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Biomedical subjects

M Sekiguchi

Publications and source records attributed to M Sekiguchi.

At least 289 records · Page 16Linked to original sources
PubMed1994

[A case of lung metastasis from Meibomian gland carcinoma of eyelid with effective chemotherapy].

A 47-year-old man was admitted to Shinshu University Hospital in 1992 because of cough and chest abnormal shadow. In 1987, he had an operation for Meibomian gland carcinoma of his right lower eyelid, and also received radiotherapy. His chest X-ray film on admission showed tumor shadows in the bilateral upper lung fields. The chest CT scan showed tumors in the right S1 and the left S3. Bronchofiberscopic findings demonstrated stenosis of the right upper bronchus and an endobronchial mass occluding the left B3. A biopsy specimen of the endobronchial mass revealed sebaceous carcinoma, which was identical with that of the resected eyelid tumor. He received two courses of chemotherapy in a combination of CDDP 75 mg/m2 and ADM 50 mg/m2. The tumors on chest X-ray and CT scan became small by the chemotherapy. Bronchofiberscopy after the chemotherapy also revealed that the stenosis of the right upper bronchus improved and the endobronchial mass in the left B3 had disappeared. He died 8 months after initial chemotherapy with a response duration of 7 months.

Adenocarcinoma, Sebaceous↗
PubMed1994

[Cardiac sarcoidosis].

To analyze the clinical features of cardiac sarcoidosis, we reviewed case reports and clinical investigations from Japan and other countries. Female patients were more frequently affected in this disease in Japan. Cardiac sarcoidosis is characterized by a high incidence of complete atrioventricular block, right bundle branch block, and ventricular arrhythmias on the electrocardiogram. Echocardiography often reveals left ventricular dilatation with systolic dysfunction and wall thickening or thinning. Radionuclide testings, such as, thallium-201, gallium-67 or technetium-99m pyrophosphate, are useful for detecting cardiac involvement and evaluating efficacy of corticosteroid therapy in patients with sarcoidosis. Most of the patients died due to recurrent or refractory heart failure. It is noteworthy that cases of sudden death during stable cardiac function have become infrequent.

Cardiomyopathies↗
PubMed1994

[Capillary endothelial cells in sarcoidosis--electron microscopic findings].

The distribution of von Willebrand (vW) factor, thrombomodulin (TM) and fibronectin (FN) in the capillary endothelial cells of the lung of patients with sarcoidosis was investigated using their monoclonal or polyclonal antibodies. The vW factor showed strong reaction with exudation towards outside and irregular dilatation or occlusion in the capillary walls surrounded sarcoid granulomas and capillaries in the remote area. The area showing alveolitis disclosed also strong reaction with exudation by vW factor. TM having a anti-coagulating function showed a very low reactivity in the lung tissues with or without of granulomas in sarcoidosis at light microscopic level, but in electron microscopically, strong reaction and broad distribution in capillary endothelial cells, involving luminal occlusion and reaction in subendothelial region. FN showed new and many capillaries formation in the growing collagenous tissues between the old sarcoid granulomas suggesting neocapillarization originating from endothelial cells. These findings suggest that the capillary endothelial cells participate strongly in formal genesis of sarcoid granulomas.

Endothelium, Vascular↗
PubMed1994

[Clinicopathological study of 4 patients with idiopathic BOOP, interstitial type on chest X-ray].

We studied four patients with idiopathic Bronchiolitis Obliterans Organizing Pneumonia (BOOP) diagnosed by open lung biopsy. All of four presented with acute onset and a rapid course with progressive dyspnea. Their chest X-ray films showed ground-glass opacities with reduced volumes in the bilateral lower lobes. Their chest CT revealed marked increases in lung density with air bronchograms. Radiologically, it was difficult to distinguish these cases from patients with acute interstitial pneumonia. Histologically, in the uninflated specimens, the collapse of alveoli and alveolar spaces filled with foamy macrophages and proteinous exudates were observed. The organizing tissues were present predominantly in the alveolar ducts, but varied in extent among cases. We considered the reduced lung volumes on chest X-ray films and the marked increases in lung density on chest CT to reflect alveolar collapse. Proliferation of type II pneumocytes was remarkable in all cases, but reactivity to antisurfactant protein-A antibody staining was decreased in the collapsed alveoli. It was suggested that the alveolar collapse was caused, in part, by decreased pulmonary surfactant in addition to obstruction of the alveolar ducts. The rapid responses to of these patients corticosteroid therapy may be due to improvement of the alveolar collapse.

