Biomedical subjects

H Ohnishi

Publications and source records attributed to H Ohnishi.

At least 55 records · Page 3Linked to original sources

PubMed2000

Expression of perlecan proteoglycan in the infarct zone of mouse myocardial infarction.

Perlecan, a basal lamina proteoglycan, has been shown to interact with other extracellular matrix (ECM) components, especially type IV collagen, and is thus involved in ECM formation. Perlecan has also been postulated to promote growth factor-receptor interactions, including the binding of basic fibroblast growth factor (bFGF) to its receptor, and to enhance mitogenesis and angiogenesis. To test our hypothesis that perlecan is increased in the myocardial infarct zone, we examined perlecan expression after experimentally induced myocardial infarction in BALb/c mice by the methods of in situ hybridization, Northern blotting, and immunohistochemistry. In situ hybridization revealed mRNA signals for perlecan in the infarct marginal zone on day 2 and in the infarct interior zone around infarct granulation tissue on day 7. On day 14 the signals were observed at the center point of the infarct. The signals were detected in spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts). Some surviving myocytes in the infarct marginal zone also showed positive signals. The sequential changes in the perlecan mRNA signal distribution paralleled those for type IV collagen mRNA. Northern blotting demonstrated increased expression of perlecan consistent with the observations of in situ hybridization. Immunopositive staining for perlecan was observed in the infarct zone around granulation tissue on day 7 and in the entire infarct zone on days 14-28. Immunostaining for bFGF was localized surrounding the infarct granulation tissue on day 7 and overlapped with perlecan immunostaining. The present results demonstrated the expression of perlecan by spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts) and some surviving myocytes in the myocardial infarct, indicating the contribution of perlecan to the pathological course of myocardial infarction.

Animals↗

PubMed2000

Clinical experience of Argatroban for anticoagulation in cardiovascular surgery.

PURPOSE: We have reviewed our experience with Argatroban-a direct thrombin inhibitor for anticoagulation--in a variety of cardiovascular operations, and in extracorporeal circulation, as a substitute for heparin. SUBJECTS AND METHODS: 60 patients receiving anticoagulation with Argatroban were classified into the following four groups. Group 1; 20 patients with anticoagulation therapy after cardiac surgery. Group 2; 8 patients with extracorporeal circulation for continuous hemofiltration for either pre- or post-operative control of acute renal failure. Argatroban was used alone or in combination with nafamostat mesilate. Group 3, one patient with replacement of the descending aorta with left heart assist and 15 patients with percutaneous cardiopulmonary support. And Group 4, 16 patients undergoing vascular surgery including the abdominal aorta. The target activated clotting time was individually set for each group. In Group 1, the coagulofibrinolytic activity and platelet function were measured precisely. Bleeding and complications were examined in all groups. RESULTS: Group 1; the targeted activated clotting time of 150-180 seconds was achieved by a dosage of 0.4-0.8 microgram/kg/min Argatroban. Group 2; the activated clotting time of 150-180 seconds was achieved by 0.05-1.6 micrograms/kg/min (concomitance), or by 0.02-2.5 micrograms/kg/min (alone). Group 3; the activated clotting time of 180-200 seconds by 0.05-3.86 micrograms/kg/min. And Group 4; the activated clotting time of around 150 seconds by 2.0 micrograms/kg/min with initial bolus infusion of 0.1 mg/kg. Argatroban did not promote post-surgery bleeding and had no unfavorable effect on coagulo-fibrinolysis or on platelet activity. CONCLUSION: Argatroban may be useful as an anticoagulant in the field of cardiovascular surgery as a substitute for heparin, without causing any post-surgery bleeding complication, or influencing the fibrinolytic activities or platelet functions.

Aged↗

PubMed2000

Hypermethylation of p16 and p15 genes and RB protein expression in acute leukemia.

