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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 469 records · Page 26Linked to original sources

[Investigation of meropenem levels in the human bone marrow blood, bone, joint fluid and joint tissues].

A solution of 0.5 g of meropenem (MEPM) in 100 ml of saline was administered to adult patients before the orthopaedic surgery via intravenous drip infusion for 30 minutes. Eleven samples of bone marrow blood, 13 bone, 8 joint fluid and 8 joint tissues obtained from 15 clinical cases were analyzed for MEPM levels. At the same time, blood samples were taken from peripheral veins and serum served as control was analyzed. The concentration of MEPM in the marrow blood at 30 minutes after administration of MEPM reached 15.4 micrograms/ml, which was above 50% of the maximum concentration in serum. Ratios of concentration in bone marrow to that in serum were between 93% and 105% at that time. MEPM levels were 5.74-0.40 micrograms/g in bones, 20.3-4.55 micrograms/ml in joint fluid and 18.2-4.05 micrograms/g in joint tissues at 30 to 75 minutes after administration. In joint fluid and joint tissues, the concentration above 50% of maximum level in serum were maintained for more than an hour. MEPM is thought to be useful for the treatment of bone and joint infections and also prophylaxis of infections in cases of major surgery of skeletal tissue in the field of orthopaedic surgery.

Adult↗

[Dietary control for out-patients in urinary stone clinic].

We studied the dietary habits of 113 upper urinary tract stone formers and 24-h urine specimens before and after dietary control. Protein intake was decreased in male patients after dietary control but urinary risk factors were not changed significantly. The excretion of urinary risk factors (calcium, uric acid and oxalate) was decreased in the patients who had calcium excretion of more than 250 mg per day or uric acid excretion more than 650 mg per day or oxalate excretion more than 45 mg per day before the control. The daily protein intake was significantly correlated to urinary uric acid, calcium, and phosphate excretion and the daily vitamin C intake to urinary citrate excretion. There was a negative correlation between the daily calcium intake and urinary oxalate. The mean stone episode rate of these patients was significantly decreased from 0.174 to 0.059 stones per year by dietary control (p < 0.005).

Adult↗

[Phase II study of a novel combination regimen composed of cisplatin, carboplatin and etoposide against unresectable non-small cell lung cancer].

Phase II study of a novel combination regimen composed of cisplatin, carboplatin and etoposide (CPVP) was conducted against unresectable non-small cell lung cancer. The treatment schedule consisted of cisplatin 50 mg/m2 on day 1, carboplatin 200 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1, 3, 5 every 3 or 4 weeks. The response rate and toxicities were evaluated in 28 patients, who were diagnosed and treated in the Cancer Institute Hospital (GANN-KEN) from March 1991 to September 1992. Partial response (PR) was found in sixteen out of 28 patients (57.1%). In myelotoxicities, 5 out of 28 patients (17.9%) showed grade 4 thrombocytopenia, but, white blood cell count and hemoglobin level stayed at grade 3 or milder in most patients, revealing safety of this regimen. In gastrointestinal toxicities, the median number of days in the patients suffered from nausea and loss of appetite was about 3 and 7 days, respectively. Median weight loss of the patients through the entire treatment was 2.3 kg. These results suggest that CPVP regimen is no less effective, but more tolerable, in other words, more favorable in QOL than standard regimens, and that it warrants further study in phase III trials.

Antineoplastic Combined Chemotherapy Protocols↗

Response to transcatheter oily chemoembolization in hepatocellular carcinoma 3 cm or less: a study in 50 patients who underwent surgery.

