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Biomedical subjects

S Nomoto

Publications and source records attributed to S Nomoto.

At least 73 records · Page 4Linked to original sources
PubMed1997

Detection of mutant K-ras in dissected paraaortic lymph nodes of patients with pancreatic adenocarcinoma.

In this study, we attempted to detect K-ras point mutations by means of two-stage polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) to diagnose micrometastases in paraaortic lymph nodes of patients with pancreatic adenocarcinoma. Main carcinoma tissues and corresponding lymph nodes in the paraaortic region were obtained from 15 patients who underwent extended radical surgery including the wide dissection of lymph nodes and who were diagnosed as lymph node negative by routine histological examination. DNA was extracted from the tissue specimens, and PCR/RFLP analysis was used to detect K-ras oncogene mutations at codon 12. Thirteen of the primary tumors were found to have K-ras mutations. In eight of the 13 cases, 42 of the 101 lymph nodes showed K-ras point mutations in the paraaortic lymph nodes. These results suggested that PCR/RFLP analysis is potentially highly sensitive for the detection of micrometastases in lymph nodes and that it may be useful in reaching an accurate assessment of the lymphatic dissemination of pancreatic adenocarcinoma at the molecular level.

Adenocarcinoma↗
PubMed1997

[A successful surgical repair of total anomalous pulmonary venous connection associated with Williams syndrome].

The surgical correction was performed successfully in a 14-year-old boy with total anomalous pulmonary venous connection (type Ia) associated with Williams syndrome. The diagnosis was made at the age of 3 and he had been well until the age of 13 when sudden chordal rupture caused severe mitral regurgitation and supraventricular tachyarrhythmia. The operational procedure includes common pulmonary vein and left atrium anastomosis through Gersony-Malm approach, chordal reconstruction of mitral valve with 4-0 Core Tex sutures. His postoperative course has been well without the sign of venous obstruction. As far as we know, this is the first documentation of a case of Williams syndrome associated with total anomalous pulmonary venous connection.

Adolescent↗
PubMed1997

[A successful surgical repair of congenital mitral stenosis due to commissural papillary muscle fusion].

A case of congenital mitral stenosis, patent ductus arteriosus, pulmonary hypertension was reported. At one year of age, the patient underwent surgical division of PDA because of persistent left heart failure. She went well after the operation. At seven year of age, she was readmitted to our hospital for easy fatigability. The cardiac catheterization revealed remarkably elevated pulmonary arterial pressure and pulmonary capillary wedged pressure. She underwent a surgical intervention for the mitral stenosis at eight year of age. At operation, the mitral valve exhibited the characteristics of type IIc according to Carpentier's classification: thickened and dysplastic leaflet, extremely short chordae tendanae fused with papillary muscles, obliteration of interchordal space and hypertrophic two papillary muscles. We replaced the valve with 23 mm Carbomedicus prosthetic valve because it seemed to be difficult to repair the native valve satisfactorily without residual stenosis or insufficiency. Her postoperative course was uneventful and the pulmonary arterial pressure and pulmonary capillary wedged pressure decreased remarkably one year after the operation.

Child↗
PubMed1996

Reperfusion causes significant activation of heat shock transcription factor 1 in ischemic rat heart.

BACKGROUND: The myocardial protective role of heat shock protein (HSP) has been demonstrated, and there has been increasing interest in stress response in the heart. We examined the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during heat shock or ischemia/reperfusion in isolated rat heart. METHODS AND RESULTS: Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element, which is present upstream of all heat shock genes. Induction of mRNAs for HSP70, HSP90, and GRP78 (glucose-regulated protein) was examined by Northern blot analysis. Although the activation of HSF during global ischemia was weak and rapidly attenuated, postischemic reperfusion induced a significant activation of HSF. In addition, although HSP70 mRNA was hardly induced during ischemia, its burst induction was detected during postischemic reperfusion. Supershift assays using specific antisera for HSF1 and HSF2 revealed that ischemia/reperfusion as well as heat shock induced the activation of HSF1 in hearts. Although the expression of HSP70 mRNA during heat shock was more vigorous than the expression during ischemia/reperfusion, the induction of HSP90 mRNA in postischemic reperfusion was significantly greater than that in heat shock. CONCLUSIONS: Our findings demonstrated that reperfusion causes a significant activation of HSF1 in ischemia-reperfused heart. The striking contrast between the induction of HSP70 mRNA and that of HSP90 mRNA suggests the presence of regulatory mechanisms other than HSF.

