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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 145 records · Page 8Linked to original sources

Completion pneumonectomy for patients with recurrent lung cancer: the impact of microvessel density on outcome.

The effectiveness of performing completion pneumonectomy (CP) to treat recurrent lung cancer was assessed in 11 patients, 6 of whom had intrapulmonary recurrence, and 5, locoregional recurrence. The pathological types of cancer were adenocarcinoma in 5 patients, squamous cell carcinomas in 5 patients, and adenoid cystic carcinoma in 1 patient. The pathological stages of the recurrent lung cancer were stage I in 8 patients, stage II in 2 patients, and stage IV in 1 patient. The microvessels in the tumors were also examined and the results compared with those in the microvessels of 61 nonrecurrent tumors. The 1- and 3-year overall survival rates after CP were 54.5% and 27.3%, respectively. The vessel densities within primary and correspondent recurrent tumors were able to be assessed in 9 patients and found to be significantly greater compared with the mean value for the nonrecurrent tumors (P < 0.0001). The vessel densities in the primary and recurrent tumors of 2 of 3 long-term survivors were found to be relatively low. These results indicate the high-grade malignant potential of recurrent tumors, which led us to conclude that the use of CP should be carefully evaluated in patients with recurrence. Assessing the vasculature in primary tumors may be a useful indicator for determining which patients could benefit from CP.

Adenocarcinoma↗

Renal disease in women with severe preeclampsia or gestational proteinuria.

OBJECTIVE: To identify women with severe preeclampsia or severe gestational proteinuria at high risk of having underlying renal disease. METHODS: Between 1980 and 1999, 86 Japanese women who had severe hypertension, severe proteinuria, or both during pregnancy had postpartum needle biopsies of their kidneys. Diagnoses before biopsies were severe preeclampsia in 74 women and severe gestational proteinuria in 12. We compared clinical characteristics, such as antepartum hematuria and postpartum proteinuria, and maternal and neonatal outcomes with regard to presence of renal disease. RESULTS: Nineteen of 86 women (22.1%, 95% confidence interval [CI] 13.9%, 32. 3%) were diagnosed with underlying renal disease. Immunoglobulin A nephropathy was present in 12. Women with renal disease had a significantly earlier onset of proteinuria than those without (median 11 versus 32 weeks' gestation, P <.001). Eighteen of 19 women with renal disease had proteinuria, hypertension, or both before 30 weeks' gestation. Ten of 12 women with severe gestational proteinuria (83.3%, 95% CI 51.6%, 97.9%) had underlying renal disease. Eight of the 19 women had antepartum hematuria, and seven had elevated serum immunoglobulin A levels. In women with severe preeclampsia, onset before 30 weeks' gestation was the best predictor of underlying renal disease (odds ratio 34.1, 95% CI 3.8, 304.5). Women with renal disease had lower rates of severe hypertension (nine of 19 versus 59 of 67, P <.01) and small-for-gestational-age infants (four of 19 versus 34 of 67, P <.05) than those without renal disease. CONCLUSION: Women who had gestational proteinuria or preeclampsia before 30 weeks' gestation were more likely to have had underlying renal disease.

Adult↗

Selection of surgical approaches for small acoustic neurinomas.

BACKGROUND: The purpose of this study was to evaluate the results of surgery for small acoustic neurinomas at our institute via the middle cranial fossa and retrosigmoid approaches, and to determine the indications for each approach. METHODS: Fifty-three patients with unilateral tumors less than 2 cm in diameter were studied. Surgery was performed via the middle cranial fossa approach in 36 tumors and via the retrosigmoid approach in 17 tumors. RESULTS: The hearing preservation rate was 68% (36/53) in all patients, 93% (14/15) in patients with intracanalicular tumors, 79% (15/19) in patients with tumors less than 1 cm in diameter, and 43% (7/19) in patients with tumors between 1 and 2 cm in diameter. The facial nerve function was excellent or good in 80% (42/53), 74% (11/15), 84% (16/19), and 78% (15/19), respectively. Among the 19 patients with tumors between 1 and 2 cm in diameter, the frequencies of hearing preservation and of excellent or good facial nerve function (47% and 87%, respectively) in the 15 patients approached via the retrosigmoid approach were higher than those (0% and 50%, respectively) in the four patients approached via the middle cranial fossa approach. CONCLUSIONS: We conclude that tumors smaller than 2 cm should be removed because preservation of hearing as well as facial nerve function may be possible in almost all of these patients. Tumors larger than 1 cm should be surgically treated through the retrosigmoid approach.