The response of 50 patients who underwent hepatectomy for hepatocellular carcinoma measuring 3 cm or less (at the time of surgery) to transcatheter oily chemoembolization was evaluated. The response was assessed in 5 categories, A: complete necrosis (100%), B: necrosis of at least 95%, C: at least 80%, but less than 95%, D: at least 50% but less than 80%, and E: less than 50% of the tumor cells. Response A was observed in 19 patients (38%), B in 7 (14%), C in 9 (18%), D in 7 (14%), and E in 8 (16%). These results were classified with respect to the histological degree of tumor differentiation, the WHO histological classification, the microscopic patterns of tumor growth, and macroscopic classification. The response was evaluated in relation to the histological grade of tumor differentiation and the WHO histological classification in all categories of response except response A, and there was no significant difference between the categories. The response was obviously better with the expansive type than with the replacing type. Single nodular type lesions were more responsive than the single nodular type lesions with extranodular growth and the contiguous multinodular type. Pretreatment estimation of the microscopic patterns of tumor growth and macroscopic classification appears to be valuable in predicting prognosis.

Adult↗

[Multilocular cystic renal cell carcinoma: a report of two cases].

Two cases of multilocular cystic renal cell carcinomas in a 48-year-old man and in a 41-year-old woman are reported. Radical nephrectomy was performed in both cases. Both histologic diagnoses were multilocular cystic renal cell carcinoma, clear cell subtype, grade 1. We had some difficulty in diagnosing the latter case with multilocular cystic mass which had smooth, glistening lining and contained clear-yellow fluid. Microscopical examination of the permanent sections revealed that the cysts were lined by a cuboidal or flattened epithelium, but no tumor cells. However, laminar growth of renal cell carcinoma of the clear cell type was present in several areas in the septa, and a few residual tumor cells were found in the hyalinized septa. When renal cell carcinoma is present in only a part of the multilocular cystic renal mass, it should be diagnosed as multilocular cystic renal cell carcinoma. The literature was surveyed.

Adult↗

[Two cases of idiopathic ventricular fibrillation with interesting electrocardiographic findings].

We encountered two cases of ventricular fibrillation (VF) without overt heart disease. The first case we report is that of a 47-year-old man, and the second case is a 39-year-old man. VF occurred in the night unrelated to myocardial ischemia or myocarditis. Their basic ECGs showed normal sinus rhythm, but neither QT prolongation nor abnormal Q wave was seen. But we could see IRBBB and ST segment elevation in the V1-2 lead not only in the acute phase, but also in the chronic phase. Abnormal findings were not found in noninvasive cardiac examinations, nor in cardiac catheterization and histological examinations. In the second case, VF was induced by electrical stimulation, and Disopyramide was found to be effective for the prevention of VF. The patient in the first case died suddenly two years after his first attack. Both cases have interesting ECG findings, and it may be that they play on important role in discovering the etiology of sudden cardiac death.

Adult↗

[Surgical aspects of automatic implantable cardioverter defibrillator (AICD) in patients with life-threatening ventricular tachyarrhythmias].

Implantations of automatic implantable cardioverter defibrillator were performed in five patients with life-threatening ventricular tachyarrhythmias. Preoperative diagnoses of arrhythmias were sustained ventricular tachycardia (VT) in two cases, ventricular fibrillation (VF) in two cases and sustained VT+VF in one case. Four of five cases had basic diseases respectively (broad anterior myocardial infarction, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy), and the other case was idiopathic. Preoperative CTR were 43-65% (mean 57.4%) and left ventricular ejection fraction were 26-76% (mean 51.2%). Implantation of AICD was indicated for patients who survived circulatory arrest or life-threatening VT. Median sternotomy (3) or left antero-lateral thoracotomy (2) were performed for implantation of large-small patch electrodes for defibrillation. AICD generators were implanted in the pocket under abdominal rectal muscle in all cases. Postoperatively myocardial insufficiency, pericarditis, pleuritis occurred in three cases respectively. In the follow-up periods (2-25 months, mean 13 months), AICD worked effectively in two patients with spontaneous VT (6 months, 1 year after operation) and no cardiac death was experienced. We concluded that AICD system is effective for the life-threatening ventricular tachyarrhythmias, although the further estimation in longer follow-up periods are warranted.

Adult↗

Transforming activity and the level of Tax protein: effect of one point mutation in HTLV-I tax gene.