Adult↗
PubMed1994

An experimental transplantable osteosarcoma with spontaneous pulmonary metastasis in hamsters.

Animal models of osteosarcoma with spontaneous pulmonary metastasis which retain metastatic capacity and osteoid formation after serial passages have been reported infrequently. In this communication we describe some biological features of a transplantable osteosarcoma, Os515, induced by BK-virus in Syrian golden hamsters. The subcutaneously transplanted tumours in 2-week-old animals grew progressively until death, with a mean survival time of 32 days. Distant metastases occurred only in the lungs in all animals. The histological appearance was osteosarcoma of osteoblastic type. Enzyme-histochemical staining showed alkaline phosphatase activity in many cells and beta-glucuronidase activity in few cells. Tumours transplanted intramuscularly in the hind limbs were amputated radically at 5 or 11 days. A small number of animals died from lung metastases without local relapse during the observation period of 140 days after grafting. All the control hamsters bearing unamputated tumours died much earlier. Necropsy revealed large metastatic nodules in the lungs of limb-amputated animals and small diffuse nodules in the lungs of untreated control animals. The development of lung metastases was monitored by soft X-ray without sacrificing the animals. This model will be useful in studies of mechanisms of metastasis and for the experimental treatment of osteosarcoma.

Animals↗
PubMed1993

Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis.

8-Oxoguanine (8-oxo-7, 8-dihydroguanine) is produced in DNA, as well as in nucleotide pools of cells, by active oxygen species normally formed during cellular metabolic processes. 8-Oxoguanine nucleotide can pair with cytosine and adenine nucleotides at almost equal efficiencies, and transversion mutation ensues. Human cells contain enzyme activity, which hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, and this enzyme is responsible for preventing misincorporation of 8-oxoguanine into DNA. We purified this particular human enzyme to physical homogeneity and determined a partial amino acid sequence. We then cloned the cDNA for human 8-oxo-dGTPase and examined its nucleotide sequence. The human protein comprises 156 amino acid residues and has some sequence homology with the Escherichia coli MutT protein, which has a distinct 8-oxo-dGTPase activity. When the human cDNA was expressed in E. coli mutT- mutant cells, there was a significant amount of 8-oxo-dGTPase activity. In such cells, the frequency of spontaneous mutation was greatly reduced. We propose that the human 8-oxo-dGTPase protects genetic information from the untoward effects of endogenous oxygen radicals.

Amino Acid Sequence↗
PubMed1993

Abnormal distribution of acetylcholinesterase activity in the hippocampal formation of the dreher mutant mouse.

The distribution of acetylcholinesterase(AChE) in the hippocampal formation of the dreher mutant mouse was studied by comparing homozygous mutant (drsst-J/drsst-J) with littermate control (+/? or +/+). In the control mice, AChE activity was most intense in the inner one-third of the stratum oriens and lacnosum of the hippocampus, and in the inner one-fifth of the molecular layer of the dentate gyrus. In contrast, in homozygous dreher mice, AChE activity in area CA3c of the hippocampus was not restricted to the stratum oriens, and extended upward into the infrapyramidal and suprapyramidal mossy fiber layers, the lower part of the stratum radiatum, the pyramidal cell layer, and downward toward the alveus. In addition, the distribution of AChE activity was modified by accompanying with ectopic pyramidal cells or with disruption of the pyramidal cell layer. AChE activity in the dentate gyrus of the dreher mouse was not confined to the inner one-fifth of the molecular layer. These findings indicated that the cholinergic input to the hippocampal formation is not normal in the dreher mutant mouse. Since the areas of AChE activity correspond to the presence of ectopic pyramidal cells in the dreher mouse, incoming cholinergic fibers may form synapses with these ectopic cells and with the dendrites of normal pyramidal cells that extend into the expanded area of AChE activity.

Acetylcholinesterase↗
PubMed1993

O6-methylguanine-DNA methyltransferase protects against nitrosamine-induced hepatocarcinogenesis.

