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Biomedical subjects

T Imamura

Publications and source records attributed to T Imamura.

At least 415 records · Page 23Linked to original sources

Possible association of p53 overexpression and mutation with high-grade chondrosarcoma.

Overexpression and point mutation of the p53 protein/gene was investigated in a series of chondrosarcoma by an immunohistochemical approach, and direct sequencing of the genomic DNA, respectively. In 2 of the 16 cases studied, both of which were high grade chondrosarcomas (grade III), immunodetectable p53 was identified. Histologically, one was ordinary type and the other a clear cell variant. However, no positivity was observed in the other cases including nine of low grade, ordinary type, three of low grade, clear cell type, and two of extraskeletal myxoid chondrosarcoma. Direct sequencing, following polymerase chain reaction amplification of exons 5-9 of the p53 gene in 14 cases, in which fresh materials were available, successfully demonstrated base substitution mutations in only two cases with detectable p53 overexpression on immunohistochemistry. Their details were GTC (valine) to TTC (phenylalanine) at codon 157 in exon 5, and CGT (arginine) to CAT (histidine) at codon 273 in exon 8. No mutation was detected in the other 12 cases which were negative for p53 immunostaining. These findings strongly suggest that p53 mutation plays a crucial role in the biologically aggressive subtype, and possibly in the process of tumor progression in human chondrosarcoma.

Adult↗

[The significance of preoperative chemotherapy for thermopreservation of limbs].

Preoperative chemotherapeutic effects on 42 osteosarcomas treated with CDDP intra-arterial infusion protocol were compared with the effects of treatment of same by local perfusion only, following administration of adriamycin (ADR) or high doses methotrexate and leucovorin (HD-MTX). Thirteen cases were further given local hyperthermic perfusion (LHP) treatment. The preoperative local treatment resulted in a poor response in cases in which the serum ALP failed to fall down the normal range, those with angiographically demonstrated tumor stains remaining, and those with reactive zones remaining as indicated by T2 MR imaging. The ratios of necrotic areas were significantly higher in the LHP group, while those of viable areas were significantly lower in the LHP group compared to other groups. Total tumor cell killing was possible in six of 13 cases in the LHP group. Post-necrotic fibrosis and post-necrotic osteosclerosis were significantly higher in the LPH group. The results suggested that, in selected cases treated with LHP, conservative surgery may well be possible so as to preserve all functional activity.

Adolescent↗

Thrombin generates monocyte chemotactic activity from complement factor H.

We have recently found that the complement factor H (H) was the precursor of the major macrophage chemotactic factor in the delayed-type hypersensitivity (DTH) reaction site in the skin and was converted to the factor by an unidentified trypsin-like protease in plasma. Thrombin and plasmin are also present in the site, and we, therefore, examined the possibility that these proteases converted H to be monocyte chemotactic. Intact H caused no monocyte migration, although it was able to do so after incubation with thrombin, but not with plasmin. The activity was chemotactic rather than chemokinetic and was absorbed by an anti-H IgG-conjugated column. The generation of monocyte chemotactic activity from H was dependent on incubation time with thrombin and also the protease activity of thrombin, and the activity was seen at concentrations of H lower than 10(-8) M. The inhibitory activity of H for C3b-Bb was not affected by incubation with thrombin or plasmin. Incubation of H with thrombin, but not with plasmin, generated a hydrophobic molecule, in a time-dependent manner, which had monocyte chemotactic activity. These results show that H becomes a monocyte chemotactic factor due to cleavage by thrombin, which converts H to a more hydrophobic molecule and also suggest that thrombin-treated H induces monocyte migration in the DTH reaction site.

Chemotaxis, Leukocyte↗

[Distal myopathy with rimmed vacuoles and sudden death--report of two siblings].

We describe two siblings with distal myopathy with rimmed vacuoles, who died suddenly presumably due to fatal arrhythmia. Case 1. A 26-year-old man with a 4 year-history of progressive muscle weakness and wasting was hospitalized in April, 1989. The family history showed that his younger brother had the same disease, but his parents, not consanguineous, and other family members had no neuromuscular diseases. On admission, neurologic examination showed muscle weakness and atrophy in the distal portions of four extremities. No myotonia or fasciculation was present. The deep tendon reflexes were absent except diminished bilateral PTR. Sensation and co-ordination were normal. The creatinine kinase (CK) level was moderately elevated to 691 IU/l, and the aldolase mildly to 6.9 IU/l. Normal laboratory values included serum electrolytes, glucose and thyroid function study. An ischemic forearm exercise test revealed a normal rise in serum lactate and pyruvate concentrations. The glucose response after glucagon was normal in the fasting state. An electrocardiogram and chest film were normal. An electromyogram revealed myopathic changes with mild neuropathic changes, including positive sharp waves and fibrillation potentials at rest. The muscle biopsy specimen from the left anterior tibial muscle showed scattered fibers with rimmed vacuoles and moderate variation in fiber size. Neither fiber necrosis nor inflammatory cellular infiltration was seen. Regenerating fiber was not present. An electron microscopic examination showed numerous lamellar bodies of various size. Nerve biopsy was normal. He was diagnosed as having distal myopathy with rimmed vacuoles. Muscle weakness progressed gradually over the next two years, but his general condition was good. He asked to receive the corticosteroid therapy, and rehospitalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[A case of obstructive sleep apnea syndrome with increased lung water during sleep].