Both p16 and p15, encoded by genes located on chromosome 9p21, are inhibitors of cyclin-dependent kinases 4/6 (CDK4/6) and upstream regulators of RB function, and set up the RB/p16 tumor suppressive pathway, which is abrogated frequently in human neoplasms, either through inactivation of the RB or p16 tumor-suppressor protein, or alteration of the cyclin D1 or CDK4 oncoproteins. In hematological malignancies, deletion of p16/p15 locus has been shown to be highly specific to lymphoid malignancies, and more particularly to T-cell acute lymphoblastic leukemia (T-ALL). However, in the other subsets of ALL, deletions of p16 and p15 are relatively rare events. To investigate whether these genes are inactivated by methylation of the 5' CpG islands, we examined 35 leukemia cell lines and 29 childhood acute myeloid leukemia (AML) patients by Southern blot, polymerase chain reaction (PCR) and Western blot analyses. We found methylation of p16 in 12 (50%) of 24 ALL cell lines, 5 (50%) of 10 AML cell lines without homozygous deletion of p16, and 11 (38%) of 29 AML patients. Those leukemia cell lines subjected to p16 methylation were found to have lost p16 protein expression. The p15 gene was methylated in 10 (34%) of 29 ALL cell lines, 6 (60%) of 10 AML cell lines without homozygous deletion of p15, and 15 (52%) of 29 AML patients. These results revealed the frequent methylation of p16 and p15 genes in B-ALL and AML despite a low frequency of p16 and p15 deletions and mutations in these leukemias. In the study for expression of RB protein, we found no expression of RB in 4 of 16 leukemia cell lines. Inactivation of the p16 gene was found in all the cell lines with expression of RB. Neither amplification nor rearrangement of cyclin D1 gene was found in any cell lines. These results suggest that inactivation of p16 and p15 genes is one of the most common genetic events in acute leukemia, and plays an important role for the RB/p16 pathway in the pathogenesis of acute leukemia.

Acute Disease↗

PubMed2000

Improvement of fuel metabolism by nocturnal energy supplementation in patients with liver cirrhosis.

Aims: patients with liver cirrhosis exhibit abnormal fuel metabolism, including increased fat and decreased glucose oxidation. Such altered energy metabolism is similar to that observed after starvation and could lead to malnutrition. We therefore studied whether nocturnal energy supplementation might improve the fuel metabolism in cirrhotic patients. Methods: 12 cirrhotic patients and 14 healthy controls participated in this study. Subjects in the two groups ate isonitrogenous (1.2 g/kg/day) and isocaloric (35 kcal/day) diets for 1 week before and during the study. On day 1 of the study, indirect calorimetry was carried out in the morning after an overnight fast. The next morning, the same measurement was performed after the patients took a liquid nutrient (Ensure Liquid(R), 250 kcal) at 23:00 on day 1. Respiratory quotient (RQ), resting energy expenditure (REE), and substrate oxidation rates of glucose (% CHO), fat (% FAT) and protein were estimated from measured VO(2), VCO(2) and urinary nitrogen. Results: Significant decreases in RQ, and % CHO and a significant increase in % FAT were observed at baseline in cirrhotic patients as compared with controls. After the nocturnal energy supplementation, RQ, % CHO and % FAT in cirrhotic patients were significantly recovered, ending at levels close to normal. Conclusions: These results suggest that nocturnal energy supplementation could be useful to correct abnormal fuel metabolism and to prevent malnutrition in cirrhosis.

Journal Article↗

PubMed2000

Synovial sarcomas of three children in the first decade: clinicopathological and molecular findings.

Synovial sarcoma in children below the age of 10 years is rare. We report on three cases of synovial sarcoma which were diagnosed in three children aged 3, 8 and 8 years, respectively. These tumors were located in the hip of the 8-year-old, the foot of the 3-year-old, and the elbow of the other 8-year-old. Histologically, one tumor was a biphasic synovial sarcoma, and the other two, which had been initially diagnosed as infantile fibrosarcoma, were of the monophasic fibrous type. In the three cases, a reverse transcription-polymerase chain reaction (RT-PCR) using ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX1 fusion gene transcripts resulting from translocation t(X;18)(p11.2;q11.2), which is specific for synovial sarcoma. ETV6-NTRK3 fusion gene transcripts that result from t(12;15)(p13;q25), which is characteristic of congenital/infantile fibrosarcoma, were not demonstrated. In conclusion, other pediatric soft tissue sarcomas, such as congenital/infantile fibrosarcoma, spindle cell rhabdomyosarcoma, leiomyosarcoma and malignant peripheral nerve sheath tumor, should be distinguished from synovial sarcoma in children, especially the monophasic fibrous type. RT-PCR analysis is a useful approach to the final diagnosis of synovial sarcoma arising at such an early age.

Base Sequence↗

PubMed2000

BIT/SHPS-1 enhances brain-derived neurotrophic factor-promoted neuronal survival in cultured cerebral cortical neurons.

