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Biomedical subjects

M Shimizu

Publications and source records attributed to M Shimizu.

At least 433 records · Page 24Linked to original sources

Skin surgery in patients 90 years of age and over.

BACKGROUND: The number of aged people is increasing. It is conceivable that we will be treating considerably more aged patients with more surgical risk factors in the very near future. METHODS: During the period between 1976 and 1996, 212 patients of 80 years of age and older underwent skin surgery at the Mie University Hospital, Japan. Among them, 25 patients of 90 years of age and over were studied. RESULTS: Fourteen patients (56.0%) have undergone skin surgery in the past 5 years; 22 patients (88.0%) had skin tumors on the face and ears; squamous cell carcinoma was found in 17 patients (68.0%), while basal cell carcinoma was seen in four patients (16.0%). Despite their advanced ages, half of the patients had no medical contraindications to performing surgery. CONCLUSIONS: Careful preoperative management may allow more cutaneous surgery to be carried out in aged people.

Aged↗

Autotransfusion supported by erythropoietin therapy in transurethral resection of the prostate.

We investigated the collection and transfusion of autologous blood after treatment with EPO in 68 BPH patients (including 10 controls) who were scheduled to undergo TUR-P. All patients received oral and/or intravenous iron supplements. Assessments were made based on the preoperative increase in blood hemoglobin levels including autologous blood predonation (deltaHb). The deltaHb in patients undergoing collection of 600 ml of blood were as follows: control group: -0.36 +/- 0.57 g/dl; EPO group, 9 x 3000 units intravenously: 1.15 +/- 0.83 g/dl; EPO group, 6 x 6000 units intravenously: 0.79 +/- 0.80 g/dl; EPO group, 3 x 12,000 units subcutaneously: 1.47 +/- 0.62 g/dl. In patients undergoing collection of 800 ml of blood, the results were as follows: EPO group, 3 x 12,000 units subcutaneously: 1.80 +/- 0.69 g/dl; EPO group, 3 x 24,000 units subcutaneously: 2.03 +/- 0.77 g/dl. All EPO-treated patients successfully underwent surgery using their own blood, and none of them required homologous transfusion. The increase of Hb was greater in the patients treated with EPO than in controls, allowing safe preoperative blood collection even in elderly patients. In patients with relatively severe BPH, homologous transfusion could be avoided and surgery was performed safely.

Aged↗

Suboptimal clinical response to anti-tumor necrosis factor alpha (TNFalpha) antibody therapy in a patient with severe rheumatoid arthritis and lymphadenopathy.

This concerns a patient with severe rheumatoid arthritis (RA) and lymphadenopathy (LA) who showed suboptimal clinical response to antitumor necrosis factor alpha (TNFalpha) antibody (Ab), cA2 therapy. The assessment of TNFalpha and IL-6 mRNA expression in the swollen lymph-node (LN) of the patient by reverse transcription, polymerase chain reaction (RT-PCR) before cA2 treatment, showed only enhanced IL-6 production, but not TNFalpha. Moreover, cA2 failed to inhibit in-vitro spontaneous IL-6 production in the LN block culture from the patient. Taken together, these results indicate that IL-6 production in the swollen LNs of the patient might not depend on TNFalpha. This might partly cause suboptimal clinical response to anti-TNFalpha Ab therapy in the patient.

Antibodies, Monoclonal↗

Effect on colon cancer cells of human interferon-beta gene entrapped in cationic multilamellar liposomes.

When cultured cells of human colon cancer cell line SW480 were transfected with human interferon-beta (hIFN-beta) gene by means of cationic multilamellar liposomes, the endogenously produced hIFN-beta exhibited a remarkable anti-proliferative effect on the cells, which was more effective than that of exogenously added hIFN-beta. This effect lasted for several days, and was blocked completely by the addition of sufficient amounts of anti-hIFN-beta antibody. From experiments using a transwell plate and an infusion pump, we found that endogenously produced hIFN-beta acted effectively on the cells around the transfectants and that the growth-inhibitory effect was totally retained upon continuous dilution of the medium. These data indicate that hIFN-beta expressed endogenously by transfer of its gene acted on these cancer cells mainly in a paracrine manner. Although the transfection with hIFN-gamma gene also revealed a definite growth-inhibitory effect on the same tumor cells, the extent was less than that of hIFN-beta gene.

Antibodies↗

Localization of apoptotic cells within the human endometrium and correlation between apoptosis and p21 expression.