Animals↗
PubMed1996

Comparison of the frequency of T-cell receptor mutants and thioguanine resistance induced by X-rays and ethylnitrosourea in cultured human blood T-lymphocytes.

We have investigated two assays for measuring the induction of mutations using human T-lymphocytes isolated from leukocyte residue buffy coats obtained from normal donors. Variant cell frequency of T-cells defective in the T-cell receptor (TCR) gene expression was measured using a 2-color flow cytometry, and 6-thioguanine-resistant (TGr) cells were determined using a cloning technique at the HPRT gene after treatment with 250 kVp X-rays or ethylnitrosourea (ENU). The frequencies of TCR mutant cells as well as those of TGr cells increased with increasing doses of X-rays or concentrations of ENU studied. For TCR mutants, the induced mutation frequencies at D37 (giving 37% survival) were 31.7 x 10(-4) and 11.0 x 10(-4) for X-rays and ENU, respectively. For TGr T-cells, the induced mutation frequencies at D37 for the same mutagens were 14.4 x 10(-6) and 75.5 x 10(-6), respectively. Over the dose range studied the relationship appears to be linear between the mutation induction of TCR and that of TGr for X-rays or ENU. However, X-rays may induce more TCR mutants against less induction TGr T-cells, and ENU may cause a reverse result. The sensitivity of the assay of each biological endpoint in human blood T-lymphocytes may be different.

Adult↗
PubMed1996

Extrapancreatic nerve plexus invasion by carcinoma of the head of the pancreas. Diagnosis with intraportal endovascular ultrasonography.

CONCLUSION: The intraportal endovascular ultrasonography (IPEUS) could diagnose the second portion of the extrapancreatic nerve plexus invasion and provide precise information in operative strategy. But, the first portion was not visualized clearly owing to poor tissue penetration of the ultrasound beam, which may have reduced diagnostic accuracy. Improvement of the scanning area is expected to make intraportal endovascular US even more useful. BACKGROUND: Pancreatic cancer easily invades the retroperitoneal tissue, especially the extrapancreatic nerve plexus. We evaluated the extrapancreatic nerve plexus invasion of the pancreatic cancer with IPEUS. IPEUS was performed intraoperatively in 20 consecutive resected cases with carcinoma of the head of the pancreas. METHODS: IPEUS was performed with an 8-French, 20 MHz intravascular ultrasound catheter. IPEUS visualized the inferior pancreaticoduodenal artery (IPDA) in the extrapancreatic nerve plexus. The high-echoic area around the IPDA corresponds to the second portion of the extrapancreatic nerve plexus. The sonographic criterion for detection of the extrapancreatic nerve plexus invasion is low-echoic infiltration around the IPDA. RESULTS: Extrapancreatic nerve plexus invasion was confirmed with resected specimens in 10 patients. The IPDA could not be visualized in two patients. In 18 patients, the diagnostic accuracy of invasion was evaluated. For diagnosis of extrapancreatic nerve plexus invasion with intraportal endovascular US, the sensitivity, specificity, and overall accuracy were 87.5, 90, and 88.7%, respectively.

Adult↗
PubMed1996

Diurnal variations in fever induced by intravenous LPS injection in pigeons.

