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Biomedical subjects

M Osaka

Publications and source records attributed to M Osaka.

At least 37 records · Page 2Linked to original sources
PubMed1999

Carcinoid syndrome: a statistical evaluation of 748 reported cases.

No statistical evaluation of patients with carcinoid syndrome in a reliable number of cases has been available in the past 35 years. To update our knowledge about the syndrome, we have evaluated from various clinicopathologic viewpoints a large series of patients with the syndrome reported up to date. The data of 748 patients with the syndrome were collected from 8876 carcinoid patients reported in the literature and analyzed by the Gut-Pancreatic Endocrinoma Analyzing System (the Niigata Registry). The results are summarized as follows. 1) The patients with the syndrome had a tendency to be older than those without it. 2) The incidence of the syndrome was 8.4% of 8876 carcinoid patients. 3) Serotonin activities were extremely high in patients with the syndrome as compared to those without it (91.7% versus 26.6%). 4) The rate of metastases was higher in patients with the syndrome than in those without it (84.8% versus 29.2%), and higher in the liver than in lymph nodes among patients with the syndrome (73.4% versus 37.4%). 5) Flushing and carcinoid heart as most specific clinical manifestations of the syndrome were recorded at 78.3% and 17.4%, respectively. 6) The 5-year survival rate after resection of primary lesions was 76.0% of 304 patients with the syndrome, lower in patients with digestive carcinoids than in those with extradigestive lesions (67.2% versus 88.7%). It is expected that the results obtained in the present evaluation on patients with carcinoid syndrome will provide investigators active in this specialized field with useful and extensive information for their future activities.

Adolescent↗
PubMed1999

Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: a comparative study between typical carcinoids and atypical varieties.

This study is aimed to provide extensive and useful information based on an analysis of a large and reliable series of cases regarding mediastinal/thymic carcinoids, both typical and atypical. It also serves to assist investigators to improve their research activities in this particular field. In the present study, 342 patients (3.8%) with mediastinal/thymic carcinoids from amongst a total series of 8,970 patients with carcinoids, registered in the Niigata Registry for gut-pancreatic endocrinomas, were analyzed to clarify their detailed clinicopathological characteristics. Added to an analysis of mediastinal/thymic series including a comparison between typical and atypical carcinoid varieties, another comparative study was performed between the present series and a bronchopulmonary series. Mediastinal/thymic carcinoids may be briefly characterized by 1) no significant difference in major factors statistically demonstrable between typical carcinoids and atypical varieties, 2) a male preponderance, 3) difficult (delayed) preoperative diagnosis, 4) a high rate of metastasis, 5) a large tumor size on average (delayed detection), 6) a low rate of the carcinoid syndrome, 7) a high rate of association of the Cushing syndrome, and 8) low postoperative survival rates.

Adolescent↗
PubMed1998

Cloning of the rat proto-oncogene bmi-1.

The bmi-1 gene was identified as a common proviral integration site in Moloney murine leukemia virus. In the present studies, we cloned and sequenced the rat bmi-1 gene by reverse transcriptase-polymerase chain reaction (RT-PCR) using degenerate PCR primers of homologous sequences between mouse and human. We found 93% identity to the mouse bmi-1 cDNA and 90% identity to the human bmi-1. The open reading frame encodes a protein of 324 amino acids. In the deduced amino acid sequence we observed 95% and 94% homology to the mouse and human, respectively. The structural motifs, a novel zinc finger motif and a putative helix-turn-helix motif, were conserved in the predicted rat BMI-1 protein. We also confirmed ubiquitous expression of bmi-1 in normal tissues except brain. These results suggest functional conservation of the bmi-1 gene in the rat.

Amino Acid Sequence↗
PubMed1998

Depressed heart rate variability and arterial baroreflex in conscious transgenic mice with overexpression of cardiac Gsalpha.

