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Biomedical subjects

K Mukai

Publications and source records attributed to K Mukai.

At least 181 records · Page 10Linked to original sources

Prognostic value of immunohistochemical staining for proliferating cell nuclear antigen, p53, and c-erbB-2 in sebaceous gland carcinoma and sweat gland carcinoma: comparison with histopathological parameter.

Thirteen cases of sebaceous gland carcinoma and 10 cases of sweat gland carcinoma were studied using immunohistochemical staining for proliferating cell nuclear antigen (PCNA), c-erbB-2, and p53 to examine correlations among them, and to determine the best predictor of patient prognosis. Many sebaceous gland carcinomas and sweat gland carcinomas showed nuclear accumulation of p53, and patients with tumors showing a PCNA index (percentage of nuclei stained for PCNA) higher than 20%, and a p53 index (percentage of nuclei stained for p53) higher than 10% had short survival. Sebaceous gland carcinomas and sweat gland carcinomas showing c-erbB-2 expression had high PCNA (> 20%) and p53 (> 10%) indices, and were associated with poor prognosis. Histologically, sebaceous gland carcinomas showing a high degree of differentiation and severe nucleolar atypia had high PCNA and p53 indices. A growth pattern of small solid nests and strands, a low degree of differentiation, and the presence of lymphatic permeation in sweat gland carcinoma were often associated with high PCNA and p53 indices. These results suggest that nuclear accumulation of p53 plays an important role in the development of sebaceous gland carcinoma and sweat gland carcinoma. Assessment of PCNA and p53 indices together was very useful for prognostication of patient outcome, using cut-off values of 20% and 10%, respectively, to separate good prognosis from poor. Differentiation of sebaceous gland carcinoma, and c-erbB-2 expression by sweat gland carcinoma were significant independent prognostic indicators.

Adult↗

Growth dynamics of acquired melanocytic nevi. Higher reactivity of proliferating cell nuclear antigen in junctional and compound nevi than intradermal nevi.

BACKGROUND: The histogenesis of acquired melanocytic nevi is still a matter of debate. OBJECTIVE: To provide data on the histogenesis, we investigated the lesional area of acquired melanocytic nevi and the proliferative activity of the nevus cells. METHODS: Proliferative activity was examined with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The lesional area of the nevus was estimated in histologic sections. RESULTS: Intradermal nevus was the largest of the acquired melanocytic nevi but had few PCNA-positive nevus cells. In contrast, junctional nevi were smallest and showed the highest PCNA positivity. Statistical analysis showed a significant inverse correlation between the largest lesional area and PCNA positivity. CONCLUSION: The findings of the present study are in accordance with an epidermal melanocytic origin of acquired melanocytic nevi.

Antigens, Neoplasm↗

Salivary gland neoplasms in children.

We reviewed 20 children with salivary gland neoplasms treated at the National Cancer Center Hospital between 1964 and 1990. Retrospective analyses of pathological features and the clinical courses of these cases constituted the bases of the present study. The age of onset was late childhood in 19 cases, ranging from 9 to 20 years, but one patient was 1 year old. Approximately half (55%) the neoplasms were malignant. Histologically, all the benign neoplasms were pleomorphic adenomas (nine cases) and the most common malignant neoplasm was mucoepidermoid carcinoma (six cases, 55%), followed by adenocarcinoma (three cases, 27%), adenoid cystic carcinoma (one case, 9%) and malignant mixed tumor (one case, 9%). Recurrences of pleomorphic adenomas occurred only in the three patients initially treated with enucleation; meanwhile, five patients treated with superficial parotidectomy, and one with submandibular glandectomy, had no recurrence. Recurrences of malignant tumors occurred in all six patients initially treated with enucleation only and in one with superficial parotidectomy but not in two patients treated with total parotidectomy. In seven patients treated with prophylactic neck dissection, no metastasis was identified pathologically. The results support no enucleation of the tumor being applied at the first operation for curing both benign and malignant salivary gland tumors. The indication for radical neck dissection appears to be limited.

