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Biomedical subjects

T Yasuda

Publications and source records attributed to T Yasuda.

At least 19 recordsLinked to original sources

Discovery of a genetic polymorphism of human plasma protein C inhibitor (PCI): genetic survey utilizing isoelectric focusing followed by immunoblotting, immunological and biochemical characterization.

The objectives of this study were to determine the genetic basis of the electrophoretic differences of human plasma protein C inhibitors (PCI) from 977 individuals. Three discrete antibodies were produced against the PCI purified from human plasma and peptides that corresponded to the N-terminal 15 amino acid residues and the C-terminal 15 residues of human PCI, the chemical structures of which were determined by cDNA sequence analysis. The combined techniques of polyacrylamide gel isoelectric focusing and immunoblotting with these three different antibodies resolved the plasma PCI into several isoprotein bands, with a pH range of 6-7. These PCI isoproteins, however, were not stained by anti-human kallikrein, anti-human protein C or anti-human urokinase antibodies. Therefore, each of the PCI bands, which were detected by immunoblotting with the anti-PCI antibody and the two different anti-peptide antibodies, were derived from free PCI, and not an inactive PCI species. Two common phenotypes, designated PCI 1 and 1-2, were recognized, and family studies showed that they represented homozygosity or heterozygosity for two autosomal codominant alleles, PCI*1 and PCI*2. A population study of plasma samples collected from 977 Japanese individuals indicated that the frequencies of the PCI*1 and PCI*2 alleles were 0.988 and 0.012, respectively.

Alleles

Significance of fibrils in the formation of the Kimmelstiel-Wilson nodule.

The pathogenesis of the nodular lesion in diabetic glomerulosclerosis is described in association with fibrils. Thirteen diabetic patients with glomerular nodular lesions and 9 diabetics without the nodules were examined by electron microscopy using periodic acid-thiocarbohydrazide-silver proteinate staining. In cases of nodular glomerulosclerosis, abundant fibrillar structures mixed with electron-dense material were detected within the nodule and the mesangial matrix. They were also occasionally observed along the subendothelial space of the glomerular capillary walls. On the cross-section, these fibrils, including the lucent periphery, were 34 nm wide. Immunohistologically, collagen V and collagen VI were detected in nodular lesions. In contrast, in cases of the diffuse type of glomerulosclerosis, the widened mesangium was composed of dense material, which resembled the original mesangial matrix. The above fibrils were not detected in the mesangium. These findings suggest that the accumulation of the peculiar fibrils in the glomerular mesangium is a major pathogenic factor in the formation of Kimmelstiel-Wilson nodules.

Adult

Radical laser segmentectomy for T1 N0 lung cancer.

Over the last 40 months, 18 lung cancer patients with T1 N0 non-small cell lung carcinoma have been treated with radical laser segmentectomy. This innovative operative method consists of a combination of anatomical or nonanatomical segmentectomy by neodymium:yttrium-aluminum garnet laser parenchyma sparing with complete hilar lymph node dissection. Although the median follow-up period is too short, there is no local recurrence and no cancer deaths. There have been no major complications. Even deep-seated tumors can be resected with a clear safety margin using this method. Radical laser segmentectomy may be a useful adjunct to preserve normal lung tissue and to perform very radical resection.

Aged

The zymogram method for detection of ribonucleases after isoelectric focusing: analysis of multiple forms of human, bovine, and microbial enzymes.

A zymogram method for detection of in situ ribonuclease (RNase) activity, combined with isoelectric focusing in a thin layer of polyacrylamide gel (IEF-PAGE), has been developed. After incubation with a dried agarose film containing substrate RNA, ethidium bromide, and an appropriate reaction buffer, which was placed tightly on the top of the focused gel, sharp and distinct dark bands corresponding to RNase isoenzymes on a fluorescent background appeared under uv light. Addition of urea to the IEF-PAGE gel at a final concentration of 4.8 M permitted optimal focusing of the RNases. This method had not only a high sensitivity of less than 0.1 ng purified RNase A, but also a high band resolution compared with the immunostaining method. It was also useful for analysis of purified enzymes, including bovine pancreatic RNases and two types of human urine RNase as mammalian enzymes, and RNases T1 and T2 as microbial enzymes, as well as for detection of RNases present in crude tissue extracts, resulting in more detailed elucidation of the multiplicity of these enzymes.

Acrylic Resins

1H-NMR assignment and secondary structure of human insulin-like growth factor-I (IGF-I) in solution.

Human insulin-like growth factor-I (IGF-I) was studied by two-dimensional 1H-NMR spectroscopy. Resonance assignments were obtained for all the backbone protons and almost all of the sidechain protons of the total 70 amino acid residues, using sequence-specific assignment procedures. The secondary structure elements of human IGF-I were identified by investigation of the sequential and medium range NOEs as a preliminary step in determining the three-dimensional structure of this protein by means of distance geometry calculations. The typical NOEs of d alpha beta(i,i + 3) and d alpha N(i,i + 3), as well as the successive strong NOEs of dNN connectivities and slowly exchanging amide protons confirmed the presence of three helical segments corresponding to the sequence regions, Ala8-Cys18, Gly42-Cys48, and Leu54-Cys61, and the existence of a beta-turn in the Gly19-Gly22 region. Our results definitely indicate that the secondary structure of human IGF-I in solution is consistent with that of insulin in the crystalline state.