Recently, we developed a transgenic mouse with cardiac-specific Gsalpha overexpression (TG mouse), which exhibits enhanced postsynaptic beta-adrenergic receptor signaling, ultimately developing a cardiomyopathy. The goal of the present study was to determine whether cardiac Gsalpha overexpression alters autonomic cardiovascular control, which could shed light on the mechanism responsible for the later development of cardiomyopathy. Mean arterial pressure was increased (P<.05) in conscious, chronically instrumented TG mice (123+/-1 mm Hg) compared with age-matched wild-type (WT) control mice (103+/-1 mm Hg). Respiratory frequency was increased (P<.05) in TG mice (269+/-26/min) compared with WT mice (210+/-20/min). By use of telemetric techniques, baseline heart rate (HR) was elevated (P<.05) in conscious, untethered TG mice (696+/-13 bpm) compared with WT mice (568+/-28 bpm). Intrinsic HR, after propranolol and atropine or after ganglionic blockade with hexamethonium, was not different between TG and WT mice. Both the normal minute-to-minute and circadian variations of HR observed in WT mice were markedly blunted in TG mice. HR variability was assessed by the time-domain and frequency-domain methods. At baseline, time-domain analysis indices were reduced (P<.05) in TG mice compared with WT mice. Although the low frequency (LF) component was higher (P<.05) than the high frequency (HF) component in WT mice, the LF component was less (P<.05) than the HF component in TG mice. In addition, arterial baroreflex regulation of HR was markedly blunted in TG mice in response to both nitroglycerin-induced hypotension and phenylephrine-induced hypertension. The reduced LF/HF ratio in TG mice was surprising in view of enhanced beta-adrenergic signaling and may be due to reduced neural tone secondary to the elevated arterial pressure or alterations in arterial baroreflex control. Dobutamine infusion in WT mice also resulted in depressed HR variability. The combination of elevated baseline HR, arterial pressure, and respiratory frequency suggests that enhanced beta-adrenergic signaling in TG mice results in reduced HR variability, in terms of both minute-to-minute variability and the lack of circadian variations in HR. The lack of normal HR variability in general and the failure of HR to decline, even during sleep, may actually be critical mechanisms contributing to the ultimate development of cardiomyopathy in these animals.

Adrenergic beta-Agonists↗
PubMed1998

ras and p53 genes are infrequently involved in N-nitroso-N-butylurea (NBU)-induced rat leukemia.

Chemically-induced rodent tumor models help us to understand a series of genetic changes during carcinogenesis. In this study, we present N-nitroso-N-butylurea (NBU)-induced rat leukemia and compare it with the genetic alterations found in 7,12-dimethylbenz[a]anthracene (DMBA)-induced erythroblastic leukemias which consistently have an A to T transversion at the second base of codon 61 in N-ras. By continuous NBU treatment for 120-150 days, 14 primary leukemias were induced in Long-Evans rats. Myeloblastic leukemia cells predominantly increased in all rats except in one case which predominantly had erythroblastic leukemia cells. Point mutations of Ha-, Ki-, N-ras and p53 were determined after RNA was transcribed into cDNA and this cDNA was used as a substrate for polymerase chain reaction (PCR) which was eventually sequenced. No abnormalities in exons 1 and 2 of Ha-, Ki- and N-ras were detected in all leukemias. In the p53 gene, an A to C transition was found at the second base of codon 198 (Asn-Thr) in one leukemia, but others had no mutation. These results suggest that ras and p53 genes are infrequently involved in NBU-induced leukemias. The genetic target of NBU during leukemogenesis seemed to be different from that of DMBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Polymerase chain reaction amplification of Trichomonas vaginalis DNA from Papanicolaou-stained smears.

DNA from Papanicolaou-stained smears was successfully amplified using the polymerase chain reaction (PCR) to investigate if it could be used for retrospective genome studies, such as for the detection of Trichomonas vaginalis. DNA was isolated from 20 archival Papanicolaou-stained smears (19 cervical and 1 seminal fluid samples) and purified by treatment with proteinase K, phenol/chloroform, and ethanol. The method of recovering DNA from the Papanicolaou-stained smear is very important in the successful amplification of Trichomonas DNA in archival cytological smears. We used a specific sequence and successfully amplified DNA in cytological smears of T. vaginalis using PCR. We conclude that the diagnostic accuracy of the detection of T. vaginalis in cervical smears is enhanced by using a combination of a Papanicolaou-stained smear and PCR.

Adult↗
PubMed1998

[Aprotinin and recombinant human erythropoietin reduce the need for homologous blood transfusion in cardiac surgery].

The effects of low dose aprotinin (Trasylol) and preoperative administration of recombinant human erythropoietin (EPO) were evaluated in 144 patients undergoing cardiopulmonary bypass divided into four groups. Group I (n = 43) received a subcutaneous administration of EPO (18,000 U) one week before operation and intraoperative administration of low-dose aprotinin (mean; 1.38 +/- 0.26 x 10(6) kallikrein inactivator units; KIU) from extracorporeal circulation, group II (n = 39) received only preoperative administration of EPO, group III (n = 28) received only intraoperative administration of low-dose aprotinin (mean; 1.46 +/- 0.25 x 10(6) KIU), and group IV (n = 34) were not administered either drug. Compared with group IV, the intraoperative blood loss was significantly lower in group I (p < 0.01), and in group II or III (p < 0.05). The postoperative drainage in 24 hours was significantly lower in groups I and III receiving aprotinin than in the other groups. The mean volume of total homologous blood transfusion and the percentage of cases not requiring a homologous blood transfusion in each group was, respectively, 74 +/- 235 ml and 88.4% in group I, 282 +/- 1289 ml and 87.2% in group II, 414 +/- 584 ml and 60.7% in group III, and 976 +/- 1931 ml and 44.1% in group IV. Significant differences were recognized between group I and group IV (p < 0.05). These findings indicate that when used in combination, both drugs reduce blood loss and the need for a homologous blood transfusion more effectively than either drug alone.

