Insulin-dependent diabetes mellitus associated with parvovirus B19 infection.
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Adult↗
Biomedical subjects
R Harada
Publications and source records attributed to R Harada.
HIV-1 reverse transcriptase shows no specificity for the binding of primer tRNA(Lys3).
The transcription initiation primer for HIV-1 is a specific cellular tRNA species, tRNA(Lys3). We used several methods to assess the binding of tRNA by recombinant HIV-1 p51/p66 reverse transcriptase (RT), gel retardation analysis, intrinsic RT protein fluorescence quenching, and nitrocellulose filter binding assays. The binding of tRNA to RT was saturable, implying a distinct site or sites on the enzyme for tRNA interaction. However, this binding was non-selective, with all tRNA isoacceptors and total unfractionated tRNA binding with similar affinity as primer tRNA(Lys3). In contrast, no significant binding of tRNA by RT was noted. Our results show that HIV-1 RT has no specificity for the binding of primer tRNA(Lys3), and imply that factors other than RT sequences may be important for the selective incorporation of primer tRNA into the virion particle.
Animals↗
The human cut homeodomain protein can repress gene expression by two distinct mechanisms: active repression and competition for binding site occupancy.
By analogy with other homeodomain proteins conserved in evolution, mammalian Cut proteins are believed, as in Drosophila melanogaster, to play an important role in determining cell type specificity in several tissues. At the molecular level, Cut proteins appear to serve as transcriptional repressors. In this study, we have examined the mechanism by which the human Cut (hCut) protein down-regulates gene expression. The homeodomain and the three regions called Cut repeats are evolutionarily conserved and were previously shown to function as DNA binding domains. The carboxy-terminal region, although it does not show amino acid sequence homology per se, in all cases is enriched in alanine and proline residues, a distinctive feature of some transcriptional repression domains. Our results reveal two distinct modes of repression: competition for binding site occupancy and active repression. On one hand, the composite DNA binding domain formed by Cut repeat 3 and the Cut homeodomain was shown to bind to CCAAT and Sp1 sites within the tk gene promoter and to reduce gene expression, presumably by preventing activation by the corresponding transcription factors. On the other hand, the carboxy-terminal region of mammalian Cut proteins was found to function as an active repression domain in a distance-independent manner. We have further narrowed this activity to two subdomains that can independently repress activated transcription. Finally, we present a model to illustrate the two mechanisms by which Cut proteins repress gene expression.
Amino Acid Sequence↗
Reticular erythematous mucinosis syndrome: glycosaminoglycan synthesis by fibroblasts and abnormal response to interleukin-1 beta.
BACKGROUND: Reticular erythematous mucinosis (REM) syndrome is characterized by an accumulation of mucin in the dermis. OBJECTIVE: To elucidate the mechanism of mucin deposition, the response of REM syndrome fibroblasts to various exogenous factors was studied. METHOD: REM and control fibroblasts were treated with potent modulators including tumor necrosis factor-alpha, basic fibroblast growth factor, interferon-gamma, transforming growth factor-beta 1 and interleukin-1 alpha (IL-1 alpha) and -4. RESULTS: IL-1 beta failed to stimulate glycosaminoglycan synthesis in REM fibroblasts whereas it stimulated glycosaminoglycan synthesis up to 6-fold in control fibroblasts. The stimulation of glycosaminoglycan was caused largely by a comparable increase in hyaluronic acid. CONCLUSION: These results suggest that the patient fibroblasts exhibit an abnormal response to stimulation by exogenous IL-1 beta and that IL- 1 beta may be involved in the abnormal hyaluronic acid metabolism in REM syndrome.
Adult↗
Lymphomatoid papulosis followed by Ki-1 positive anaplastic large cell lymphoma: proliferation of a common T-cell clone.
We report a case of lymphomatoid papulosis (LyP) followed by Ki-1 positive anaplastic large cell lymphoma (LCL). A 33-year-old man developed subcutaneous nodules in the left inguinal region and the left thigh after a seven-year-history of self-healing papulonecrotic lesions of LyP. Histological and immunohistochemical examination of the subcutaneous nodules revealed LCL. DNA was isolated from a nodule of the initial stage of LyP in 1988, a subcutaneous nodule of LCL in 1993, and a papule of LyP in 1993 which appeared after chemotherapy for LCL. T cell receptor gene rearrangement analysis demonstrated an identical rearranged pattern in all the three specimens, indicating that a common T cell clone proliferated throughout the course in both the LyP and LCL lesions.