The aim of the present study was to gain a better understanding of the localization of apoptotic cells within the human endometrium during the menstrual cycle and to elucidate the relationships among the following for the human endometrium: apoptosis, p21 expression, and cell proliferation. Apoptosis and p21 expression were identified mainly in the glandular cells of the basal layer in the late secretory phase. In contrast, cells positive for Ki-67 were observed predominantly in the functional layer (in the proliferative phase in glandular cells and in the secretory phase in stromal cells). A very strong positive correlation (r = 0.81; P < 0.001) was demonstrated between the number of apoptotic cells and the number of p21-positive cells present among the glandular cells but, topographically, individual apoptotic cells were not coincident with p21-positive cells in serial sections. The results of this study suggest that the proliferation of the glandular cells of the basal layer is regulated by both apoptosis and p21 expression, particularly in the late secretory phase. Such regulation may be necessary to maintain a healthy population of glandular cells in the basal layer of the endometrium.

Adult↗

Bone wound healing after maxillary molar extraction in ovariectomized aged rats.

We studied bone wound healing processes after maxillary molar extraction in ovariectomized (OVX) aged rats, as an experimental model of postmenopausal osteoporosis, by means of scanning electron microscopy. Six-month-old female rats were either sham-operated or bilaterally OVX; and at 60 days postoperatively, the maxillary first molars were extracted. On postextraction days 4, 7, 30 and 60, the dissected maxillae were fixed and the alveolar bone surfaces around the extracted alveolar sockets were examined. In sham-operated controls, new bone formation was recognized on the buccal-side bone surfaces on day 4 and then increased in extent daily through day 60 mainly on the buccal and mesial sides. On day 60, the extracted sockets were filled with new bone mass and the surrounding alveolar bone surfaces had become smooth, indicating decreased bone metabolism. Bone resorption was prominent throughout the bone surfaces around and within the extracted sockets, increased in extent through day 7, but had decreased by day 60. In comparison to sham-operated controls, new bone formation in OVX rats was slightly increased in the early phase but subsequently showed a marked decrease. Bone resorption in OVX rats was greatly stimulated and was comparatively long-lasting. These results suggest that, under the present experimental conditions, in bone wound healing after maxillary molar extraction, (i) ovariectomy stimulates sustained bone resorption and (ii) bone formation and resorption both take place at specific sites on alveolar bone surfaces.

Aging↗

Antitumor activity of KW-2170, a novel pyrazoloacridone derivative.

5-(3-Aminopropyl)amino-7,10-dihydroxy-2-(2-hydroxethyl)-aminoethyl -6H-pyrazolo[4,5,1-de]acridin-6-one dihydroxy-chloride (KW-2170), a novel derivative of pyrazoloacridone, was selected and evaluated for its antitumor activity and toxicity in mice. KW-2170 exhibited antitumor activity superior to adriamycin (ADM) against Sarcoma 180, breast carcinoma MM102 and fibrosarcoma Meth A inoculated s.c. in mice. Its therapeutic index (LD10/ED50) was higher than that of ADM on two murine carcinoma models, MM102 and Meth A. KW-2170 showed significant antitumor activity against 17 human tumor xenografts of a total of 24 tumors tested and the total tumor response rate by treatment with KW-2170 was significantly higher than that by ADM (70.8 versus 58.3%). In particular, human lung carcinoma was highly sensitive to KW-2170, and a marked tumor regression was observed on Lu-65 and Lu-99 human lung carcinoma xenograft models. Ovary and pancreas carcinomas were also sensitive to the drug. Additionally, its therapeutic index was also high on these human carcinoma models in comparison with that of ADM. The best antitumor efficacy of KW-2170 was observed by a weekly treatment schedule followed by a single treatment schedule and a successive administration schedule also tended to be toxic to the hosts. KW-2170 exhibited very low cross-resistance against four lines of multidrug resistant tumors expressing high levels of P-glycoprotein, and the drug showed significant antitumor activity against ADM-resistant human ovary carcinoma A2780/ADM and against nasopharynx carcinoma KB-A1 xenografts which were not sensitive to ADM. These results indicate that KW-2170 has a very potent antitumor activity and is feasible as a new antitumor drug against ADM-refractory solid tumors in clinics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Differentiation of benign from malignant nodules by accumulation of Tc-99m pertechnetate using TI-201 delayed scans.

Thyroid carcinoma usually is characterized by a nonfunctioning or "cold" nodule depicted on the Tc-99m scan. Twelve patients with functioning "hot" thyroid nodules underwent thyroidectomy (nine hemithyroidectomies, two nodulectomies, and one subtotal thyroidectomy). Histologic examination revealed that five patients (42%) had malignant nodules (papillary carcinoma in two and follicular carcinoma in three). Of the seven patients with benign nodules, five had follicular adenoma and two had adenomatous hyperplasia. TI-201 scanning (early and delayed) was performed at the same time as Tc-99m scanning. Only one of the seven benign nodules showed accumulation on the delayed TI-201 scan, whereas all five malignant nodules showed accumulation. The delayed TI-201 scan is useful for the differentiation of benign from malignant nodules that show accumulation of Tc-99m pertechnetate.

