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Biomedical subjects

T Matsumoto

Publications and source records attributed to T Matsumoto.

At least 19 recordsLinked to original sources
PubMed1992

[Abnormal chest shadow on CT in immunosuppressed patients].

An abnormal chest shadow was observed on CT scans in 25 cases of 23 immunosuppressed patients. Pulmonary disease was pathologically confirmed to be pneumocystis carinii pneumonia (PC pneumonia) in four patients, cytomegalovirus pneumonia (CMV pneumonia) in one, bacterial pneumonia in seven, fungal infection in three, miliary tuberculosis in one, leukemic infiltration in two, lymphangitis carcinomatosa in three, drug-induced pneumonitis in three, and ARDS in one. In almost all patients, especially those with infectious diseases such as PC pneumonia, CMV pneumonia, and bacterial pneumonia, the abnormal shadow was wide and visible in the bilateral lung fields. We presumed that such findings as lobular shadow, centrilobular shadow, and mosaic pattern reflected the extension of disease via the respiratory tract, and that those findings are typical of infectious diseases. Because such findings as abnormal linear shadow and swelling of a broncho-vascular bundle were very frequently recognized in patients with lymphangitis carcinomatosa and frequently recognized in those with drug-induced pneumonitis, these diseases may be distinguished from other diseases. An area of slightly increased density was frequently recognized in patients with PC pneumonia, bacterial pneumonia, and drug-induced pneumonitis. Such lesions were pathologically confirmed to be located in the interstitium and/or alveolus. CT was extremely useful in comprehending the character and extension of particular diseases among various diseases. As the number of patients studied was small, the utility of CT in immunosuppressed patients requires further investigation in a larger number of patients.

Adolescent↗
PubMed1992

Endotoxin transduces Ca2+ signaling via platelet-activating factor receptor.

Lipopolysaccharide (LPS) is a pathogenic substance causing severe multiple organ failures and high mortality. Although several LPS binding proteins have been identified, the molecular mechanism underlying the LPS signaling pathway still remains obscure. We have found that the LPS-induced Ca2+ increase in platelets and platelet aggregation is blocked by selective platelet-activating factor (PAF) receptor antagonists, thus suggesting a cross-talk between LPS and the PAF receptor. Next, we confirmed this hypothesis using the cloned PAF receptors [(1991) Nature 349, 342-346; (1991) J. Biol. Chem. 266, 20400-20405] expressed in Xenopus oocytes and Chinese hamster ovary (CHO) cells. In both systems, cells responded to LPS only when PAF receptors were expressed, and specific PAF binding was successfully displaced and reversibly dissociated by LPS. PAF receptor activation by LPS may represent a novel important pathway in the pathogenesis of circulatory collapse and systemic thrombosis caused by endotoxin.

Animals↗
PubMed1992

Trace levels of pyrroloquinoline quinone in human and rat samples detected by gas chromatography/mass spectrometry.

A detailed procedure for the assay of free pyrroloquinoline quinone (PQQ) in human and rat samples by gas chromatography/mass spectrometry (GC/MS) has been established with stable-isotopic PQQ as internal standard. PQQ was extracted from the samples, after addition of the internal standard, with butanol under acid conditions and with Sep-Pak C18 cartridges. After derivatization of PQQ with phenyltrimethylammonium hydroxide, molecular peaks at m/z 448 and 462 were used for detection of PQQ and [U-13C]PQQ by selected ion monitoring, respectively. Trace amounts of free PQQ were detected in eight organs, plasma and urine of the human, and in three organs of the rat. The PQQ level was highest in the human spleen (5.9 +/- 3.4 ng/g tissue, followed by the pancreas and lung, and it was below detection limits for human brain and heart. Trace levels of PQQ were also found in rat small intestine, liver and testis. Our data are far below those measured by the redox cycling method of Gallop's group for human plasma, adrenal and urine.

Animals↗
PubMed1992

Effect of a dihydropyridine analogue, 2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo- 1,3,2-dioxaphosphorinan-2-yl)-1-(2-morpholinoethyl)-4-(3-nitrophenyl)-3 -pyridinecarboxylate on reversing in vivo resistance of tumor cells to adriamycin.

