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Biomedical subjects

K Sudoh

Publications and source records attributed to K Sudoh.

31 records · Page 2Linked to original sources

The effect of intravenous recombinant human renin on blood pressure in pithed spontaneously hypertensive rats.

The effect of highly purified recombinant human renin (rh-renin), expressed in Chinese hamster ovary cells, on mean blood pressure (MBP) was evaluated in pithed spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous bolus injection of rh-renin produced dose-dependent increases in MBP in pithed SHR and WKY. The pressor response to rh-renin in pithed SHR was about 3 times as potent as that in pithed WKY. Intravenous infusion of rh-renin produced dose-dependent progressive increases in MBP during the first 40 min, reaching plateaus and thereafter MBP was maintained up to 120 min. This hypertensive response to rh-renin was antagonized by renin inhibitors, YM-21095 and KRI-1314, which inhibited the reaction between rh-renin and tetradecapeptide competitively, with Ki values of 5.1 x 10(-10) and 4.3 x 10(-9) M, respectively. In rh-renin-infused pithed SHR, the hypotensive effect of YM-21095 was 37 times as potent as that of KRI-1314. These results suggest that rh-renin can stimulate the rat renin-angiotensin system, thereby producing hypertension. Moreover, the rh-renin-infused rat model could be useful to evaluate the effect of renin inhibitor.

Animals↗

Effect of the optical isomers of YM-12617 on increased intra-urethral pressure induced by phenylephrine in anaesthetized dogs.

1. Effects of the individual optical isomers of YM-12617 (R, S 5-[2-[[2-(o-ethoxyphenoxy)ethyl]-amino]propyl]-2- methoxybenzenesulphonamide HCl, (+/-)-YM), a potent selective alpha 1-adrenoceptor antagonist, on the increase in intraurethral pressure (IUP) and diastolic blood pressure (DBP) induced by phenylephrine were evaluated in pentobarbital-anaesthetized female dogs. 2. Phenylephrine (0.1-30 micrograms kg-1 i.v.), an alpha 1-adrenoceptor agonist, dose-dependently increased IUP and DBP. 3. alpha-adrenoceptor antagonists (i.v.) dose-dependently antagonized the increase in IUP and DBP induced by phenylephrine, with a potency ranking of R(-)-YM greater than (+/-)-YM greater than prazosin greater than phentolamine greater than S(+)-YM greater than yohimbine. 4. These results suggest that the alpha 1-adrenoceptor mediates the increase in IUP as well as DBP in anaesthetized dogs, and that alpha 1-adrenoceptors in the urethra and arteries show a stereochemical preference for R(-)-YM.

Adrenergic alpha-Agonists↗

Characterization of [3H]YM617, R-(-)-5-[2-[[2[ethoxyring(n)-3H](o-ethoxyphenoxy)ethyl]amino]- propyl]-2-methoxybenzenesulfonamide HCl, a potent and selective alpha-1 adrenoceptor radioligand.

The binding properties of a new radioligand, R(-)-5-[2-[[2[ethoxyring(n)-3H](o- ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide++ + HCl ([3H]YM617), were studied in membranes of the rat hippocampus and spleen. [3H]YM617 rapidly associated with its binding sites in both membranes and reached steady state by 20 min at 25 degrees C. The specific binding of [3H]YM617 appeared to be saturable, and Scatchard analysis revealed a linear plot, suggesting a single population of binding sites with a dissociation constant of 0.170 +/- 0.016 nM (n = 6) in the hippocampus and 0.195 +/- 0.036 (n = 4) in the spleen. The maximal binding sites in the hippocampus and spleen were 203.0 +/- 43.2 (n = 6) and 72.4 +/- 17.0 (n = 4) fmol/mg protein, respectively. Chlorethylclonidine (10(-5) M for 10 min) treatment reduced the Bmax values of [3H]YM617 and [3H]prazosin to a similar degree in the rat hippocampus (10-15%) and spleen (40-50%). Alpha adrenoceptor agonists and antagonists competed with [3H]YM617 for binding sites in the following order: YM617 > prazosin > WB4101 > bunazosin > 5-methylurapidil > S(+)-isomer of YM617 > phentolamine > yohimbine > norepinephrine = phenylephrine > methoxamine in the hippocampus, and prazosin > YM617 > bunazosin > WB4101 > 5-methylurapidil > phentolamine > S(+)-isomer of YM617 > yohimbine > norepinephrine > phenylephrine > methoxamine in the spleen. In the hippocampus, prazosin and bunazosin produced biphasic displacement of [3H]YM617, but not [3H]prazosin binding. In contrast, only monophasic curves were obtained against either radioligand in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

In vitro "progression" of bovine papillomavirus-transformed cells: loss of contact sensitivity after multiple rounds of selection.