Brain-derived neurotrophic factor (BDNF) activates a variety of signaling molecules to exert various functions in the nervous system, including neuronal differentiation, survival, and regulation of synaptic plasticity. Previously, we have suggested that BIT/SHPS-1 (brain immunoglobulin-like molecule with tyrosine-based activation motifs/SHP substrate 1) is a substrate of Shp-2 and is involved in BDNF signaling in cultured cerebral cortical neurons. To elucidate the biological function of BIT/SHPS-1 in cultured cerebral cortical neurons in connection with its role in BDNF signaling, we generated recombinant adenovirus vectors expressing the wild type of rat BIT/SHPS-1 and its 4F mutant in which all tyrosine residues in the cytoplasmic domain of BIT/SHPS-1 were replaced with phenylalanine. Overexpression of wild-type BIT/SHPS-1, but not the 4F mutant, in cultured cerebral cortical neurons induced tyrosine phosphorylation of BIT/SHPS-1 itself and an association of Shp-2 with BIT/SHPS-1 even without addition of BDNF. We found that BDNF-promoted survival of cultured cerebral cortical neurons was enhanced by expression of the wild type and also 4F mutant, indicating that this enhancement by BIT/SHPS-1 does not depend on its tyrosine phosphorylation. BDNF-induced activation of mitogen-activated protein kinase was not altered by the expression of these proteins. In contrast, BDNF-induced activation of Akt was enhanced in neurons expressing wild-type or 4F mutant BIT/SHPS-1. In addition, LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, blocked the enhancement of BDNF-promoted neuronal survival in both neurons expressing wild-type and 4F mutant BIT/SHPS-1. These results indicate that BIT/SHPS-1 contributes to BDNF-promoted survival of cultured cerebral cortical neurons, and that its effect depends on the phosphatidylinositol 3-kinase-Akt pathway. Our results suggest that a novel action of BIT/SHPS-1 does not occur through tyrosine phosphorylation of BIT/SHPS-1 in cultured cerebral cortical neurons.

Adenoviridae↗

PubMed2000

Shp-2 specifically regulates several tyrosine-phosphorylated proteins in brain-derived neurotrophic factor signaling in cultured cerebral cortical neurons.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophins, promotes differentiation and survival and regulates plasticity of various types of neurons. BDNF binds to TrkB, a receptor tyrosine kinase, which results in the activation of a variety of signaling molecules to exert the various functions of BDNF. Shp-2, a Src homology 2 domain-containing cytoplasmic tyrosine phosphatase, is involved in neurotrophin signaling in PC12 cells and cultured cerebral cortical neurons. To examine the roles of Shp-2 in BDNF signaling in cultured rat cerebral cortical neurons, the wild-type and phosphatase-inactive mutant (C/S mutant) forms of Shp-2 were ectopically expressed in cultured neurons using recombinant adenovirus vectors. We found that several proteins tyrosine-phosphorylated in response to BDNF showed enhanced levels of tyrosine phosphorylation in cultured neurons infected with C/S mutant adenovirus in comparison with those infected with the wild-type Shp-2 adenovirus. In addition, in immunoprecipitates with anti-Shp-2 antibody, we also observed at least four proteins that displayed enhanced phosphorylation in response to BDNF in cultured neurons infected with the C/S mutant adenovirus. We found that the Shp-2-binding protein, brain immunoglobulin-like molecule with tyrosine-based activation motifs (BIT), was strongly tyrosine-phosphorylated in response to BDNF in cultured neurons expressing the C/S mutant of Shp-2. In contrast, the level of BDNF-induced phosphorylation of mitogen-activated protein kinase and coprecipitated proteins with anti-Trk and Grb2 antibodies did not show any difference between neurons infected with these two types of Shp-2. Furthermore, the survival effect of BDNF was enhanced by the wild type of Shp-2, although it was not influenced by the C/S mutant of Shp-2. These results indicated that in cultured cerebral cortical neurons Shp-2 is specifically involved in the regulation of several tyrosine-phosphorylated proteins, including BIT, in the BDNF signaling pathway. In addition, the phosphatase Shp-2 may not influence the level of BDNF-induced activation of mitogen-activated protein kinase in cultured cortical neurons. Further, Shp-2 may have potential to positively regulate BDNF-promoting neuronal survival.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Kinesin is involved in regulation of rat pancreatic amylase secretion.