A 22-year-old man was admitted to the department of plastic surgery in our university with diagnosis of ankylosis and microgeniea. His complaints were snoring and somnolence in the daytime, so we performed a Respigraph (Chest) that showed obstructive apnea during sleep. We diagnosed obstructive sleep apnea syndrome. So we observed pulmonary circulation and measured lung water using the double indicator dilution method (Nihon Koden, MTV-1100) during sleep. During the period of apnea, arterial oxygen pressure and mixed venous saturation decreased, reversely, mean pulmonary arterial pressure rose, lung water (ETV) and central blood volume increased. We considered that the increase of lung water during sleep apnea is caused by hemodynamic change due to hypoxia and increase of venous return. After operation, the value of blood gas assay and apnea index were improved.

Adult↗

[Natural course of asymptomatic gallstone disease].

Of 1850 patients with cholelithiasis diagnosed in the past 17 years, 1116 female and 734 male, 598 patients (32.3%) presented with one or more of three major symptoms, i.e., abdominal pain, fever and jaundice, whereas the remainder (67.7%) had none of these symptoms. The proportion of the asymptomatic patients was similar in all age groups, being around 70%. Only 20 per cent of 680 asymptomatic patients, followed for 10 to 17 years (median 13.3 years), developed biliary symptoms. Older patients over 70 years of age had a higher rate of change to the symptomatic group, as compared with younger patients under 70, 29.5% vs. 19.3%, respectively. During this period, carcinoma of the gallbladder developed in one of the asymptomatic patients (0.1%). Oral dissolution therapy was successful in only 4.2 per cent of attempted cases and associated with a recurrence rate of as high as 20%. We conclude that asymptomatic gallstone patients should only be followed up by ultrasound twice a year without any treatment.

Adult↗

[A graphic presentation of the anesthesiologist's action pattern].

The action patterns of anesthesiologists are different among individuals. We have developed a graphic presentation system for anesthesiologists' action patterns using computer graphics. The resulting representation is called "thought map". Data were obtained from 6 anesthesiologists (4 certified instructors and 2 new doctors) with a time interval of 2 years, regarding the use of 3 drugs (enflurane, sevoflurane and isoflurane). The "maps" were compared among individuals, dates and drugs. The following results were obtained: 1) significant differences existed among individuals, 2) during the 2-year time interval, 2 new drugs were introduced and the practice pattern alterations were seen in the maps, 3) for the 2 new anesthesiologists, the maps show the process of professional knowledge acquisition. We propose an index ("immovable rate"), denoting the proportion of the map where concentration of the drug didn't change. This index is to be used for evaluating human thinking.

Anesthesia, Inhalation↗

Flow cytometric analysis of nuclear DNA content of duct cell carcinoma of the pancreas.

BACKGROUND: This study was designed to evaluate the efficacy of nuclear DNA content analysis in determining the prognosis of carcinoma of the pancreas. METHODS: Resected and paraffin-embedded specimens from 72 patients with duct cell carcinoma of the pancreas were examined, and flow cytometry was used to explore the relationship between DNA ploidy and TNM classification or histologic grade. RESULTS: DNA aneuploidy was found histologically in 42.9%, 56.8%, and 71.4% of Grade 1, 2, and 3 tumors, respectively. DNA ploidy showed a statistically significant correlation with T category and retroperitoneal invasion. The cumulative survival rate of patients with retroperitoneal invasion was shorter than that of those without retroperitoneal invasion. Among the patients with retroperitoneal invasion, those with DNA aneuploidy had a significantly shorter survival time than did those with DNA diploidy. CONCLUSIONS: The DNA ploidy pattern, in combination with the presence or absence of retroperitoneal invasion, appears to be useful in predicting the prognosis for duct cell adenocarcinoma of the pancreas.