Adult↗

Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors.

More than 40 mutants in Caenorhabditis elegans have been demonstrated to lead to increased life span (a rigorous, operational test for being a gerontogene) of 20% or more ("Age" mutants). Age mutants alter rate-limiting determinants of longevity; moreover, important genes are identified independent of prior hypotheses as to actual mode of gene action in extending longevity and/or "slowing" aging. Age mutants define as many as nine (possibly) distinct pathways and/or modes of action, as defined by primary phenotype. Three well-studied mutants (age-1, clk-1, and spe-26) alter age-specific mortality rates in characteristic fashions; in age-1 mutants, especially, the changes in mortality rates are quite dramatic. All Age mutants (so far without exception) increase response to several (but not all) stresses, including heat, UV, and reactive oxidants. We have used directed strategies, as well as random mutagenesis, to identify novel genes increasing the worm's ability to resist stress. Two genes (daf-16 and old-1) yield over-expression strains that are stress resistant and long-lived. A variety of approaches to assess transcriptional alterations associated with increased longevity are underway. We suggest that the role of the Age genes in both longevity and stress resistance indicates that a major evolutionary determinant of longevity is the ability to respond to stress.

Aging↗

Transcriptional mechanisms of chondrocyte differentiation.

With the goal of identifying master transcription factors that control the genetic program of differentiation of mesenchymal cells into chondrocytes, we first delineated a 48-bp chondrocyte-specific enhancer element in the gene for proalpha1(II) collagen (Col2a1), an early and abundant marker of chondrocytes. Our experiments have demonstrated that the HMG-box-containing transcription factor, Sox9 which binds and activates this enhancer element, is required for chondrocyte differentiation and for expression of a series of chondrocyte-specific marker genes including Col2a1, Col9a2, Col11a2 and Aggrecan. In the absence of Sox9 the block in differentiation occurs at the stage of mesenchymal condensation, suggesting the hypothesis that Sox9 might also control expression of cell surface proteins needed for mesenchymal condensation. Since Sox9 also contains a potent transcription activation domain, it is a typical transcription factor. Two other members of the Sox family, L-Sox5 and Sox6, also bind to the 48-bp Col2a1 enhancer and together with Sox9 activate this enhancer as well as the endogenous Col2a1 and aggrecan genes. L-Sox5 and Sox6 have a high degree of sequence identity to each other and are likely to have redundant functions. Except for the HMG-box, L-Sox5 and Sox6 have no similarity to Sox9 and, hence, are likely to have a complementary function to that of Sox9. Our experiments suggest the hypothesis that, like Sox9, Sox5 and Sox6 might also be needed for chondrocyte differentiation. Other experiments, have provided evidence that the Sox9 polypeptide and the Sox9 gene are targets of signaling molecules that are known to control discrete steps of chondrogenesis in the growth plate of endochondral bones. Protein kinase A (PKA) phosphorylation of Sox9 increases its DNA binding and transcriptional activity. Since PKA-phosphorylated-Sox9 is found in the prehypertrophic zone of the growth plate, the same location where the gene for the receptor of the parathyroid hormone-related peptide (PTHrP) is expressed and since PTHrP signaling is mediated by cyclic AMP, we have hypothesized that Sox9 is a target for PTHrP signaling. Other experiments have also shown that fibroblast growth factors (FGFs) increase the expression of Sox9 in chondrocytes in culture and that this activation is mediated by the mitogen-activated protein kinase pathway. These results favor the hypothesis that in achondroplasia, a disease caused by activating mutations in FGF receptor 3, there might also be an abnormally high Sox9 expression.

