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Biomedical subjects

M Hamada

Publications and source records attributed to M Hamada.

At least 109 records · Page 6Linked to original sources

Serum creatinine level underestimates hypertensive renal involvement in elderly patients with essential hypertension.

It is well recognized that serum creatinine level provides a quick general assessment of renal function. However, we frequently encounter elderly hypertensive patients with renal involvement whose serum creatinine levels are within normal limits. The aim of this study was thus to determine whether serum creatinine level is a sensitive indicator of renal function in elderly hypertensive patients. Study groups were classified according to age: 82 elderly patients (aged 65 yr or older) and 98 middle-aged patients (aged 40-65 yr) with essential hypertension. To assess hypertensive renal involvement, serum creatinine and serum uric acid levels were measured. We also measured the left ventricular mass (LVM) index by using echocardiography as a marker of hypertensive target organ damage. There was no age-related difference in the LVM index, but the serum creatinine level in elderly hypertensive patients was significantly lower than that in middle-aged hypertensive patients. There was no significant difference in serum uric acid level between the two groups. In addition, the LVM index was correlated with the serum uric acid level (r = 0.46, p = 0.0001) but not with the serum creatinine level in elderly hypertensive patients. In middle-aged hypertensive patients, the LVM index was related to both serum uric acid level (r = 0.41, p = 0.007) and serum creatinine level (r = 0.43, p = 0.003). In conclusion, serum creatinine level may underestimate hypertensive renal involvement in elderly hypertensive patients. In contrast, serum uric acid level may be a sensitive indicator of hypertensive target organ damage irrespective of age.

Adult↗

Conagenin derived from Streptomyces roseosporus enhances macrophage functions.

In contrast to the studies that describes the effects of conagenin (CNG) on the cellular immunity of lymphocytes (references), we investigated the in vitro effect of CNG on macrophage function. Phagocytosis of alveolar macrophages (AM) against opsonized-sheep red blood cells (SRBC) was significantly enhanced following in vitro incubation with CNG for 12 hours at 37 degrees C, which was closely associated with increased expression of Fc-receptor in AM membranes. Macrophage-activating factor (MAF), prepared from splenic lymphocytes in vitro stimulated with concanavarin A (Con A) for 48 hours at 37 degrees C, had also the enhancing effect on phagocytosis of AM against opsonized-SRBC. Preincubation with CNG (0.1 microg/ml) and MAF (1/100 dilution) induced the additional effect on phagocytosis of AM, which was associated with the increased expression of Fc-receptor in AM membranes. These results suggest that CNG enhances AM phagocytosis by increasing the expression of Fc-receptor on their membranes via either effecting different sub-populations of AM cells or by activating independent mechanism on the same AM cell population.

Adjuvants, Immunologic↗

Decatromicins A and B, new antibiotics produced by Actinomadura sp. MK73-NF4. I. Taxonomy, isolation, physico-chemical properties and biological activities.

New antibiotics designated decatromicins A and B were isolated from the culture broth of Actinomadura sp. MK73-NF4. They were purified by butyl acetate extraction, silica gel column chromatography, silica gel TLC and Sephadex LH-20 column chromatography. Decatromicins A and B inhibited growth of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA).

Actinomycetales↗

Vinylamycin, a new depsipeptide antibiotic, from Streptomyces sp.

A new depsipeptide antibiotic, vinylamycin, was isolated from the culture broth of an actinomycete strain. The producing organism, designated MI982-63F1, was identified as a member of Streptomyces. Vinylamycin was isolated from the culture broth by extraction with EtOAc and purified by crystallization from EtOAc. The structure of vinylamycin was determined by spectroscopic analysis and degradation studies. Vinylamycin showed antimicrobial activities against Gram-positive bacteria including MRSA.

Animals↗

Serial changes in sarcoplasmic reticulum gene expression in volume-overloaded cardiac hypertrophy in the rat: effect of an angiotensin II receptor antagonist.