The transformed phenotype of C127 cells harboring bovine papillomavirus shuttle vector pdBPVMMT neo(342-12) was suppressed by direct contact with untransformed C127 cells. By repeated selections of rare foci developing on untransformed cell monolayers, we obtained a cellular clone of BPV transformants which formed foci on the untransformed C127 cells as efficiently as on plastic surface. The BPV genome in the mutant cells showed extensive genetic rearrangements, duplication of upstream regulatory region and deletion of pBR322-derived sequence and its flanking. There was an increase in BPV-transformant in contact with the untransformed C127 cells resulted in a marked reduction of the BPV transcripts, while in the case of the mutant transformant the reduction was much slighter. This indicates that the transcription level of the BPV genome was controlled by a cell-cell contact signal.

Animals↗

Effects of YM-14673, a new thyroid-releasing hormone analogue, on neurological deficits in stroke-prone spontaneously hypertensive rats.

The effects of YM-14673, a new thyroid-releasing hormone (TRH) analogue (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), on neurological deficits were examined in stroke-prone spontaneously hypertensive rats (SHRSP). The neurological deficits were evaluated for more than 21 days after stroke. Administration of YM-14673 was started the day stroke was observed and repeated daily for 3 weeks. YM-14673 (0.1 and 0.3 mg/kg i.p.) improved the neurological deficits and reduced mortality. These results demonstrate that YM-14673 mitigates cerebral ischemic changes in SHRSP.

Animals↗

Site-related difference in the prevalence of mitral valve prolapse. Relation to the prevalence and severity of mitral regurgitation.

In this study, 431 consecutive patients with mitral valve prolapse (MVP) diagnosed by two-dimensional echocardiography were employed to further investigate the site-related difference in the prevalence of MVP. Following echocardiographic determination of the site and severity of MVP, a pulsed-Doppler technique was further performed to assess the existence and severity of mitral regurgitation (MR) in all patients. These patients were then classified by age in 10-year groups with patients older than 60 years being enrolled in one group. The younger groups accounted for a large number of the patients with MVP in our study, with the number of patients being reduced with age. In addition, female patients tended to predominate up until the 50s, but not in the 50 and older groups. The prevalence of MVP at the centro-medial site of the anterior mitral leaflet (AML) predominated in all age groups, gradually decreasing with age, except for a peak in the 40s, before continuing to decline in the 50 and older groups. On the other hand, the prevalence of MVP at the lateral site of the AML and at the posterior mitral leaflet (PML) increased with age. In the 50 and older age groups, the prevalence of MVP at these sites increased steeply with age. However, the prevalence of MVP at both the lateral site of the AML and PML did not significantly increase with age. The trend shown above was not significantly different for gender. The number of patients with MR increased with age independent of the site of MVP. However, the prevalence and severity of MR associated with MVP at the lateral site of the AML and/or at the PML were significantly greater than at the other sites up until the 50s (p less than 0.05). When patients were older than 50 years, this significant site-related difference in the prevalence of MR was not observed because of the higher prevalence of MR in the older patients in this study. Forty-one patients could be followed for 2 to almost 5 years. Three of the 41 patients were observed to have MVP at the centro-medial site of the AML in the initial examination, but the site of MVP had extended to the lateral side of the AML in the final examination. Two patients with MVP at all 3 sites of the AML demonstrated an increase in the severity of MVP. However, there were no newly documented cases of MR among those patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[An autopsy case of amyotrophic lateral sclerosis associated with cervical syringomyelia].

An autopsied case of amyotrophic lateral sclerosis complicated by cervical syringomyelia was reported. The case was a 59-year-old man, who first noticed weakness of both lower extremities at 54-year-old. The weakness spread to both upper extremities within 2 years. Cervical myelography revealed multi-level cervical spondylosis and anterior fusion of C5-C7 was done. But the weakness and atrophy of proximal muscle, diminished deep tendon reflex on upper extremities, hyperreflexia and pathological reflexes on both legs, tongue fasciculation and respiratory muscle weakness developed successively, and the patient died of respiratory distress at 59-year-old. Autopsy revealed multiple independent four syrinxes located at the level between C2-C7. One of these syrinxes had ependymal cell lining and thought to be idiopathic syringomyelia. The other three syrinxes were considered to be the cavitation in association with cervical spondylotic myelopathy. Degeneration and decreasing of spinal anterior horn cells, atrophy of medullary pyramis and Bunina bodies were observed as features of typical amyotrophic lateral sclerosis. Cervical spondylosis as causative lesion of multiple syrinxes was discussed, and relationship between ALS and the syrinxes was not indicated clearly.

Amyotrophic Lateral Sclerosis↗

Light and electron microscopical demonstration of c- erB-2 gene product-like immunoreactivity in human malignant tumors.

