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Biomedical subjects

Y Matsui

Publications and source records attributed to Y Matsui.

At least 19 recordsLinked to original sources

Malignant lymphoma of the stomach associated with systemic sarcoidosis.

The case of a patient with gastric malignant lymphoma associated with systemic sarcoidosis is reported. The patient's sarcoidosis was identified by the findings of bilateral hilar lymphadenopathy and secondary glaucoma. Biopsy of a cervical lymph node showed epithelioid cell granuloma; the sarcoidosis was diagnosed 15 years previously. She had been treated with prednisolone for 5 years until 1979. Proximal gastrectomy, splenectomy, and lymph node dissection were done in 1989. The tumor was diagnosed as malignant lymphoma of the diffuse large cell type according to the Working Formulation. There was no infiltration of lymphoma cell in the 45 dissected lymph nodes, but sarcoid nodules were observed in all nodes. Only three cases of gastric malignant lymphoma complicating sarcoidosis have been reported to the authors' knowledge. Further study should be done in support of the concept of a sarcoidosis-lymphoma syndrome.

Aged

Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture.

Steel factor (SF) and LIF (leukemia inhibitory factor) synergistically promote the proliferation and survival of mouse primordial germ cells (PGCs), but only for a limited time period in culture. We show here that addition of bFGF to cultures in the presence of membrane-associated SF and LIF enhances the growth of PGCs and allows their continued proliferation beyond the time when they normally stop dividing in vivo. They form colonies of densely packed, alkaline phosphatase-positive, SSEA-1-positive cells resembling undifferentiated embryonic stem (ES) cells in morphology. These cultures can be maintained on feeder layers for at least 20 passages, and under appropriate conditions give rise to embryoid bodies and to multiple differentiated cell phenotypes in monolayer culture and in tumors in nude mice. PGC-derived ES cells can also contribute to chimeras when injected into host blastocysts. The long-term culture of PGCs and their reprogramming to pluripotential ES cells has important implications for germ cell biology and the induction of teratocarcinomas.

Alkaline Phosphatase

Characterization of the factors binding to a PEPCK gene upstream hypersensitive site with LCR activity.

A previously described upstream hypersensitive site (HS) in the PEPCK gene at -4800 bp, termed HS A (1), has been characterized and determined to bind at least two factors. One of these is a member of the ubiquitous CREB/ATF family, and the second is a novel tissue specific protein, pep A. A construct carrying HS A and the PEPCK proximal promoter was tested in transgenic mice and its CAT activity compared to the proximal promoter alone. The HS A was shown to drive tissue-specific, position-independent transcription of the CAT reporter gene 2-3 fold more effectively than the proximal promoter alone, with a concommitant 4-5 fold higher expression of CAT. Protein binding activity has been localized to a 33 bp region. This region contains a CRE (2) which is shown to bind a member of the CREB/ATF family through competition assays with an oligo containing a CRE from the proximal promoter and by the appearance of a supershift when the factor/oligo complex was exposed to CREB polyclonal antibody. Through restriction enzyme digests and competition of protein binding with an oligonucleotide homologous to HS A with a mutated CRE we have characterized a putative binding site for a liver-specific factor. In vitro and 'in vivo' footprinting studies complement each other, as well as, mobility shift assay data in designating the binding site of the proteins. The CREB/ATF factor and Pep A bind independently of each other during short term incubations, however, both factors can be accomodated on the DNA substrate as a function of extended time of incubation. Preliminary biochemical analysis defines the subunit molecular mass of the CREB/ATF like proteins at 55, 42, and 35 kD, while the tissue specific material exists as a single homogeneous subunit polypeptide in SDS of molecular mass = 49 kD.

Animals

Isolation and characterization of two novel ras superfamily genes in Saccharomyces cerevisiae.

We have isolated two novel genes, designated as RHO3 (on chromosome IX) and RHO4 (on chromosome XI), belonging to the ras superfamily, from the yeast Saccharomyces cerevisiae. Deletion of RHO4 did not affect cell growth, but deletion of RHO3 caused a severe growth delay and a decrease in cell viability. The rho3 and rho4 disrupted genes displayed synthetic lethality at 30 degrees C. RHO3 and RHO4 seem to have overlapping functions in cell growth, because the growth defect in rho3 cells was suppressed by overexpression of RHO4 despite the low homology (about 35%) at the amino acid sequence level between the RHO3 and RHO4 proteins.

