The inhibition of murine lung metastasis by synthetic polypeptides [poly(arg-gly-asp) and poly(tyr-ile-gly-ser-arg)] with a core sequence of cell adhesion molecules.
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Biomedical subjects
Publications and source records attributed to K Sugimura.
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From July 1985 to June 1987, 303 patients with ureteral stones were treated by either extracorporeal shock-wave lithotripsy (ESWL) or transurethral ureterolithotripsy (TUL). The ureteral stones were classified into two groups, upper and lower ureteral stones. The upper ureteral stone was defined as a stone located above the pelvic brim in radiological examinations. ESWL was performed using a Dornier lithotriptor HM-3. For TUL, following the insertion of a guide wire and dilatation of the intramural ureter by ureteral bougie, a ureteroscope was introduced into the ureter. The success rate included both patients who became stone free and patients whose stones were disintegrated into less than 4 mm. The success rate of ESWL for upper ureteral stones was 90%, and 8.5% were treated subsequently by TUL. The success rate of TUL for upper ureteral stones was 42%, and the remaining required another session of TUL or another procedure, mainly ESWL. On the other hand, the success rate of TUL for lower ureteral stones was 71%, and the remainder also required another session of TUL or another procedure, mainly ESWL. The efficacy of TUL for stone street was comparably low by the evaluation done at 5 days after the procedure. However, almost all patients with stone street, which had developed after ESWL treatment, became stone free several weeks after TUL and insertion of a stent catheter. Major complications or side effects for ESWL were fever of more than 37.5 degrees C (7.5%) and pain attacks (8.9%).(ABSTRACT TRUNCATED AT 250 WORDS)
During the 39 months since the introduction of transurethral lithotripsy (TUL) for the treatment of ureteral stones at our hospital in August 1985, TUL was performed a total of 200 times in 178 patients with ureteral stones. Among them, 111 patients had left ureteral stones and 65 had right ureteral stones, while 2 patients had ureteral stones in both sides. The stones were divided into upper ureteral stone (84 patients) and lower ureteral stone (94 patients) at above and below the iliac brim. 89% of the stones were less than 2 cm in diameter. Most of the patients were given lumbar anesthesia, and a guide wire was inserted into the ureter. The ureter was dilated with a ureteral bougie, and a 13F or 14F Storz ureteroscope was inserted. The stones were disintegrated by an ultrasound lithotripto and removed using forceps and a basket catheter. After the TUL procedure, a double J catheter was indwelled and removed within 5 days. The results were evaluated by DIP which was done 2 to 3 months after TUL. The success rate included residual stones less than 4 mm in diameter, as they could be spontaneously discharged. As a result, the success rate for upper ureteral stones was 53%, and it was higher for smaller stones. On the other hand, the success rate for lower ureteral stones was 85% and significantly higher. The main reasons for failure were the upper migration of the stones (60%) and inability to insert the ureteroscope up to the stone due to ureterostenosis and ureteral perforation (39%).(ABSTRACT TRUNCATED AT 250 WORDS)
A seventy-year-old woman was admitted to the hospital because of paresthesias and progressive weakness of the extremities. Ten months previously, tightness in the thighs and numbness in the fingers developed, with subsequent tingling sensations of the hands and feet. Three months before entry, she had difficulty in walking because of severe paresthesias in the extremities. She was found to have an abnormal mass in a X-ray film of the chest, and transferred to our hospital. Neurological examination showed generalized hyporeflexia, marked loss of deep and discriminative sensations in the distal portion of the limbs, positive Romberg sign and severely ataxic gait. Cerebellar sign was negative. Cytologic examination of a transbronchial lung biopsy disclosed small cell carcinoma of the lung. A sural nerve biopsy showed severe loss of myelinated fibers accompanied by axonal degeneration of residual fibers. Immunohistochemically antineuronal antibody was found in the serum but not in the CSF, which reacted to nuclei and cytoplasm of the dorsal root ganglion neurons as well as Purkinje cells. Titers of this autoantibody in the serum were markedly reduced after chemotherapy and irradiation. Western blot analysis demonstrated that autoantibody in the serum recognized neuronal antigen with single band at 38 kd. Pathogenesis of carcinomatous neuropathy is still unexplained, but the findings here presented have given rise to the speculation that antineuronal antibody may be a contributory factor in carcinomatous neuropathy.