The transcriptional trans-activator molecule of HTLV-I, Tax, is known to transform rodent fibroblasts. A revertant clone expressing Tax was obtained by treating transformed Rat-I cells harboring a single copy of the tax gene with a mutagen. Sequence analysis of the tax gene of the revertant clone revealed that it had one point mutation at codon 12(CTT----TTT), resulting in a change from Leu to Phe. The colony-forming efficiencies of the cells transfected with the mutant tax gene (mu71 tax) were significantly lower than those transfected with the wild-type by the soft-agar method. This difference was shown to be due to the instability of mu71 Tax.

Amino Acid Sequence↗

Modulation of myeloid proliferation and differentiation by monoclonal antibodies directed against a protein that interacts with the interleukin-3 receptor.

Hematopoietic cells can be transformed through the acquisition of autocrine growth factor production. Because of their ability to inhibit autocrine growth, antibodies directed against the growth factor or its receptor may have therapeutic potential. However, these agents may also inhibit normal cell development. We have developed two monoclonal antibodies, 4G8 and 2F2, directed against a protein of 110 to 150 Kd that interacts with the interleukin-3 (IL-3) receptor (R) complex. These antibodies inhibit IL-3-induced proliferation of nonleukemic and leukemic IL-3-dependent cell lines, as well as the autonomous growth of WEHI-3B in vitro and in vivo. These results suggest the possibility that anti-IL-3R antibodies may be useful in the treatment of some leukemias. However, the effect of anti-IL-3R antibodies on normal myeloid development in vitro has not been examined. We examined the effect of 4G8 and 2F2 on the growth in vitro of colony-forming unit granulocyte-macrophage (CFU-GM) colonies induced by IL-3, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and macrophage-CSF (M-CSF). Our results show that while 4G8 and 2F2 inhibited CFU-GM colony formation induced by IL-3, they augmented colony formation induced by the other hematopoietins. 4G8 and 2F2 also enhanced G-CSF-induced proliferation of 32Dc13 and GM-CSF-induced proliferation of PT18, confirming that the effect on CFU-GM was a direct effect. Finally, 4G8 and 2F2 inhibited G-CSF-induced differentiation of 32Dc13, similar to low levels of IL-3; yet, neither 4G8 nor 2F2 blocked binding of G-CSF to its receptor. These results indicate that, in the absence of IL-3 and in the presence of other hematopoietins, 4G8 and 2F2 can function as weak IL-3 agonists. These studies suggest that antibodies such as 4G8 and 2F2, directed against components of the IL-3R, could potentially augment myeloid growth in vivo, rather than inhibit myeloid growth.

Animals↗

[Regenerating nodules in liver cirrhosis--patho-MR-serological correlation study].

An MR study was performed in 73 clinically diagnosed cirrhotic patients to determine correlations among the demonstration of small low intensity nodules (SLINs), secondary changes due to cirrhosis, and serological data. In 32 patients, liver cirrhosis was proved histologically. SLINs were observed in 38 of the 73 patients on gradient echo (GRE) images and in 28 patients on T2-weighted SE images. Patho-MR correlation study of the liver in the 32 histologically proved cirrhotic patients revealed that SLINs were seen on GRE images only in patients with iron deposits in regenerating nodules (RNs). There was no significant correlation between secondary changes due to liver cirrhosis and the demonstration of SLINs. Serological data indicating liver cell injury and iron store in the body were significantly higher in patients with iron deposits in RNs than in those without iron deposits.

Adult↗

Chromosome abnormalities in adult T-cell leukemia/lymphoma: a karyotype review committee report.