Amino Acid Sequence

Electrophysiological findings in paraneoplastic retinopathy.

Paraneoplastic retinopathy is a cancer-related non-metastatic retinopathy mainly associated with lung cancer. We examined two patients with presumed paraneoplastic retinopathy, both ophthalmologically and electrophysiologically. Both patients presented with initial visual complaints of moderate reduction of visual acuity. No specific fundus anomaly was found in the fundus except for a mild attenuation of the retinal arteries. The electroretinogram and pattern reversal visual evoked responses were either markedly reduced in amplitude or non-recordable. The electrooculogram recorded in one patient demonstrated a markedly reduced light peak/dark trough ratio. These results indicate the presence of a severe and diffuse bilateral retinal dysfunction, despite the relatively good visual acuities and mild fundus changes. Electrophysiological evaluations play an important role in the diagnosis of paraneoplastic retinopathy.

Aged

The extracellular matrix of cartilage in the growth plate before and during calcification: changes in composition and degradation of type II collagen.

Calcification occurs in the extracellular matrix of the hypertrophic zone of the growth plate when the extracellular matrix volume is reduced to a minimum and alkaline phosphatase content is maximal. The present study shows that significant quantitative and qualitative changes occur in the composition and structure of macromolecules in the extracellular matrix before and during calcification in the proximal tibial growth plate of the bovine fetus. These were detected in part by using microchemical and microimmuno-chemical analyses of sequential transverse frozen sections at defined sites throughout the growth plate. Concentrations of matrix molecules in the extracellular matrix have not previously been determined biochemically. They were measured per unit matrix volume by using combined immunochemical/chemical-histomorphometric analyses. The concentrations within the extracellular matrix of the C-propeptide of type II collagen, aggregating proteoglycan (aggrecan), and hyaluronic acid all progressively increased in the maturing and hypertrophic zones, being maximal (or near maximal) at the time of initiation of mineralization. These results for proteoglycan are contrary to some earlier reports of a loss of proteoglycan are contrary to some earlier reports of a loss of proteoglycan prior to mineralization which measured the tissue content of proteoglycan rather than that present in the extracellular matrix, the volume of which is progressively reduced as the growth plate matures. The C-propeptide data provides a quantitative confirmation of previous immunohistochemical studies. Total collagen concentration (measured as hydroxyproline) in the extracellular matrix initially increased through the proliferating and maturing zones but then rapidly decreased in the hypertrophic zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase

Protein phosphorylation regulates the mouse sperm acrosome reaction induced by the zona pellucida.

Recently, the ligand-receptor signal transduction mechanism has been implicated in mediating the zona pellucida (ZP)-induced acrosome reaction. Little is known about the role of protein phosphorylation in this specific event. We examine whether modification of protein phosphorylation and dephosphorylation affects the kinetics of the acid-solubilized ZP-induced acrosome reaction of mouse sperm. Mouse epididymal sperm were incubated in modified Krebs-Ringer bicarbonate medium for a period of 90 to 120 min and then treated with 2 acid-solubilized ZP/microliters for an additional 60 min. The chlortetracycline fluorescence assay was used to monitor the acrosome reaction. Capacitated sperm were inhibited from undergoing acid-solubilized ZP-induced acrosome reaction in the presence of an inhibitor of cyclic nucleotide-dependent protein kinase, H8; activators of the Ca(2+)- and phospholipid-dependent protein kinase (protein kinase C); an inhibitor of phosphatases 1 and 2A, okadaic acid; or an inhibitor of protein tyrosine kinases, genistein. The addition of inhibitors of protein kinase C, such as staurosporine, H7, and protein kinase C [19-36] pseudosubstrate, inhibited the phorbol ester-dependent inhibition of the acid-solubilized ZP-induced acrosome reaction. The present study suggests that protein phosphorylation and dephosphorylation play a regulatory role in the process of the ZP-induced acrosome reaction.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

A pathological study of bovine alimentary mycosis.