Animals↗

Enzymatic formation of ether linkage producing shoyuflavones from genistein and (+/-)-trans-epoxysuccinic acid.

The production mechanism of shoyuflavones, conjugated ethers of isoflavones with tartaric acid and isolated from fermented soy sauce, was studied. In the high molecular weight fraction of the culture extract of Aspergillus oryzae, genistein was transformed into shoyuflavone B in the presence of (+/-)-trans-epoxysuccinic acid but not in the low molecular one. Asp. sojae and Asp. tamarii showed high activity similar to Asp. oryzae but none of Asp. niger, Rhizopus oligosporus, and Mucor praini did. The contents of epoxysuccinic acids in the starting materials of soy sauce and the cultures of various Asp. fungi were determined as dimethyl 2-chloro-3-hydroxysuccinate derivatives by GC-MS. Although epoxysuccinic acids were contained in Asp. oryzae, Asp. sojae, and Asp. tamarii cultures, they were not found in soybeans and wheat. A possible producing mechanism for shoyuflavones by enzymatically conjugating isoflavones to (+/-)-trans-epoxysuccinic acid with ether linkage was suggested.

Aspergillus niger↗

Adenosine regulates the production of interleukin-6 by human gingival fibroblasts via cyclic AMP/protein kinase A pathway.

Adenosine has been reported to alter a variety functions of the cells that participate in inflammatory responses. However, the effect(s) of adenosine on human gingival fibroblasts (HGF), one of the immunomodulator cells in inflamed periodontal lesions, remains to be established. In this study, we examined the influence of adenosine on the production of interleukin (IL)-6 by HGF. Ligation of adenosine receptors with adenosine or its related analogue, 2-chloroadenosine (2-CADO), increased IL-6 production by HGF without any other stimuli. In addition, adenosine and 2-CADO enhanced the cyclic AMP (cAMP) level in HGF as did prostaglandin E1 (PGE1) and forskolin. Interestingly, these cAMP-arising reagents and the permeable cAMP analogue, dibutyryl cAMP (dbtcAMP), also increased IL-6 production by HGF. These results suggest that cAMP is involved in adenosine-induced IL-6 production by HGF. Adenosine-induced IL-6 production was suppressed by protein kinase A (PKA) inhibitor, H89, indicating that cAMP/PKA pathway is involved in the induction. Moreover, the experiments using antagonists specific for adenosine receptor subtypes revealed that the adenosine-induced IL-6 production by HGF was, at least in part, mediated by the adenosine A2b receptor. These results provide new evidence for the possible effects of adenosine or its related analogue as an immunomodulator in inflammatory periodontal lesions.

2-Chloroadenosine↗

Expression of T-cell-associated antigens in B-cell non-Hodgkin's lymphoma.

We performed the immunophenotyping of 101 patients with B-cell non-Hodgkin's lymphoma (B-NHL) using two-colour flow cytometry (FCM) and found that lymphoma cells coexpressed at least one kind of T-cell-associated antigen (T-Ag; CD2, CD5, CD7) in 25 patients (24. 8%). Among these three T-Ags, CD5 was the most frequently expressed, in 21 patients (20.8%), followed by CD7, expressed in five patients (5.0%), and CD2, which was expressed in two patients (2.0%). Two kinds of T-Ag were simultaneusly expressed in three patients (CD2/CD5, CD2/CD7, and CD5/CD7, each expressed in one patient). Concerning the expression pattern of T-Ag, there were no significant differences between lymph nodes and extranodal organs in the three patients with T-Ag-positive B-NHL (T-Ag(+) B-NHL) who were analysed. When comparing the clinical features between T-Ag(+) B-NHL and T-Ag-negative B-NHL (T-Ag(-) B-NHL), extranodal involvement and higher International Prognostic Index (H and H.I.) were significantly frequent in the former subgroup (P = 0.0119 and P = 0. 0302 respectively).