Pigeons show a profound circadian rhythmicity of core temperature (Tcore). The Tcore is about 43 degrees C during the daytime and about 40 degrees C at night. Intravenous injections of bacterial endotoxin (LPS: lipopolysaccharide) during the day and night in pigeons evoked fevers of different magnitude. When LPS was injected during the day, Tcore first decreased from 41.8+/-0.2 degrees C to 41.4+/-0.3 degrees C, then started to increase after about 1.5 hrs, reaching 42.9+/-0.2 degrees C about 5 hrs after the injection. When LPS was injected at night, Tcore immediately increased from 40.3+/-0. 2 degrees C to 41.8+/-0.3 degrees C within 5 hrs after the injection. Fever continued for about 13 hrs when endotoxin was injected during the day, but only for about 9 hrs when it was injected at night. Compared with the diurnal pattern of afebrile core temperatures, fever was superimposed on the circadian rhythmicity. This suggests that the control of circadian rhythm of core temperature is not disturbed during fever.

Animals↗
PubMed1996

Identification and characterization of transcriptional regulatory elements of the human aromatase cytochrome P450 gene (CYP19).

Aromatase cytochrome P450, a member of the cytochrome P450 gene super family, catalyzes conversion of androgens to estrogens in a form of an enzyme-complex with NADPH-cytochrome P450 reductase. Transcription of the aromatase cytochrome P450 gene (CYP19) is regulated in part by tissue-specific promoters coupled with alternative splicing mechanisms. The transcription in human placenta is governed by a promoter activity of the 5' flanking region of exon I.1, which is mapped more than 40 kb upstream from the translational start codon observed in exon II. Transient expression analyses with chimeric constructs containing the 5' flanking sequences linked to the bacterial chloramphenicol acetyltransferase (CAT) gene in human BeWo choriocarcinoma cells localized a cell-type specific enhancer element between -242 and -166 relative to the major cap site. DNase I footprinting and transient expression analyses of the enhancer element indicate that it consists of two sub-elements and that both sub-elements are necessary for the maximum enhancement of the transcription. In addition to the enhancer element, a cis-acting element important for transcriptional enhancement of the gene in response to 12-O-tetradecanoylphorbol 13-acetate in BeWo cells is localized between -2141 and -2115. A nuclear factor binding to the element is identified as NF-IL6 (also termed as LAP and C/EBP beta). Transient expression analyses using the CAT constructs containing the NF-IL6 binding sites involvement of the factor in transcriptional regulation of CYP19.

Aromatase↗
PubMed1996

Influence of hepatic mitochondrial redox state on complement biosynthesis and activation during and after cardiopulmonary bypass operations.

We have proposed the hazardous phenomena associated with cardiopulmonary bypass (CPB) are due to metabolic derangement by hepatic mitochondrial dysfunction during and after CPB. On the contrary, complement activation and consumption during CPB is reported to be related to the morbidity associated with cardiac surgery. To determine the significance of the hepatic mitochondrial function on the morbidity of cardiac surgery, we measured the serum levels of complements (C3 and C4), activated complements (C3a and C4a), and the arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, in 30 patients undergoing CPB. The AKBR, which was at a normal level preoperatively, dropped to a critical level after the initiation of CPB and remained at a low level during the CPB, returning to the preoperative level on the second postoperative morning in a time dependent fashion. The patients group were assigned to two groups according to their AKBR on the first postoperative morning. Group I consisted of patients whose AKBR had recovered to above 0.7 on the first postoperative morning (n = 16). Group II consisted of the rest of the patients (n = 14). The serum complement concentration had considerably decreased by the end of bypass, but recovered in a time-dependent fashion after CPB. The group I patients (C3: 71% of its preoperative value, C4: 85% of its preoperative value) recovered their complements more quickly than the group II patients (C3: 56% of its preoperative value, C4: 54% of its preoperative value). However, the serum C3a and C4a concentrations increased by the end of bypass (C3a: 806% of its preoperative value, C4a: 341% of its preoperative value). The activated complements were significantly higher in the group II patients (C3a: 124% of its preoperative value, C4a: 236% of its preoperative value) than in the group I patients (C3a: 75% of its preoperative value, C4a: 113% of its preoperative value) on the first postoperative morning. It is suggested that hepatic mitochondrial function is related to recovering the complements and to reducing the activated complements after CPB.