The kidney stone of less than 2 cm can be effectively treated by extracorporeal shock wave lithotripsy (ESWL) using a Dornier kidney lithotripter HM3 without any complication that might need other therapy. However, in the case of a large kidney stone and ureteral stone, there are some difficulties in the treatment with ESWL. To obtain better results for these stones with a Dornier kidney lithotripter HM3, in the patient having a large stone a double-J stent was placed and ureteral catheter was indwelling for the ureteral stone before ESWL. In some cases high frequency positive pressure ventilation (HFPPV) was applied to make respiratory movement of the stone minimum. An indwelling double-J stent can significantly decrease the necessity of auxiliary treatment and the incidence of high fever attack. Manipulation of a ureteral stone with a ureteral catheter did not facilitate stone disintegration, and also the success rate as compared with in situ ESWL. HFPPV can decrease the stone movement within 2 mm judged on the X-ray monitor and increase the effectiveness of the shock wave on the stone, leading to minimize not only shock wave dose but also side effects from shock wave exposure.
A 22-year-old woman admitted to the hospital on Mar. 19, 1985 because of syncopal attacks and numbness on the limbs. Examination revealed peripheral sympathetic as well as parasympathetic dysfunctions and loss of myelinated as well as unmyelinated fibers in a biopsied sural nerve. A diagnosis of acute autonomic and sensory neuropathy (AASN) was made. She was treated with prednisolone but did not respond to the therapy. Only L-DOPS was effective on orthostatic hypotension. Recovery of the neurological conditions was insufficient till May 1987, when she complained of easy fatigability when speaking and chewing. Pharmacological and electrodiagnostic tests showed typical myasthenic phenomenon. At this time, serum anti-ACh receptor antibody was 741nmol/l and a diagnosis of myasthenia gravis was confirmed. Anti-ACh receptor antibody was proven to be elevated in the serum collected on April 1985 when the initial symptom of AASN had appeared. A thymectomy resulted in prompt and complete remission of semiologies of both myasthenia gravis and AASN. These suggest that immunological abnormality might play an important role in the pathogenesis of AASN in this case.
Three siblings with hereditary motor and sensory neuropathy with spastic paraplegia (HMN V) were described. Their grandfather was suspected to have the similar symptoms. Their parents were normal and not consanguineous. The first case was a 54-year-old woman. She has suffered from difficulty in walking since the age of 10 years. Distal muscular weakness and wasting began at 20 years old. She was admitted to our hospital for investigation in 1988. Results of examination of the brain, cranial nerve, and cerebellar function were normal. The deep reflexes were hyperactive in the arm and knee, while absent at the ankle. Babinski's sign was definitely positive. Muscular weakness and wasting were noted in intrinsic hand muscles and in those below her knees. There were pes cavus and hammer toes, and the gait was spastic. Mild sensory disturbance was noted in distal limbs. The conduction velocity of motor nerve fibers of her limbs was below normal and that of sensory nerve fibers normal. Muscle biopsy of biceps brachii revealed neurogenic changes. Sural nerve biopsy showed decreased number of myelinated fibers of large diameter and formation of small oinion-bulb. The second and third cases were her brothers and proven to have the similar condition, but their onset of illness were earlier and their affections were more severe. A few cases of HMSN V with nerve biopsy findings have so far been reported and the family presented here is the first report in Japan.
Three-dimensional reconstruction from N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography has been applied clinically to the detection of perfusion defects in 22 cases (15 cerebrovascular diseases and 7 normal controls confirmed by CT and MRI), with data being analyzed in terms of receiver operating characteristic curves (ROC). The results showed that three-dimensional (3-D) image could make better diagnostic capability especially in inexperienced examiner and that it was useful decreasing of difference of diagnostic capability. 3-D image could be taken within 1 minute and 15 seconds. We concluded that the three-dimensional brain imaging with IMP using this system was clinically useful because examiner could easily diagnose perfusion defects.
Rat cytotoxic cell-generating factor (CGF) was purified from cell-free supernatants of a T cell hybridoma (6B2-B8) that constitutively produces CGF. CGF activity was assessed by its ability to generate cytotoxic cells against 51Cr-labeled T-9 cells from spleen cells of T-9-immunized rats. The purification scheme consisted of ammonium sulfate precipitation, AcA 54 gel permeation, Mono Q anion exchange chromatography, Superose 12HR 10/30 gel permeation, SDS-PAGE with subsequent electroelution, and ProRPC HR5/10 reverse phase column chromatography. Overall, CGF was purified approximately 13,000-fold, with a maximum 2.5% recovery of activity, and the sp. act. of the purified CGF was approximately 19,000 U/mg. The purified CGF is distinct from the other lymphokines such as IL-1, IL-2, IL-3, IL-4, T cell-replacing factor/IL-5, IL-6, and IFN-gamma. It is capable of promoting the generation of cytotoxic T cells from R1-10B5 (+) spleen cells of T-9-immunized rats and also stimulates a W3/25 (+) T cell hybridoma to express the IL-2R. The CGF has an apparent m.w. of 28,000 under non-reducing and 14,000 and 16,000 under reducing conditions. 125I-labeled CGF binds to normal thymocytes as well as splenic T cells. The highest level of binding of CGF was detected on splenic T cells derived from T-9-immunized rats that were previously shown to contain CTL precursors. The binding analysis with 125I-labeled CGF demonstrated that CGF binds to a specific cell surface molecule with an approximate m.w. of 60,000 to 70,000.
