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Biomedical subjects

R Yoshioka

Publications and source records attributed to R Yoshioka.

At least 37 records · Page 2Linked to original sources

Two patients with polymyositis or dermatomyositis complicated with massive pleural effusion.

Two patients with polymyositis (PM) or dermatomyositis (DM) complicated with massive pleural effusion are reported here. Both patients presented a high-grade fever, pleural effusion prominent on the right, and good response to steroid therapy. In a 50-year-old woman with PM, combined process of pleural inflammation, cardiomyopathy and coexisting hypothyroidism were considered to be responsible for the accumulation of the massive pleural effusion. However, in a 34-year-old man with DM, pleural inflammation associated with interstitial pneumonia or pleural microvasculopathy in DM was considered to be responsible for the accumulation of the massive pleural effusion.

Adult↗

Aggressive natural killer cell lymphoproliferative disorder associated with Epstein-Barr viral RNA.

Lymphoproliferative disorder of natural killer cells is a heterogeneous disorder, and an association with Epstein-Barr virus (EBV) is suggested in some cases. A Japanese male presenting with recurrent nasopharyngeal problems developed fever, generalized lymphadenopathy, and hepatosplenomegaly. Separated cells from lymph nodes were shown to have a natural killer (NK) cell, CD2(+), CD3(-), CD16(+), CD56(+), HLA-DR(+) phenotype. A progressive abnormality of hepatic function was associated with hepatorenal failure and death. A serologic study suggested reactivated EBV infection. In situ hybridization (ISH) studies showed Epstein-Barr virus-encoded RNA (EBER)-1 in lymph nodes, with lymphocytes infiltrating the liver and tissue from ethmoid sinus surgery 3 years prior to development of obvious lymphoproliferative disease. Polymerase chain reaction performed on lymph node DNA, using oligonucleotide primers specific for the EBV lymphocyte-determined membrane antigen (LYDMA) gene, revealed a single band, suggesting monoclonal proliferation of the tumor. NK activities of the lymphocytes from the lymph node and peripheral blood were markedly decreased. These findings suggest a close relationship between EBV infection and development of NK cell lymphoproliferative disorder.

Adult↗

Optical resolution of a 1,5-benzothiazepine derivative, a synthetic intermediate of diltiazem, by preferential crystallization and diastereomeric salt formation.

Practical preparation methods of an optically active intermediate of diltiazem, (+)-(2S,3S)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy- 2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one [(+)-7], have been developed by the use of physicochemical and chemical resolutions. 1) The salt of (+/-)-7 with 3-amino-4-hydroxy-benzenesulfonic acid (AHS), was found to exist as a conglomerate and could be reproducibly resolved into (+)-7.AHS and (-)-7.AHS of 94-98% ee by a preferential crystallization procedure. 2) (+)-(1R)-3-Bromocamphor-9-sulfonic acid [(+)-BCS] was found to be an efficient resolving agent for (+/-)-7 and the diastereomeric resolution provided (+)-7.(+)-BCS.2H2O salt in > 43% yield and > 97% ee by fractional crystallization. It is presumed that the crystal water of (+)-7.(+)-BCS.2H2O plays an important role in the selective crystallization during this efficient resolution.

Crystallization↗

Genetic heterogeneity in Charcot-Marie-Tooth neuropathy type 2.

Charcot-Marie-Tooth neuropathy type 2 (CMT2) is a common inherited axonal neuropathy. The locus for one form of CMT2 (CMT2A) is assigned to the short arm of chromosome 1. There is genetic heterogeneity in CMT2 because additional pedigrees do not demonstrate linkage to chromosome 1 and are designated as CMT2B. Further clinical heterogeneity is suggested by CMT2 pedigrees with diaphragm and vocal cord weakness and are designated as CMT2C. To address the possible genetic distinction between CMT2A and CMT2C, we tested markers from the CMT2A locus for linkage in a large CMT2C pedigree. There was no evidence to support linkage of the CMT2C gene to the region of the CMT2A locus on chromosome 1. CMT2C is not an allelic variant of CMT2A. This analysis provides further evidence for genetic heterogeneity within inherited axonal neuropathies.

Charcot-Marie-Tooth Disease↗

[A case of Sjögren's syndrome with an eyelid tumor, a so-termed pseudolymphoma of the iacrimal gland].