Adult↗
DNA-binding specificity of the cut repeats from the human cut-like protein.
The Drosophila Cut and mammalian Cut-like proteins contain, in addition to the homeodomain, three other DNA-binding regions called Cut repeats. Cut-like proteins, therefore, belong to a distinct class of homeodomain proteins with multiple DNA-binding domains. In this study, we assessed the DNA-binding specificity of the human Cut repeats by performing PCR-mediated random oligonucleotide selection with glutathione S-transferase fusion proteins. Cut repeat 1, Cut repeat 3, and Cut repeat 3 plus the homeodomain selected related yet distinct sequences. Therefore, sequences selected by one of the fusion proteins were often, but not always, recognized by the other proteins. Consensus binding sites were derived for each fusion protein. In each case, however, some selected sequences diverged from the consensus but were confirmed to be high-affinity recognition sites by electrophoretic mobility shift assay. We conclude that Cut DNA-binding domains have broad, overlapping DNA-binding specificities. Determination of dissociation constants indicated that in addition to the core consensus, flanking sequences have a moderate but significant effect on sequence recognition. Evidence from electrophoretic mobility shift assay, DNase footprinting, and dissociation constant analyses strongly suggested that glutathione S-transferase/Cut fusion proteins bind to DNA as dimers. The implications of these findings are discussed in relation to the DNA-binding capabilities of Cut repeats. In contrast to other studies, we found that the human Cut-like protein does not preferably bind to a site that includes an ATTA homeodomain-binding motif. Here we demonstrate that the native human Cut-like protein recognizes more efficiently a site containing an ATCGAT core consensus flanked with G/C-rich sequences.
Base Sequence↗
[Combination therapy with arbekacin and fosfomycin against postoperative severe mixed-pneumonia of MRSA in primary lung cancer patients].
We experienced successful treatment of postoperative severe pneumonia of Methicillin-resistant Staphylococcus aureus (MRSA) with combination therapy of Arbekacin (ABK) and Fosfomycin (FOM) in three lung cancer patients. Case 1 was a advanced age of seventy-nine man who had had right upper lobectomy. Case 2 was a 61-year-old man who had had left lower lobectomy and extended bilateral mediastinal lymph-node dissection through the median sternotomy. And case 3 was a 59-year-old man who had suffered from pulmonary embolism after right pneumonectomy and partial resection of left atrium and superior vena cava. All cases were immuno-compromised patients and super-infected with Gram-negative rods, and Pseudomonas aeruginosa in case 1 and case 3. Clinical symptoms were improved after the start of administration of ABK and FOM inspite of ineffectiveness of prior treatment with other antibiotics. We added staggered chemotherapy of Sulbactam/Cefoperazone (SBT/CPZ) and Ceftazidime (CAZ) for case 1 and case 3 respectively. Thus, the combination therapy of ABK and FOM might be useful for severe pneumonia of MRSA in the immunocompromised patients, and the combined staggered chemotherapy of beta-lactum agents and above would be the first choice in the treatment for the case involving Pseudomonas aeruginosa.
Aged↗
[A case of diffuse malignant mesothelioma diagnosed by thoracoscopic biopsy].
We report a case of diffuse malignant mesothelioma discovered by thoracoscopic examination undertaken while formulating a preoperative diagnosis. A 61-year-old male complained of coughing and sputum production, and was admitted because his chest roentgenogram indicated an abnormal shadow. Chest CT scanning demonstrated right pleural effusion and multiple nodules sited on the diaphragm. Because aspiration biopsy of such nodules was difficult, we performed a thoracoscopic examination. The thoracoscopic findings demonstrated bloody pleural effusion in the right thoracic cavity and multiple nodules on the diaphragm, parietal and pulmonary pleura. They were white and 0.5 to 2 cm in size. By excisional biopsy, these were diagnosed as epithelial-type diffuse malignant mesothelioma. We therefore performed panpleuropneumonectomy. Even though we completely resected the canal of thoracoscope and drainage tube, microscopic findings showed invasion of mesothelioma cells into this thoracoscopic canal. Although we suggest that, in preoperative diagnosis of pleural tumor, thoracoscopy is efficient to perform a pathological examination and confirm the extension of tumor, in the actual operation, we believe that the thoracoscopic canal should be resected.
Biopsy↗
[A case report of intralobar sequestration associated with lung aspergillus].
