of patients with advanced stages of cancer.

Aged↗

Belactins A and B, new serine carboxypeptidase inhibitors produced by Actinomycete. I. Taxonomy, production, isolation and biological activities.

Belactins A and B, new inhibitors of serine carboxypeptidase were discovered in the fermentation broth of Saccharopolyspora sp. MK19-42F6. They were purified by ethyl acetate extraction, silica gel chromatography, Sephadex LH20 chromatography, Capcellpak C18 SG120 reversed phase HPLC and centrifugal partition chromatography (CPC) following their inhibitory activity against carboxypeptidase Y (CP-Y). The inhibition constants (Ki) of belactins A and B against CP-Y are 0.14 and 0.27 microM respectively. Belactins A and B have highly specific inhibitory activities for CP-Y among various peptidases, have no antimicrobial activities at 100 micrograms/ml and have low toxicities.

Benzamides↗

Belactins A and B, new serine carboxypeptidase inhibitors produced by Actinomycete. II. Physico-chemical properties, structure determinations and enzymatic inhibitory activities compared with other beta-lactone containing inhibitors.

Belactins A and B, new inhibitors of serine carboxypeptidase were discovered in the fermentation broth of Saccharopolyspora sp. MK19-42F6. The structures of belactins A and B were determined to be 4-[3-[(2-amino-5-chlorobenzoyl)amino]-1,1-dimethyl-2-oxobutyl]-3- methyl-2-oxetanone and 4-[3-[[2-(beta-glucopyranosylamino)-5-chlorobenzoyl]amino]-1,1- dimethyl-2-oxobutyl]-3-methyl-2-oxetanone respectively by various spectral analyses. Belactins A and B do not inhibit esterase or lipase at 100 micrograms/ml but have more specific inhibitory activities towards carboxypeptidase Y (CP-Y) compared with other beta-lactone-containing inhibitors, such as ebelactones A, B and esterastin.

Benzamides↗

[Middle fossa acoustic neuroma surgery--indications and predictive factors for hearing restoration].

Between June 1990 and May 1993, 17 acoustic tumors were removed by the middle cranial fossa approach with attempted hearing preservation. Measurable hearing was restored in 13 patients (76.5%) and useful hearing (PTA < 50 dB, SDS > 50%) in 10 patients (58.8%). In addition, significant hearing improvement, greater than 10 dB in pure-tone average, was noted in 6 patients (35.3%). In the hearing improvement group, useful hearing was restored after tumor resection in two patients with poor preoperative hearing. These six patients with hearing improvement exhibited several findings in common: smaller tumors, sudden deterioration of hearing, trough type of audiogram, inferior vestubular nerve origin and short duration of hearing loss before surgery. Such signs suggested favorable preoperative prognostic factors for potential postoperative hearing improvement. Because there was no significant difference between postoperative facial nerve outcome in the middle cranial fossa approach and the translabyrinithine approach in our series of small tumors, we recommend the use of the middle cranial fossa approach for hearing preservation in patients with small tumors, even when their hearing is poor preoperatively.

Adult↗

[A case of CABG in a patient complicated with von Willebrand's disease secondary to polycythemia vera].

We report a case of 47-year-old patient with von Willebrand's disease (VWD) caused by polycythemia vera (PV) who underwent CABG surgery. The patient has been suffering of PV for 10 years and was admitted because of post infarction angina. On admission, she was found to have a decreased von Willebrand factor which was suggested by prolonged APTT. CABG was safely performed without undue bleeding with the use of Factor VIII concentrates. The appropriate control of polycythemic state before surgery and perioperative use of Factor VIII concentrates was considered to be important for successful open heart surgery associated with such complication.

Angina Pectoris↗

[Reoperation for recurrent and second primary lung cancer].

Thirty patients have undergone multiple resections for non-small cell lung cancer from 1973 to July 1994, constituting 2.6% of 1,153 who had undergone pulmonary resection for such tumor. In the 22 patients for recurrent cancer, 15 resections of the ipsilateral lung and 9 of the contralateral lung were performed with no operative death. The survival rate following second resection in 22 patients was 33.8% at 3 years and 13.5% at 5 years. Survival rate was poor in patients with DNA aneuploid primary tumor and there was not a patients of 5 years survival. Three out of the 5 patients which had a diploid pattern in the primary tumor, showed an aneuploid pattern in the recurrent tumor. Long survival patients were founded only in the patients which had a diploid primary tumor. In the 8 patients for second primary lung cancer, 4 resections of the ipsilateral lung and 4 of the contralateral lung were performed, including two bronchoplastic surgery for early hilar squamous cell carcinoma. The survival rate following second resection in 8 patients was 64.2% at 5 years with good result. We concluded that an aggressive surgical approach is safe and warranted in patients with second primary lung cancer.

Adenocarcinoma↗

[Successful treatment of acute myelomonocytic leukemia developed from MDS with cytarabine ocfosfate (SPAC)].

A 65-year-old female with acute myelomonocytic leukemia (AMMoL) developed from myelodysplastic syndrome (MDS), successfully treated with cytarabine ocfosfate (SPAC) is reported. Ubenimex, calcitriol and corticosteroid had a minor effect on her MDS. Since she had severe anemia and congestive heart failure on developing leukemia, she was treated with oral administration of SPAC, a cytidine deaminase resistant derivative of Ara-C. After the second course of SPAC (200 mg/day, for 14-28 days), marked erythroid bursts were found and she entered complete remission. The samplings of SPAC and its metabolites of SPAC were investigated in 2 cases including this case, but there seemed to be no relation between their content and effects. In AML patients, especially in cases developed from MDS, SPAC might be useful because it can be given orally even in an outpatient.

Aged↗