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A mutant of Escherichia coli lacking protease VII, the outer membrane-associated protease which specifically cleaves paired basic residues (1), was isolated by using N-methyl-N'-nitro-N-nitrosoguanidine treatment. The mutant exhibited no significant change as for its growth rate and microscopic feature compared with wild cells. The gene encoding protease VII was cloned by using complementation analysis of protease VII (-) mutation. The minicell experiment showed that the gene encoded a putative precursor protein of 38,000 Mr which was processed into a protein of 36,000 Mr suggesting the presence of a signal peptide on the putative precursor.
The human macrophage-like cell line U937 constitutively produces a lymphocyte blastogenesis inhibitory factor (LBIF). Using fast protein liquid chromatography (FPLC)-chromatofocusing, FPLC-anion-exchange chromatography and high-performance liquid chromatography-gel permeation chromatography, LBIF has been purified to homogeneity. It is a single polypeptide chain and has a molecular weight of 57,000 daltons according to sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions. LBIF shows pI 4.28-4.56 upon chromatofocusing on Mono P.
A 21-year-old woman in a family with a history of Fabry's disease showed orthostatic hypotension and whorl-like corneal opacity typical for Fabry's disease. Biochemical studies revealed that she was a heterozygote of the Fabry gene. A variety of autonomic function tests demonstrated both sympathetic and parasympathetic dysfunction. To our knowledge, the present case is the first report of a heterozygous female carrier of Fabry's disease presenting dysfunction of the autonomic nervous system.
Escherichia coli cells were found to contain a novel outer membrane-associated protease, designated protease VII (K. Sugimura and N. Higashi, J. Bacteriol. 170:3650-3654, 1988). This enzyme was purified to homogeneity and exhibited an apparent molecular weight of 36,000 on sodium dodecyl sulfate gels and 180,000 on a TSK G-3000SW column in the presence of Triton X-100. It was capable of cleaving several peptides at the center of paired basic residues but not at single basic residues, implying that it is distinct from trypsinlike proteases. Protease VII was most active at pH 6.0 and was sensitive to a serine protease inhibitor, diisopropylfluorophosphate, and to the bivalent cations Zn2+, Cu2+, and Fe2+. The nucleotide sequence of a protease VII gene-carrying DNA fragment, which had been cloned by complementation analysis (K. Sugimura, Biochem. Biophys. Res. Commun. 153:753-759, 1988) was determined. It carried two putative promoter regions and a putative Shine-Dalgarno sequence in addition to the complete structural gene, which encoded pre-protease VII of 317 amino acid residues, with the N-terminal 20 residues being a signal peptide. By comparing their amino acid sequences, protease VII and OmpT, which specifically cleaves ferric enterobactin receptor protein, were found to be identical.
Human gamma interferon produced by recombinant Escherichia coli was degraded by endogenous protease after cell disruption. Specific cleavages took place at the center of two pairs of basic amino acids (Lys-131-Arg-132 and Arg-142-Arg-143) in the C-terminal region, giving rise to products with molecular weights of 17,500 and 16,000. The proteolytic activity was associated with the outer membrane of E. coli. It was insensitive to the protease inhibitors diisopropylfluorophosphate, phenylmethylsulfonyl fluoride, tosyl-L-lysine chloro-methyl ketone, EDTA, and p-chloromercuribenzoate. Benzamidine and the bivalent cations Zn2+ and Cu2+ inhibited the activity. Dynorphin A(1-13) (Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys) was a good substrate and was preferentially cleaved at the center of Arg-6-Arg-7. Neither the amino nor carboxyl sides of Arg-9 and Lys-11 were digested. These results indicate that the protease specifically cleaves the peptide bond between consecutive basic residues and therefore is different from the known membrane enzymes, proteases IV, V, and VI. We have designated this new enzyme protease VII.
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We have isolated a putative phosphorylcholine (PC)-T cell suppressor factor (TsF) cDNA clone, p6-5, from a cDNA library of a T hybridoma which constitutively secretes a PC-TsF in vitro [8]. In the present study, we determined the nucleotide sequence of the p6-5 gene and found that the p6-5 sequence is 86% homologous to rat preproelastase 1 gene, one of the serine protease genes. An oligopeptide (14 mer, TsF14) deduced from the p6-5 sequence was synthesized and antisera against TsF14 were prepared in rabbits. Anti-TsF14-conjugated Sepharose 4B specifically absorbed the PC-TsF activity from the culture supernatant of PC-TsF-secreting T hybridomas. In contrast, the binding molecule eluted from the anti-TsF14-conjugated Sepharose suppressed the antibody response PC specifically. These results indicated that the p6-5 polypeptide is a component of the PC-TsF molecule.