Biomedical subjects
Publications and source records attributed to S Kudo.
The localized form of tenosynovial giant-cell tumor is rarely located intraarticularly, especially in the large weight-bearing joints. We report the first case of localized, intraarticular tenosynovial giant-cell tumor arising from the anterior cruciate ligament of a knee in which locking and effusion had occurred. After arthroscopic removal of this tumor, the patient became asymptomatic.
We have recently shown that mechanical stress activates a phosphorylation cascade of protein kinases including Raf-1 and the extracellular signal-regulated kinases (ERKs) in cultured cardiac myocytes partially through the enhanced secretion of angiotensin II. Osmotic stress in budding yeast has been shown to activate similar signaling molecules including Hog-1, a distant relative of the ERK family. In the present study, we examined whether mechanical stretch of cardiac myocytes activates the stress-activated protein kinases (SAPKs)/c-Jun NH2-terminal kinase, the mammalian homologs of yeast Hog-1 that regulate gene expression through activation of the transcription factor, AP-1. When cardiac myocytes of neonatal rats cultured on a deformable silicone dish were stretched, activity of SAPKs was increased from 10 min, peaked at 30 min, and gradually decreased thereafter. The increase in activity of SAPKs was proportional to the stretch. Unlike ERKs, the activation of SAPKs by stretching cardiac myocytes was not dependent on the secreted angiotensin II. The chelation of extracellular Ca2+ or down-regulation of protein kinase C did not attenuate activation of SAPKs by stretch. Transfection experiments using an AP-1 binding site-containing reporter gene revealed that stretch increases AP-1 activity in cardiac myocytes. In conclusion, like osmotic stress in yeast, mechanical stretch activates SAPKs in cardiac myocytes without the participation of angiotensin II. These results suggest that the activation of SAPKs may regulate gene expression during mechanical stress-induced cardiac hypertrophy.
An 82-year-old Japanese male developed nodules and ulcers along the lymphatics after a fall in the garden of his house resulting in injuries to the dorsum of his left hand which lasted for 3 months. Nocardia brasiliensis was isolated from a nodule, supporting a diagnosis of the lymphocutaneous type of nocardiosis. He had previously developed generalized bone metastasis from prostatic cancer, and his resulting depressed immunity might have played a part in the nocardiosis genesis. Sixteen cases of the lymphocutaneous type of nocardiosis reported in Japan were reviewed.
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Acute renal failure (ARF) with loin pain after exercise with development of wedge-shaped contrast enhancement on computed tomography (CT) has been described as a new disease entity. We report 2 patients who developed ARF with severe loin pain after exercise, showing wedge-shaped lesions both on CT and ultrasonography. Renal ultrasonography showed indistinct wedge-shaped lesions when performed at oliguric or recovery phase of ARF, whereas it showed distinct lesions when done between these two phases. Contrast CT performed at the recovery phase disclosed distinct wedge-shaped lesions. Our findings suggested that the best time to detect these lesions by ultrasonography is between at the beginning of diuresis and at the time of serum creatinine levels of 2 mg/dl.
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We report a case of Takayasu arteritis. A woman, 24 years old, was admitted because of fever of unknown etiology. Infection was ruled out. Bruit and asymmetrical pulsation were not found. Ga-scintigram showed abnormal uptake in her upper abdomen. Abdominal echogram revealed neither evidence of abscess nor lymphadenopathy. On abdominal computed tomography, a wall thickening of the abdominal aorta was revealed. In addition, abdominal magnetic resonance imaging(MRI) showed a wall thickening and an enhanced image by gadrinium enhancement. Although we could not carry out conventional aortography because of an allergy to lidocaine, she was diagnosed as having Takayasu arteritis. In response to steroid therapy, the fever promptly dropped and the data indicating inflammation were improved. On the MRI examination after 40 days of steroid therapy, the wall thickening of the abdominal aorta was found to be less prominent. We conclude magnetic resonance imaging is useful for diagnosis and follow-up of early and acute stage of Takayasu arteritis.