Aged↗
PubMed1998

Mutual information discloses relationship between hemodynamic variables in artificial heart-implanted dogs.

A mutual information (MI) method for assessment of the relationship between hemodynamic variables was proposed and applied to the analysis of heart rate (HR), arterial blood pressure (BP), and renal sympathetic nerve activity (RSNA) in artificial heart-implanted dogs to quantify correlation between these parameters. MI measures the nonlinear as well as linear dependence of two variables. Simulation studies revealed that this MI technique furnishes mathematical features well suited to the investigation of nonlinear dynamics such as the cardiovascular system and can quantify a relationship between two parameters. To constitute a model free of the natural heart, two pneumatically actuated ventricular assist devices were implanted as biventricular bypasses in acute canine experiments. RSNA was detected with the use of bipolar electrodes attached to the renal sympathetic nerve. Analysis of data during control revealed that correlation between HR and RSNA was higher than that between HR and BP and that between RSNA and BP (P < 0.05). Although RSNA seemed to fluctuate noncorrelatedly with BP in higher pacing rates, the MI values between them disclosed their strong correlation. Surprisingly, correlation between RSNA and BP was stronger during a pacing rate of 60 beats/min than during higher pacing rates and control (P < 0. 05). It is suggested that the baroreflex system may be susceptible to pacing rates during the total artificial heart state. We calculated the time delay between HR and RSNA, between RSNA and BP, and between HR and BP by regarding a time delay at which the maximum MI value between each pair of parameters was given as a physiological delay. Our results indicate that RSNA leads BP, BP leads HR, and RSNA leads HR during control (P < 0.05). We conclude that this method could provide a powerful means for measuring correlation of physiological variables.

Algorithms↗
PubMed1998

Insulinoma/hypoglycemic syndrome: a statistical evaluation of 1085 reported cases of a Japanese series.

Over the past 25 years and more, very few statistically reliable evaluations dealing with clinicopathologic features of patients with insulinoma and/or hypoglycemic syndrome (HGS), including recently popularized diagnostic modalities, have been published. The aims of this study are threefold: first, to evaluate the clinicopathologic features of patients with insulinoma/HGS from various viewpoints; secondly, to update our knowledge about this subject which has been retained up to date, and thirdly to supply reliable information to investigators working in the specialized field of gut-pancreatic endocrinomas. We collected data from literature on a total of 1085 Japanese patients with insulinoma/HGS and undertook a statistical evaluation. The results are summarized as follows. 1) Association of HGS was recognized in 88.4% of the 1085 patients. 2) Islet B-cell hyperplasia/nesidioblatosis was found in 4.1%; 2.6% in association with insulinoma and 1.6% without it. 3) Patients with small tumors of 20 mm or less comprised 81.1%. 4) The overall rate of metastases was 6.6% (72 patients) and that of malignancy 13.6% (148 patients). 5) Multisecretors immunohistochemically proved were found in 32.4% and multiplicity of tumor growth in 12.6%. 6) The 10-year survival rate after removal of lesions was 90.5% overall; 98.4% in patients with benign lesions and 75.7% in those with malignant tumors. It is expected that the results obtained in the present study will provide extensive and useful information for future investigation.

Adult↗
PubMed1997

WT1 contributes to leukemogenesis: expression patterns in 7,12-dimethylbenz[a]anthracene (DMBA)-induced leukemia.

The Wilms'-tumor gene WT1 may have a different function from a tumor-suppressor gene in some leukemias. Using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat leukemia system, we examined whether WT1 expression was involved during leukemogenesis, since this model enabled us to analyze cells altered by DMBA at various stages of leukemogenesis. By the semi-quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) method, WT1 expression was detected in 15 (71%) of 21 DMBA-induced erythroblastic leukemias. Among 15 WT1-expressing leukemias, GATA-1, which is an erythroid-specific transcription factor and might regulate WT1 expression, was also expressed in 13 cases (p < 0.05). On the other hand, WT1 expression was not detected in any normal or early pre-leukemic rats and was detected in 1 of 8 rats in late pre-leukemic stages. These results showed that cells with a high expression level of WT1 tended to develop into leukemia and that WT1 contributed to leukemogenesis in the late stage, suggesting that the expression of WT1 plays an important role in cell proliferation and in maintaining the viability of some leukemia cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Loss of heterozygosity at the N-ras locus in 7,12-dimethylbenz[a] anthracene-induced rat leukemia.