A 21-year-old woman with fever and dyspnea was admitted to our hospital. X-ray examination of this patient showed abscess forming in the right lower lobe of the lung. Aspergillus fumigatus was detected by percutaneous lung biopsy. She had repeated pneumonia since her childhood, so congenital lung disease was suspected. Aortic angiography showed the flow of an aberrant artery originated from the right inferior phrenic artery into the right lower lobe. Preoperative diagnosis of the patient was lung sequestration associated with aspergillosis. The operative procedure included right lower lobectomy with ligation of the aberrant artery. Postoperative diagnosis was intralobar sequestration of Pryce III type which was infected with aspergillus. Intralobar sequestration associated with aspergillosis is very rare, perhaps this is the third case in the literature of Japan.
Adult↗
[Evaluation of neck lymph node dissection and extended lymphadenectomy through a collar incision and median sternotomy for lung cancer].
Since 1983, 421 patients have been treated for lung cancer at this institute. Since 1988, neck lymph node dissection (11 cases) and new extended lymphadenectomy through a collar incision and median sternotomy (22 cases) have been conducted. Indications for this new radical operation are scalene, supraclavicular or highest mediastinal node involvement, or superior pulmonary sulcus carcinoma, in patients aged 70 or less without distant metastasis and NSCLC. No major complications and operative mortality were encountered in this study. Patients with scalene or supraclavicular node involvement showed poor prognosis. Postsurgical local recurrence was frequent. Whether resection in N3 disease should be conducted or not, remains a point of controversy. The authors consider that lymphadenectomy should be conducted more extensively. A significant better survival of N2 disease and satisfactory prognosis of patients without metastasis of cervical lymph nodes demonstrates the effectiveness of neck lymph node dissection in the present superradical operation for lung cancer.
Adult↗
Conserved cut repeats in the human cut homeodomain protein function as DNA binding domains.
Homeodomain-containing proteins are believed to function as sequence-specific DNA binding proteins, regulating gene expression. Specificity of sequence recognition is conferred by the homeodomain acting either alone or in conjunction with other conserved DNA binding domains as is the case for Pou domain and Paired domain proteins. The recent isolation of cDNAs encoding mammalian homologues of the Drosophila Cut homeodomain protein has revealed that the 72-amino acid Cut Repeats are conserved in evolution. We have investigated the biochemical activity of human Cut Repeats by expressing fusion proteins containing glutathione S-transferase linked to various combinations of Cut Repeats and Cut homeodomain. We show by gel retardation and DNase footprinting assays that Cut Repeats can function as DNA binding domains, either independently or in cooperation with the homeodomain. The binding affinity (KD) to a specific recognition site was estimated to be 8 x 10(-9) M for Cut Repeat 3 and 4 x 10(-10) M for Cut Repeat 1. When both Cut Repeat 3 and the Cut homeodomain were present in the fusion protein, the binding affinity was increased to 4 x 10(-11) M. These results define a novel class of proteins that contain in addition to the homeodomain a second conserved protein domain, the Cut Repeats, that also function as a DNA binding domain.
Animals↗
[Application of the polyglycolic acid (PGA) pledgets or sheet for pulmonary fistulas and defects of the pleura].
A felt-like bioabsorbable prosthesis (Polyglycolic Acid (PGA) pledget and sheet; Medifit feft) was used for pulmonary fistula in a total of 10 patients. "Fibrin glue A" was absorbed into the PGA prosthesis previously. And next, the part of pulmonary fistula was coated with "Fibrin glue B", and then covered with the fibrin-absorbed PGA prosthesis. The prosthesis adhered to the diseased part of pulmonary pleura immediately, and therefore, in all these 10 patients, the post-operative air-leakage was stopped up to 4 days and neither side effect nor complication was observed.
Adult↗
[The necessity of extended systemic dissection of the regional lymph node in radical operation for lung cancer].
Since 1979, 109 patients underwent bilateral mediastinal lymph node dissection through a median sternotomy as a routine procedure in the treatment of left lung cancer, because of the high possibility of contralateral mediastinal node involvement in cases of left lung cancer. The five-year survival rates of the initial 50 patients who underwent this operation from Oct. 1979 till Mar. 1988 were 76.5% in N0 (n = 17), 69.2% in N1 (n = 13), 50.0% in N2 (n = 10) and 20.0% in N3 (n = 10). The five-year survival rate of 7 patients with pT1-2 N2M0 disease was 71.4%. This survival rate was only slightly different from that of the pT1-2N0-1M0 group. From May 1985 till April 1993, 20 patients who had the cervical or the highest mediastinal lymph node involvement underwent cervical and bilateral mediastinal lymph node dissection through a cervical collar incision and median sternotomy. Two patients with the scalene node involvement (one each of right and left lung cancer) are surviving for five years or more after surgery. Extended ipsilateral mediastinal lymph node dissection (R2b) has been adopted as a routine procedure in the treatment of right lung cancer in our institute since 1990. The survival rate at forty months in 15 patients with N2 disease who underwent R2b operation was 51%. In 3 of these fifteen patients the anterior mediastinal lymph node metastases were revealed by post-operative pathological investigation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Immunoglobulin variable region sequences of two human monoclonal antibodies directed to an onco-developmental carbohydrate antigen, lactotetraosylceramide (LcOse4Cer).