Adenocarcinoma↗

Kinetic study of free-radical-scavenging action of biological hydroquinones (reduced forms of ubiquinone, vitamin K and tocopherol quinone) in solution.

Kinetic study of free-radical-scavenging (FRS) action of eight kinds of biologically important hydroquinones (HQ's) (ubiquinol-10 (UQ10H2 1), ubiquinol-0 (UQ0H2 2), vitamin K1 HQ (VK1H2 3), vitamin K3 HQ (VK3H2 4), alpha-, beta-, gamma-tocopherol HQ's (alpha-, beta-, gamma-TQH2 5, 6, 7), and 2,3,5-trimethyl-1,4-HQ (TMQH2 8)) has been performed. The second-order rate constants, k3, for the reaction of HQ's 1-8 with substituted phenoxyl radical (PhO.) in ethanol, diethyl ether, benzene, and n-hexane have been measured with a stopped-flow spectrophotometer, as a model reaction of HQ's with unstable free radicals (LOO., LO., and HO.) in biological systems. The rate constant of UQ10H2 1 is similar to that of alpha-tocopherol in ethanol. The HQ's 3-8 showed higher reactivity than alpha-tocopherol in ethanol. Especially, the rate constants of VK1H2 3 and VK3H2 4 were found to be 31- and 21-fold larger than that of alpha-tocopherol, respectively, which has the highest reactivity among natural tocopherols. The rate constant of these HQ's increased by decreasing the polarity of solvents. The approximate order of magnitude of k3 value was (i) VK1H2 and VK3H2 > (ii) alpha-, beta-, and gamma-TQH2's and TMQH2 > (iii) alpha-tocopherol > (iv) UQ10H2 and UQ0H2 in solution. The result suggests that these biological HQ's also scavenge the active oxygen free radicals and prevent lipid peroxidation in various tissues and membranes. On the other hand, the reaction between substituted phenoxyl and biological quinones has not been observed.

Free Radical Scavengers↗

Isolation and characterization of rat CYP11B genes involved in late steps of mineralo- and glucocorticoid syntheses.

We isolated and characterized four forms of rat CYP11B genes, which were tentatively named CYP11B1, -B2, -B3, and -B4. Genomic Southern analyses indicated that the members of the rat CYP11B gene subfamily were confined to these four genes; among them, CYP11B1 and -B2 encoded steroid 11 beta-hydroxylase and aldosterone synthase, respectively, while CYP11B3 was a gene highly homologous to CYP11B1 without a known expression product. By being devoid of a region spanning two exons conserved in the other three, CYP11B4 was presumably a pseudogene. In the nucleotide sequences, CYP11B1, -B3, and -B4 showed 95-96 and 93-100% identities in the coding and 0.5-kilobase 5'-flanking regions, respectively. However, the homology between the nucleotide sequences of one of the three and CYP11B2 was rather low, about 90 and 50% in the coding and 0.5-kilobase 5'-flanking regions, respectively. As a whole, CYP11B2 rather than CYP11B1, -B3, or -B4 was more homologous to CYP11B genes of other animals such as cow and human. In transient transfection experiments using mouse adrenocortical Y1 cells and chloramphenicol acetyltransferase gene constructs, the 0.5-kilobase 5'-flanking region of CYP11B1 had a 4- and 10-fold higher promoter activity than the corresponding regions of CYP11B2 and -B3, respectively. The possible presence of a suppressive element(s) was noted in the upstream of the 0.5-kilobase region of CYP11B1. Although a variant of cAMP-responsive element, which was present in rat CYP11B2 and all known CYP11B genes of other animals, was modified in rat CYP11B1 and -B3 genes, dibutyryl cAMP stimulated all the promoter activities of the 5'-flanking regions of the rat genes by 3-fold.

Amino Acid Sequence↗

Enzymatic degradation of poly(hydroxyalkanoates) by Pseudomonas pickettii.