Karyotypes of 107 cases with adult T-cell leukemia/lymphoma (58 male, 49 female; 81 acute or lymphoma type, 26 chronic or smoldering type) were reviewed by a panel of cytogeneticists and were correlated with the subtypes of the disease. Clonal chromosome abnormalities were found in 103 (96%) cases, of which four had hypotetraploidy. Of 184 numerical abnormalities in the remaining 99 cases with near- or pseudodiploidy, trisomies for chromosomes 3 (21% of cases), 7 (10%), and 21 (9%), monosomy for X chromosome (38%) in the female, and loss of a Y chromosome (17%) in the male were more frequent than expected (P less than 0.01). Of 373 structural abnormalities in all the 103 aneuploid cases, translocations involving 14q32 (28%) or 14q11 (14%) and deletion of 6q (23%) were most frequent, followed by deletion of 10p (9%), 3q (8%), 5q, 9q, and 13q (7% each), and 1p and 7p (6% each). The proportion of cases with aneuploid clones (with greater than or less than 46 chromosomes), the average numbers per case of both numerical and structural abnormalities, and marker chromosomes were larger in the aggressive acute or lymphoma type than in the nonaggressive chronic or smoldering type (P less than 0.01). The combination of rearrangement in 14q32 and monosomy X (seven cases) or deletion of 10p (six cases), and that of trisomy 3 and deletion in 6q21 (six cases), occurred only in the acute or lymphoma type and may be associated with the aggressiveness in adult T-cell leukemia/lymphoma.

Adult↗

Altered expression of sialyl-Tn, Lewis antigens and carcinoembryonic antigen between primary and metastatic lesions of uterine cervical cancers.

Immunohistochemical examination was performed of serial sections of 24 normal human adult cervical tissues and 53 human cervical carcinomas including 36 cases with lymph node metastasis. For this investigation, monoclonal antibodies directed to Lewis-X, Lewis-Y, sialyl-dimeric Lewis-X (SDLX), sialyl-Tn (STn) and carcinoembryonic antigen (CEA) were used. STn and CEA antigens were expressed very weakly in the normal cervical epithelium but strongly in the cancer cells, indicating the antigens to be oncogenic antigens of cervical squamous cell carcinoma. No significant difference in immunoreactivity was observed between primary and metastatic lesions of carcinoma or between primary lesions with and without metastasis. However, the expression patterns of STn and Lewis-Y antigens were quite different between primary lesions and metastatic lesions. In primary lesions the cancer cell nests tended to be stained centrally, but in metastatic lesions the cancer cell nests tended to be stained peripherally. This finding may reflect an important role of these carbohydrate chains in the process of metastasis of cervical squamous cell carcinoma to regional lymph nodes.

Antibodies, Monoclonal↗

Selection of therapeutic modalities for hepatocellular carcinoma in patients with multiple hepatic lesions.

In the present study, we compared the survival of patients with multi tumor hepatocellular carcinoma (HCC) following their treatment with liver resection versus TAE. A total of 336 HCC patients were treated at Osaka University Hospital between 1980 and 1989. Of these, 140 patients underwent liver resection in the presence or absence of TAE and 173 subjects were treated with TAE alone. Our TAE protocol consisted of 50 mg Adriamycin, 3-5 ml lipiodol, and Gelfoam. The 1-, 3-, and 5-year survival values found for the liver resection group were 87.4%, 66.0%, and 47.4%, respectively, whereas the values calculated for the TAE group were 64.6%, 29.9%, and 15.8%, respectively. The survival of patients in the resection group was clearly better than that of subjects in the TAE group. Of the 140 patients who underwent resection, 36 cases were proven to have multiple lesions by histopathological examination. The 1- and 3-year survival values determined for this special group were 67.9% and 33.3%, respectively. Of the TAE cases, 113 were diagnosed as having multiple lesions by imaging examination, and their 1- and 3-year survival values were 59.7% and 24.9%, respectively. No significant differences in survival was found between these two different treatment modalities for these multiple-lesion cases. The results of this study indicate that it is unlikely that surgical resection is superior to TAE alone for the treatment of HCC patients with multiple lesions.

Adult↗

Cellular immunosuppression in children with acute lymphoblastic leukemia: effect of consolidation chemotherapy.