A human monoclonal antibody, 11-50, was generated and was shown to recognize an onco-developmental carbohydrate antigen, LcOse4Cer. The isotype of this antibody was IgM, lambda, similar to the previously known human anti-LcOse4 antibodies, such as IgMWOO and HMST-1. We raised a murine anti-idiotypic antibody G3 (IgG1, kappa) against 11-50, and tested its reactivity towards the affinity purified human polyclonal anti-LcOse4 antibodies prepared from pooled human sera using a Gal beta 1-->3GlcNAc beta-immobilized column. The results indicated that at least a part of the human polyclonal anti-LcOse4 antibodies shared the G3 idiotype with 11-50. We further analyzed the sequence of variable regions of the two anti-LcOse4 antibodies, 11-50 and HMST-1. Sequence analysis of the heavy chain variable regions indicated that the VH regions of these two antibodies were highly homologous to each other (93.5% at the nucleic acid level), and these antibodies utilized the germline genes VH1.9III and hv3005f3 as the VH segments, which are closely related germline genes of the VHIII family. It was noted that these germline VH genes are frequently utilized in fetal B cells. The JH region of both antibodies was encoded by the JH4 gene. For the light chain, the V lambda segments of the two antibodies were 96.3% homologous to each other at the nucleic acid level. The V lambda segments of both antibodies showed the highest homology to the rearranged V lambda gene called V lambda II.DS among reported V lambda genes, while the exact germline V lambda genes encoding the two antibodies were not yet registered in available sequence databanks. The amino acid sequences of the J lambda segments of both antibodies were identical. These results indicate that the two human antibodies recognizing the onco-developmental carbohydrate antigen Lc4 are encoded by the same or very homologous germline genes.
Amino Acid Sequence↗
Parapsoriasis en plaques: its potential for progression to malignant lymphoma.
BACKGROUND: Parapsoriasis en plaques (large-plaque type) is a premalignant condition capable of developing into cutaneous T-cell lymphoma (CTCL). However, it is not known whether the early stage of CTCL can be distinguished from parapsoriasis en plaques. OBJECTIVE: Our purpose was to determine whether parapsoriasis en plaques can develop into CTCL. METHODS: The clinical appearance, histopathologic features, immunophenotype, DNA rearrangements, and clinical course were analyzed in 20 cases. RESULTS: T-cell receptor beta-chain gene rearrangement was detected in four of the 20 cases. No clinical, histopathologic, or immunohistochemical differences were found between patients with and without gene rearrangement. CONCLUSION: The early stage of CTCL cannot be differentiated from parapsoriasis en plaques by clinical features, histopathologic characteristics, or immunophenotype. Patients with parapsoriasis en plaques exhibit heterogeneous findings, which may include monoclonal proliferation. Patients with long-standing parapsoriasis-like lesions resistant to conventional treatment require careful monitoring for the possible development of cutaneous lymphoma.
Adult↗
[Study of anti-idiotype antibodies to human monoclonal antibody].