A newly synthesized dihydropyridine analogue, 2-[benzyl(phenyl)-amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2-yl)-1- (2-morpholinoethyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate (PAK-200), at 5 microM inhibited the efflux of [3H]vincristine from KB-C2 cells and increased the accumulation of [3H]vincristine in KB-C2 cells to a level similar to that in KB-3-1 cells. PAK-200 inhibited the photoaffinity labeling of P-glycoprotein in KB-C2 membranes by [3H]azidopine. At 5 microM, PAK-200 enhanced the cytotoxic effect of Adriamycin on drug-sensitive KB-3-1 cells, multidrug-resistant KB-8-5 cells, and two human colorectal carcinoma tumor lines, COK-28LN and COK-36LN, by factors of 2, 5, 2, and 3 times, respectively. The calcium antagonistic activity of PAK-200 was about 1000 and 5 times lower than that of another dihydropyridine analogue, nicardipine, and of verapamil, respectively. PAK-200 in combination with Adriamycin completely suppressed the growth of KB-3-1 and COK-36LN and partially suppressed the growth of KB-8-5 but had no significant effect on COK-28LN cells xenografted in nude mice. The level of MDR1 expression of COK-36LN was about 3 times higher than that of COK-28LN, but lower than that of KB-8-5 cells. These results suggest that the interaction of PAK-200 with P-glycoprotein may be partly correlated with the enhancement of the antitumor effect of Adriamycin on xenografted KB-8-5 and COK-36LN cells in nude mice.

Animals↗
PubMed1992

Synthesis and antiulcer activity of N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with a potent mucosal protective activity.

As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal protective activities. A QSAR study showed that the most favorable N-substituents were electron-donating straight-chain alkyl groups of short length such as ethyl group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were selected as candidates for further study.

Animals↗
PubMed1992

[Cell differentiation and vitamin D].

After the discovery of the effect of vitamin D on cell differentiation by Abe, Suda and their colleagues, it has become clear that many of the vitamin D actions are mediated by their effect on terminal differentiation of various cells. Similarly important are the findings that the vitamin D receptors are almost ubiquitously distributed in various tissues, and the active metabolite of vitamin D exerts its effects in almost all types of cells. Thus, the actions of vitamin D are not confined to their classical target tissues that regulate calcium metabolism, but also are extended to the regulation of the proliferation and differentiation of various cells such as immunoregulatory cells, epidermal cells and malignant tumor cells. These discoveries have created a new era in the field of vitamin D endocrinology, and led to the development of vitamin D analogues that exert their effects mostly in the nonclassical target tissues with little effects on calcium metabolism. Efforts are currently under way to apply these analogues to the treatment of various disturbances such as immunological disorders, skin lesions and malignant tumors. This review briefly summarizes the current understandings on the effect of vitamin D on cell differentiation and proliferation, and discusses the future prospects of the application of these effects on the treatment of various disorders.

Animals↗
PubMed1992

[Potential usefulness of computer-aided diagnosis (CAD) in a mass survey for lung cancer using photo-fluorographic films].

We investigated the potential usefulness of computer-aided diagnosis (CAD) in a mass survey for lung cancer. When the sensitivity of the computer output was adjusted nearly equal to that of the mass survey in our database which contained 198 photofluorographic films, some shadows detected by the computer output were different from those detected by human observers. Therefore, the best estimated sensitivity of an observer using the computer output was equal to or greater than the sensitivity of double reading. It is expected that CAD may have a role in a mass survey for lung cancer using photofluorographic films.

Diagnosis, Computer-Assisted↗
PubMed1992

Site-directed mutagenesis of active site residues in Bacillus subtilis alpha-amylase.

Site-directed mutagenesis of Bacillus subtilis N7 alpha-amylase has been performed to evaluate the roles of the active site residues in catalysis and to prepare an inactive catalytic-site mutant that can form a stable complex with natural substrates. Mutation of Asp-176, Glu-208, and Asp-269 to their amide forms resulted in over a 15,000-fold reduction of its specific activity, but all the mutants retained considerable substrate-binding abilities as estimated by gel electrophoresis in the presence of soluble starch. Conversion of His-180 to Asn resulted in a 20-fold reduction of kcat with a 5-fold increase in Km for a maltopentaose derivative. The relative affinities for acarbose vs. maltopentaose were also compared between the mutants and wild-type enzyme. The results are consistent with the roles previously proposed in Taka-amylase A and porcine pancreatic alpha-amylase based on their X-ray crystallographic analyses, although different pairs had been assigned as catalytic residues for each enzyme. Analysis of the residual activity of the catalytic-site mutants by gel electrophoresis has suggested that it derived from the wild-type enzyme contaminating the mutant preparations, which could be removed by use of an acarbose affinity column; thus, these mutants are completely devoid of activity. The affinity-purified mutant proteins should be useful for elucidating the complete picture of the interaction of this enzyme with starch.

Acarbose↗
PubMed1992

The replication of DNA containing the simian virus 40 origin by the monopolymerase and dipolymerase systems.