The present study was designed to evaluate the chemotherapy-induced cellular immunosuppression in 20 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy. Peripheral blood was serially obtained from leukemic children during vincristine/cyclophosphamide/6-mercaptopurine/prednisone combined consolidation chemotherapy. The mean absolute number of peripheral blood lymphocytes as well as the mean absolute numbers of lymphocyte subsets (T cells, T cell subsets, B cells, and natural killer cells) from leukemic children before consolidation chemotherapy were all significantly lower than in control subjects; however, the percentages of lymphocyte subsets were similar in both groups. After consolidation chemotherapy, the percentages of CD4+ T lymphocytes and natural killer (NK) cells were significantly decreased and the percentages of monocytes and CD8+ T lymphocytes were significantly increased. Phytohemagglutinin- and 12-O-tetradecanoylphorbol-13-acetate-induced production of interleukin-2 (IL-2) and NK-cell-mediated cytotoxic activity by peripheral blood mononuclear cells (PBMC) were also substantially decreased in the post-therapy groups. NK activity correlated with the percentage of NK cells in PBMC. In contrast, OK432-induced production of tumor necrosis factor alpha (TNF alpha) and killer activity against NK-resistant target cells were significantly increased after therapy as compared with the pre-therapy and control groups. TNF alpha production correlated with the percentage of monocytes in PBMC. These results demonstrate that substantial quantitative and qualitative chemotherapy-induced abnormalities of the cellular immune system are present in the majority of patients treated with ALL. It is also suggested that the increased TNF alpha production by monocytes and the appearance of potent killing activity against NK-resistant targets might compensate for the defects of IL-2 production and NK activity during intensive consolidation chemotherapy.

Animals↗

Relationship between pathologic prognostic factors and abnormal levels of des-gamma-carboxy prothrombin and alpha-fetoprotein in hepatocellular carcinoma.

The relationship between pathologic prognostic factors and abnormal levels of des-gamma-carboxy prothrombin and alpha-fetoprotein was investigated in 42 patients with resectable hepatocellular carcinoma. The frequencies of macroscopic massive type, intrahepatic metastasis, and portal vein tumor thrombus were significantly higher in patients with positive des-gamma-carboxy prothrombin (p less than 0.05) but not with alpha-fetoprotein. Other histologic factors in tumorous and nontumorous tissues were not significantly different irrespective of the positivity of these markers. In patients with tumors not more than 6 cm in diameter, the frequency of intrahepatic metastasis was positively correlated with the positivity of des-gamma-carboxy prothrombin (p less than 0.05) and inversely with that of alpha-fetoprotein (p less than 0.05). Furthermore, intrahepatic metastasis was most frequently observed in patients with positive des-gamma-carboxy prothrombin and negative alpha-fetoprotein (eight of nine) and least frequently in cases with negative des-gamma-carboxy prothrombin and positive alpha-fetoprotein (one of eight). These findings indicated that both des-gamma-carboxy prothrombin and alpha-fetoprotein might be useful markers for the prediction of intrahepatic spread of hepatocellular carcinoma.

Biomarkers↗

New side-holed sheath for intraaortic balloon pumping to maintain limb perfusion.

We developed a new side-holed shunt sheath for inserting intraaortic balloon pumps to maintain lower limb perfusion in patients with stenotic and tortuous aortoiliac arteries. This sheath has a large internal diameter and several side holes, which act as an internal shunt. It was useful and effective in 11 patients with severe aortoiliac occlusive lesions who required assistance by intraaortic balloon pumping.

Aortic Diseases↗

Hydration of oligosaccharides: anomalous hydration ability of trehalose.

The disaccharide trehalose extensively exists in anhydrobiotic organism and is considered to play an important role in preserving the integrity of biomembrane. However, the preserving mechanism remains unclear. In this report, we examine the hydration abilities of trehalose and several oligosaccharides composed of alpha-D-glucopyranosyl residues. The unfrozen water fraction per molecule was determined from differential scanning calorimetry measurements of their aqueous solutions. Further, the NMR relaxation time of the natural abundance 17O of water is measured for several saccharide solutions. These results indicate that trehalose has the highest hydration ability among the saccharides studied. In other words, trehalose can effectively lower the mobility of water molecules hydrogen-bonded with saccharides. It is thus reasonable that, among the disaccharides studied, trehalose exhibits the maximum stabilizing effect on the bilayer structure of lipid whose acyl chains are bonded with each other by the apolar interaction, because the apolar interaction is strengthened with the stabilization of the surrounding water structure.

Animals↗