C-erbB-2 is a human protooncogene homologous with the well-known c-erbB. Genes and gene products of the EGF receptor and c-erbB are known to be closely related and to be closely homologous in their intracellular domain. Inspection of the deduced amino acid sequence suggested that the c-erbB-2 gene encodes a receptor for a yet unidentified growth factor. An immunohistological study was performed by introducing an antibody raised in the rabbit by immunization with a synthetic peptide corresponding to a part of the intracytoplasmic domain of predicted gene product. Specimens from 13 normal human organs, fresh frozen tissue from 41 surgically excised human malignant tumors and eight cell lines maintained in nude mice were studied. Positive staining was found in 4 of the 41 (9.8%) malignant tumors. All of the positive tumors were adenocarcinomas and two adenocarcinoma cell lines were also positive. Amongst the normal human tissues, epithelial cells in stomach, small and large intestine were faintly stained. When the positively stained cell lines were studied by immunoelectronmicroscopy, the reaction was most prominent in the membrane of microvilli, but part of the nuclear membrane, the endoplasmic reticulum and the outer cell membrane were also stained. DNA and mRNA blot assays, as well as our immunoprecipitation test, revealed that immunohistologically positive cell lines bore amplified c-erbB-2 DNA, c-erbB-2 mRNA and 185 kD protein which is supposed to be the gene product, while negative cell lines did not.

Cell Line↗

Skeletal myoclonus in olivopontocerebellar atrophy: treatment with trihexyphenidyl.

We studied two patients with nonfamilial olivopontocerebellar atrophy with skeletal myoclonus. Palatal or skeletal myoclonus is probably not a coincidental finding but another manifestation of the underlying disease. In both cases, the myoclonus was suppressed by administration of trihexyphenidyl, indicating a cholinergic disorder.

Brain↗

Structural polymorphism of murine complement factor H controlled by a locus located between the Hc and the beta 2M locus on the second chromosome of the mouse.

Structural polymorphism of murine factor H protein was demonstrated by using three different methods. 1) By prolonged agarose electrophoresis and immunofixation, factor H protein was visualized in the beta region as a single, distinct protein band in freshly bled EDTA-plasmas from many laboratory and wild mice. Two variants were detected among a large number of tested strains; one, referred to as H.1, moved faster to the anodal region (type strain, BALB/c), and the other, referred to as H.2, moved more slowly to the anodal region (type strain, STR). The F1 hybrid between BALB/c and STR exhibited a combining type of factor H protein, which was observed in each parent. 2) Two-dimensional peptide mapping analysis was carried out with tryptic peptides of these two factor H allotypes. Almost all of the spots in the maps of tryptic peptides were common to both allotypes. However, three distinct spots among the 57 spots detected in the map of tryptic peptides of the H.1 allotypes were not detected in that of H.2 allotype, whereas two spots among the 56 spots in the map of H.2 allotype were unique for this allotype. The F1 hybrid between BALB/c and STR showed a combining type of the map of parent. 3) Alloantisera against each of H allotypes were successfully produced in BALB/c or BALB/c-H.2 (a congenic strain with H.2 allotype) by repeated injection of each purified factor H protein either from the BALB/c or the STR strain. These findings indicated that the observed variants of factor H represent antigenically and structurally distinguishable allotypes. The allotypes of murine factor H protein are controlled by a single codominant locus located between the Hc locus and the beta 2M locus on the second chromosome of the mouse. This was shown by phenotyping the Hc locus and H locus with backcross progenies between A/J (one of strain with H.1) and MoA (one of strain with H.2). The recombination frequency between these two loci was 0.17 +/- 0.046.

Animals↗

[Brain tissue damage in congenital hydrocephalus of the inbred rat, LEW/Jms--intracerebral cavity formation].

Brain tissue damage in congenital hydrocephalic rat (LEW/Jms) was studied in the aspects of the hydrocephalic brain edema and the changes of the vascular apparatus. The characteristic findings in this study were the changes of the small blood vessels and the intracerebral cavity formation. In the acute stage of hydrocephalus (2 to 5 days after birth), spongy appearance and necrosis of the brain edema were observed in the periventricular white matter. The stenotic or obstructive vascular changes were located in connection with the hydrocephalic brain tissue. In this stage, the intracerebral cavity was formed particularly in the periventricular edematous white matter resulting in a thinning of the occipital lobes. In the late stage of hydrocephalus (9 to 15 days after birth), the lateral ventricles were severely dilated, and a markedly dilatated intracerebral cavity was observed in the periventricular white matter. The edematous area was observed adjacent to the dilated lateral ventricles or the intracerebral cavity. In the late stage, the number of small vessels filled with carbon black decreased in the area of the CSF edema when compared to the acute stage, and many obstructive blood vessels were observed in the same area. Moreover, dilatated blood vessels without carbon black were observed in the border zone between the normal and the edematous area adjacent to the intracerebral cavity. These vascular changes may occur by the accumulation of the CSF as well as the mechanical compression, and consequently lead to the microcirculatory disturbance. These microcirculatory disturbances may contribute to the intracerebral cavity formation with the accumulation of the CSF in the extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