The female subject, 64 years old, subjectively noticed a mild dryness of the eyes and bilateral, submandibular swelling in 1988. The clinical symptom was mild, and such autoantibody and hyper-gammaglobulinemia as often observed in Sjögren's syndrome were not recognized. However, by judging from the results of gum test (9 mL/10 min), salivary gland scan (Grade 2) and the labial biopsy, we diagnosed the case as Sjögren's syndrome. We then administered prednisolone at 40 mg at the onset of treatment and gradually decreasing the dosage over 3.5 years, and the symptoms improved. As an eyelid tumor in the left eye was noticed in 1991 and began to enlarge, the subject was hospitalized in June of 1992. The biopsy of the tumor (2.0 x 1.7 cm) showed marked polyclonal lymphoproliferation with lymphoid follicles which was determined by immunohistological staining. The case was a patient with a lymphoproliferative lesion from a lacrimal gland which is equal to a so-termed pseudolymphoma. Since there are some reports concerning the transition from pseudolymphoma to malignant lymphoma, this patient should be followed carefully.

Eyelid Neoplasms↗

A case of idiopathic portal hypertension complicated with narrowing of intrahepatic bile ducts.

A 37-year-old woman who had portal hypertension followed by splenomegaly, developed collateral blood flow of spleno-renal shunt and paraesophageal veins, esophageal varices and further with narrowing of intrahepatic bile ducts shown by endoscopic retrograde cholangiography was described. Liver function was almost normal except the slight elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase levels. However, endoscopic retrograde cholangiography revealed the narrowing of the intrahepatic bile ducts. The histological examination of biopsied specimen showed no prominent change in portal tracts and bile ducts without cell infiltration or fibrosis in the portal area. This case will be considered as idiopathic portal hypertension complicated by narrowing of the intrahepatic bile ducts.

Adult↗

Association of primary sclerosing cholangitis, thymoma and hypogammaglobulinemia.

A 64-year-old Japanese woman with thymoma has been suffering from diarrhea and increased alkaline phosphatase levels without jaundice. Her serum immunoglobulin levels of IgM and IgG were less than half of the normal levels, with an increase in CD8 (suppressor/cytotoxic) T cell percentage and a decrease in CD4 (helper) T cell percentage, resulting in a lower CD4/CD8 ratio of 0.31. These immunological features are in accordance with those of hypogammaglobulinemia complicating thymoma. Cholangiography and a liver biopsy specimen disclosed the presence of primary sclerosing cholangitis (PSC). PSC has been recognized in various immunodeficiency syndromes and this case shows that thymoma complicated by hypogammaglobulinemia is associated with PSC.

Agammaglobulinemia↗

[Successful VEP-IFN-alpha therapy in a case of non-secretory plasma cell leukemia (BJ-kappa type)].

Plasma cell leukemia is a rare disorder with poor prognosis. We present a case of non-secretory primary plasma cell leukemia (Bence-Jones kappa type), which was treated successfully by VEP-IFN-alpha therapy. A 82-year old man was admitted to Kanazawa Medical University in May 1991, because of emaciation and dehydration. Clinical findings showed decreased level of gamma-globulin (IgG, IgA and IgM were all decreased markedly), hypercalcemia, renal dysfunction and increased serum beta-2 microglobulin. The peripheral blood leukocyte count was 30,100/microliters with 64% plasma cells, and 80.4% plasma cells were also observed in the bone marrow. Only light chain-kappa was detected in plasma cells by an immunohistochemical staining method, but immunoelectrophoresis showed no M-bow either in serum or urine. Electron microscopy revealed typical plasma cells with prominently developed rough endoplasmic reticulum. From these results, the diagnosis of non-secretory primary plasma cell leukemia was established. He was treated with VEP-IFN-alpha regimen, and plasma cells decreased markedly in both peripheral blood and bone marrow. Serum immunoglobulin recovered to within the normal range. After 6 courses of VEP-IFN-alpha, complete remission was achieved and the remission was maintained until he died of an unrelated event, bronchial obstruction due to misswallowing, in April 1992.

Aged↗

[A case of Sjögren's syndrome at the age of 91 with a lymphoepithelial lesion].