The influence of DNA polymerase (pol) alpha and DNA primase on SV40 DNA replication was examined in both the monopolymerase and dipolymerase systems. The synthesis of oligoribonucleotides in the monopolymerase and dipolymerase systems, followed by pulse labeling with deoxynucleoside triphosphates, yielded short Okazaki fragments approximately 35 nucleotides in length that were chased into full-length Okazaki fragments with time. In the presence of activator 1 and proliferating cell nuclear antigen (PCNA), but no pol delta, these short fragments hardly increased in size with time. DNA fragments of similar size (approximately 35 nucleotides) were previously observed in SV40 replication reactions carried out with crude extracts of HeLa cells in the presence of antibodies directed against PCNA (Bullock, P. A., Seo, Y.S., and Hurwitz, J. (1991) Mol. Cell. Biol. 11, 2350-2361). Thus, the pol alpha-primase complex appears to act processively for only a short distance. At high levels of pol alpha and primase, both short and long DNA products were formed in both systems. In the presence of limiting amounts of pol alpha and excess primase, the monopolymerase system inefficiently yielded longer length Okazaki fragments than those formed with excess pol alpha and primase, whereas the dipolymerase system yielded both short and long DNA fragments. In the presence of limiting amounts of primase and excess pol alpha, long products were formed in both systems, and virtually no short products accumulated. Thus, the ratio between the polymerase and primer ends available controls the size of the nascent product DNA strands. We examined whether PCNA, the T4 phage-encoded gene product 45 (T4 gp45), and the Escherichia coli beta subunit of DNA polymerase III (dnaN gene product) supported SV40 DNA replication and the elongation of single-stranded DNA-binding protein-coated singly primed DNA in reactions catalyzed by pol delta, T4 DNA pol, and E. coli DNA pol III*, respectively. In the presence of T4 gp44/62 and T4 gp32 (but not human single-stranded DNA-binding protein isolated from HeLa cells), T4 DNA pol was weakly activated by PCNA and the beta subunit in lieu of T4 gp45 in the elongation of singly primed phi X174 DNA. However, the other systems were specific for their analogous auxiliary factors. This specificity indicates the importance of protein-protein interactions.

Antibodies, Monoclonal↗
PubMed1992

[2D time of flight stereoscopic MR angiography of pulmonary vessels].

Two-dimensional (2D) time-of-flight (TOF) stereoscopic MR angiographies (MRA) of the pulmonary vessels were obtained from 15 healthy volunteers and five patients with pulmonary cancer in the mediastinum and pulmonary hilum. Fifteen healthy volunteers were examined using FLASH (Fast Low Angle Shot) with breath holding (40/8/40, TR/TE/flip angle). Except for the left superior pulmonary vein, pulmonary vessels in the mediastinum and hilum were well defined on stereoscopic MRA images. Although it was difficult to define the pulmonary arteries in the peripheral zone, intersegmental veins were easily defined with this method. In five cases of pulmonary cancer that were confirmed to show definite tumor involvement of the pulmonary vessels in the mediastinum and hilum by enhanced CT and MRI (SE method), irregular narrowing and interruption of the vessels were shown on MRA. In conclusion, 2D TOF stereoscopic MRA is considered a noninvasive, effective method for evaluation of the morphology of pulmonary vessels adjacent to the tumor in the mediastinum and hilum.

Adenocarcinoma↗
PubMed1992

[Evaluation of breath-hold multislice dynamic MRI of hepatocellular carcinomas].

The breath-hold multislice dynamic study (BMDS) in MRI, which can scan the entire liver during a single breath-holding, was applied to 16 patients with 30 focal lesions of hepatocellular carcinoma (HCC). The BMDS was performed at 20 seconds and 3 minutes after the bolus injection of Gd-DTPA, by gradient echo pulse sequence (FLASH). 29 nodules were detected in the BMDS, showing rapid enhancement on early phase and decline on delayed phase images. The BMDS was more sensitive than conventional MR images. Therefore, the BMDS seems to be useful for the diagnosis of HCC with multiple as well as solitary nodules.

Carcinoma, Hepatocellular↗
PubMed1992

[Preliminary specification of X-ray CT for lung cancer screening (LSCT) and its evaluation on risk-cost-effectiveness].