Adolescent↗
PubMed1996

p53-dependent apoptosis suppresses radiation-induced teratogenesis.

About half of human conceptions are estimated not to be implanted in the uterus, resulting in unrecognizable spontaneous abortions, and about 5% of human births have a recognizable malformation. In order to find clues to the mechanisms of malformation and abortion, we compared the incidences of radiation-induced malformations and abortions in p53 null (p53-/-) and wild-type (p53+/+) mice. After X-irradiation with 2 Gy on day 9.5 of gestation, p53-/- mice showed a 70% incidence of anomalies and a 7% incidence of deaths, whereas p53+/+ mice had a 20% incidence of anomalies and a 60% incidence of deaths. Similar results were obtained after irradiation on day 3.5 of gestation. This reciprocal relationship of radiosensitivity to anomalies and to embryonic or fetal lethality supports the notion that embryonic or fetal tissues have a p53-dependent "guardian" of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of cells with apoptotic DNA fragments was greatly increased in tissues of the p53+/+ fetuses but not in those of the p53-/- fetuses.

Animals↗
PubMed1996

Intracaval endovascular ultrasonography for preoperative assessment of retrohepatic inferior vena cava infiltration by malignant hepatic tumors.

The accurate diagnosis of inferior vena cava infiltration is important not only for preoperative staging but also for performing surgery for hepatic tumor involving the inferior vena cava (IVC). We investigated the diagnostic value of intracaval endovascular ultrasonography (ICEUS) in the diagnosis of invasion of the IVC by a prospective study of 30 consecutive patients with hepatic tumors with possible invasion of the IVC. The procedure was performed using an 8F, 20-MHz intravascular ultrasonography (US) from the right femoral vein. Twenty-nine of the 30 patients underwent surgery, and the tumor was resected in 25 cases, including 3 cases of combined resection of the IVC. The diagnostic criterion for IVC infiltration with ICEUS was obliteration of a single echogenic layer of the IVC wall or intracaval tumor mass. The results of ICEUS were compared with those of computed tomography (CT), cavography, conventional US, and intraoperative US. Vascular invasion was identified in 7 of 30 cases and was subsequently confirmed by pathological examination of four resected specimens, including one autopsy and two operative findings. The sensitivity, specificity, and overall accuracy of ICEUS for the diagnosis of the IVC invasion was 100%, 95.8%, and 96.7%, respectively, against 85.7%, 60.8%, and 66.7% for CT, and 71.4%, 73.9%, and 73.3%, respectively, for cavography. The sensitivity, specificity, and overall accuracy of conventional US was 87.5%, 59%, and 66.7%, respectively; those of intraoperative US were 100%, 81.8%, and 86.2%, respectively. ICEUS is a useful technique that can precisely evaluate the IVC for possible hepatic tumor invasion.

Aged↗
PubMed1996

Detection of ras gene mutations in perioperative peripheral blood with pancreatic adenocarcinoma.

Surgeons wish to know of any correlation between an operation and the incidence of metastasis. In perioperative periods, pancreatic cancer cells were identified by detecting mutant K-ras gene by two-step PCR and RFLP analysis in blood samples taken from peripheral blood. In no case was K-ras point mutation detected in blood before operation, although the mutant hand was observed in all cases at the time the lesion was resected. Surprisingly, in five of ten cases, positive bands were identified just after laparotomy, before we had reached the primary lesion. In almost all cases, mutant K-ras was detected until the fourteenth postoperative day. These findings suggest that cancer cells exist in the circulation, and have a potential for hematogenous metastasis during the perioperative period. In conclusion, surgical stress causes hematogenous dissemination of pancreatic cancer cells, and surgeons should employ the appropriate anti-metastasis therapy in the perioperative period.

