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Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 1,171 records · Page 65Linked to original sources
PubMed1989

Transgenic mouse model of familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is a dominantly inherited disorder, characterized by the extracellular deposition of amyloid fibrils composed of variant transthyretin (TTR), and by prominent peripheral nerve involvement. We demonstrate that the main cause of this disease is the presence of a point mutation in the TTR gene. However, neither the time of onset nor the clinical course is predictable. To elucidate the molecular pathogenesis of this disease, we constructed transgenic mice carrying and expressing the human mutant TTR gene. In these mice, amyloid is deposited in the alimentary tract as early as age six months, and becomes more remarkable with aging. These transgenic mice should be useful in elucidating factors which modulate the time of onset and the clinical course of FAP, and in establishing therapy for this intractable disorder.

Amyloidosis↗
PubMed1989

Temperature-induced alterations in protein composition of newt papilloma cells.

Protein patterns of Japanese newt papilloma in vivo at low (4 degrees C), normal (10 degrees C, control) and elevated (30 degrees C) temperature were investigated by two-dimensional gel electrophoresis. There were nine protein spots in normal skin (skin specific spots: SSS) which did not exist in papillomas. At 10 degrees C, the papillomas possessed three specific protein spots (papilloma specific spots: PSS) which did not appear in normal skin. At the reduced environmental temperature, eight of the nine missing proteins in papillomas had reappeared by 12 weeks exposure. Differential responses in reappearance of SSS in papillomas varied with environmental temperature. The PSS generally were unchanged by environmental temperature modulation, although one specific protein disappeared at 12 weeks at 4 degrees C. Reappearance of normal SSS in papillomas occurred early in treatment and reflected only minor variations in high versus low temperature exposures. These data suggest that temperature-induced tumor regression may be associated with changes in protein composition.

Animals↗
PubMed1989

The modulation of heparin-like activity of endothelial cells in experimental systems.

Anticoagulantly active heparin-like glycosaminoglycans are apparently present on the vascular surface. We have tried to modulate heparin-like substances on endothelial cells using an experimental cell culture system. Perturbation of the endothelial proteoglycan metabolism by beta-D-xyloside resulted in a reduced biosynthesis of cell surface heparan sulfate, and impaired antithrombin III binding to endothelial cells in parallel with an inhibition of endothelial cell heparin-like activity. In a separate series of experiments, treatments of endothelial cells with interleukin 1 beta and tumor necrosis factor alpha, physiological mediators of immunologic and inflammatory responses, were shown to cause an inhibition of the synthesis of endothelial cell surface heparan sulfate. The endothelial heparin-like activity was partially diminished by these cytokines, suggesting that cytokine-mediated suppression of heparin-like substance on endothelial cells is another cytokine-inducible endothelial effect affecting coagulation. The modulation of endothelial heparin-like activity by these pharmacological and physiological agents may have pathophysiological implications in thrombosis.

Animals↗
PubMed1989

Ha-ras oncogene product in human oral squamous cell carcinoma.

The expression of Ha-ras oncogene product (Ha-ras p21) in the biopsy or operation materials derived from 70 oral squamous cell carcinomas, 10 oral leukoplakias and 10 normal oral mucosae was examined immunohistochemically using anti-Ha-ras p21 antibody. Ha-ras p21 was detected in 43 (61%) of 70 carcinomas, 3 (30%) of 10 oral leukoplaskias and 3 (30%) of 10 normal oral mucosae. Patients with Ha-ras p21-positive carcinomas had a significantly worse prognosis than those with Ha-ras p21-negative carcinomas. These observations strongly suggest that the expression of Ha-ras p21 is a common event in oral squamous cell carcinomas, and that Ha-ras p21 serves as a tissue tumor marker for determining the prognosis of patients with oral squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed1989

[Transurethral ureterolithotripsy under hydraulic ureteral dilatation].