The 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat leukemia model enables scientists to analyze cells altered by carcinogens at various stages of leukemogenesis. We have reported that a consistent type of point mutation. A-->T transversion at the second base in codon 61 of the N-ras gene, was present in this leukemia and that this mutation appeared in bone marrow cells as early as 48 h after a single dose of DMBA. In addition, two leukemia cell lines with the N-ras mutation had no wild-type N-ras allele. Therefore, we examined whether these alterations were essential to the DMBA-induced leukemias. In the study reported here, we confirmed the occurrence of this N-ras mutation in 18 (86%) of 21 primary leukemias and loss of the N-ras wild-type allele in 12 (67%) of 18 leukemias with the mutated N-ras. By using microsatellite markers on chromosome 2, loss of heterozygosity (LOH) at the N-ras locus was observed in eight leukemias, all of which were shown to have lost the wild-type N-ras allele by mutant-allele-specific amplification. These results suggest that LOH related to loss of the wild-type N-ras allele reproducibly occurs in leukemias with the N-ras mutation. Considering the timing of the N-ras mutation and LOH, it is likely that the N-ras mutation is induced early, and cells that have lost the wild-type N-ras allele seem to develop into leukemia. We believe that this system provides a suitable model for studying a series of genetic alterations from the earliest stage of carcinogenesis that cannot be approached in human malignancies.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

The specific N-ras mutation in rat 7,12-dimethylbenz[a]anthracene (DMBA)-induced leukemia.

Intravenous injections of 7,12-dimethylbenz[a]anthracene (DMBA) induce erythroblastic leukemia (erythroleukemia) with #2 trisomy and Long #2 in Long-Evans rats. Recently, a consistent type of mutation, A to T transversion in codon 61 of N-ras gene, was found in all of 6 cultured leukemia cell lines and 13 primary leukemias induced by DMBA using polymerase chain reaction (PCR) and direct sequencing. On the contrary, no mutation was observed in Ha- and Ki-ras genes in these leukemias. The consistent occurrence of the above N-ras mutation in DMBA-induced leukemias indicates that N-ras gene plays an important role in DMBA-leukemogenesis. Mutations in ras genes generally takes place during the initiation stage of carcinogenesis because they often appear in the premalignant stage of tumors. In order to detect the N-ras mutation in an early stage of leukemogenesis, we designed the mutant-allele-specific amplification (MASA) method to detect the mutation in bone marrow (BM) cells of DMBA-treated rats. The MASA method was sensitive enough to detect one mutant cell mixed in 10(6) normal cells. Using this method, the N-ras mutation was found in BM cells 2 days after single DMBA injection and thereafter throughout the preleukemic stage. These results suggest that the N-ras mutation is an earliest event in DMBA-induced leukemogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Establishment and characterization of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat erythroleukemia cell lines.

To investigate molecular mechanisms and biological behaviors of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat erythroleukemia, we established 8 new culture cell lines from 7 primary erythroleukemias. We designated them KYD-10, 12, 17, 32, 38, 44A, 44B, and 49. Representative clones isolated from each cell line in early passage were analyzed cytogenetically and genetically. All cell lines except KYD-12 possessed the specific N-ras mutation at the 2nd base of codon 61. Four of them showed #2 trisomy (KYD-10, 32, 38, 44B), and the rest normal diploid karyotype (2n). KYD-32 cells showed Robertson type II #2 trisomy which had never been clonally isolated in vitro although it was reported in some DMBA leukemias in vivo. We further studied the genomic imbalance related to the N-ras allele using mutant-allele-specific amplification (MASA) method. Deletion of normal N-ras allele was found in 5 of 8 cell lines. KYD-32 and 38 retained the normal N-ras allele. The specific N-ras mutation and allelic loss of wild type N-ras were correlated with advanced cell proliferation in culture probably independent of #2 trisomy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

[An adult case of aortic coarctation associated with two thoracic aneurysms].

A 57-year-old woman in whom an abnormality was detected on the chest X-ray presented with no signs or symptoms other than hypertension. Several examinations revealed that she had aortic coarctation of the isthmus with two aneurysm in the arch. One aneurysm was located in the root of the left subclavian artery, another was just distal of the first aneurysm. For prevention of rupture of the aneurysms and treatment of hypertension, aortic arch reconstruction was performed with the aid of selective cerebral perfusion. The postoperative course was uneventful and she was discharged 19 days after the operation with normalization of her blood pressure. At the operation in this case, the combination of the two approaches, median sternotomy and left 4th thoracotomy, was useful.

Aorta↗