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Biomedical subjects

M Nagao

Publications and source records attributed to M Nagao.

At least 145 records · Page 8Linked to original sources
PubMed1998

Detection of the sarin hydrolysis product in formalin-fixed brain tissues of victims of the Tokyo subway terrorist attack.

One of the hydrolysis products of sarin (isopropyl methylphosphonofluoridate) was detected in formalin-fixed brain tissues of victims poisoned in the Tokyo subway terrorist attack. Part of this procedure, used for the detection of sarin hydrolysis products in erythrocytes of sarin victims, has been described previously. The test materials were four individual cerebellums, which had been stored in formalin fixative for about 2 years. Sarin-bound acetylcholinesterase (AChE) was solubilized from these cerebellums, purified by immunoaffinity chromatography, and digested with trypsin. Then the sarin hydrolysis products bound to AChE were released by alkaline phosphatase digestion, subjected to trimethylsilyl derivatization (TMS), and detected by gas chromatography-mass spectrometry. Peaks at m/z 225 and m/z 240, which are indicative of TMS-methylphosphonic acid, were observed within the retention time range of authentic methylphosphonic acid. However, no isopropyl methylphosphonic acid was detected in the formalin-fixed cerebellums of these 4 sarin victims, probably because the isopropoxy group of isopropyl methylphosphonic acid underwent chemical hydrolysis during storage. This procedure will be useful for the forensic diagnosis of poisoning by protein-bound, highly toxic agents, such as sarin, which are easily hydrolysed. This appears to be the first time that intoxication by a nerve agent has been demonstrated by analyzing formalin-fixed brains obtained at autopsy.

Acetylcholinesterase↗
PubMed1998

Hyperthermo-chemo-hypoxic isolated liver perfusion for hepatic metastases: a possible adjuvant approach.

As a possible intraoperative adjuvant approach to treating hepatic metastases we developed a method of hyperthermo-chemo-hypoxic isolated liver perfusion in combination with hepatic resection. This method was applied to 11 patients with colorectal hepatic metastases between 1992 and 1995. One patient died on postoperative day 14 of hepatic failure (9% mortality), the cause of which was live temperature that reached 42.9 degree C, which seems to be the maximum limit for thermal toxic effect on the human liver. The other 10 patients tolerated the perfusion well, with mild hepatic and non systemic toxicity after minor or even major hepatic resection; the serum aminotransferase and total bilirubin levels returned to normal levels by postoperative day 14. Only one of eight patients (13%) for whom cytotoxic drugs were added to the perfusate (mitomycin C 10 micrograms/ml or cisplatin 2 micrograms/ml) had hepatic recurrence by 19 months after the perfusion (mean follow-up 25.8 months; median 23 months; range 8-57 months). Two patients were alive with no evidence of disease at 13 and 57 months, respectively after the perfusion; the other five patients had postperfusion extrahepatic recurrences (median: 19 months; range 7-20 months). In contrast, hepatic metastases recurred 7 and 20 months after the perfusion, respectively, in the two patients not given a cytotoxic drug.

Aged↗
PubMed1998

Serum interleukin-6, interleukin-8, hepatocyte growth factor, and nitric oxide changes during thoracic surgery.

Thoracic surgery creates a different environment from abdominal surgery in respect to the surgical procedure with pulmonary collapse under unilateral ventilation. Definitive evidence whether surgical trauma during thoracotomy is involved in postoperative pulmonary infections has not been clearly demonstrated. The objectives of this study were to evaluate the influence of surgical trauma during thoracotomy on postoperative infections and to investigate the clinical significance of postoperative humoral mediators in pulmonary infections after surgery. We measured serum interleukin-6 (IL-6), IL-8, hepatocyte growth factor (HGF), and nitric oxide (NO) levels in 27 patients undergoing thoracic surgery; the measurements were before and during thoracotomy, 60 minutes after reinflation, and after surgery. The patients were divided into three groups: lobectomy patients (group A), and esophagectomy patients without (group B) or with (group C) postoperative infections. The serum IL-6 and IL-8 levels in group C were markedly elevated 60 minutes after reinflation and were significantly higher than those in group A. The serum IL-8 levels during that period in group C were significantly higher than those in group B. The postoperative serum IL-6, IL-8, HGF, and NO levels were significantly higher in group c than in group B. Taken together, intraoperative hypercytokinemia, especially IL-8, following the thoracic procedure and subsequent reinflation preceded the clinical onset of postoperative infections. Hence postoperative serum IL-6, IL-8, and HGF levels may be useful predictors of infection after esophagectomy.