A 91 year old woman with Sjögren's syndrome who developed a lymphoepithelial lesion and showed an active state of the disease is described. Since June, 1990, the patient had been complaining of dry eyes and mouth and a left submandibular tumor (1.0 x 1.5 cm in diameter). A biopsy of the tumor revealed lymphoepithelial lesions in the salivary gland. Mild anemia (Hb 9.6 g/dl) and an elevated erythrocyte sedimentation rate (80 mm/hr) were noted. The gamma-globulin level was 2.7 g/dl, IgG 2789 mg/dl, IgA 469 mg/dl, RAHA x80, antinuclear antibody x20, anti-SS-A x256, thyroid test x400 and microsome test x102400. The Schirmer's test showed decreased tear secretion (Lt. 3mm, Rt. 9mm) and keratoconjunctivitis sicca were noticed by an ophthalmologist. Salivary scintigraphy revealed decreased uptake and slow excretion of the isotope (grade II). A biopsy of a minor salivary gland showed periductal lymphocytic infiltration and acinar cell destruction. Immunohistochemical analyses revealed the cross-reactive idiotype of a monoclonal rheumatoid factor which is associated with a patient with Sjögren's syndrome, in the infiltrating lymphocytes and plasma cells of the minor salivary glands, but not in the lymphoepithelial lesions of the left submandibular gland. This was a rare case concerning a 91-year old patient with Sjögren's syndrome who developed a lymphoepithelial lesion and showed high activity in the serum and gives us valuable information on the relationship between aging and autoimmunity.

Aged↗

Establishment of a CD4-positive plasmacytoma cell line (AMO1).

A human plasmacytoma cell line (AMO1) was established. The AMO1 cells had the light and electron microscopic characteristics typical of plasmacytoma cells and did not harbor Epstein-Barr virus. These cells expressed cytoplasmic immunoglobulin A kappa and the immunoglobulin heavy-chain gene (JH) and kappa light-chain gene (C kappa) were rearranged. Coexpression of a CD4 antigen and plasma cell antigens (CD38 and PCA-1) was an unusual and sustained feature. Neither the T-cell receptor beta nor the gamma chain gene displayed the rearranged form. Other lineage-specific surface antigens, namely T, B, monocytoid, and myeloid antigens, were all negative in AMO1. In accordance with the surface CD4 expression, polymerase chain reaction analysis indicated constitutive expression of CD4 mRNA, and the cytogenetic findings revealed that AMO1 cells had a derivative chromosome 12, which had a structural abnormality of the short arm carrying the CD4 gene locus. These findings provide strong evidence for the presence of CD4-positive malignant plasma cells and raise the possibility that the CD4 expression in the AMO1 cell line is closely associated with the derivative chromosome.

Biomarkers, Tumor↗

Interleukin-7 (IL-7)-induced proliferation of CD8+ T-chronic lymphocytic leukemia cells.

Interleukin-7 (IL-7) is a growth factor for pro-B cells, pre-B cells, and thymocytes and is known to induce the proliferation of normal human peripheral T cells. Moreover, human B and T acute leukemia cells with immature surface markers proliferate in response to IL-7. Here we describe a case of T-chronic lymphocytic leukemia, in which the leukemic cells showed a proliferative response to human recombinant IL-7 in vitro. The patient was a 74-year-old woman with anemia and thrombocytopenia, whose bone marrow was fibrosed and infiltrated with pathologic cells. Surface markers of the leukemic cells were CD2(+), CD3(+), CD5(+), CD7(+), CD8(+), and CD4(-). Both T-cell receptor beta-chain and gamma-chain genes were found to be rearranged by immunogenotypic analysis. The leukemic cells proliferated in response to IL-7 dose dependently. The DNA synthesis of CLL cells was stimulated by not only IL-7 but also IL-2 and IL-4. The IL-7-induced proliferation was not inhibited by antibodies to IL-2 receptors or the anti-IL-4 antibody. These findings indicate that IL-7 may induce the proliferation of peripheral CD8+ T cells, even on its pathological counterpart.

Aged↗

[Malignant lymphoma developing from the wall of chronic empyema following artificial pneumothorax].

A 60-year-old man who had had chronic empyema following an artificial pneumothorax for pulmonary tuberculosis when he was 26 years old developed malignant lymphoma of the chest wall. The patient was admitted because of right pyothorax as a result of pseudomonas aeruginosa infection and underwent right thoracotomy. During lavage of the right thoracic cavity a tumor was found arising from the empyematic wall. Pathologic examination revealed that it was malignant lymphoma (diffuse large, immunoblastic, B cell type). Treatment with VEAP-Bleomycin elicited a good response. Seven months after chemotherapy, the patient underwent thoracoplasty in addition to packing the cavity with the latissimus dorsi and the greater omentum. Following this, the patient received chemotherapy once a month for one and a half years, after which he was kept under close observation without treatment. Complete remission has now lasted for 49 months since the initial treatment. This is the first reported lymphoma case with closure of the empyematic wall and is remarkable since this patient has remained in complete remission for the last two years without any treatment.