A 10-year study showed that 45 of 692 cattle aged > 6 months had systemic mycosis and, of these, 38 had alimentary mycosis. The percentages of these 38 cattle with lesions in various sites were: rumen (73.7), omasum (71.1), abomasum (34.2), reticulum (21.1), intestine (15.8), omasoabomasal orifice (7.9) and tongue (2.6). Infections in both the forestomachs and abomasum occurred in 31.6 per cent; mucormycosis was found in 94.7 per cent and aspergillosis in 31.6 per cent; 26.3 per cent (10 cattle) had complicated infections with both Mucorales and Aspergillus and eight of these animals had mixed lesions of both mucormycosis and aspergillosis. Macroscopically, focal haemorrhagic necrosis was seen in all 38 cattle. Histologically, thrombosis, coagulative necrosis and hyphae typical of the order Mucorales or of Aspergillus spp. were found. Many of the cattle were also affected by ruminal acidosis-inducing factors (ruminal atony 81.6 per cent, mastitis 63.2 per cent, "downer cow syndrome" 57.9 per cent and parturition 50.0 per cent), which may have predisposed to alimentary mycosis.

Animals

Pulmonary vascular involvement in sarcoidosis: a report of 40 autopsy cases.

We examined pulmonary vascular involvement in 40 autopsy cases of sarcoidosis. In these cases granulomatous involvement was observed at all levels from large elastic pulmonary arteries to venules, and venous involvement was more prominent than arterial involvement. The extent of granulomatous vascular involvement was related to that of parenchymal granuloma. No significant difference was found between upper and lower lobes in the incidence of granulomatous vascular involvement. The distribution of granulomata in the blood vessels was segmental and adventitial, and medial involvement was prominent in the larger vessels. Healed lesions of granulomatous vascular involvement also were observed at various levels in blood vessels. Prominent granulomatous involvement was found in the lymphatic capillaries and collecting lymphatic vessels in lungs with sarcoidosis. Serial sections of the lungs demonstrated interstitial granuloma directly connecting the lymphatic capillaries around small blood vessels. Granulomatous involvement in vasa vasorum and lymphatic capillaries is likely to be an important factor in the pathogenesis of granulomatous vascular involvement in lungs with sarcoidosis. The present study suggests that granulomatous vascular involvement and its sequelae may contribute to the development of pulmonary sarcoidosis.

Aged

The modulation of collagen synthesis in cultured arterial smooth muscle cells by platelet-derived growth factor.

Changes on collagen synthetic activity of cultured arterial smooth muscle cells of rabbits induced with purified platelet-derived growth factor (PDGF) were examined. PDGF treatment (final concentration was 5 units/ml) decreased the total collagen synthesis per cell, while the rate of collagen synthesis against total protein synthesis was raised by PDGF. Type analysis of collagen revealed substantial reduction of type IV collagen and relative increase of type V collagen in the PDGF-treated cells. By immunofluorescence study using anti-type IV collagen antibody, the lacework fluorescence was decreased with PDGF supplement. These findings indicate that PDGF induces the decrease of type IV collagen synthesis with the simultaneous diminution of basement membrane formation probably in association with phenotypic modulation of smooth muscle cells.

Animals

c-Myc interferes with the commitment to differentiation of murine erythroleukemia cells at a reversible point.

When murine erythroleukemia (MEL) cells, containing the transferred rat c-myc gene under the control of human metallothionein II gene promoter, are induced to differentiate with dimethyl sulfoxide, the level of differentiation is dependent on the c-Myc level, which is modulated by the addition of Zn ions. In this work, we examined the point of inhibition of differentiation by elevated levels of c-Myc in one (clone 38-2) of the typical transformants. Commitment assay indicated that elevated levels of c-Myc interfere with entry of the transformant into the commitment event, but when c-myc expression was reduced by removing Zn ions from the medium, the cells could reenter the commitment program. However, once the cells were committed, such cells could not return to the uncommitted state. In addition, time-dependent expression of two erythroid specific genes was inhibited by elevated levels of c-Myc in time-dependent manner. These results suggest that c-Myc modulates MEL cell differentiation at a reversible point of commitment.