Adolescent↗

Change in the ratio of free-to-total prostate-specific antigen during progression of advanced prostate cancer.

BACKGROUND: The ratio of free-to-total prostate-specific antigen (PSA) is different in benign prostatic hyperplasia and in the early stage of prostate cancer. The present study was undertaken to examine the ratio of free-to-total PSA in the advanced stage of this cancer and its subsequent change during course of the disease. METHODS: Free and total PSA were measured in sera collected from the following patients with benign and cancerous prostatic diseases: 47 cases of benign prostatic hypertrophy, nine in TIC with less than 10 ng/mL of total PSA, 11 in stage C, 16 in D2, 22 in remission under endocrine therapy, and 12 in relapse. In addition, PSA was measured sequentially in four other patients who were also in relapse. RESULTS: The ratio of free-to-total PSA was similar in early and advanced stages of untreated prostate cancer and was lower than that in benign prostatic hyperplasia. The ratio increased to the level of benign prostatic hyperplasia during remission from stages C and D2 under endocrine therapy. There was no correlation with the intervals from the start of the therapy to examination. Following relapse, the ratio came down gradually to the level obtained in untreated prostate cancer. CONCLUSION: The ratio of free-to-total PSA was similar in all stages of untreated prostate cancer. Response and relapse to endocrine therapy were associated with increase and decrease in ratio, respectively.

Disease Progression↗

Edematous swelling of the facial nerve in Bell's palsy.

Surgical decompression of the intratemporal facial nerve from the geniculate ganglion to the stylomastoid foramen was carried out in 91 patients with Bell's palsy. All of the patients had denervation exceeding 95%, and a suprastapedial lesion. Edematous swelling of the nerve was assessed using the following three grades: + +, nerve swells beyond the bony facial canal; +, nerve swells beyond the nerve sheath, but within the bony canal, and -, no notable swelling observed. Varying degrees of swelling of the nerve were noted in all of the patients from onset to the end of the ninth week. The incidence of + + swelling was highest within 3 weeks of onset and then declined. + + swelling was most often noted in the vicinity of the geniculate ganglion, and was thought to be a manifestation of inflammation due to herpes simplex virus infection. There was a clear time dependency of the swelling in the horizontal and pyramidal segments, but not in the mastoid segment. After the ninth week, the incidence of swelling decreased sharply and no swelling of the nerve was observed in about one-third of the patients. Considering the etiology and the analysis of edematous swelling, we propose that the course of Bell's palsy be differentiated into an acute phase (the first 3 weeks after onset), a subacute phase (from the fourth to ninth weeks) and a chronic phase (after the tenth week).

Adolescent↗

Histological rearrangement in the facial nerve and central nuclei following immediate and delayed hypoglossal-facial nerve anastomosis.

The timing of hypoglossal-facial nerve anastomosis is controversial. The present study was performed to clarify the influence of the timing of hypoglossal-facial nerve anastomosis on histological changes in the facial nerve and central nuclei using guinea pigs. The facial nerve was transected first at the labyrinthine portion, and then transected again at the stylomastoid foramen. Hypoglossal-facial nerve anastomosis was carried out immediately or 3 months later. Nerve regeneration and survival of the neurons in the facial and hypoglossal nuclei were evaluated by toluidine blue staining and horseradish peroxidase (HRP). Immediate anastomosis resulted in better nerve regeneration of the facial nerve, but the numbers of surviving neurons in the facial and hypoglossal nuclei were almost the same in both the immediate and delayed anastomosis groups.

Anastomosis, Surgical↗

Paralogy and orthology of tyrosine kinases that can extend the life span of Caenorhabditis elegans.