This study was designed to clarify whether gene expression in the cardiac sarcoplasmic reticulum [sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban, ryanodine receptor and calsequestrin] changes in accordance with left ventricular functional alterations in the volume-overloaded heart. Further, the effect of the angiotensin II type 1 receptor antagonist, TCV-116, on the expression of these genes was also evaluated. Left ventricular fractional shortening was significantly increased at 7 days, had returned to control levels at 21 days, and had significantly decreased at 35 days after the shunt operation, compared with sham-operated rats. The level of SERCA mRNA was significantly decreased at both 21 days and 35 days after the shunt operation. The levels of ryanodine receptor and phospholamban mRNAs were significantly decreased at 35 days in shunt-operated rats. The decrease in the SERCA mRNA level preceded the development of cardiac dysfunction. The levels of SERCA and ryanodine receptor mRNAs were correlated positively with left ventricular fractional shortening (r=0.73, P<0.0001 and r=0.61, P<0.01 respectively). Attenuation of the decrease in left ventricular fractional shortening occurred on treatment with TCV-116. After the treatment with TCV-116, the levels of SERCA and phospholamban mRNAs were restored to the respective values in sham-operated rats. Ryanodine receptor mRNA levels remained unchanged after treatment with TCV-116. These results indicate that the down-regulation of SERCA and ryanodine receptor mRNA levels may be related to cardiac dysfunction in the volume-overloaded heart. In addition, treatment with an angiotensin II receptor antagonist may restore the altered sarcoplasmic reticulum mRNA levels to control levels, and this may result in attenuation of the functional impairment in the volume-overloaded heart.

Angiotensin II↗

[Effects of human atrial natriuretic polypeptide in a patient with acute pulmonary edema during living-related kidney transplantation].

A 19-year-old female was scheduled for living-related kidney transplantation under general anesthesia. Eight units of fresh frozen plasma were infused in 30 minutes before the recanalization of renal vessels. Twenty minutes after the first urination, end-tidal-CO2 suddenly increased showing CVP of 18 mmHg. We considered that she had developed acute pulmonary edema. Continuous hANP infusion was initiated at the rate of 0.1 microgram.kg-1.min-1. By this infusion, end-tidal-CO2 and CVP gradually decreased and operation was concluded successfully. This case demonstrates that hANP works also on the transplanted kidney.

Acute Disease↗

Radiation-induced leukocyte entrapment in the rat retinal microcirculation.

PURPOSE: To evaluate the effects of irradiation on leukocyte dynamics in the rat retinal microcirculation. METHODS: Thirty-five Brown-Norway rats received a dose of 10 Gy irradiation in one fraction. Leukocyte dynamics were studied with acridine orange digital fluorography, in which a nuclear fluorescent dye of acridine orange is used and examined by scanning laser ophthalmoscope. This technique allowed visualization of fluorescent leukocytes in vivo. The leukocyte dynamics were evaluated at 0, 4, 7, 14, 30, and 60 days after the irradiation. RESULTS: Mean leukocyte velocity in the retinal capillaries decreased immediately. It partially recovered on day 4 but then gradually decreased up to the 2-month mark. Low-dose irradiation induced entrapment of leukocytes in the retinal microcirculation. The number of entrapped leukocytes gradually increased with time. The major retinal vessels significantly constricted immediately after irradiation. The diameter was reduced by 76% in arteries and 75% in veins, 2 months after irradiation. CONCLUSIONS: Entrapped leukocytes may be activated and exacerbate vascular injury and microinfarction and thus may participate in the pathogenesis of radiation retinopathy.

Acridine Orange↗

Contribution of non-cardiomyocyte apoptosis to cardiac remodelling that occurs in the transition from compensated hypertrophy to heart failure in spontaneously hypertensive rats.