A bacterium capable of degrading poly(3-hydroxybutyrate) [P(3HB)] was isolated from laboratory media and identified as Pseudomonas pickettii. The strain P. pickettii excreted an extracellular poly(hydroxyalkanoate) (PHA) depolymerase and grew on P(3HB) as the sole carbon source. P. pickettii also grew on 3-hydroxybutyrate, glucose, fructose, citrate or succinate. However, only 3-hydroxybutyrate apart from P(3HB) induced the secretion of PHA depolymerase. The PHA depolymerase was purified from the culture medium containing 3-hydroxybutyrate at the sole carbon source by hydrophobic column chromatography and gel filtration, and its molecular weight was determined as about 40,000 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. The optimum activity of degrading P(3HB) by the depolymerase was observed at pH 5.5 and 40 degrees C. The enzymatic degradation of microbial copolyesters was studied by the weight loss (erosion) of solution-cast films of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate). 1H-n.m.r. analysis of the water-soluble products after the hydrolysis of P(3HB) film by PHA depolymerase revealed that the main product was the monomer 3-hydroxybutyric acid.

Bacterial Proteins↗

Kinetics and mechanism of heterogeneous hydrolysis of poly[(R)-3-hydroxybutyrate] film by PHA depolymerases.

The kinetics and mechanism of enzymatic degradation on the surface of poly[(R)-3-hydroxybutyrate] (P[(R)-3HB]) film have been studied using three types of extracellular poly(hydroxyalkanoate) (PHA) depolymerases from Alcaligenes faecalis, Pseudomonas picketti and Comamonas testosteroni. The monomer and dimer of 3-hydroxybutyric acid were produced during the course of the enzymatic degradation of P[(R)-3HB] film, and the rate of production was determined by monitoring the increase in absorbance at 210 nm on a spectrophotometer. The rate of enzymatic degradation increased to a maximum value with the concentration of PHA depolymerase, followed by a gradual decrease. The kinetic data were accounted for in terms of a heterogeneous enzymatic reaction, involving enzymatic degradation on the surface of P[(R)-3HB] film via two steps of adsorption and hydrolysis by a PHA depolymerase with binding and catalytic domains. The kinetic results suggest that the properties of the catalytic domains are very similar among the three PHA depolymerases, but that those of the binding domains are strongly dependent on the type of depolymerase.

Alcaligenes↗

[Hyalinizing trabecular adenoma of the thyroid].

We experienced a very rare case of hyalinizing trabecular adenoma of the thyroid. The histopathological features of this case included the following. 1) In puncture-aspiration cytodiagnosis, tumor cells aggregated around pink-stained hyaline acellular areas in an ellipsoidal or spindly configuration, with a part of the cytoplasm appearing as filamentous with unclear borders. In addition, a large number of intranuclear "holes" and nuclear grooves were evident. 2) In biopsy, tumor cells appeared in ellipsoidal or spindly configuration, with cytoplasm that easily stained with thyroglobulin but did not stain with calcitonin. The nuclei were irregular in size and some of the nuclei appeared strongly atypical, occasionally seen with cytoplastic inclusion body in the nucleus. These cells showed funicular structures in a radical arrangement with a hyaline material at the center. The hyaline material was stained positively with PAS or Laminin, but not with Cong red.

Adenoma↗

[A case of cryptococcal meningitis in an HTLV-1 carrier].

We report a case of 73-year-old male HTLV-I carrier with cryptococcal meningitis. The patient, who was born in Taiwan, has raised golden pheasants for ten years and bantams for five years. Antibody to HIV was negative. Flow cytometric study of the peripheral lymphocytes showed reduced CD4+CD45RA+ (naive cells) and increased CD4+CD45RO+ (memory cells), CD3+CD25+ and CD3+ HLA-DR(DR)+ cells. Lymphocyte responses to phytohemagglutinin and concanavalin A were depressed. Cerebrospinal fluid (CSF) cells and serum and CSF antigen to cryptococcal neoformans were decreased by therapy with fluconazole and flucytosine. Although the naive, memory and CD3+DR+ cell abnormalities showed no change, the CD45RA/CD45RO ratio and CD3+CD25+ level tended to improve. Opportunistic infections such as cryptococcal meningitis may be induced by severe decreases in naive cells and increases in memory cells in HTLV-I carriers.