Modification of any one of three transmembrane protein tyrosine kinase (PTK) genes, old-1, old-2 (formerly tkr-1 and tkr-2, respectively), and daf-2 can extend the mean and maximum life span of the nematode Caenorhabditis elegans. To identify paralogs and orthologs, we delineated relationships between these three PTKs and all known transmembrane PTKs and all known mammalian nontransmembrane PTKs using molecular phylogenetics. The tree includes a number of invertebrate receptor PTKs and a novel mammalian receptor PTK (inferred from the expressed-sequence tag database) that have not previously been analyzed. old-1 and old-2 were found to be members of a surprisingly large C. elegans PTK family having 16 members. Interestingly, only four members of this transmembrane family appeared to have receptor domains (immunoglobulin-like in each case). The C-terminal domain of this family was found to have a unique sequence motif that could be important for downstream signaling. Among mammalian PTKs, the old-1/old-2 family appeared to be most closely related to the Pdgfr, Fgfr, Ret, and Tie/Tek families. However, these families appeared to have split too early from the old-1/old-2 family to be orthologs, suggesting that a mammalian ortholog could yet be discovered. An extensive search of the expressed-sequence tag database suggested no additional candidate orthologs. In contrast to old-1 and old-2, daf-2 had no C. elegans paralogs. Although daf-2 was most closely related to the mammalian insulin receptor family, a hydra insulin receptor-like sequence suggested that daf-2 might not be an ortholog of the insulin receptor family. Among PTKs, the old-1/old-2 family and daf-2 were not particularly closely related, raising the possibility that other PTK families might extend life span. On a more general note, our survey of the expressed-sequence tag database suggested that few, if any, additional mammalian PTK families are likely to be discovered. The one novel family that was discovered could represent a novel oncogene family, given the prevalence of oncogenes among PTKs. Finally, the PTK tree was consistent with nematodes and fruit flies being as divergent as nematodes and mammals, suggesting that life extension mechanisms shared by nematodes and fruit flies would be reasonable candidates for extending mammalian life spans.

Amino Acid Sequence↗

Nonfunctioning islet cell carcinoma of the pancreas with high serum CEA & CA19-9, K-ras codon 12 mutation, and microsatellite instability.

A 55-year-old man with nonfunctioning islet cell carcinoma showing elevation of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels is described with genetic analyses. Pathological examination of the resected specimen revealed two independent islet cell carcinomas, one in the body and the other in the tail of the pancreas. It was proved immunohistochemically that the tumor cells, particularly those in the tail, were immunoreactive to CEA and CA 19-9 and had the property of duct cells, as well as endocrine cells. Gastrin was demonstrated immunohistochemically in these tumor cells, although its level in serum was not elevated. Genetic analyses of the fresh specimens from the tumor in the body revealed K-ras codon 12 mutation and microsatellite instability. These findings are consistent with its progressive clinical course and strongly suggest that these tumors originate, not from the islet cells of Langerhans, but from protodifferentiated cells, capable of giving rise to all the pancreatic cell types.

Biomarkers↗

Molecular genetic mechanisms of life span manipulation in Caenorhabditis elegans.

Aging and a limited life span are fundamental biological realities. Recent studies have demonstrated that longevity can be manipulated and have revealed molecular mechanisms underlying longevity control in the soil nematode Caenorhabditis elegans. Signals from both neurons and the gonad appear to negatively regulate longevity. One tissue-specific signal involves an insulin-like phosphatidylinositol 3-OH kinase pathway, dependent upon the DAF-16 forkhead transcription factor. These signals regulate mechanisms determining longevity that include the OLD-1 (formerly referred to as TKR-1) receptor tyrosine kinase. Interestingly, increased resistance to environmental stress shows a strong correlation with life extension.

Animals↗

Functional bladder capacity as predictor of response to desmopressin and retention control training in monosymptomatic nocturnal enuresis.