Transurethral ureterolithotripsy was performed in 32 patients with ureteral stones. A rigid ureteroscope was used and for the purpose of ureteral dilatation a hydraulic ureteral dilator (Ureteromat) was used. In total 39 stones were treated and of these 30 stones (77%) were successfully extracted or disintegrated. The success rate according to the location of the stone was as follows; 50% for the upper ureteral stone, 55% for middle ureteral stone and 96% for lower ureteral stone. As a complication of the procedure a lower ureteral stricture was noted in one patient. Hydraulic ureteral dilatation is a useful method of ureteral dilatation in transurethral ureterolithotripsy.

Adolescent↗
PubMed1989

Ornithine transcarbamylase deficiency resulting from a C-to-T substitution in exon 5 of the ornithine transcarbamylase gene.

To define the molecular basis for the TaqI site alteration in the ornithine transcarbamylase (OTC) (E.C.2.1.3.3) gene of a female patient with mild OTC deficiency, we used a combination of genomic amplification followed by direct sequencing and oligodeoxyribonucleotide hybridization. We obtained evidence for a C-to-T substitution in exon 5 (codon 141) of this gene. This mutation generates a stop codon, in place of Arg, at amino acid 109 of the mature OTC protein. The mutation arose, de novo, in a germ cell of one of the parents.

Adolescent↗
PubMed1989

[A case of aseptic meningoencephalitis with recurrent abnormal behavior, status epilepticus and aphthous stomatitis, improved by acyclovir].

A case of aseptic meningoencephalitis with recurrent abnormal behavior, status epilepticus and aphthous stomatitis was described. A 39-year-old man, who had a history of low grade fever and abnormal behavior over 2 years without mucocutaneo-ocular symptoms, was admitted to Shinshu University Hospital because of status epilepticus. On admission, neurological examination revealed comatose state with neck stiffness, anisocoria (right greater than left), conjugate deviation to right and bilateral pyramidal tract signs. His cerebrospinal fluid examination revealed a total protein content of 206 mg/dl with 22 lymphocytes and 134 polymorphonuclear leukocytes/mm3. EEG recorded on the 3rd hospital day showed periodic sharp waves and polyspikes, occurring every 1 seconds, predominantly arise from the right hemisphere, which corresponds to periodic lateralized epileptiform discharges (PLEDs). Herpes simplex encephalitis was suspected and acyclovir was administered. Neck stiffness and cerebrospinal fluid findings were improved and PLEDs disappeared. But aphthous stomatitis appeared and meningoencephalitis was relapsed. Laboratory examination revealed erythrocyte sedimentation rate 40 mm/hr, positive C-reactive protein, elevated CH50 and sialic acid, enhanced migration of neutrophils and HLA-B 51. Neuro-Behçet's syndrome was strongly suspected with laboratory data but the clinical course was atypical. His clinical signs were markedly improved after administration of prednisolone. The present case suggests that neuro-Behçet's syndrome with only a part of major symptoms could be diagnosed as viral encephalitis and acyclovir may be effective for the treatment of neuro-Behçet's syndrome.

Acyclovir↗
PubMed1989

[Water and electrolyte metabolism in the elderly with cardiovascular disease--hormonal aspects in elderly hypertension].

Study I: A retrospective survey of the data base on serum electrolyte measurements in our hospital (approximately 50,000 cases) revealed that the incidence of hyponatremia increased with age. Its major cause in the elderly hospital inpatients with cardiovascular disease was congestive heart failure, frequently accompanied by renal dysfunction and the use of diuretics. Another interesting finding from this analysis was that the use of potassium sparing diuretics were often associated with hyperkalemia in elderly patients whose renal functions were apparently normal based on the serum creatinine level. Study II: The resting hemodynamics and the plasma levels of various hormones related to water and electrolyte metabolism were compared between normal elderly and young subjects. The resting hemodynamic parameters, including cardiac index and blood pressure, did not differ between the two normal groups. Plasma atrial natriuretic peptide and norepinephrine levels were significantly higher in the elderly, while plasma renin activity and aldosterone levels were significantly decreased. No differences were observed in antidiuretic hormone levels. The same parameters were then compared between normal and hypertensive elderly subjects. Elderly hypertensives had lower cardiac index and higher peripheral resistance than normal elderly subjects. Plasma norepinephrine level and plasma renin activity were lower, but aldosterone level was not significantly lower in hypertensives than in normotensives. There was no difference in antidiuretic hormone. In the elderly group as a whole, atrial natriuretic peptide correlated positively with blood pressure, and negatively with plasma norepinephrine and renin activity. Multivariate analysis showed that the strongest correlation was that with plasma renin activity. These results suggest that the plasma levels of various hormones related to water and electrolyte metabolism were altered with age and hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Clinical statistics on outpatients, inpatients and operations in 1987].