Aged↗

[A case of treating abrupt closure due to post PTCA dissection by emergent CABG-reoperation, via extracorporeal circulatory method conducted with the heart "beating"].

A female patient, 73 years of age, who underwent CABG for the RCA and First Diagonal Branch by SVG 39 months ago was readmitted to our clinic after an onset of acute angina pain, whereupon successful PTCA was performed to Cx segment 13. However, with the angina pain continuing unabated, and with the recognition through emergent CAG that the graft to the RCA was occluded. PTCA was performed again to the RCA segment 1. The segment was closed off by dissection. The emergent CABG was carried out via femoro-femoral extracorporeal circulation and intra aortic balloon pumping. This CABG was of a RCA to RCA bypass nature, with SVG performed with the heart "beating" and without cooling. The patient was thus relieved of her angina pain and her cardiac function has since been in good order.

Aged↗

Emergency myocardial revascularization for myocardial infarction evolving outside the hospital. A feasible option when thrombolysis and coronary angioplasty have failed.

Most reports on emergency coronary revascularization deal with failed percutaneous transluminal coronary angioplasty (PTCA) or refractory ischemia which developed after hospital admission. The objective of this study was to evaluate the feasibility and prognosis of emergency revascularization for acute myocardial infarction evolving outside the hospital. Between 1974 and 1992 54 cases were included in this study. The patients had both electrocardiographic and clinical evidence of ongoing ischemia. One or more infarct-related obstructed coronary arteries were documented by emergency angiography. Since 1981, the patients have been given urokinase, and, since 1986, they have undergone PTCA initially and, when reperfusion failed, revascularization was started. Overall in-hospital mortality has been 11.1% (6/54). All other patients were discharged in satisfactory condition. Follow-up for periods of up to nearly twenty years has been uneventful with the exception of two late sudden deaths. The above results confirm that emergency coronary revascularization is a therapeutical option worth considering.

Adult↗

Laryngeal metastasis from a pulmonary papillary adenocarcinoma: a case report.

Metastases to the larynx from distant primaries are very rare. The present article reports a case of metastatic papillary adenocarcinoma of the larynx of lung origin. The patient was a 59-year-old female non-smoker, who had a history of adenocarcinoma of the right lung. For the laryngeal tumor, we performed a partial laryngectomy following biopsy. The tumor of the larynx was a papillary adenocarcinoma resembling the lung tumor, both demonstrating positive immunohistochemical staining for pulmonary surfactant apoprotein. The findings emphatically indicated the laryngeal tumor to be metastasis from the primary papillary adenocarcinoma of the lung. The present case report presents the clinical findings, course of disease and histopathological findings with brief reviews of the literature.

Adenocarcinoma, Papillary↗

Pathology and DNA cytophotometry of small hepatocellular carcinoma with a nodule-in-nodule appearance--evidence for stepwise progression of hepatocellular carcinoma.