Biomarkers↗
PubMed1998

Pattern of recurrence after resection for intraductal papillary mucinous tumors of the pancreas.

The objective of this study was to clarify the patterns of recurrence and prognosis after resection of intraductal papillary mucinous tumors (IPMTs). Fourteen patients with IPMT were reviewed histologically; intraductal papillary adenocarcinoma was present in 12 cases and intraductal papillary adenoma in 2. Six patients were alive with no evidence of disease. Two patients died from other causes. Six patients had recurrences. The median survival time was 46 months. In the six recurrent cases, the median postoperative disease-free interval was 38 months. Four patients died of recurrence, and the median survival time after recurrence was 6 months. The major site of recurrence was the remnant pancreas. The other sites were the liver in two cases, peritoneum in two, and local in one. These results suggest the multicentric or metachronous oncogenesis of IPMT. Because of the low frequency of lymph node metastases, an operation to preserve pancreatic function may be recommended, especially for localized tumors such as the branch type. It is important to avoid an incomplete resection using intraoperative pancreatoscopy and ultrasonography. Long-term follow-up after surgery is necessary even for a curative resection. We should perform total pancreatectomy for recurrences without distant metastases.

Aged↗
PubMed1998

Repeat hepatectomy for recurrent colorectal metastases.

Recurrence rates after hepatic resection in patients with colorectal metastases are reported to range from 47% to 80%. Hepatic recurrence is seen in 35% to 50% of patients. Aggressive surgical resection appears to be a worthwhile treatment in patients with recurrent hepatic metastases to promote longer patient survival because surgical resection remains the only curative therapy available. This is a retrospective review of our experience with 15 patients undergoing repeat hepatic resection culled from 67 patients undergoing initial hepatectomy for metastatic colorectal cancer. Of 67 patients who underwent hepatectomy for colorectal hepatic metastases, 33 developed hepatic recurrence at a median interval of 23 months (range 1-176 months) after the first hepatectomy. The second hepatectomy was performed in 15 patients 5 to 29 months after the first hepatectomy, with no mortality. The mean operating time and blood loss at the second hepatectomy were similar to those at the first hepatectomy. The mean hospital stay at the second hepatectomy was significantly shorter than that at the first hepatectomy. The cumulative survival rate for the 15 patients was 42.4% at 3 years and 21.2% at 5 years, respectively, which compared favorably with the survival rate of the 67 patients who underwent initial hepatectomy. Patients who underwent the second hepatectomy had significantly higher survival rates from the first hepatectomy than the 18 patients with unresectable hepatic recurrence. Repeat hepatectomy can be performed safely and provides long-term survival rates similar to those of first hepatectomies. In appropriately selected patients, repeat hepatectomy for colorectal metastases is a worthwhile treatment.

Adult↗
PubMed1998

Isolation of 48 genetic markers appropriate for high throughput genotyping of inbred rat strains by B1 repetitive sequence-representational difference analysis.

Mapping of genetic suppressors, modifiers, and quantitative trait loci (QTLs) requires genetic markers that can be efficiently and inexpensively genotyped for a large number of individuals. To isolate rat genetic markers suitable for this purpose, representational difference analysis (RDA) was performed with amplicons prepared by PCR with the B1 repetitive sequence used as the primer (B1-amplicons). In total, 48 polymorphic DNA fragments were isolated by five series of RDA, subtracting the B1-amplicons prepared from an ACI/N (ACI) rat from those prepared from BUF/Nac (BUF), and vice versa. All the polymorphic fragments detected "presence-or-absence" polymorphisms with B1-amplicons prepared from ACI, BUF, and their F2 progeny, and each fragment was linkage mapped. Dot-blotting amplicons onto filters at a high density and hybridization of the filters with these B1-RDA markers made it possible to genotype a large number of rats simultaneously for multiple loci. These B1-RDA markers were polymorphic between two given inbred strains of rat at frequencies between 30% and 70%. This is the first report on the isolation of B1-RDA markers among inbred strains of rats.

Animals↗
PubMed1998

Decrease of protein kinase C in the spinal motor neurons of amyotrophic lateral sclerosis.