Various alterations in molecular and cellular events have been considered as possibly contributing to the cardiac remodelling that occurs during the transition from compensated hypertrophy to heart failure. The aim of the present study is to clarify (1) whether cardiac apoptosis occurs during the transition from compensated hypertrophy to decompensated heart failure, and (2) whether expression of the genes encoding Bax (an apoptosis inducer) and Bcl-xL and Bcl-2 (apoptosis inhibitors) is altered during this transition. We used 12-month-old and 20-month-old male spontaneously hypertensive rats (SHR(12) and SHR(20) respectively) and age-matched Wistar-Kyoto rats (WKY(12) and WKY(20) respectively). These rats were killed after measurement of haemodynamic parameters by transthoracic echocardiography and use of a tipmanometer via the right carotid artery. The expression of bcl-2, bcl-xL and bax was analysed by Northern blotting. Samples were also fixed in 4% paraformaldehyde for in situ nick end-labelling (TUNEL) methods and immunohistochemistry. SHR(12) had well compensated left ventricular hypertrophy with normal fractional shortening and normal end-systolic wall stress. In contrast, the hearts of SHR(20) developed decompensated dilatation, with a decrease in fractional shortening and an increase in end-systolic wall stress. TUNEL-positive cells were seen exclusively in the hearts of SHR(20). The major cell types that showed TUNEL-positive nuclei were non-cardiomyocytes. The expression of bax remained unchanged during the transition to heart failure. However, there was increased expression of bcl-xL in the failing stage, whereas the expression of bcl-2 remained unchanged. Immunohistochemical studies revealed that Bcl-xL protein was up-regulated in the hearts of SHR(20). In conclusion, non-cardiomyocyte apoptosis may play a contributory role in the remodelling that occurs in the transition from compensatory hypertrophy to decompensated heart failure. In addition, it is suggested that enhanced expression of bcl-xL plays an important role in the preservation of cardiomyocytes during this transition.

Animals↗

[Clinical evaluation and significance of measurement of airway hyperresponsiveness in COPD].

Airway hyperresponsiveness (HR) is one of the clinical characteristics of bronchial asthma and COPD. HR of COPD has been known to correlate with progress of pulmonary function in COPD. In order to evaluate the necessity of HR measurement, HR of COPD alone, COPD with asthma, asthma and control subjects was compared. Patients with COPD alone exhibited weak HR, while COPD with asthma represented severe HR, which was the same degree with asthmatics. From these results, we should be cautious in measurement of HR in COPD. Especially patients with FEV1 less than 1 L should be prevented from HR test.

Adult↗

[A surgically treated case of giant pseudoaneurysm arising as a complication following carotid endarterectomy].

We reported a case of giant pseudoaneurysm (PA) originating at the left extracranial internal carotid artery after carotid endarterectomy (CEA). A 60-year-old man underwent CEA for severe stenosis of the left internal carotid artery. A day after the operation, a left cervical painful and pulsatile mass beneath the operative scar was noticed. Soon after that, the patient showed dyspnea, and intratracheal intubation was carried out. 6 days after CEA, a painful swelling reoccurred. A left carotid angiogram visualized a 5 x 5 cm sized PA in the region of the left carotid bifurcation and demonstrated patency of the two major carotid branches. After a balloon catheter had been inserted and inflated at the carotid bifurcation, the patient underwent a second operation. The bleeding from arteriotomy was well controlled by the inflated balloon catheter at the carotid bifurcation. The continuous SURGILENE suture appeared to be disrupted and a saccular PA was found to have arisen from a defect on the lateral surface of the carotid bifurcation. The suture was completely removed and arteriotomy was closed with a continuous SURGILENE suture again and some single sutures were added. A PA arising as a complication following CEA is rare, but the possibility of PA after CEA should be considered in any patient presenting with a painful or/and pulsatile mass in the neck at any time interval following the operation. Angiography at the early post-op stage is necessary to rule out the various complications after CEA. To control the bleeding, the balloon catheter was thought to be very useful.

Aneurysm, False↗

Hypertrophic cardiomyopathy with mid-ventricular obstruction and splenic infarction associated with paroxysmal atrial fibrillation: a case report.