Among 92 surgically resected human hepatocellular carcinomas (HCCs) < or = 3 cm in diameter, 23 tumors (25%) grossly showed a nodule-in-nodule appearance indicating stepwise progression of HCC. The central nodules showed destructive growth of HCC, which was less differentiated than the surrounding area histologically, while the surrounding area showed growth of very-well-differentiated HCC with no, or only minimal, destruction of the underlying liver structures. Previously, we proposed the term "early HCC" for HCCs without definite destructive growth, and the nodule-in-nodule lesions described here are considered to be in the transitional stage from early HCC to advanced HCC, and are therefore named early advanced HCC (eAd HCC). DNA cytophotometry was performed in 12 cases of eAd HCC, in which the early HCC component, advanced HCC component and non-tumorous liver tissue showing chronic hepatitis or cirrhosis were analyzed separately. The early HCC component showed a diploid pattern in eight of the 12 cases. The advanced HCC component showed an aneuploid peak in seven cases, and in three of these the peak was detected only in the advanced HCC component and not in the early HCC component. The mean nuclear DNA content was significantly increased from non-tumorous liver to the early HCC component and from the early HCC component to the advanced HCC component. Polyploid cells containing more than 4.8C DNA were exceptional in non-tumorous liver, but were detectable in the early HCC component and increased in number in the advanced HCC component. These findings suggest that DNA instability may have an important role to play in the subclonal progression of human HCC.

Adult↗

[A clinicopathologic study of thymomas: a review of 52 cases, with particular reference to results of treatment].

Clinicopathologic aspects of 52 thymomas were reviewed. Masaoka staging revealed stage I in 32, stage II in 2, stage III in 12, stage IV a in 3, and stage IV b in 3. Eleven patients (21%) had associated myasthenia gravis (MG), and three (6%) had pure red cell aplasia (PRCA). Operation was complete resection in 39 patients (stage I 32, stage II 2, stage III 2, and stage IV b 3), subtotal resection in 4 patients (stage III 2, stage IV a 2), partial resection or simple biopsy in 7 patients (stage III 6, stage IV a 1). Survival rates at 5 years and 10 years were 88%, 88% in noninvasive thymomas, and 65%, 45% in invasive thymomas, respectively. Statistical analysis indicated that patients with noninvasive thymomas had significantly longer survival than those with invasive thymomas. Significant difference was not found in survival on the basis of tumor cell type according to lymphocyte/epithelial cell ratio. Associated MG had no influence on the survival of thymoma patients, however, the presence of PRCA was an adverse factor in survival. In cases of invasive thymomas, there was statistically significant difference in the survival rates between the group of patients undergoing complete or subtotal resection and the group undergoing partial resection or only biopsy. Irradiation was of value in local control of thymoma, but lymphogeneous or hematogeneous recurrence occurred in 21% of patients with invasive thymomas from 3 months to 12 years postoperatively. Lifelong follow-up should be necessary in thymoma patients since late recurrence is not so rare.

Adolescent↗

[Successful aorto-circumflex coronary bypass grafting through left thoracotomy following aortic and mitral valve replacement].

We report successful descending thoracic aorto-circumflex coronary artery bypass grafting using a saphenous vein graft through left thoracotomy in a 44-year-old female. The patient developed severe angina attack after aortic and mitral valve replacement. Coronary angiography showed 99% stenosis of the circumflex coronary artery. Under general anesthesia, left femoral vein to arterial partial cardiopulmonary bypass was performed via left 4 th intercostal space. Body temperature was lowered to 22 degrees centigrade, and spontaneous cardiac fibrillation occurred. After minimal exposure by pericardial dissection of the circumflex coronary artery, distal anastomosis and then proximal anastomosis at the descending thoracic aorta was carried out under cardiac fibrillation. This surgery was done with minimal intra-and postoperative bleeding. Postoperative course was very smooth, and the patient was discharged and leading a normal life for 6 months after surgery.

Adult↗

Neoplasia of the ampulla of Vater. Ki-ras and p53 mutations.