In Japan mass screening for lung cancer is widely performed by chest X-ray film of 10 x 10 cm, with sputum cytology for high-risk groups. However, the effectiveness of the present mass screening program for lung cancer has been less than expected, although some date have shown improvement of the survival rate as a result of mass screening. We propose a new X-ray CT method of screening for lung cancer called Lung Cancer Screening CT (LSCT). The preliminary specifications for LSCT are as follows: scan speed is within 10 sec for a 40 cm length with a 1 cm slice thickness, and the absorption dose for lung is less than 1 cGy. A computer-assisted diagnostic system is necessary for image reading. The risk-benefit analysis of LSCT indicates that Japanese men and women over 45 years old can be screened in 1992 and thereafter. The cost per person.year of LSCT screening is estimated to be 1.4 x 10(6) yen for a population incidence rate of 50 x 10(-5) person/year and average life expectancy of 30 years. In 1992 the above condition will be satisfied by men aged 55 years old and above, but not by women of any age. We believe that LSCT should be developed further and tested in the high-risk group of men with an incidence rate of 100 x 10(-5) persons/year or more.

Adult↗
PubMed1992

Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase.

Human 5-lipoxygenase contains a non-heme iron essential for its activity. In order to determine which amino acid residues are involved in the iron-binding and the lipoxygenase activity, nine amino acid residues in highly homologous regions among the lipoxygenases were individually replaced by means of site-directed mutagenesis. Mutant 5-lipoxygenases in which His-367 or His-550 was replaced by either Asn or Ala, His-372 by either Asn or Ser, or Glu-376 by Gln were completely devoid of the activity. Though mutants containing an alanine residue instead of His-390 or His-399 lacked the activity, the corresponding asparagine substituted mutants exhibited. The other mutants retained the enzyme activity. These results strongly suggest that His-367, His-372, His-550 and Glu-376 are crucial for 5-lipoxygenase activity and coordinate to the essential iron.

Amino Acid Sequence↗
PubMed1992

Identification of carrot cDNA clones encoding a second putative proliferating cell-nuclear antigen, DNA polymerase delta auxiliary protein.

The proliferating cell-nuclear antigen (PCNA) plays a key role in the control of eukaryotic DNA replication. We have isolated two cross-hybridizing groups of cDNA encoding carrot homologs of PCNA. Sequence analysis and Southern-blot experiments showed that the cDNA were derived from two distinct genes. One corresponded to the typical PCNA, which is known to be highly conserved in eukaryotes from yeast to man; its mRNA is 1.2 kb in size and the calculated molecular mass of the protein is 29 kDa. The other encoded a larger PCNA homolog which has not previously been reported; the mRNA is 1.5 kb in size, the N-terminal three quarters (calculated molecular mass, 29 kDa) of the protein product is 88% identical at the amino acid level to the typical PCNA, but the protein has an extra C-terminal domain of 11 kDa. Both PCNA homologs were apparently coexpressed concomitant with somatic embryogenesis. The mRNA level of the novel homolog is 10-20% that of the typical PCNA in the embryos. The presence of the second putative PCNA may provide new insight into studies on the mechanism of DNA replication in eukaryotes.

Amino Acid Sequence↗
PubMed1992

[Evaluation of performance in diagnosis of pneumoconiosis using FCR (Fuji Computed Radiography)].

The purpose of this study was to determine the applicability of the FCR system to the diagnosis of pneumoconiosis. In the study, images of pneumoconiosis obtained by FCR were collected from the Rosai Hospital for Silicosis, and the distribution, shape and size of small opacities of pneumoconiosis were determined by three of the authors. An image data base was prepared, and diagnosis of pneumoconiosis using FCR test films was performed by 12 physicians with reference to reduced ILO films. Among the data obtained, data relating to profusion were analyzed. The results were compared with those obtained in the previous study. It was found that, if suitable image processing was carried on FCR test films, profusion could be classified with an accuracy equal to that of the diagnosis of pneumoconiosis with usual full-size films. It was necessary to establish standard films obtained by FCR in order to improve the accuracy of diagnosis of pneumoconiosis using FCR.

Evaluation Studies as Topic↗
PubMed1992

Significance of wall thickness in symptomatic gallbladder disease.

One hundred cases of patients who underwent urgent cholecystectomy after presenting with symptoms of acute or subacute gallbladder disease were retrospectively reviewed. Sixty patients had pathologically proved acute cholecystitis, and 40 had chronic cholecystitis alone. One patient had an incidental gallbladder carcinoma, and four had global gangrene of the gallbladder. Focal ischemia, transmural hemorrhage, or focal necrosis (indicating more severe disease) was present in 19 patients. Fifty-four percent of patients had thin-walled gallbladders. Among patients with more severe acute disease, 56% had thin walls. Conversely, 24% of thin-walled gallbladders and 22% of thick-walled gallbladders had evidence of focal necrosis or gangrene. We conclude that gallbladder wall thickness, although demonstrable on preoperative ultrasound examination in all patients, does not correlate directly with severity of disease or pathologic findings.

Acute Disease↗