Amino Acid Sequence

In vitro antibacterial activities of tosufloxacin against and uptake of tosufloxacin by outer membrane mutants of Escherichia coli, Proteus mirabilis, and Salmonella typhimurium.

The antibacterial activities of tosufloxacin and other quinolones against and apparent uptakes of tosufloxacin and other quinolones by outer membrane mutants of Escherichia coli, Proteus mirabilis, and Salmonella typhimurium were studied. The hydrophobicity of tosufloxacin was nearly equal to that of ofloxacin or lower than those of sparfloxacin and nalidixic acid. OmpF- and OmpC-deficient E. coli and 40-kDa porin-deficient P. mirabilis mutants were twofold more susceptible to tosufloxacin and sparfloxacin but two- to fourfold less susceptible to other quinolones than their parent strains. In S. typhimurium lipopolysaccharide-deficient (rough) mutants, the differences in susceptibility to tosufloxacin were similar to those to sparfloxacin and nalidixic acid. The apparent uptake of tosufloxacin by intact cells was increased in porin-deficient mutants compared with that by their parent strain. These results suggest that the permeation route of tosufloxacin across the outer membrane is different from that of other fluoroquinolones and that tosufloxacin may permeate mainly through the nonporin pathway, presumably phospholipid bilayers. However, this characteristic is independent of the hydrophobicity of the molecule.

4-Quinolones

Secretion of beta-2-microglobulin from human hepatoblastoma and hepatoma cells on stimulation with interleukin-6.

beta 2-microglobulin (beta 2-M) was secreted in a dose- and time-dependent manner after interleukin-6 (IL-6) treatment of human hepatoblastoma (HuH-6) and hepatoma cells (HuH-7). Pancreatic secretory trypsin inhibitor, which is one of the acute phase proteins secreted in these cells, was also secreted dose- and time-dependently in HuH-6 cells and dose-dependently in HuH-7 cells. It is conceivable that IL-6 induces the production of beta 2-M as an acute phase protein in the liver.

Carcinoma, Hepatocellular

Inhibition of neutrophil priming and tyrosyl phosphorylation by cepharanthine, a nonsteroidal antiinflammatory drug.

Receptor-mediated superoxide (O2.-)-generation and tyrosyl phosphorylation of neutrophil proteins, such as 58, 65, 84, 108 and 115 kDa, were enhanced by priming cells with granulocyte colony stimulating factor (G-CSF) [Akimura, K. et al. Arch. Biochem. Biophys. 298: 703-709, 1992]. To elucidate the possible involvement of tyrosyl phosphorylation of neutrophil proteins in the enhancing mechanism of O2.- generation, the effect of cepharanthine, a biscoclaurine alkaloid that inhibits phorbol 12-myristate 13-acetate (PMA)- and receptor-mediated O2.- generation, on the priming of human peripheral neutrophils (HPPMN) was studied. Both enhancement of formyl-methionyl-leucyl- phenylalanine (FMLP)-mediated O2.- generation and tyrosyl phosphorylation of some neutrophil proteins, i.e., 115, 108 and 84 kDa proteins, by HHPMN after treatment with G-CSF were strongly inhibited by cepharanthine in a concentration- and treatment-time-dependent manner. In contrast, inhibition of PMA-mediated O2.- generation by cepharanthine was weak and independent of treatment time. These results suggest that cepharanthine might inhibit the priming step of neutrophil activation concomitantly with its inhibition of the tyrosyl phosphorylation of some neutrophil proteins that might underlie the mechanism for priming of neutrophils with G-CSF.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

[A case of multiple sclerosis with intractable hiccups and sleep apnea syndrome].

A 48-year-old female with multiple sclerosis (MS) accompanied by intractable hiccups of over one month' duration and the sleep apnea syndrome was reported. This MS patient had been well controlled until September 16, 1991 when she experienced nausea, vomiting and hiccups. The patient was admitted to Kawasaki Medical School Hospital on October 9, 1991. A physical examination revealed intractable hiccups. T1-weighted MRI showed a low and T2-weighted image disclosed a high signal intensity area in the tegmentum of the medulla oblongata. The intractable hiccups and vomiting improved with intravenous high dose methylprednisolone injection therapy. The following day, she complained of insomnia and her family observed severe snoring and apnea during the night. These symptoms and the results of a breathing monitor were compatible with the sleep apnea syndrome. These symptoms disappeared following the administration of amitriptyline. There have been few reports of the combination of intractable hiccups and the sleep apnea syndrome in MS. The MRI findings suggest that the causative lesion of these symptoms is in the tegmentum of the medulla oblongata.

Amitriptyline

[Clinical significance of carotid and ocular bruits in cerebrovascular disease].