Soybean transphosphatidylated phosphatidylserine (SB-tPS) was prepared from soybean phosphatidylcholine by transphosphatidylation using phospholipase D, and the fatty acids composition and pharmacological properties were compared with those of bovine brain cortex-derived phosphatidylserine (BC-PS) which was reported to improve cognitive disorders of senile dementia patients by oral administration (300 mg/day). The molecular species of SB-tPS are rich in linoleic and palmitic acids whereas those of BC-PS are stearic and oleic acids. Despite the differences in fatty acid composition, SB-tPS displayed significant activities on the increase in brain glucose concentrations in mice (79 mg/kg, i.v.) and the restoration of scopolamine-induced amnesia in rats (60 mg/kg, i.p.) as did BC-PS. These results suggest the possibility that SB-tPS may prevent and/or improve senile dementia by oral administration.
BACKGROUND: Nephron-sparing surgery is ideal in the treatment of renal angiomyolipoma (AML). But, in fact, occasional cases are found in post-ruptured AML and/or in bilateral multiple AMLs, that is seen in tuberous sclerosis. And we cannot perform nephron sparing surgery so easily. We proposed the treatment selection in such complicated AML. METHODS: We experienced 10 cases (12 kidneys) for about ten years, and studied our treatment selection and prognosis on each cases retrospectively. RESULTS: Of the 5 kidneys with AML less than 4 cm in diameter, 4 have not encountered with rupture. Of the 7 kidneys with AML more than 4 cm in diameter, 4 kidneys had rupture. Of the 3 kidneys unruptured AML more than 4 cm in diameter, 2 kidneys were treated by enucleation and we performed preventive embolization for rupture in residual one kidney. The patients was suffered from tuberculosis sclerosis, and she had bilateral multiple AMLs. Of the 4 kidneys with ruptured AML, 2 kidneys were treated by enucleation, and the other 2 kidneys were entirely resected. We succeeded enucleation in 2 of 4 kidneys with ruptured complicated AML. In those cases, we did long term watching after rupture and in-situ perfusion technique at the operation. CONCLUSIONS: Active treatment of AML, that is more than 4 cm in diameter, might be recommended. Because most of those will be ruptured. The ideal treatment, nephron-sparing surgery is difficult in complicated situation, such as after rupture and bilateral multiple AMLs. In our opinion, the point of success of nephron-sparing surgery might be long term watching after rupture and in-situ perfusion technique at the operation.
The diagnostic value of high N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) uptake in histologically proven intracranial tumors was evaluated in 54 patients with both early (15-35 min after injection) and delayed (4 hours) SPECT before treatment. Higher uptake in the tumor compared with normal cerebral cortex was observed in early scans in all of the five patients with primary intracranial malignant lymphoma, in two of 16 meningiomas, two of seven astrocytomas, one of three pituitary adenomas, and one central neurocytoma. Among these 11 cases all the malignant lymphomas showed persistent high uptake in delayed scans, whereas other tumors showed decreased uptake in delayed scans. This persistent high 123I-IMP uptake was characteristic of primary intracranial malignant lymphomas and was useful in the diagnosis of intracranial malignant lymphoma.
We describe a case of giant cell reparative granuloma in the cranial vault, which is an extremely rare location for this entity. CT scans showed an enhancing skull tumor with no surrounding sclerosis in the frontal bone. MR images showed a mass isointense with gray matter on both T1- and T2-weighted images.
A late phase II study of LY188011 (gemcitabine hydrochloride), a new synthetic anticancer agent, was conducted at 20 Japanese institutions to evaluate the efficacy and safety of the agent administered alone in patients previously untreated with chemotherapy for primary non-small-cell lung cancer (NSCLC). All of the total 73 patients enrolled were eligible and 69 completed at least one course of LY188011 therapy. All patients were evaluated for safety. The response rate was 26.0% (19/73) of eligible patients. The most common adverse reactions included decreased hemoglobin, leukopenia, neutropenia, anorexia, nausea/vomiting, and malaise. Most adverse reactions were of grade 1 or 2 and only a few grade 3 or 4 reactions were reported. However, since a death occurred due to interstitial pneumonia, careful observation for this event is needed. Based on these results, it may be concluded that LY188011, a new anticancer agent, has adequate efficacy for the treatment of NSCLC and causes few clinically relevant adverse reactions.