The expression of protein kinase C (PKC), a calcium- and phospholipid-dependent signaling molecule, was studied immunohistochemically in the spinal motor neurons of cases of sporadic amyotrophic lateral sclerosis (SALS). In the normal spinal cord, intense PKC immunoreactivity was found in subsets of large motor neurons. PKC immunoreactivity was markedly decreased in the spinal motor neurons of SALS. The result suggests that down-regulation of PKC is associated with the degeneration of spinal motor neurons in SALS.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Expression of phosphotyrosine and SNAP-25 immunoreactivity in grumose (foamy) spheroid bodies suggests axonal regeneration.

To investigate the origin of grumose (foamy) spheroid bodies (GFSB), the expression of two proteins associated with axonal regeneration, i.e., phosphotyrosine and 25-kDa synaptosomal-associated protein (SNAP-25), was immunohistochemically assessed in GFSB in the substantia nigra pars reticulate (SNPR) of progressive supranuclear palsy (PSP). Phosphotyrosine immunoreactive (-IR) and SNAP-25-IR were found in many GFSB. Both were expressed intensely on eosinophilic debris and grumose aggregates in GFSB. Our result suggests that GFSB are structures associated with aberrant sprouting of axons in the degenerated SNPR from other regions such as the globus pallidus to the SNPR, and that the aberrant sprouting may be associated with cell signaling involving tyrosine kinase systems.

Aged↗
PubMed1998

Connatal Pelizaeus-Merzbacher disease: a missense mutation in exon 4 of the proteolipid protein (PLP) gene.

We investigated the proteolipid protein (PLP) gene in two brothers in a Japanese family with a connatal form of Pelizaeus-Merzbacher disease (PMD). Direct sequencing of the PLP gene revealed an A-to-T transition in exon 4, which led to an Asp-to-Val substitution at residue 202. Their mother was confirmed to be heterozygous for the mutation. The mutation was not found in 78 X-chromosomes of normal Japanese individuals. A correlation between the clinical severity of the disease in the brothers and the Asp202-to-Val mutation in the PLP gene was suggested.

Child↗
PubMed1998

Mutation analysis of the phenylalanine hydroxylase gene and its clinical implications in two Japanese patients with non-phenylketonuria hyperphenylalaninemia.

We describe a mutation analysis for the phenylalanine hydroxylase gene and the clinical outcome of two Japanese patients with non-phenylketonuria (PKU) hyperphenylalaninemia (serum phenylalanine level below 600 mumol/l under a free diet) detected by a mass-screening program. Single strand conformation polynorphism analysis and direct sequencing of their genomic DNAs revealed that non-PKU hyperphenylalaninemia resulted from compound heterozygosity for a mutation causing classical PKU and a mutation with a milder effect on phenylalanine hydroxylase activity. The mutations were R241C and R243Q in exon 7, and R413P in exon 12. The mutation genotypes of the two patients were R241C/R243Q and R241C/R413P. It has been demonstrated that homozygosity for the R243Q or R413P mutation is associated with a severe phenotype of PKU and low in vitro expression activity. In contrast, the R241C mutation has much less effect on phenylalanine hydroxylase activity. The metabolic consequence of each variant allele was confirmed by a phenylalanine loading test in the patients and their parents. The patients achieved normal results in all intellectual and neurologic tests. Brain magnetic resonance imaging revealed no abnormalities. The dietary restriction was continued until 10 years of age in order to maintain the serum phenylalanine level below 400 mumol/l. The genetic analysis to distinguish non-PKU hyper-phenylalaninemia from classical PKU helps to determine the principles of dietary management in the early infantile period.

Adolescent↗
PubMed1998

A new evaluation of pancreatic function after pancreatoduodenectomy using secretin magnetic resonance cholangiopancreatography.

BACKGROUND: The remnant pancreatic function after pancreatoduodenectomy influences greatly postoperative quality of life. However, it has been difficult to evaluate the exocrine remnant pancreatic function postoperatively. The aim of this study was to assess the usefulness of secretin-stimulated magnetic resonance cholangiopancreatography (secretin MRCP) in evaluating the remnant pancreatic function and ascertaining the anastomotic patency after pancreatoduodenectomy. METHODS: Thirty-four patients who underwent pancreatoduodenectomy were evaluated with secretin MRCP. The results of MRCP were determined by the amount of exocrine pancreatic secretion, and were graded as follows: grade I (poor secretion), grade II (moderate secretion), and grade III (good secretion). RESULTS: Secretin MRCP could visualize the pancreatic secretion dynamically. MRCP grades were grade I in 11 patients, grade II in 12, and grade III in 11. There was a significant correlation between MRCP grade and glucose tolerance. We confirmed visually the patency of the anastomotic site in 24 patients (71%). MRCP grades correlated significantly with clinical symptoms. CONCLUSION: Our results demonstrated secretin MRCP was feasible for evaluating the remnant pancreatic function after pancreatoduodenectomy.