Animals

Yeast RHO3 and RHO4 ras superfamily genes are necessary for bud growth, and their defect is suppressed by a high dose of bud formation genes CDC42 and BEM1.

RHO3 and RHO4 are members of the ras superfamily genes of the yeast Saccharomyces cerevisiae and are related functionally to each other. Experiments using a conditionally expressed allele of RHO4 revealed that depletion of both the RHO3 and RHO4 gene products resulted in lysis of cells with a small bud, which could be prevented by the presence of osmotic stabilizing agents in the medium. rho3 rho4 cells incubated in medium containing an osmotic stabilizing agent were rounded and enlarged and displayed delocalized deposition of chitin and delocalization of actin patches, indicating that these cells lost cell polarity. Nine genes whose overexpression could suppress the defect of the RHO3 function were isolated (SRO genes). Two of them were identical with CDC42 and BEM1, bud site assembly genes involved in the process of bud emergence. A high dose of CDC42 complemented the rho3 defect, whereas overexpression of RHO3 had an inhibitory effect on the growth of mutants defective in the CDC24-CDC42 pathway. These results, along with comparison of cell morphology between rho3 rho4 cells and cdc24 (or cdc42) mutant cells kept under the restrictive conditions, strongly suggest that the functions of RHO3 and RHO4 are required after initiation of bud formation to maintain cell polarity during maturation of daughter cells.

Adaptor Proteins, Signal Transducing

RSR1, a ras-like gene homologous to Krev-1 (smg21A/rap1A): role in the development of cell polarity and interactions with the Ras pathway in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae ras-like gene RSR1 is particularly closely related to the mammalian gene Krev-1 (also known as smg21A and rap1A). RSR1 was originally isolated as a multicopy suppressor of a cdc24 mutation, which causes an inability to bud or establish cell polarity. Deletion of RSR1 itself does not affect growth but causes a randomization of bud position. We have now constructed mutant alleles of RSR1 encoding proteins with substitutions of Val for Gly at position 12 (analogous to constitutively activated Ras proteins) or Asn for Lys at position 16 (analogous to a dominant-negative Ras protein). rsr1Val-12 could not restore a normal budding pattern to an rsr1 deletion strain but could suppress a cdc24 mutation when overexpressed. rsr1Asn-16 could randomize the budding pattern of a wild-type strain even in low copy number but was not lethal even in high copy number. These and other results suggest that Rsr1p functions only in bud site selection and not in subsequent events of polarity establishment and bud formation, that this function involves a cycling between GTP-bound and GDP-bound forms of the protein, and that the suppression of cdc24 involves direct interaction between Rsr1p[GTP] and Cdc24p. Functional homology between Rsr1p and Krev-1 p21 was suggested by the observations that expression of the latter protein in yeast cells could both suppress a cdc24 mutation and randomize the budding pattern of wild-type cells. As Krev-1 overexpression can suppress ras-induced transformation of mammalian cells, we looked for effects of RSR1 on the S. cerevisiae Ras pathway. Although no suppression of the activated RAS2Val-19 allele was observed, overexpression of rsr1Val-12 suppressed the lethality of strains lacking RAS gene function, apparently through a direct activation of adenyl cyclase. This interaction of Rsr1p with the effector of Ras in S. cerevisiae suggests that Krev-1 may revert ras-induced transformation of mammalian cells by affecting the interaction of ras p21 with its effector.

Adenylyl Cyclases

Collagens in human atherosclerosis. Immunohistochemical analysis using collagen type-specific antibodies.