We previously generated transgenic C3H/HeN mice by introducing the Escherichia coli O6-methylguanine-DNA methyltransferase (MGMT, DNA-O6-methylguanine:protein-L-cysteine S-methyltransferase, EC2.1.1.63) gene, ada, attached to the Chinese hamster metallothionein I gene promoter. One transgenic mouse line expressing both ada-specific mRNA and Ada protein could be propagated over many generations in a homozygous state with respect to the integrated DNA. Liver extracts from transgenic homozygous mice have consistently demonstrated about 3 times the control activity of normal mice. Furthermore, in the transgenic homozygotes treated with ZnSO4, activity is increased to 6-8 times the normal level in mice and is equivalent to that for man. To examine whether these increased levels of MGMT activity can actually decrease the susceptibility of animals to N-nitroso compounds, we studied liver carcinogenesis in our transgenic mice expressing high amounts of MGMT. Groups of transgenic and nontransgenic mice, each comprising about 200 suckling animals (14 +/- 1 days old), were divided each into eight subgroups, providing paired groups of transgenic and nontransgenic mice. They received an i.p. injection of ZnSO4 to induce MGMT, and 10 hr thereafter were given an i.p. injection of either dimethylnitrosamine or diethylnitrosamine. Liver tumor development was quantitatively assessed at 7-11 months. Here, we report statistically significant reduction of tumor formation in transgenic mice of four of the six paired groups that received treatment. The remaining two demonstrated results in line with dose dependence. Therefore, our data indicate that MGMT can indeed protect animals from low-dose exposure to environmental alkylating carcinogens.

Animals↗
PubMed1993

Folding topology and DNA binding of the N-terminal fragment of Ada protein.

Three amino terminal fragments of Escherichia coli Ada protein (39 kDa) with different molecular masses (14 kDa, 16 kDa and 20 kDa) were prepared in large quantities from an E. coli strain harboring plasmids constructed for the overproduction of the truncated proteins. The three fragments can be methylated to an extent similar to that of the intact molecule. The methylated 16 kDa fragment specifically binds to the ada box on a DNA duplex. NMR analyses revealed that the 14 kDa fragment comprises two alpha-helices and a beta-sheet with parallel and anti-parallel mixed strands. A comparison of the 15N-1H HMQC spectra of the fragments has led to the conclusion that this tertiary structure within the 14 kDa fragment is retained in the larger 16 kDa and 20 kDa fragments.

Amino Acid Sequence↗
PubMed1993

Effects of continuous infusion of nitroglycerin on pulmonary hemodynamics, lung lymph balance, and prostanoid products in the response to endotoxin in awake sheep.

We examined the effects of continuous intravenous infusion of nitroglycerin (NTG) on lung dysfunction induced by endotoxemia in awake sheep chronically instrumented with lung lymph fistula. We measured the responses of hemodynamics, lung lymph balance, and thromboxane (Tx)B2 and 6-keto-prostaglandin (PG) F1 alpha levels in plasma and lung lymph to endotoxin administration (1 microgram/kg, intravenously [IV], over 30 min) with and without continuous infusion of NTG (1 microgram/kg/min). Continuous infusion of NTG alone (n = 5) over 5 hr did not significantly alter systemic, pulmonary hemodynamics, and/or lung lymph fluid filtration. Infusion of endotoxin alone (n = 7) caused remarkable increases in pulmonary artery pressure (Ppa) and lung lymph flow (Qlym) in the early phase. Continuous infusion of NTG (n = 6) significantly prevented the early increases in Ppa and Qlym after endotoxin. The increased values of TxB2 and 6-keto-PGF1 alpha in both plasma and lung lymph after endotoxemia showed the same increases in groups with and without NTG. These findings suggest that the reduction of pulmonary artery pressure induced by NTG decreased the filtration of fluid into the lungs associated with endotoxemia in sheep, and that the mechanism of vasodilating action of NTG is not due to modifications of constrictive-dilated cyclo-oxygenase products of arachidonate, such as TxA2 and PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Characteristics of specific 125I-omega-conotoxin GVIA binding in rat whole brain.

Characteristics of specific 125I-omega-conotoxin (omega-CgTX) binding were systematically investigated in crude membranes from rat whole brain. Kd and Bmax Values for the binding were 49.7 pM and 181.5 fmol/mg of protein, respectively. The effects of various types of Ca channel antagonists on the binding were investigated. Dynorphin A (1-13), in particular, specifically inhibited 125I-omega-CgTX binding, but not that of [3H](+)PN200-110. Spider venom from Plectreurys tristes did not specifically inhibit specific binding of 125I-omega-CgTX, because the venom also inhibited the binding of [3H](+)PN200-110 to a similar degree. The amount of specific binding of 125I-omega-CgTX was less in the cerebellum than that in any other area of whole brain. The cross-linker disuccinimidyl suberate did not label with 125I-omega-CgTX and its binding sites in rat whole brain, although it did in chick whole brain, which was used as a positive control. These findings suggested that dynorphine A (1-13) was a selective blocker of omega-CgTX-sensitive Ca channels in crude membranes from rat whole brain and that omega-CgTX-sensitive Ca channels were mainly present a rat brain except cerebellum.