Adult↗
PubMed1998

Chromosome aberrations induced in mice by chronic feeding of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ).

Dietary intake of mutagenic compounds is considered to be an important factor for the induction of some human cancers. Highly mutagenic compounds are known to be formed in meat during the cooking process. Since the discovery of such compounds, many studies have been conducted to evaluate their carcinogenic potential. One of the most mutagenic compounds formed in the cooking of meat is 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). The recent development of mouse chromosome painting probes expand the capability of evaluating these food mutagens as potential clastogens in vivo. In this paper, we demonstrate the induction of chromosome aberrations in mice chronically exposed to MeIQ in their diet. CDF1 female mice were fed 400 ppm MeIQ beginning at 7 wk of age. At 76 wk of age, five control and eight exposed mice were euthanized. Blood and bone marrow cells were obtained and arrested in metaphase. Whole chromosome painting probes were used for fluorescence in situ hybridization of metaphase cells from blood and bone marrow. MeIQ-exposed mice were found to have a twofold increase in translocations and a 16-fold increase in fragments in their peripheral blood compared with controls. No aberrations were observed in the bone marrow. All organs were examined for the presence of tumours and routine histopathological analysis was performed on all organs as well as any tissue with macroscopic abnormalities. Forestomach and/or liver tumours developed in all but one of the mice fed MeIQ, but no such tumours were observed in the control mice. These data indicate that MeIQ is clastogenic and carcinogenic in vivo.

Animal Feed↗
PubMed1998

Formation of keto and hydroxy compounds of linoleic acid in submitochondrial particles of bovine heart.

To observe lipid peroxidation of additive-free submitochondrial particles, we incubated submitochondrial particles in the absence of exogenous irons and t-butyl hydroperoxide. After the incubation, the phospholipids were hydrolyzed by phopholipase A2, and the fatty acid constituents were analyzed by high-performance liquid chromatography, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry. Contrary to a commonly accepted theory, lipid peroxidation in the submitochondrial particles did not need the addition of NADH. In the phospholipid constituent fatty acids of the oxidized submitochondrial particles, derivatives of hydroperoxides of linoleic acid such as keto, hydroxy, trihydroxy, and hydroxyepoxy compounds were generated. Lipid peroxidation in the submitochondrial particles was not inhibited by the addition of catalase, superoxide dismutase, hydroxyl radical scavengers, or ethylenediaminetetraacetic acid, but was inhibited by the addition of KCN, antimycin-A, NADH, ubiquinol, deferoxamine mesylate, ascorbic acid, and alpha-tocopherol. The cardiolipin-cytochrome c lipid peroxidation system could mimic the lipid peroxidation of the submitochondrial particles, in terms of linoleic acid products and the inhibitory patterns of radical scavengers and electron transfer chain inhibitors. Thus, lipid peroxidation in the submitochondrial particles seems to be due to phospholipid-hemoprotein lipid peroxidation systems such as the cardiolipin-cytochrome c system.

Animals↗
PubMed1998

Denture mobility with six degrees of freedom during function.

The purpose of this study was (1) to assemble and verify a system to measure the three-dimensional (3-D) movement of the upper and lower complete dentures and the movement of the mandible simultaneously, and (2) to analyse the relation between denture movements and the path of closure of the mandible during function. A 3-D motion capture system with four infrared TV cameras was used for this purpose. The relation between the dentures and the mandibular movements was analysed through the change of the inner product of normal vectors of the denture occlusal planes and mandibular planes. The mandibular movements were classified into two types; the normal stroke (the path of closure was on the ipsilateral side of mastication) and the reverse stroke (on the contralateral side). The results showed that the system could measure the denture mobility within a 0.3 mm error. The mobility of the upper dentures had a correlation to the path of closure of the mandible regardless of the working side or nonworking side, and the lower dentures had a tendency to move toward the working side.

Aged↗