A 54-year-old woman had been treated for hypertrophic cardiomyopathy and paroxysmal atrial fibrillation since 1992. She was admitted with paroxysmal atrial fibrillation which was resolved by medical treatment. However, on the next day, left lateral chest pain appeared. Computed tomography disclosed a low density area in the spleen. She received anticoagulant therapy under a diagnosis of splenic infarction, and the pain disappeared. Echocardiography showed hypertrophic cardiomyopathy with mid-ventricular obstruction. She was treated with cibenzoline to prevent paroxysmal atrial fibrillation attack and attenuate the hemodynamic load. After treatment, the pressure gradient decreased from 41 to 7 mmHg. This patient with hypertrophic cardiomyopathy suffered a rare isolated splenic infarction associated with paroxysmal atrial fibrillation.

Anti-Arrhythmia Agents↗

Gene expression of neurotrophins and their receptors in cultured rat vascular smooth muscle cells.

Most previous researches on neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have focused on the nervous system, because their receptors are widely distributed in neuronal tissues. Recently, however, the participation of neurotrophins in inflammation and atherosclerosis has been proposed. Therefore, the gene expression of neurotrophins is now an urgent issue is to be investigated in nonneuronal tissues. Here, we evaluated the gene expression of neurotrophins and their receptors in rat cultured vascular smooth muscle cells (VSMCs) by the reverse transcriptase-polymerase chain reaction method. The transcripts of NGF, NT-3, and TrkC (high-affinity receptor for NT-3), and two BDNF alternative spliced transcript variants with exons 3 and 4 were clearly detected in VSMCs cultured under conventional culture conditions. The upregulation of mRNA levels for NGF, two BDNF variants with exons 1 and 2, low-affinity neurotrophin receptor, and high-affinity receptors, TrkA (for NGF) and TrkB (for BDNF), was observed in response to the treatment with serum and phorbol-ester following the serum-starvation. In contrast, the expression of NT-3 and TrkC genes was downregulated under these conditions. Co-expression of these factors and their receptors and the characteristic regulation of their gene transcriptions suggest that these factors play crucial roles in the function of VSMCs through an autocrine mechanism.

Alternative Splicing↗

A useful method to evaluate bone resorption inhibitors, using osteoclast-like multinucleated cells.

Since excessive bone resorption in postmenopausal osteoporosis is a pathological manifestation of the disease, it is important to control bone resorption activity of osteoclasts as a means of controlling the disease. To screen bone resorption inhibitors, a simple and quantitative method to assay bone resorption is needed. However, it has been difficult to prepare a lot of osteoclasts required for the screening of many compounds in vitro. We used the method for the preparation of mouse osteoclast-like multinucleated cells in vitro and developed a useful method in which osteoclast-like multinucleated cells were placed on dentin slices and the calcium released from dentin into the culture medium was measured. Under the optimal conditions, the increase of the calcium concentration caused by bone resorption activity of the osteoclast-like cells was significant and inhibited by calcitonin in a dose-dependent manner. We also examined the inhibitory effect of calcitonin on the pit area caused by bone resorption and found that the decrease of the calcium released from dentin was correlated with that of the pit area. Furthermore, several known bone resorption inhibitors such as bisphosphonate, bafilomycin A1, and herbimycin A showed inhibitory effects on the calcium release from dentin slices. Thus, this simple method provides us a useful screening system to find bone resorption inhibitors with novel mechanisms.

Animals↗

In vivo neutralization of P-selectin inhibits leukocyte-endothelial interactions in retinal microcirculation during ocular inflammation.