Diagnosis, Differential↗

Malignant melanoma imaging with Tl-201.

Two patients with malignant melanoma were evaluated using Tl-201 scintigraphy. Planar scintigraphy showed tumor accumulation, and SPECT Tl-201 imaging revealed exact tumor localization. The findings indicate the utility of Tl-201 to detect the primary lesion and to identify postoperative recurrence in malignant melanoma.

Aged↗

Endothelin-1 enhances nitric oxide-induced cell death in cultured vascular smooth-muscle cells.

Increased expression of endothelin-1 (ET-1) immunoreactivity is demonstrated in the active atherosclerotic plaque. Here we show that both ETA and ETB receptors are expressed in rat vascular smooth-muscle cells (VSMCs). ET-1 binding to ETB receptors enhances nitric oxide-induced cell death in VSMCs. These findings suggest that ET-1 may participate in the mechanism of cell death (apoptosis) in the plaque through activation of ETB-mediated pathways and that a selective ETB receptor antagonist could be useful in preventing acute plaque alterations, such as plaque rupture.

Amino Acid Sequence↗

Angiotensin II type 1 receptor blockade with candesartan protects the porcine myocardium from reperfusion-induced injury.

Angiotensin-converting enzyme (ACE) inhibitors reduce myocardial ischemia/reperfusion injury. It is unclear whether reduced formation of angiotensin II or attenuated degradation of bradykinin is responsible for the beneficial effects. We investigated the role of endogenous angiotensin II in ischemia/reperfusion injury by studying the effects of the angiotensin II type 1 receptor antagonist candesartan on myocardial function, infarct size, and perfusion after ischemia/reperfusion. Anesthetized pigs were subjected to 45 min of regional ischemia and 240 min of reperfusion. Starting 5 min before reperfusion, four groups of pigs (n = 6 in each) received coronary venous retroinfusion of candesartan (0.2, 2, or 20 microg/kg) or vehicle for 30 min. Myocardial regional blood flow was measured with radioactive microspheres in two separate groups (n = 6 in each) given 20 microg/kg candesartan or vehicle. Retroinfusion of 20 microg/kg of candesartan improved recovery of left ventricular systolic segment shortening measured by sonomicrometry in the ischemic area compared with 0.2 microg/kg of candesartan and vehicle. Infarct size, as a percentage of the area at risk, was smaller in the 2 and 20 microg/kg groups than in the vehicle group (39.1 +/- 11.6% and 34.8 +/- 10.2% vs. 78.3 +/- 8.9%, p < 0.01). There was no difference between candesartan and vehicle in their effects on regional myocardial blood flow. Angiotensin II type 1 receptor blockade supports myocardial functional recovery and reduces infarct size. This effect is not related to improved regional myocardial blood flow during reperfusion.

Angiotensin Receptor Antagonists↗

Myocardial fatty acid imaging with 123I-labelled 9-methyl-branched pentadecanoic acid (9MPA) using SPET.

123I-labelled 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA) is a modified long-chain fatty acid that shows some beta-oxidation. Some basic aspects of this fatty acid, including myocardial uptake, distribution, clearance and differences from 201Tl myocardial perfusion, have yet to be evaluated. An average of 150 MBq of 123I-9MPA was injected intravenously into 16 patients with coronary artery disease. Planar images were obtained 45, 120 and 240 min post-injection, and single photon emission tomography (SPET) was performed at the initial (5 min), middle (45 min) and late (120 min) phases after injection. Myocardial uptake and clearance were evaluated by planar imaging, and a segmental comparison between 123I-9MPA and reinjection or resting 201Tl was performed on the SPET images. 123I-9MPA showed good uptake between 5 and 60 min, but a severe decrease was seen after 120 min in three (19%) patients. The heart-to-mediastinum ratio was 1.68 +/- 0.19, 1.55 +/- 0.19 and 1.40 +/- 1.40 at 45, 120 and 240 min, respectively. The washout rate after background subtraction was 28% for 45 min to 2 h and 47% for 45 min to 4 h. The segmental comparison (n = 182) between 123I-9MPA and 201Tl showed complete agreement of 72, 75 and 65% at 10, 45 and 120 min, respectively. The grading of the uptake of 123I-9MPA was less than that of 201Tl in 20-30% of the segments indicating myocardial fatty acid metabolic impairment relative to perfusion. The regional clearance from 5 to 120 min in the reduced-count region was lower than that in the normal region (28 +/- 7% vs 36 +/- 8%, P < 0.01). All 123I-9MPA SPET images showed good contrast if the data were acquired within 60 min. Based on the clearance of 123I-9MPA from the myocardium, imaging within 120 min is desirable. A mismatch of fatty acids and perfusion was seen in one-quarter of patients, and differential regional clearance may be clinically significant and should be investigated.