Adult↗

A new biological activity of the complement factor H: identification of the precursor of the major macrophage-chemotactic factor in delayed hypersensitivity reaction sites of guinea pigs.

The guinea pig complement factor H(FH) and the plasma precursor(PMCFS-1) of the major monocyte-chemotactic factor(MCFS-1) found in the skin site of delayed hypersensitivity reaction(DHR) induced in the guinea pigs were compared in the antigenicity and the function. Both anti-FH-IgG and anti-MCFS-1-IgG formed a single precipitation line against FH, PMCFS-1, MCFS-1 and guinea pig plasma, and these lines fused one another without any spur formation. The inhibition activity of FH for C3bBb was absorbed by anti-MCFS-1-F(ab')2 in a dose-dependent manner. PMCFS-1 inhibited C3bBb activity dose-dependently as FH. These results show that FH is identical to PMCFS-1 and imply that FH, converted to MCFS-1 plays as a monocyte-chemotactic factor in the site of DHR.

Animals↗

Chromosomal deletions and K-ras gene mutations in human endometrial carcinomas.

Forty-two endometrial carcinomas of various stages of progression were analyzed to search for loss of chromosomal regions and for point mutations of ras genes and amplification of Int-2 gene. This approach is particularly favorable for observation of genetic events and their significance in the process of neoplastic conversion by considering the clinico-pathological characteristics of each tumor. At least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K-ras gene, are implicated in the development of endometrial carcinomas. Likely targets for allelic losses on chromosomes 18q and 17p are the DCC gene and the p53 gene sequences, respectively. Overall numbers of allelic losses in individual tumors appeared to increase in case of advanced stage tumors, thereby indicating the association of allelic loss accumulation with tumor progression. The genetic features seen in 2 juvenile-type adenocarcinomas and 2 clear-cell carcinomas suggested the possibility that etiological factors providing selective pressure for particular mutation sub-sets during carcinogenesis are probably heterogeneous.

Adult↗

Identification of a heparin-binding growth factor-1 nuclear translocation sequence by deletion mutation analysis.

We have shown previously that a deletion mutant of human heparin-binding growth factor (HBGF)-1, HBGF-1U, lacking the sequence Asn-Tyr-Lys-Lys-Pro-Lys-Leu is capable of initiating c-fos mRNA expression and polypeptide phosphorylation on tyrosine residues at concentrations that do not induce either DNA synthesis or cell proliferation (1). The fact that addition of the nuclear translocation signal from the yeast histone 2B protein to the HBGF-1U mutant caused reconstitution of the biological activity of HBGF-1 indicated that nuclear translocation may be an important component of the mitogenic signal induced by HBGF-1. In order to examine the nuclear translocation potential of HBGF-1 alpha, the deletion mutant HBGF-1U, and the yeast histone 2B-HBGF-1 chimera, HBGF-1U2, we expressed these forms of HBGF-1 in murine endothelial cells. Western blot and two-dimensional Western blot analysis of cytosol and nuclei demonstrate that although the three forms of HBGF-1 are readily detectable in the cytosol of the individual transfectants, HBGF-1 alpha and HBGF-1U2 but not HBGF-1U was detected in the nucleus. Furthermore, murine endothelial cells expressing HBGF-1 alpha and HBGF-1U2 exhibited an atypical cellular phenotype in vitro that was absent in the HBGF-1U transfectants. These data suggest that HBGF-1 contains a functional nuclear translocation sequence that may be responsible for the initiation of DNA synthesis, and these data further correlate the presence of the nuclear translocation sequence with an abnormal endothelial cell phenotype in vitro.

Animals↗

Effect of 3-hour pancreatic duct obstruction on pancreatic lysosomal and digestive enzymes in rabbits.

We studied the effect of short-term (3 hours) pancreatic duct obstruction (PDO) on the exocrine pancreas and on the secretion of lysosomal enzymes into the pancreatic juice of rabbits during stimulation by pancreatic secretagogues. The following evaluations were made: serum amylase levels, pancreatic water content, pancreatic amylase, trypsinogen and cathepsin B content, and output of pancreatic enzymes and lysosomal hydrolases when stimulated by secretin and caerulein as well as the distribution of cathepsin B in subcellular fraction. PDO for 3 hours plus secretin infusion caused a significant rise in serum amylase levels, pancreatic water content, and pancreatic amylase and trypsinogen content due to congestion of digestive enzymes during PDO. There was also a redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. In normal rabbits and in those with only secretin infusion, caerulein stimulated the secretion of cathepsin B, into pancreatic juice. Just after PDO, the secretion of cathepsin B, amylase and trypsinogen significantly decreased. By 24 hours after PDO, the output of cathepsin B stimulated by caerulein and secretin had increased significantly. Amylase and trypsinogen output were also significantly increased at this stage, in both the secretin and caerulein fractions. These results indicate that the secretion of lysosomal enzymes into pancreatic juice is stimulated by gut hormones, such as caerulein, in the normal physiological state and in pathological states, such as PDO. These results also show augmented secretion of both lysosomal enzymes and pancreatic digestive enzymes in the recovery stage after PDO and their important roles at this stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗

Capsaicin-sensitive nonadrenergic and noncholinergic depressor response to spinal cord stimulation in the pithed rat.