P-selectin is one of the adhesion molecules involved in leukocyte rolling during an inflammatory reaction. The aim of this study was to examine the role of P-selectin in leukocyte-endothelial interactions in retinal microcirculation during ocular inflammation, known as endotoxin-induced uveitis (EIU), in vivo. EIU was induced in Lewis rats by footpad injection of lipopolysaccharide (LPS). At the time of LPS treatment or 12 h later, anti-rat P-selectin mAb (ARP) was injected intravenously, and its effect on leukocyte behavior in the retina was studied after intravital staining with acridine orange using a scanning laser ophthalmoscope. P-selectin gene expression in the retina was also studied by a semiquantitative polymerase chain reaction (PCR) method. Administration of ARP at the time of LPS treatment significantly reduced the number of rolling leukocytes at 6 and 12 h by 68% (P < 0.05) and 83% (P < 0.01), respectively, and the number of cells infiltrating the vitreous at 48 h by 61% (P < 0.05). Interestingly, ARP significantly inhibited the vasodilation observed during EIU. In contrast, delayed administration of ARP blocked neither cellular infiltration nor vasodilation. P-selectin gene expression was upregulated during the course of EIU. In conclusion, P-selectin may significantly contribute to the development of inflammation in the early stage of endotoxin-induced ocular inflammation.

Animals↗

In vivo influence of p53 status on proliferation and chemoradiosensitivity in non-small-cell lung cancer.

Alteration of the p53 gene product is a frequent event in the progression of lung cancer. However, its importance to proliferation and response to chemoradiotherapy remains unclear. Thus, to assess its influence directly in vivo, we implanted into nude mice two kinds of human non-small-cell lung cancer (NSCLC) cells: H226br having a homozygous gene mutation in p53 (mt-p53) and H226b with intact p53 (wt-p53). We found that mt-p53 tumors grew substantially faster than wt-p53 tumors. Furthermore, treatment with cisplatin and radiation did not reduce the size of mt-p53 tumors, while wt-p53 tumors regressed by approximately 60%. Terminal-deoxytransferase-mediated dUTP-biotin nick-end labeling assay revealed apoptosis to be the mechanism responsible for the regression. Interestingly, apoptosis occurred in mt-p53 tumors although only at high doses of cisplatin and not at the magnitude detected in wt-p53 tumors. Cell labeling by staining with bromodeoxiuridine indicated that p53 is an important factor in modulating growth in NSCLC tumors. Our results are consistent with the notion that correction of a single genetic lesion enhances the therapeutic effect of chemotherapy.

Animals↗

MR imaging of meniscal tears with discoid lateral meniscus.

OBJECTIVE: To study MR findings of meniscal tears with discoid lateral menisci (DLMs) and to evaluate the incidence and accuracy of MRI compared to arthroscopical surgery. MATERIAL AND METHODS: MR appearances of surgically proved torn discoid lateral menisci (DLM) were studied in 57 knees (40 patients). They were all performed with a 1.5T MR before surgery. MR sequences included T1- and T2* weighted images on both coronal and sagittal planes and 3D-axial images with a slice thickness of 0.7 mm. RESULT: Of 57 DLMs, there were 32 complete DLMs and 25 incomplete DLMs. Twenty-five of 32 complete DLMs had tears; including seven with intrasubstance tear, five with radial tear, five with other kinds of tears and eight with severe tears involving whole meniscus. On the other hand, 13 of 25 incomplete DLMs had tears; including two with intrasubstance tear, six with radial tear, four with other kinds of tears and one with severe tears. All DLMs were correctly diagnosed on MR images. Twenty-seven of 38 tears with DLM were correctly identified on conventional 2D MR images. This yielded 71.1% sensitivity, 100% specificity and 80.7% overall accuracy. When adding axial 3D MR images to 2D MR images, 36 of 38 tears were correctly diagnosed. A combination of both techniques yielded a sensitivity of 94.7% and a specificity of 100%. Ten of 11 radial tears with DLM were correctly identified on 3D axial images, where only three of them could be diagnosed on conventional 2D images. Eight of nine intrasubstance tears were correctly identified on 3D axial images, where six of them could be diagnosed on conventional 2D images. CONCLUSION: DLMs had a much higher incidence of meniscal tears than normally shaped lateral menisci and MR is the only modality of choice to evaluate them before surgery. Especially 3D axial MR images were quite useful in the detection of intrasubstance and radial tears often associated with DLMs.

Adult↗