This study represents a systematic analysis of the distribution of collagen types in human atherosclerotic lesions. Formalin-fixed, paraffin-embedded aortic tissues of 40 lesions from 16 different individuals ranging in age from 1 month to 84 years were examined immunohistochemically using antibodies to type I, III, IV, V, and VI collagens. Preembedding immunoelectron microscopy was used to simultaneously localize type V and VI collagens within the lesions. Localization of type III collagen was very similar to that of type I, and type VI collagen appeared together with these two types of collagen in the thickened intimas of all stages of the lesion. Type V collagen was not detected in either fatty streaks or the mild intimal thickening of the aortas of children. With advancing age and lesion progression, the immunoreactivity with anti-type V collagen antibody became more intense. Type IV collagen was detected in the basement membrane region of intimal cells. In advanced lesions thick deposits of type IV collagen were found around the elongated smooth muscle cells. Using immunoelectron microscopy, type V collagen was found to be localized to cross-banded collagen fibers, and type VI collagen was found to be localized to beaded filaments present throughout the interstitium of the thickened intima. These findings suggest that collagens preserve the pathophysiological and functional integrity of the vascular wall by providing mechanical support as well as assuring the proper interaction of cells during the formation of atherosclerotic lesions.

Adult

Disseminated mycoses in cattle. A study on nine autopsy cases.

Nine cases affected with disseminated mucormycosis (1.3% of all autopsy cases and 20.0% of systemic mycosis) were found among bovine systemic mycosis examined from 1975 to 1985. The disseminated lesions were found in the lungs (3 cattle), heart (2 cattle), liver (2 cattle), spleen (1 beef cattle), kidneys (1 cattle), central nervous system (1 cattle) and lymph node (1 cattle). Histological examination revealed granulomatous lesions, necrotic foci including infarcts, and thromboangiitis with the hyphae of a member of the Zygomycetes and neutrophil reaction. Granulomatous lesions with asteroid bodies were found in the liver. Metastatic foci were established from the primary lesions found in the alimentary organ (4 from the forestomach or abomasum and 1 from the tongue). One case resulted from uterine mucormycosis, and no primary lesion was found in the other 3 cattle. Complicated infection with respiratory aspergillosis occurred in 4 cases with alimentary mucormycosis. All of the 9 cattle had predisposing disorders. Six cattle had been manifested with prolonged debilitating conditions. Anemia was present in 4, leukopenia in 2 and lymphopenia in 1 cattle.

Animals

Progressive systemic sclerosis complicated with immune thrombocytopenia during D-penicillamine therapy.

Immune thrombocytopenia is a rare complication of progressive systemic sclerosis (PSS). A 47-year-old female with PSS treated with D-penicillamine developed immune thrombocytopenia, which promptly responded to prednisolone and withdrawal of D-penicillamine. Platelet-associated IgG was elevated and the bone marrow megakaryocyte count was normal. There was an inverse relationship between the level of platelet-associated IgG and the platelet count. A lymphocyte stimulation test sensitized by D-penicillamine was positive. The present case suggests that immune thrombocytopenia may be regarded as one of the D-penicillamine-related immune abnormalities. To our knowledge, its association with PSS has never been reported.

Blood Platelets

Diagnosis and management of endobronchial tuberculosis.

We examined the records of sixty-one patients (17 males and 44 females) with endobronchial tuberculosis (EBTB). Smear tests of acid-fast bacilli were positive in 42 cases and cultures of tubercle bacilli (TB) were positive in 57. The main findings of chest roentgenogram on admission were as follows: no abnormal findings in 8, atelectasis in 30, infiltration in 25, and cavitary lesions in 6. The localization and cross-sectional extension of lesions confirmed bronchoscopically were as follows: trachea in 15, with 3 circular lesions (CLs). Right (R-) main bronchus in 19 with 11 CLs, left (L-) main bronchus in 18 with 11 of CLs, R-truncus intermedius in 14 with 6 of CLs, R-upper lobar bronchus (UB) in 17 with 12 CLs, R-middle lobar bronchus in 14 with 11 of CLs, R-lower lobar bronchus (LB) in 6 with 2 CLs, L-UB in 10 with 7 CLs and L-LB in 3 with 2 CLs. All cases were treated by combination chemotherapy with isoniazid, rifampicin, streptomycin and/or ethambutol and the rate of negative conversion of TB was good, but most of circular lesions resulted in severe bronchial stenosis or complete obstruction during and after chemotherapy, and no improvement was seen in any of the atelectasis cases at the cessation of chemotherapy. We discuss the points of early diagnosis and management of EBTB.

Adult