BACKGROUND & AIMS: Kinesin has recently been localized to zymogen granules of pancreatic acini and is suggested to participate in exocytosis of exocrine pancreas. We examined the function of kinesin in regulated exocytosis of pancreatic acini in this study. METHODS: Kinesin function in exocytosis was examined by introducing hexahistidine-tagged recombinant kinesin protein and antikinesin monoclonal antibody into streptolysin-O-permeabilized acini. Intracellular localization of introduced recombinant kinesin was investigated by immunohistochemistry. Interaction between recombinant kinesin and the microtubule network was confirmed by nocodazole pretreatment of acini. Kinesin regulation by secretagogues was investigated by examining their effect on adenosine triphosphatase (ATPase) activity of endogenous kinesin. RESULTS: Recombinant kinesin enhanced calcium-stimulated amylase release from streptolysin-O-permeabilized acini. Introduced recombinant kinesin was localized to both the microtubule network and zymogen granule. Nocodazole pretreatment of acini abolished the enhancing effect of recombinant kinesin on calcium-stimulated amylase release. Antikinesin antibody inhibited amylase release stimulated by the combination of calcium and cyclic adenosine monophosphate (cAMP) but not that stimulated by calcium alone. Secretin and 8-bromo-cAMP increased ATPase activity of endogenous kinesin. CONCLUSIONS: Kinesin plays a stimulatory role in regulated exocytosis of pancreatic acini and is involved in stimulus-secretion coupling through a cAMP-dependent pathway.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Greater than normal expression of the collagen-binding stress protein heat-shock protein-47 in the infarct zone in rats after experimentally-induced myocardial infarction.

BACKGROUND: The heat-shock protein with relative molecular mass 47,000 (HSP47) can bind to procollagen molecules in the endoplasmic reticulum, and acts as a molecular chaperone during the processing and secretion of procollagen. OBJECTIVE: To test our hypothesis that HSP47 is expressed in the myocardial infarct zone. METHODS: We induced myocardial infarction in male Sprague-Dawley rats by ligation of left coronary artery. The expression of HSP47 was examined by Northern blotting, in-situ hybridization, Western blotting and immunohistochemistry. The time-dependent change in the distribution of HSP47 messenger RNA (mRNA) signal was compared with the changes in expression of alpha 1(I) and alpha 1(III) collagen mRNA by in-situ hybridization. The hypoxic induction of HSP47 in cultured cardiac fibroblasts was examined by Northern-blot analysis. RESULTS: Northern blotting demonstrated that the expression of HSP47 mRNA had increased on day 2, reaching a maximum level around day 14 (induced 3.5-fold compared with the preligation hearts) and was maintained at a high level up to day 28. In-situ hybridization analysis revealed HSP47 mRNA signals in spindle-shaped mesenchymal cells located between surviving myocytes in the infarct's peripheral zone 24 h after the ligation, and in the entire infarct zone on day 14. The sequential changes in distribution of HSP47 mRNA signal were identical to those of the alpha 1(I) and alpha 1(III) collagen mRNA. Western blotting demonstrated that expression of HSP47 protein in the infarct zone had increased. Immunofluorescent staining revealed positivity for HSP47 in the infarct's peripheral zone on day 2 and in the entire infarct zone on day 14. Northern blotting revealed that the expression of HSP47 mRNA in cultured cardiac fibroblasts in hypoxic cultures was greater than that in normoxic cultures. CONCLUSION: The present data demonstrated that an increase in expression of HSP47 is produced by spindle-shaped mesenchymal cells in the infarct zone. Expression of HSP47 mRNA was concurrent with the expression of collagen mRNA of types I and III. Hypoxia is one of the factors which induces expression of HSP47.

Animals↗

PubMed2000

[A case of pulmonary Nocardia farcinica infection in a patient with non-tuberculous mycobacteriosis].

A 64 years old woman without systemic immunological disorders was admitted to our hospital because of a productive cough, low grade fever and bloody sputum. Chest X-ray revealed multiple nodules with calcification, infiltrates and bronchiectasis. Laboratory findings showed mild hypoproteinemia and elevated sedimentation rate. Both Nocardia farcinica and Mycobacterium intracellulare were isolated from the bronchial lavage fluid. Administration of sulfamethoxazole-trimethoprim improved her symptoms. In a recurrent study of bronchial lavage N. farcinica was not isolated, but M. intracellurale was still isolated. We believe that N. farcinica may cause infectious exacerbation of chronic lung disease: non-tuberculous mycobacteriosis and bronchiectasis.