Adenocarcinoma↗
PubMed1996

Individual variation and age dependency in the radiosensitivity of peripheral blood T-lymphocytes from normal donors.

To investigate individual variation and age dependency in normal cell radiosensitivity, we measured the in vitro radiosensitivity of cultured peripheral blood T-lymphocytes derived from 56 healthy male blood donors. Dose-survival tests using colony formation assay were done with exponential growing T-cells (day 3, PHA-stimulated cells). 6-Thioguanine (6-TG)-resistant mutation assays at the hypoxanthine phosphoribosyl transferase (HPRT) locus were done with G0 phase T-cells (day 0, unstimulated cells). The mean inactivation dose (MID) computed by integration of the fitted survival curves was 1.25 +/- 0.23 Gy (mean +/- SD). The X-ray dose required to kill 90% of the cells (D10) was 2.81 +/- 0.51 Gy. The MID ranged from 0.82 to 1.86 Gy with a coefficient of variation (CV) of 18%. The induced mutation frequencies (MF) per 10(6) cells at 2 Gy of X-rays ranged from 9.10 to 54.80 with a mean +/- SD value of 24.63 +/- 12.51 and a CV of 51%. It appears that the radiosensitivity of cell killing and mutagenicity varies among individuals. Although the spontaneous MF at the HPRT locus increases with age, the induced MF after exposure to 2 or 4 Gy of X-rays was not associated with age. Moreover, there were no significant correlations between age and MID values or the other dose-survival parameters. The findings indicate there is significant inter-individual variation in cellular radiosensitivity, but that in human T-lymphocytes aging does not affect the cytotoxic and mutagenic effects of X-irradiation.

Adolescent↗
PubMed1995

Classic steroid 11 beta-hydroxylase deficiency caused by a C-->G transversion in exon 7 of CYP11B1.

Steroid 11 beta-hydroxylase deficiency (11 beta OHD) is derived from mutations in the P45011 beta gene (CYP11B1) and inherited in an autosomal recessive manner. In the present study, we have performed a molecular genetic analysis of CYP11B1 in a Japanese patient clinically diagnosed as classic 11 beta OHD. Nucleotide sequencing of the PCR-amplified exons from the patient's genomic DNA reveals a unique C-->G transversion that converts codon 384 CGA (arginine) to GGA (glycine) in exon 7. Restriction fragment length polymorphism (RFLP) data demonstrate that the patient is homozygous for this mutation. When the full-length cDNA corresponding to CYP11B1 of the patient is transfected into COS-7 cells, no steroid 11 beta-hydroxylase activity is detectable in mitochondria of the cells. These results indicate that this point mutation completely abolishes P45011 beta activity and causes the classic 11 beta OHD.

Adolescent↗
PubMed1995

Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family.

A hereditary ceruloplasmin deficiency associated with severe iron deposition in visceral organ and brain tissues found on histopathological examination at autopsy is discussed. Three siblings of consanguineous Japanese parents were studied. Their clinical symptoms were progressive dementia, extrapyramidal disorders, cerebellar ataxia, and diabetes mellitus, all of which appeared when they were between 30 and 50 years old. All had serum ceruloplasmin deficiencies and increased serum ferritin concentrations. The dentate nucleus, thalamus, putamen, caudate nucleus, and liver of each one showed low signal intensities on T1- and T2-weighted magnetic resonance images. Examination of the central nervous system revealed severe destruction of the basal ganglia and dentate nucleus, with considerable iron deposition in neuronal and glial cells, whereas the cerebral cortex showed mild iron deposition in glial cells without neuronal involvement. An electron microscopic study with energy-dispersive x-ray analysis showed iron depositions in the hepatocytes, of both the neural and glial cells of the brain. We consider this a new disease entity because of the primary ceruloplasmin deficiency.

Adult↗