Eleven tumors of the ampulla of Vater (5 stage IV and 2 stage II adenocarcinomas, 1 stage II papillary carcinoma, 1 neuroendocrine carcinoma, and 2 adenomas, one with foci of carcinoma) were examined for Ki-ras and p53 gene mutations by single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA fragments. Ki-ras mutations were found in one adenocarcinoma and in the adenoma with foci of carcinoma, both involving mainly the intraduodenal bile duct component of the ampulla. Seven cases showed p53 gene mutations: four advanced-stage adenocarcinomas, the papillary carcinoma, the neuroendocrine carcinoma, and the adenoma with foci of carcinoma. Nuclear accumulation of p53 protein was immunohistochemically detected in the morphologically high-grade areas of the five cancers harboring a p53 gene missense point mutation. The adenomas, the two frame shift-mutated cancers, and the adenomatous and low-grade cancer areas of mutated carcinomas were immunohistochemically negative. Our data suggest that in ampullary neoplasia 1) p53 mutations are common abnormalities associated with the transformation of adenomas and low-grade cancers into morphologically high-grade carcinomas, and 2) Ki-ras mutations are relatively less frequent and might be restricted to tumors originating from the bile duct component of the ampulla.

Aged↗

Pancreatic adenocarcinomas frequently show p53 gene mutations.

Thirty-four pancreatic adenocarcinomas were studied for the presence of p53 gene mutations by the single-strand conformation polymorphism method and by direct sequencing of PCR-amplified fragments. p53 protein expression was immunohistochemically evaluated using monoclonal PAb1801 and polyclonal CM1 antibodies. Mutations were detected in 14 cases. The transitions were six G to A and two A to G; the transversions were one C to G and two A to C; the remaining three were frameshift mutations. Immunostaining results were identical with both antibodies. Nuclear immunohistochemical p53-positive cells were found in nine p53 mutated cases and in 12 cases in which no mutation was detected. In most of these latter cases only a minority of cancer cells showed immunohistochemical positivity. Twenty-nine cases, including all p53 mutated cancers, were known to contain codon 12 Ki-ras gene mutations. Also in the light of the demonstrated cooperation of ras and p53 gene alterations in the transformation of cultured cells, our data suggest that p53 mutation is one of the genetic defects that may have a role in the pathogenesis of a proportion of pancreatic cancers.

Adenocarcinoma↗

Stopped-flow kinetic study of vitamin E regeneration reaction with biological hydroquinones (reduced forms of ubiquinone, vitamin K, and tocopherolquinone) in solution.

A kinetic study of the regeneration reaction of vitamin E (tocopherol) with eight biological hydroquinones (HQs) (ubiquinol-10 (Q10H2 1); ubiquinol-0 (Q0H2 2); vitamin K1 HQ (VK1H2 3); vitamin K3 HQ (VK3H2 4); alpha-, beta-, and gamma-tocopherol-HQs (alpha-, beta-, and gamma-TQH2 5-7); and 2,3,5-trimethyl-1,4-HQ (TMQH2 8)) in solution was performed. The second-order rate constants (k4) for the reaction of HQs 1-8 with alpha-tocopheroxyl and 5,7-diisopropyltocopheroxyl radicals in ethanol, benzene, and isopropyl alcohol/water (5:1, v/v) solutions were measured with a stopped-flow spectrophotometer. The order of magnitude of k4 values obtained for HQs is VK1H2 > VK3H2 > alpha-TQH2 > beta-TQH2 approximately gamma-TQH2 approximately TMQH2 > Q10H2 > Q0H2, being independent of the kinds of tocopheroxyl radicals and the polarity of the solvents. The log of the k4 values obtained for HQs was found to correlate with their peak oxidation potentials. Comparing the k2 value (2.68 x 10(6) M-1 s-1 obtained for the reaction of alpha-tocopheroxyl with vitamin C (sodium ascorbate) with those (k4 = 2.54 x 10(5) and 8.15 x 10(5) M-1 s-1) obtained for the reaction of alpha-tocopheroxyl with Q10H2 and alpha-TQH2 in isopropyl alcohol/water mixtures, the former is approximately 11 and 3 times as reactive as the latter, respectively. On the other hand, the k2 value obtained for sodium ascorbate is smaller than the k4 values obtained for VK1H2 and VK3H2. These results suggest that mixtures of vitamin E and these HQs (as well as those of vitamins E and C) may function synergistically as antioxidants in various tissues and mitochondria.

Ascorbic Acid↗