Female↗

PubMed2000

Transcription of emrKY is regulated by the EvgA-EvgS two-component system in Escherichia coli K-12.

Spontaneous mutations have been isolated in Escherichia coli that result in the constitutive expression of an emrKY promoter. These mutations were found to be single-nucleotide substitutions within the linker region of the sensor protein EvgS, which is part of a two-component regulatory system along with EvgA. In the linker mutants (evgSI and evgS4), emrKY expression became constitutive and MIC against sodium deoxycholate was 20 mg/ml, eight-fold higher than in the wild type. Furthermore, the start site of transcription from the promoter of emrKY was identified; EvgA was shown to bind at the -52 to -84 region by the footprinting experiment.

Amino Acid Sequence↗

PubMed2000

Tissue response to titanium implants in the rat maxilla: ultrastructural and histochemical observations of the bone-titanium interface.

BACKGROUND: The detailed mechanism of osseointegration, the most appropriate implant-bone interface, remains unclear in jaw tissues at the ultrastructural level in contrast to the many reports using long bones. The present study reports on tissue response to titanium-implantation on an animal model using rat maxilla. METHODS: Animals were sacrificed at 1 to 28 days post-implantation and prepared tissue specimens, freed from implants by a cryofracture technique, were processed for transmission electron microscopy and histochemistry for tartrate resistant acid phosphatase activity (TRAPase). RESULTS: Different patterns in bone formation were recognized between lateral and base areas of implant cavities. In the lateral area with narrow gaps, bone deposition took place from the pre-existing bone towards the implant after active bone resorption by osteoclasts reactive to TRAPase. However, no distinct bone formation appeared in the lateral area where the implant had been installed close to the osteotomy margin. On the other hand, new bone formation was found at the base area without any apparent bone resorption. Interestingly, mononuclear cells reactive to TRAPase, presumably preosteoclasts, frequently occurred near preosteoblasts. Osseointegration around the implants was obtained in this model by 28 days post-implantation except for the lateral area with complete contact with implants, where the thin layer remained in contact with the implant surface. CONCLUSIONS: These findings indicate that ossification proceeds at different modes around the titanium implant in rat maxilla, depending on the nature of the recipient bones and the dimension of the gap between the implant and osteotomy margin.

Animals↗

PubMed2000

A histochemical investigation of the bone formation process by guided bone regeneration in rat jaws. Effect of PTFE membrane application periods on newly formed bone.

BACKGROUND: Guided bone regeneration (GBR) has been widely utilized for the promotion of bone augmentation in bone loss areas. However, little information has been available regarding chronological changes in newly formed bone and alterations in the nature of newly formed bone after removal of a barrier membrane. The present study attempted to establish a GBR model for rat maxillae. We also examined the effects of membrane application periods on newly formed bone and its remodeling process after removal of the membrane in this experimental model. METHODS: Thirty-five Wistar rats were divided into 2 groups: a membrane application group and a membrane removal group. The chronological changes of newly formed bone were evaluated histologically and statistically. RESULTS: At 2 weeks after the GBR procedure, bony cavities had completely filled the newly formed bone in the experimental side. In the control side, corticalization on the surface of the newly formed bone proceeded with a decrease in the bone marrow cavity, whereas the bone marrow space had enlarged by 12 weeks post-surgery in the experimental side. In the membrane removal group, the osteoblasts appeared on newly formed bone at 1 week after membrane removal. Comparatively thick compact bone had formed on the surface of the newly formed bone at 4 weeks after membrane removal, and corticalization proceeded later. CONCLUSIONS: The long-term application of a barrier membrane induces the enlargement of the bone marrow spaces. We suggest that PTFE membrane removal in adequate time promotes the corticalization and maturation of the newly formed bone by the GBR technique.

Acid Phosphatase↗

PubMed2000

Type II citrullinemia in an elderly patient treated with living related partial liver transplantation.

A 60-year-old woman was admitted to our hospital for repeated consciousness disturbance. Blood examination showed hyperammonemia, and plasma amino acid analysis revealed a marked increase in the citrulline level. To establish a diagnosis, a percutaneous needle biopsy of the liver was performed. The determination of the urea cycle enzyme activities revealed a selective marked decrease in argininosuccinate synthetase activity, indicating the final diagnosis of type II citrullinemia. The mean survival period of this disease after the appearance of symptoms has been reported as 26.4 months, and most conservative treatments are not effective. We performed a living related partial liver transplantation. Over the subsequent 13-month follow-up, the patient's condition has remained fairly good.