Protruded polyps can usually be treated with conventional polypectomy technique. Slightly elevated lesions without malignant findings are treated with hot biopsy method if they are small enough (less than 5 mm). In order to treat flat or slightly depressed lesions or slightly elevated lesions larger than 5 mm, endoscopic mucosal resection (EMR) technique has been invented. Cancers confined to the mucosa or those only minimally invading the submucosa can be completely removed with this method. However, if histological analysis of the resected specimen shows that the cancer invades the submucosa massively or permeating the vessels, surgical treatment should be added, because otherwise there would be risk of cancer residue or metastasis. When a lesion is suspected to be a submucosal cancer by endoscopic findings and pit pattern analysis from the beginning, then surgical resection is the treatment of choice. Laterally spreading tumors, especially the homogeneous granular type, are good indication for EMR or endoscopic piecemeal mucosal resection (EPMR). It is important to remove the lesion completely confirming that the resection margin is covered with normal pits.
Golgi alpha-mannosidase II (alpha-MII) is an enzyme involved in the processing of N-linked glycans. Using a previously isolated murine cDNA clone as a probe, we have isolated cDNA clones encompassing the human alpha-MII cDNA open reading frame and initiated isolation of human genomic clones. During the isolation of genomic clones, genes related to that encoding alpha-MII were isolated. One such gene was found to encode an isozyme, designated alpha-MIIx. A 5-kb cDNA clone encoding alpha-MIIx was then isolated from a human melanoma cDNA library. However, comparison between alpha-MIIx and alpha-MII cDNAs suggested that the cloned cDNA encodes a truncated polypeptide with 796 amino acid residues, while alpha-MII consists of 1144 amino acid residues. To reevaluate the sequence of alpha-MIIx cDNA, polymerase chain reaction (PCR) was performed with lymphocyte mRNAs. Comparison of the sequence of PCR products with the alpha-MIIx genomic sequence revealed that alternative splicing of the alpha-MIIx transcript can result in an additional transcript encoding a 1139-amino acid polypeptide. Northern analysis showed transcription of alpha-MIIx in various tissues, suggesting that the alpha-MIIx gene is a housekeeping gene. COS cells transfected with alpha-MIIx cDNA containing the full-length open reading frame showed an increase of alpha-mannosidase activity. The alpha-MIIx gene was mapped to human chromosome 15q25, whereas the alpha-MII gene was mapped to 5q21-22.
Lymphadenectomy of the regional lymph nodes of the rat liver resulted in the direct influx of peripheral hepatic lymph into the thoracic duct after regeneration of lymphatic vessels. Thus, we could obtain the dendritic cells in the hepatic lymph by cannulating the thoracic duct. By the double immunostaining, dendritic cells in cytosmears could be easily determined as non-B, non-T, and MHC class II-positive cells. The yield of dendritic cells after enrichment by the metrizamide density gradient was about 5 x 10(5)/first 16 hr collection/rat, with viability of more than 95% and purity of more than 70%. About 80% of dendritic cells were positive for OX62, which recognized the rat dendritic cell subpopulation. They showed strong stimulating activity in the primary allogeneic mixed leukocyte reaction. The method presented here should be applicable to studies of the roles of liver dendritic cells, especially in transplantation immunity.