We investigated the clinical significance of carotid and ocular bruits in 250 consecutive patients with cerebrovascular disease (CVD). The incidence of bruits was compared with that in 100 age- and sex-matched neurological controls without CVD. In the cerebrovascular disease group, carotid bruits alone were found in 12 patients, both carotid and ocular bruits in 7, and ocular bruits alone in 2. Carotid bruits were found only in 3 controls. We then evaluated cerebrovascular disease in the 25 patients (16 men and 9 women) who had bruits. The patients ranged from 55 to 81 years in age (mean: 70.6 years). The patients with carotid bruits alone constituted the largest group, and those with ocular bruits alone were the smallest group. Carotid bruits were heard and abnormal blood flow was observed in 19/28 arteries of the 21 patients who underwent echo-flow studies. Carotid artery stenosis/occlusion was detected in 24/31 arteries (77%) in 23 patients who underwent digital subtraction angiography (DSA). Thus, the sensitivity was 0.77 and specificity of a carotid bruit 0.91, respectively. In 9/10 patients with unilateral ocular bruits, ipsilateral or contralateral carotid artery stenosis/occlusion was detected. Diminished cerebral blood flow was observed in 10/15 patients with bruits who underwent SPECT. Of these 8 had reduced cerebral blood flow ipsilaterally to the bruit. Blood flow was reduced in the carotid artery territory in all of the patients, and watershed reductions were commonest. Among the 25 patients, some showed neurological semiology of the vertebrobasilar territory in addition to that of the carotid territory.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Neuron-specific enolase (NSE) and S-100b protein in cerebrospinal fluid of patients with cervical spondylosis--the relations with MRI findings and the changes of NSE and S-100b protein levels through Glisson's traction].

We have previously reported that NSE and S-100b protein (S-100) could be used as reliable markers to evaluate the damage of the spinal cord in cervical spondylosis (CS) and ossification of posterior longitudinal ligament (OPLL). In the present study we made MRI in 21 patients with CS. There was a positive correlation between the NSE level in CSF and the degree of the spinal cord compression shown by MRI. In 10 cases of CS we examined these specific protein levels in CSF before and after the Glisson's traction therapy for one month. In seven of them the NSE levels decreased with the clinical improvements. On the other hand, 2 cases showed the rise of NSE levels after the traction. One of them became clinically worse during the therapy, while in another case the NSE levels changed within the normal range. The level of NSE in the other case was unchanged. In 57-year-old patient with CS myelopathy we examined the NSE levels chronologically. The NSE level changed in parallel with his clinical features. We suggest that NSE level in CSF may be a useful marker to estimate the change of the degree of the spinal cord damage in CS.

Female

[A case of Sotos syndrome associated with peripheral nerve involvements].

A case of the Sotos syndrome associated with peripheral nerve involvements was reported. A 52-year-old male was admitted to Kawasaki Medical School Hospital because of gait disturbance, muscle atrophy, and weakness in both hands. This case was diagnosed as the Sotos syndrome based on the following symptoms and findings, acromegaloid features, hypertrophic changes in the hands and feet, a history of epileptic episodes, a low IQ, a normal growth hormone value, and no tumor lesion in the pituitary gland. Radiological examination disclosed a cauliflower-like appearance of the finger tips and thickness of the heel pads. Brain CT and MRI revealed diffuse mild brain atrophy. An electroencephalogram showed diffuse theta waves with sharp waves in the right parietal region. A needle electromyogram revealed neurogenic change in both upper and lower limbs. A nerve conduction study disclosed the carpal tunnel syndrome and cubital tunnel syndrome. These findings suggest that, as in the case of acromegaly, entrapment neuropathy and peripheral neuropathy can also be induced in the Sotos syndrome.

Brain Diseases

Circumferential mesangial interposition: a form of mesangiolysis.

A wide variety of glomerular lesions express circumferential mesangial interposition (CMI). The pathomorphogenesis of CMI involves low-grade mesangiolysis and subsequent passive dislocation of mesangial cells towards the lateral wall of glomerular capillaries through a high hydraulic pressure of blood flow penetrating the lytic mesangium. This is in contrast to the previous theories which advocate an active movement of mesangial cells. Moreover, circumferential mesangial interposition can disappear spontaneously or after treatment, suggesting that mesangial cells may return to the original site with their inherent contractility after the insults are removed, in order to restore handicapped filtering surfaces. But the precise mechanisms of its regression will be a subject for future investigation.

Capillaries

Ultrastructural changes in the alveolar epithelium in response to mycobacterial infection.

Electron microscopic examination of the lung of mice infected with a virulent strain of M. bovis (Ravenel) revealed marked alterations in the alveolar epithelial cells, particularly Type 2 cells (granular pneumocytes), in addition to the development of interstitial and intra-alveolar granuloma. Unlike the feature in uninfected mice, more than one Type 2 epithelial cells were often found adjacent to one another within a single alveolus. Some of these cells showed mitotic figures. Their characteristic lamellar inclusions were morphologically altered.

Animals