A human monoclonal antibody, ll-50 (IgM, lambda), was generated, which reacted specifically with a major of glycolipid present in LS174T colon cancer cells. The glycolipid antigen which reacted with the ll-50 antibody was expected to four sugar residues from its TLC mobility, and it was ascertained that the glycolipid antigen which reacted with ll-50 antibody might be Lc4 antigen [Gal beta 1----3 GLcNAc beta 1----3 Gal beta 1----4 Glc beta 1----1 Cer] judging from TLC immunostaining and ELISA when the reactivity of ll-50 antibody was tested using various pure glycolipids in 3-5 sugar residues as an antigen. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated ll-50 antibody. The serum of the Lc4 antigen recognized by ll-50 antibody was significantly higher in patients with malignant disorders than that in healthy individuals (p less than 0.05). Three mouse monoclonal anti-idiotype antibodies, G3, B3 and C5 (all IgG1), were generated by the immunization of BALB/c mice with ll-50 antibody. These anti-idiotype antibodies specifically bound to to human monoclonal antibody, ll-50 and had a significant inhibitory activity towards the binding of ll-50 antibody to the Lc4 antigen. This indicated that these anti-idiotype antibodies, G3, B3, and C5, were paratope-related anti-idiotype antibodies. G3, B3, and C5 were expected to define the nearest idiotope because they could mutually inhibit ll-50 antibody. Sera in patients with malignant disorders and healthy individuals were analyzed by Sandwich assay of immobilized and biotinylated anti-idiotype antibodies, G3, B3, and C5. As to the ll-50 like antibodies defined by C5 (Id-C5+), the mean serum level in patients with malignant disorders was significantly higher than that in healthy individuals (p less than 0.05). As to the ll-50 like antibodies defined by B3 (Id-B3+), the mean serum level in patients with malignant disorders was significantly higher than that in healthy individuals.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
[Effects of steroid therapy in IgA nephropathy].
In order to estimate the effects of corticosteroid therapy in IgA nephropathy cases with daily urinary protein excretion of 1.0 g/day or more. 26 patients (8 men and 18 women, aged 32.6 +/- 14.0 years old) were subjected to this study. The results obtained were as follows: Urinary protein excretion after 1 year from the beginning of steroid therapy (1.56 +/- 1.14 g/day) was significantly (p less than 0.05) lower than that at the beginning of the therapy (4.61 +/- 6.01 g/day). In serum creatinine levels, there was no statistically significant difference with them between at the beginning (1.15 +/- 0.48 mg/dl) of steroid therapy and at the time of 1 year after (1.05 +/- 0.34 mg/dl) the therapy. As for the outcome at the end of this study setting (mean follow-up duration: 3.7 +/- 2.6 years), complete remission was attained in 7 cases, improvement in 5 cases, unchanged condition in 11 cases, increased urinary protein excretion in 2 cases and aggravated renal function in 1 case. In clinical findings at the renal biopsy, duration of the disease (3.4 +/- 1.6 months) in complete remission cases before biopsy was significantly (p less than 0.01) shorter than that in unchanged cases (65.0 +/- 40.0 months). In histological findings, rate of global sclerosing glomeruli (2.6 +/- 4.6%) in complete remission cases was significantly (p less than 0.05) lower than that (24.6 +/- 23.1%) in unchanged cases. These results suggest that steroid therapy in IgA nephropathy with persistent proteinuria of 1.0 g/day or more is beneficial, especially in cases that are in early stage of the disease with lower rate of global sclerosing glomeruli.
Adolescent↗
[A case of familial lecithin: cholesterol acyltransferase deficiency].
Lecithin: cholesterol acyltransferase (LCAT) is an enzyme that catalyzes the esterifying reaction of cholesterol in plasma high density lipoprotein (HDL). Deficiency of LCAT is a rare hereditary disease characterized by several clinical symptoms such as proteinuria, corneal opacity, and anemia due to a shortened life span of erythrocytes. In this communication, we report a case of 40 year-old female patient of LCAT deficiency. She visited a hospital for work-up of proteinuria, corneal opacity and anemia. Activity of her serum LCAT was found to be extremely low, and characteristic changes in plasma lipids due to deficiency of LCAT was observed: those were marked decreases in HDL-cholesterol, degree of esterification in serum cholesterol, and apoprotein A-I, A-II, B and C-II levels. The diagnosis of LCAT deficiency was finally made. We studied about histopathological changes in the patient's kidney, and erythrocyte membrane lipid composition and fluidity. Histopathological findings in renal biopsy were follows: a) Light microscopy showed spherical deposits stained with periodic acid-Schiff in mesangial matrix and adjacent capillary loops, and hyaline deposits in arterioles, b) Electron microscopy showed vacuoles in mesangial matrix and along the glomerular basement membranes. In erythrocyte membrane lipids, increase of cholesterol to phospholipid molar ratio was evident, being accompanied by changes in phospholipid fractions: increase of phosphatidylcholine, and decreases of phosphatidylethanolamine, sphingomyelin and lysophosphatidylcholine. In phospholipid acyl chains, increase of C18:2 and decreased of C18:1 were evident in the patient. Erythrocyte membrane fluidity was found to be decreased in the patient in a measurement by pyrene, probably being related to the changes in membrane lipid composition.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