Statistical studies were made on 1,859 outpatients, 587 inpatients and 601 operative procedures at our department in 1987. The most frequent diseases among the outpatients were urogenital infections followed by anomalies, tumors and stones. The major diseases among the inpatients were hypospadias, vesicoureteral reflux, congenital urethral stenosis, benign prostatic hypertrophy and bladder tumor. A total of 601 operations were performed. The five major operations were hypospadias repair, optic internal urethrotomy, transurethral resection of prostate, ureterocystoneostomy and transurethral resection of bladder tumor.

Hospital Departments↗
PubMed1989

Histidine-rich glycoprotein does not interfere with interactions between antithrombin III and heparin-like compounds on vascular endothelial cells.

The role of histidine-rich glycoprotein in controlling heparin-like compounds on the endothelial cell surface is still unclear. The effects of this heparin-neutralizing protein on the interaction between antithrombin III and cultured porcine aortic endothelial cells were examined. Displacement of 125I-labeled antithrombin III specifically bound to endothelial cells by unlabeled histidine-rich glycoprotein was much less potent than that by unlabeled antithrombin III. One hundred-fold molar excess of histidine-rich glycoprotein displaced specific 125I-antithrombin III binding only by 20%. Furthermore, the endothelial cell-mediated acceleration of thrombin inactivation by antithrombin III was diminished by protamine sulfate, but was not affected by histidine-rich glycoprotein even at a histidine-rich glycoprotein/antithrombin III molar ratio of approximately 7:1. These data indicate that histidine-rich glycoprotein does not interfere with the interaction of endothelial cell heparin-like compounds with antithrombin III. Thus, it may not play an important role in the modulation of anticoagulant activity of endothelial cells in vivo, suggesting that the commonly accepted view of the probable function of this protein is erroneous.

Animals↗
PubMed1988

Messenger RNA expressed in mouse teratocarcinoma stem cells and down-regulated by a tumor-promoting phorbol ester codes for a novel transmembrane protein.

Cloning and sequence analysis of a DNA complementary to the mRNA expressed in undifferentiated mouse F9 teratocarcinoma stem cells but disappearing rapidly after treatment with a tumor-promoting phorbol ester revealed it to be a 1.9 kilobase pairs-long cDNA encoding a protein of 323 amino acid residues. Computer-assisted analyses of the deduced amino acid sequence indicated that this protein contains a typical hydrophobic signal peptide consisting of 33 amino acid residues and six putative membrane-spanning segments. The deduced amino acid sequence, as a whole, bears no significant sequence homology to any previously described protein.

Amino Acid Sequence↗
PubMed1988

Structure of the mouse C-reactive protein gene.

A genomic DNA clone corresponding to the mouse C-reactive protein (CRP) has been isolated and characterized. The mouse CRP gene is 1.9-kilobase pairs in length and contains a single intron of 213-base pairs which interrupts the codon for the 2nd amino acid residue of the mature CRP protein. We compared nucleotide sequences of the mouse and human CRP genes and discussed structures of possible regulatory sequences. With this characterization, the isolation and sequence analyses of a set of mouse and human pentraxin genes, i.e. CRP and serum amyloid P component genes is not complete.

Amino Acid Sequence↗