The effects of capsaicin on nonadrenergic, noncholinergic depressor responses to spinal cord stimulation were studied in pithed rats. Mean blood pressure (MBP was maintained at a level of 100 mmHg by continuous infusion of methoxamine and hexamethonium to block autonomic outflow. Electrical stimulation of the lower thoracic region (T9-12) via a pithing rod produced a frequency (1-8 Hz)-dependent fall in elevated MBP. The depressor response was abolished by tetrodotoxin, whereas atropine, propranolol, and cimetidine plus pyrilamine did not affect the response. Capsaicin treatment abolished the depressor response. These results suggest that spinal cord stimulation causes neurogenic vasodilation which is mediated by capsaicin-sensitive nonadrenergic and noncholinergic vasodilator nerves.

Animals↗

The major plasma kallikrein inhibitor of guinea pig plasma.

A plasma kallikrein inhibitor in guinea pig plasma (KIP) was purified to homogeneity. KIP is a single chain protein and the apparent molecular weight is estimated to be 59,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In amino acid composition, KIP is similar to human and mouse alpha 1-proteinase inhibitors and mouse contrapsin. KIP forms an equimolar complex with plasma kallikrein in a dose- and time-dependent fashion. The association rate constants for the inhibition of guinea pig plasma kallikrein by KIP, alpha 2-macroglobulin, C1-inactivator and antithrombin III were 2.5 +/- 0.3.10(4), 2.4 +/- 0.4.10(4), 6.6 +/- 0.5.10(4) and 9.1 +/- 0.6.10(2), respectively. Comparison of the association rate constants and the normal plasma concentrations of the four inhibitors demonstrates that KIP is ten-times as effective as alpha 2-MG and other two inhibitors are marginally effective in the inhibition of kallikrein. KIP inhibits trypsin and elastase rapidly, and thrombin and plasmin slowly, but is inactive for chymotrypsin and gland kallikrein. These results suggest that KIP is the major kallikrein inhibitor in guinea pig plasma and the proteinase inhibitory spectrum is unique to KIP in spite of the molecular similarity to alpha 1-proteinase inhibitor.

Amino Acids↗

A clinicopathological and immunohistochemical study of osteofibrous dysplasia, differentiated adamantinoma, and adamantinoma of long bones.

A clinicopathological and immunohistochemical study of 12 cases of osteofibrous dysplasia (OFD), two cases of differentiated adamantinoma, and five cases of adamantinoma of long bones is presented. Although OFD and differentiated adamantinoma showed similar radiologic findings, differentiated adamantinoma was more likely to be a recurrent lesion than osteofibrous dysplasia and seemed to require a more extensive surgical procedure. Immunohistochemically, cytokeratin- and vimentin-positive cells were seen in both OFD and differentiated adamantinoma. The positive cells were scattered in the former, and were both scattered and nest-like in the latter. Both these lesions, however, were negative for epithelial membrane antigen. Excluding two cases of Ewing-like adamantinoma, the other three cases of adamantinoma were also positive for cytokeratin and vimentin. These results suggest that these three lesions share the same histogenetic origin. The two cases of Ewing-like adamantinoma differ from tibial adamantinoma in their radiological, histological and immunohistochemical aspects, and seem to constitute a distinct variant of adamantinoma with a different histogenesis.

Adolescent↗

Beta-thalassemia major resulting from a compound heterozygosity for the beta-globin gene mutation: further evidence for multiple origin and migration of the thalassemia gene.

We describe in a Japanese family beta zero-thalassemia resulting from a compound heterozygosity for a beta-globin gene mutation. One mutation is a C-to-T transition at IVS-2 nucleotide position 654 on the background of Mediterranean haplotype IX. Another mutation is a G-to-A transition at IVS-2 nucleotide position 1, associated with a novel haplotype XI. The occurrence of these mutations on various chromosomal backgrounds provides strong evidence for an interplay of gene migration, interallelic gene conversion, and multiple origins of the same mutation.

Adult↗