Adult↗

Reproducibility of 99Tcm-MAG3 clearance in normal volunteers with the two-sample method: comparison with 131I-OIH.

The aim of this study was to evaluate the reproducibility of 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) clearance and to compare it with that of 131I-orthoiodohippurate (131I-OIH), which is widely used in clinical practice. Twelve young healthy volunteers with a mean age of 23.4 years (range 19-28) were enrolled in the study. The investigations were repeated at an interval of 1 month under similar physiological conditions. Each volunteer received a simultaneous injection of 99Tcm-MAG3 and 131I-OIH that was commercially available in an already labelled form. Blood samples were obtained at 44 and 104 min post-injection. Clearance values were calculated using the two-sample method. The mean (+/- S.D.) change from the first to the second measurement was -7.1 +/- 11.1% for 99Tcm-MAG3 and 1.7 +/- 13.6% for 131I-OIH. There were no significant differences between the first and the second measurements of 99Tcm-MAG3 and 131I-OIH clearance, respectively. 99Tcm-MAG3 clearance was shown to be very similar to that of 131I-OIH in healthy volunteers.

Adult↗

A case of subcutaneous cysticercosis.

We report the fourth case of subcutaneous cysticercosis infected in Japan since 1975. The patient noticed a subcutaneous nodule on his left shoulder without symptoms for three years. No remarkable changes were found in laboratory findings and physical examination after surgical excision of the subcutaneous nodule. The adult worm of Taenia solium could not be found in the intestine. Histological findings revealed a cystic structure with a fibrous capsule and a protoscolex with suckers, hooks, and calcareous corpuscula. It was identified as a Cysticercus cellulosae hominis based on morphological characteristics. The patient has been living in the Kanto area of Japan and has never been outside Japan since he was born.

Adult↗

Toxic epidermal necrolysis with severe gastrointestinal mucosal cell death: a patient who excreted long tubes of dead intestinal epithelium.

TEN is a severe inflammatory disease which is characterized by generalized epithelial destruction. The epidermis is the most common target of TEN, however, any epithelium can be involved. We report a toxic epidermal necrolysis (TEN) patient who excreted long tubes of dead intestinal epithelium. Epidermal keratinocytes and intestinal epithelium were found to undergo extensive apoptosis by TUNEL method. Drugs were speculated as the causative agents for this case, the causative drug has not been identified. In contrast to marked improvement of cutaneous manifestation and hepatic function by methyl prednisolone pulse therapy, the gastrointestinal symptoms did not respond to therapies, and the patient died by heart failure. Present case suggested a pathogenetic mechanism targeting antigens commonly expressed on the gastrointestinal epithelium and epidermis.

Fatal Outcome↗

HLA class I and II alleles and susceptibility to generalized pustular psoriasis: significant associations with HLA-Cw1 and HLA-DQB1*0303.

HLA alleles in generalized pustular psoriasis (GPP) were investigated to clarify the etiology and/or pathogenesis of this disease. Not only serological typing of HLA class I and II antigens but also genotyping of HLA class II alleles were carried out in twenty-six unrelated Japanese patients with GPP. These patients were classified according to their history of psoriasis vulgaris (PV). Serological typing revealed a significantly high incidence of HLA-Cw1 (Pc = 0.04) in the patients as compared with Japanese healthy controls. The frequency of HLA-B46 was particularly high in the patients with GPP and a previous history of PV. Genotyping of HLA class II alleles showed a highly significant increase in HLA-DQB1*0303 (Pc = 0.01) in the patients vs. the healthy controls. In particular, HLA-DQB1*0303 was significantly more frequent in the patients with no prior history of PV than in those with a history of PV. Analysis on linkage disequilibrium showed remarkably different patterns for HLA class II haplotypes between the patients and the healthy controls. Based on the comparative analysis among the amino acid sequences of the beta 1-domain of the HLA-DQB1*03 alleles, proline at residue 55 was suggested to be important as a common amino acid for determination of the susceptibility to GPP. These results revealed not only an association between the etiology and/or pathogenesis of GPP and HLA, but also different mechanisms of the immune response between the patients with GPP and PV.

Amino Acid Sequence↗