Empyema, Pleural↗

Light and electron microscopic study of vacuolated cells in immunoblastic lymphadenopathy-like T-cell lymphoma.

Three cases of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma were analyzed immunologically, and the ultrastructure of mononuclear cells in the lymph nodes and peripheral blood was examined. In the peripheral blood, light microscopic examination revealed vacuolated lymphocytes. These vacuolated lymphocytes formed rosettes with sheep erythrocytes, and they were CD3- and CD4-positive using the avidin-biotin method in cases 1 and 2. Electron microscopic examination revealed two kinds of abnormal lymphocytes. One kind was of B-cell nature with rich lamellated rough-surfaced endoplasmic reticulum and mitochondria. The other kind had a large cytoplasm, in which Golgi apparatus, some endoplasmic reticulum, some mitochondria and a few vacuoles were seen. Some of these vacuoles had remnants of mitochondrial cristae or were enlarged endoplasmic reticulum. The vacuolated T lymphocytes and activated lymphocytes of B-cell nature disappeared with chemotherapy but reappeared with relapse of the disease. These observations suggest that vacuolated cells are related to pale cells in lymph node sections. In other words when these vacuolated cells are found in the peripheral blood of patients with lymphoid malignancies, IBL-like T-cell lymphoma can be suspected.

Aged↗

Establishment of two interleukin 6 (B cell stimulatory factor 2/interferon beta 2)-dependent human bone marrow-derived myeloma cell lines.

Two IL-6-dependent human multiple myeloma cell lines, ILKM2 and ILKM3, were established from the bone marrow of patients with IgG-K multiple myeloma. Both cell lines had the typical morphology and immunocytochemical features of myeloma cells. The surface phenotype of both cell lines was PCA-1+, OKT10+, CD10(J-5)-, CD19(B4)-, CD20(B1)-, CD21(B2)-, and OKIa-1-. A monoclonal cytoplasmic Ig, IgG-K or K L chain, was positive in ILKM2 or ILKM3, respectively. EBV nuclear antigen was negative in both cell lines. They proliferated in the presence of macrophages or macrophage-derived factors (MDF). Among the recombinant cytokines examined, IL-6 most strongly augmented the growth of both cell lines. The anti-IL-6 antibody completely inhibited the IL-6-dependent growth and almost completely inhibited the MDF- or purified MDF-dependent growth of both cell lines, ILKM2 and ILKM3 are now being maintained in the culture medium containing 2 ng/ml rIL-6. These results suggest that IL-6 produced by macrophages may play an important role in the growth of myeloma cells in vivo and that macrophages or IL-6 can be used for establishing human myeloma cell lines.

Antigen-Antibody Reactions↗

[Two cases of miliary tuberculosis with SIADH].

Two cases of miliary tuberculosis with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) were reported. Case 1. A 70-year-old woman suffering from general fatigue and appetite loss developed neck stiffness and stupor three days after admission. The chest X-ray film showed a miliary pattern in both lungs. The lumber puncture showed high pressure and increased leucocytes in the cerebrospinal fluid. Serum natrium concentration was 113 mEq/L. Tubercle bacilli were seen in the broncho-alveolar lavage fluid by the Ziehl-Nielsen staining. An improvement in electrolytes balance was produced by 2.5% NaCl and antituberculous treatment, then her mental function recovered. Case 2. A 71-year-old man was admitted with gastric ulcer. When he developed dry cough thirty days after admission, the chest X-ray film showed a miliary pattern in both lungs. Acute respiratory failure advanced concomitantly. Tubercle bacilli were seen in the sputum (Gaffky 5) by the Ziehl-Nielsen staining. Antituberculous treatment was started. Although the miliary shadow improved gradually, hyponatremia was rather progressing. The following values for serum constituents were determined: sodium, 118 mEq/L; antidiuretic hormone, 10.3 pg/ml. Antituberculous treatment and supplement of NaCl (10 g/day) improved serum natrium level. He had no mental disturbance in his clinical course. In both cases, thyroid, renal and adrenal function were normal. Systemic edema and dehydration did not exist at the state of hyponatremia, and it was very clear that laboratory data were compatible with SIADH criteria. Miliary tuberculosis is one of the least commonly recognized causes of SIADH.

Aged↗