Biopsy, Needle↗

PubMed2000

Direct clipping of a large basilar trunk aneurysm via the posterior petrosal (extended retrolabyrinthine presigmoid) approach--case report.

A 53-year-old female presented with an unruptured, large basilar trunk aneurysm manifesting only as headache with no neurological deficits, including absence of cranial nerve dysfunction. Cerebral angiography disclosed a large aneurysm with a wide neck arising from the midbasilar artery. We treated the aneurysm surgically via the posterior petrosal approach. Five angled clips were applied sequentially to the aneurysm and the basilar artery was successfully reconstructed. Electrophysiological monitoring was continued during the operation and showed no changes. Following the operation, the patient suffered from transient right abducens nerve palsy, which persisted for 3 months. Postoperative angiography showed that the aneurysm was obliterated, and the patency of the basilar artery was preserved.

Basilar Artery↗

PubMed2000

Dysembryoplastic neuroepithelial tumor of the cerebellum and brainstem. Case report.

The authors present a case in which dysembryoplastic neuroepithelial tumors (DNETs) occurred in the cerebellum and brainstem of a 44-year-old woman. A magnetic resonance image of the brain revealed multiple cystic lesions in the right cerebellar hemisphere, vermis, tonsil, and brainstem. Partial removal of the tumors was performed. There were gray multinodular gelatinous lesions on the cerebellar hemisphere. Histologically, the tumors exhibited areas of multiple microcystic nodules in the cerebellar white matter, which were composed of oligodendroglia-like cells (OLCs), astrocytes, and neurons. There were multiple, variable nodules in the lesions, lined by OLCs. The adjacent cerebellar cortex displayed dysplastic features. Reduction of granule neurons and dislocation of Purkinje cells into the molecular layer were observed. The pathological profile of this patient agrees with that described by Daumas-Duport, et al., as a "dysembryoplastic neuroepithelial tumor."

Adult↗

PubMed2000

Nutritional pharmacotherapy of chronic liver disease: from support of liver failure to prevention of liver cancer.

Many patients with liver cirrhosis are in a state of protein and energy malnutrition and require careful nutritional support. Our research has revealed that approximately 30% of the patients have protein-energy malnutrition, 40% protein malnutrition, and 10% energy malnutrition; 20% are in a normal nutritional state. Supplementation with branched-chain amino acids alleviates chronic liver failure, improves the protein nutritional state, and subsequently prolongs survival. In contrast, therapeutic modalities for energy malnutrition have not yet been fully elucidated and await further studies. Improved survival of the cirrhotic patients essentially brings a higher incidence of hepatocellular carcinoma (HCC). A synthetic analogue of vitamin A (acyclic retinoid or 4,5-dehydrogeranyl geranoic acid) prevents at least the development of second primary tumors after curative treatment of preceding HCC. The mechanism of this cancer chemo-prevention is clonal deletion of premalignant and latent malignant cells by the retinoid. We describe our clinical experiences with these two nutritional pharmacotherapies of chronic liver diseases and review their basic mechanisms.

Amino Acids, Branched-Chain↗

PubMed2000

[Sjögren's syndrome with malignant lymphoma, interstitial pneumonia, and pulmonary hypertension].

A 62-year-old woman was admitted to our hospital for further examination of cough and dyspnea on exertion. She had suffered xerostomia and xerophthalmia for 7 years. Physical examinations showed purpura on the lower extremities, Raynaud's phenomenon, and swelling of the parotid glands. Laboratory data disclosed thrombocytopenia, hypergammaglobulinemia, and high titers of anti-nuclear antibody, anti SS-A, and anti SS-B antibodies. Sicca symptoms, a positive Schirmer's tear test, and laboratory findings together yielded a diagnosis of Sjögren's syndrome. Chest X-P and computed tomographic films demonstrated diffuse reticulonodular shadows and multiple nodules in the left lower lung. Echocardiography and right cardiac catheterization revealed enlargement of the right ventricle, tricuspid regurgitation, and elevated pulmonary arterial pressure. Histologic findings from an open-lung biopsy specimen revealed accumulation of inflammatory cells and fibrosis around broncho-vascular bundles, and diffuse large cell lymphoma. Despite a favorable response to chemotherapy, the patient died of right ventricular failure.

Female↗