Animals↗
PubMed1993

Differential production of interleukin 6 in human osteosarcoma cells and the possible effects on neoplastic bone metabolism.

Interleukin 6 (IL-6) exerts well-established effects on cells of the immune system as well as on various other cell types. We have investigated the effects of IL-6 produced by human osteosarcoma cells on tumor cells from two clonal human osteosarcoma cell lines, KSU.C3 and NOS-1.C8. We were unable to identify any effects of IL-6 such as cell proliferation, alkaline phosphatase activity, osteocalcin production, or collagen synthesis on the bone-forming phenotypes. However, the KSU.C3 cell line, which showed a little osteoid and no bone formation and was accompanied by a few osteoclasts in the xenografted tumors, produced high levels of IL-6, the production of which was quickly and easily stimulated by various agents. On the other hand, the NOS-1.C8 cell line, which formed abundant osteoid or bone and was accompanied by no osteoclasts in the xenografted tumors, produced no detectable levels of IL-6 without stimulation, and the production of IL-6 in response to IL-1 beta was slower. Our data suggest that IL-6 produced by osteosarcoma cells does not play an important role in bone formation, but may mediate osteoclastic bone resorption.

Alkaline Phosphatase↗
PubMed1993

Body surface potential maps in patients with familial amyloid polyneuropathy.

The purpose of this study was to evaluate the characteristics of body surface potential maps in patients with cardiac amyloidosis. The study population consisted of 30 patients with familial amyloid polyneuropathy and 50 age-matched normal volunteers. The patients were classified into one of the following three stages: stage I, peripheral neuropathy limited to the lower limbs; stage II, neuropathy involving both the lower and upper limbs; and stage III, bedridden because of extensive progressive neuropathy. Electrodes for the body surface potential maps were placed at 87 points (59 anterior and 28 posterior) on the chest. To analyze these body surface electrocardiograms, isopotential maps, isochrone maps, and isointegral maps were used. The mean values of the positive potential were significantly lower in the advanced stage (1.9 +/- 0.2 mV in stage I, 1.0 +/- 0.2 mV in stage II, and 0.7 +/- 0.2 mV in stage III). Prolongation of ventricular activation time was observed on the anterior and lateral chest. The mean QRST isointegral maps of the patients in the advanced stage of cardiac amyloidosis showed a large negative area over the anterior and left lateral chest, the positive areas were small and their potentials were very low. In addition, 18 (60%) of the 30 patients had a multipolar pattern in the QRST isointegral maps. The changes of the body surface potential maps correlated with clinical staging and echocardiographic findings.

Adult↗
PubMed1993

Organization and expression of the human gene for O6-methylguanine-DNA methyltransferase.

O6-Methylguanine-DNA methyltransferase plays an important role in cellular defence against mutagens and carcinogens with alkylating activity. Certain tumor-derived cell lines, termed Mer-, are defective in the enzyme activity and have an increased sensitivity to alkylating agents. We cloned the genomic sequence coding for the human O6-methylguanine-DNA methyltransferase and elucidated the structure. The gene consisted of 5 exons and spanned more than 170 kb, while mRNA for the enzyme was 950 nucleotides long. No or only little mRNA for the enzyme was formed in Mer- cells, though there was no gross difference in the coding and promoter regions of the gene between Mer+ and Mer- cells. The putative promoter region, derived from Mer+ cells, was placed upstream of the chloramphenicol acetyltransferase reporter gene and the constructs were introduced into Mer+ and Mer- cells. In Mer- cells, a lowered level of transient expression of the gene was observed as compared with Mer+ cells, but this difference alone does not account for the in vivo difference of expression of the gene in the two types of cells; there might be difference in cis-acting elements. The DNA sequence in the 5' upstream region of the gene was extremely GC-rich and there were no consensus sequences, such as the TATA and CAAT boxes. There were lower levels of methylation in the putative promoter of various Mer- cells, as compared with findings in Mer+ cells. Methylation in this region may be involved in regulating expression of the gene.

Base Sequence↗