OBJECTIVE: To evaluate the efficacy of intranasal desmopressin (DDAVP) and retention control training (RCT) for monosymptomatic nocturnal enuresis in childhood and to assess the predictive value of daytime functional bladder capacity for both methods. MATERIALS AND METHODS: A total of 114 children with monosymptomatic nocturnal enuresis, of whom 99 (86.8%) wetted the bed every night, were treated with 1 of the 2 methods: intranasal DDAVP in 54 and RCT in 60 subjects. RESULTS: Twenty-one of 54 patients (38.9%) and 14 of 60 patients (23.3%) in the DDAVP group and the RCT group, respectively, achieved strong improvement (p = 0.061). Forty-five of 54 (90.0%) in the DDAVP and 35 of 60 (58.3%) in the RCT group had a more than 50% decrease in wet nights (p = 0.004). In the DDAVP group, the functional bladder capacities at baseline in responders and nonresponders were 82+/-22% and 56+/-20% of the predicted bladder capacity for their age (p<0.001). In the RCT group, responders and nonresponders did not differ in functional bladder capacity at baseline. CONCLUSION: DDAVP treatment is more effective than RCT in decreasing the number of wet nights in childhood nocturnal enuresis, but not so effective in children with a low functional bladder capacity. Daytime functional bladder capacity is a valuable predictor of response to DDAVP, but not so to RCT.

Adolescent↗

Dietary taurine decreases hepatic secretion of cholesterol ester in rats fed a high-cholesterol diet.

The effects of dietary taurine on lipid secretion and ketone body production were examined in the livers of Wistar and Sprague-Dawley rats fed high-cholesterol diets. The weight gain of the Sprague-Dawley rats tended to be higher than that of the Wistar rats, although food intake was comparable between the strains. The concentration of hepatic triglyceride was significantly higher but that of phospholipid was significantly lower in the Sprague-Dawley rats. Ketone body production by livers of Sprague-Dawley rats was significantly higher than that by the livers of Wistar rats. Dietary taurine repressed the weight gain of Wistar rats, perhaps due to decreased food intake, but it had no apparent effect on these growth parameters in Sprague-Dawley rats. There was a significant reduction in the hepatic concentration of cholesterol ester, but not other lipid components following feeding of taurine. Taurine feeding resulted in a stimulation of hepatic ketogenesis, whereas it markedly reduced the hepatic secretion of cholesterol ester in both strains of rats. The effect of dietary taurine on the hepatic secretion of triglyceride, phospholipid and free-cholesterol was marginal in either strain. These results suggest that taurine feeding significantly ameliorated the dietary cholesterol-dependent increase in hepatic accumulation and secretion of cholesterol ester, regardless of strain differences, and the decrease in the hepatic secretion of this cholesterol ester appeared to be partly responsible for the observed reduction in the concentration of serum cholesterol following feeding of taurine in these cholesterol-fed rats.

Animals↗

Experience with ureteral stone management in 1,082 patients using semirigid ureteroscopes.

OBJECTIVES: To assess the efficacy and complications of ureteroscopic lithotripsy (URS) using semirigid ureteroscopes. METHODS: We retrospectively analyzed the records of 1,082 consecutive patients with ureteral stones who were treated with URS with or without auxiliary extracorporeal shock wave lithotripsy for stone fragments. The efficacy was estimated using the stone-free rate and efficiency quotient (EQ). RESULTS: The stone-free rates were 79.0, 90.4 and 93.2% for upper, middle and lower ureteral stones, respectively. The EQ was 0.49 for upper, 0.79 for middle and 0.87 for lower ureteral stones. Ureteral perforation occurred in 54 cases (5.0%), of which 13 cases (1.2%) required nephrostomy (n = 11, 1.0%) or open surgery (n = 2, 0.2%). CONCLUSIONS: URS is a reasonable procedure with minor complications for stones located in the lower and middle ureter, but cannot be recommended as a first-line treatment for upper ureteral stones.

Adolescent↗