The Na(+)-driven flagellar motor in Vibrio alginolyticus rotates very fast. Rotation of a single flagellum on a stuck cell was measured by laser darkfield microscopy with submillisecond temporal resolution. The rotation rate increased with increasing external concentration of NaCl, and reached 1000 r.p.s. at 300 mM NaCl. The Na+ influx through the motor should determine the rotation period (tau) and affect the speed stability. Fluctuation of the rotation period was analyzed at various rotation rates (from approximately 50 r.p.s. to approximately 1000 r.p.s.), which were changed by changing the external concentration of NaCl and the addition of a protonophore or a specific inhibitor. At high rotation rates (over 400 r.p.s.), the observed rotation was stable, and the standard deviation of tau (sigma tau) ranged from 7% to 16% of the average rotation period (< tau >). At low rotation rates (under 100 r.p.s), the rotation period tended to fluctuate, and the distributions of tau were non-Gaussian. The value of sigma tau ranged from 10 to 30% of < tau >. However, the observed minimum value of sigma tau at various rotation rates was approximately equal to the calculated standard deviation due to the rotational diffusion of the flagellar filament. These results suggest that the torque was stably generated at various Na+ influxes through the motor. We observed large fluctuations that cannot be explained by rotational diffusion. We discuss the factors that induce the large fluctuation.
The regulatory element (RE) of the human leukosialin (LS)-encoding gene, that encodes a major sialoglycoprotein of human leukocyte and platelet membranes, was used to develop a novel expression vector, pKX. The vector was constructed by cloning a RE fragment and the SV40 fragment containing polyadenylation and splicing signals between HindIII and BamHI sites of the pCAT-Basic vector. The transcription level controlled by this vector was evaluated in six different cell lines using a transient expression assay of chloramphenicol acetyltransferase (CAT). The CAT activity of the pKX vector was compared to the other common expression vectors, namely pMSG (driven by the mouse mammary tumor virus LTR), pcDL-SR alpha (SV40 promoter/enhancer and HTLV-I LTR), pcDNAI (cytomegalovirus promoter/enhancer) and pCAT-Control (SV40 promoter/enhancer). The level of expression provided by the pKX vector was comparable to that observed with pcDNAI and pcDL-SR alpha vectors. In different mammalian cell lines, the highest efficiency of expression of the pKX vector was observed in the human T-cell lines, Jurkat and CEM, although the expression of pcDL-SR alpha-CAT in those cell lines was in the same range. The expression of the pKX vector driven by a non-viral promoter and/or enhancer can be as efficient as that driven by a viral promoter and/or enhancer. Potential uses of this vector may be found in studies of transient gene expression in hematopoietic cells and for gene therapy, particularly the ones involving T-cells.
Human DNA-binding proteins, dbpA and dbpB (YB-1), are members of a protein family containing a cold-shock domain, and are regarded as transcriptional regulators. Here, we isolated genomic fragments of these genes and characterized their transcriptional regulation. Analysis of lambda phage genomic clones revealed that the dbpA gene consists of 10 exons spanning a 24-kb genomic region. The cold-shock domain, composed of about 70 amino acid residues, is encoded separately by exons 2-5. The exon 6, encoding 69 amino acid residues, was found to be an alternative exon. Northern-blot analysis showed that both genes were highly expressed in skeletal muscle and heart compared with in other tissues. The dbpA gene contains no typical TATA box or CAAT box at the immediate 5' region, but a sequence similar to an initiator consensus sequence was revealed at a major transcription-start site. A transient expression assay using the chloramphenicol acetyltransferase reporter gene revealed that the sequence located at positions -17 to +70 relative to the major transcription-start site was critical for promoter function. Within this region, the consensus sequence for serum-response element, CC(A/T)6GG, is present at positions -13 to -4 in addition to the initiator sequence. Immunofluorescence showed the cellular localization of dbpA to be both in the cytoplasm and nucleus, particularly at the perinuclear region. In situ hybridization demonstrated the localization of the dbpA gene on chromosome 12 band p13.1, whereas dbpB-(YB-1)-related genes were dispersed on many chromosomes with strongest hybridization signals on chromosome 1. All 16 dbpB (YB-1) clones, isolated from the same genomic library used for dbpA genomic cloning, were processed genes because of their intronless structures and multiple mutations. One of these processed genes possesses an open reading frame, which encodes most of the amino acid residues of dbpB (YB-1). These results indicate that dbpA and dbpB (YB-1) genes evolved in different fashions after deviation from a common ancestral gene.