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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 847 records · Page 47Linked to original sources

Vasopressin-induced pressor responses in rats to bilateral electrolytic lesioning of the caudal portion of the nucleus tractus solitarii.

Bilateral electrolytic lesioning of the nucleus tractus solitarii elicited a pressor response in rats with spinal transection. This response was abolished by a vasopressin pressor antagonist and plasma vasopressin was increased during the response. This evidence suggests that the nucleus tractus solitarii is involved in inhibiting vasopressin release and that an impaired function would lead to an enhancement of vasopressin release, to the extent of eliciting a pressor response.

Animals↗

Effects of various tricyclic antidepressants on amine uptake.

A comparative study of the ability to block the amine pump was carried out on tricyclic antidepressants including dothiepin and northiaden in vivo. Dothiepin was found to prevent the 6-OHDA-induced depletion of cardiac noradrenaline but not the PCA-induced depletion of intracerebral serotonin. Northiaden, an active metabolite of dothiepin, also possessed the same ability with a greater potency than the parent drug. Neither compound affected the biosynthesis of catecholamines and indoleamine. However, neither dothiepin nor northiaden affected 5-HT uptake, as was also observed with imipramine and amitriptyline. These results suggest that the clinical efficacy of dothiepin may be due to inhibition of the amine pump, especially of the catecholamine uptake mechanism, which is qualitatively the same as for imipramine and amitriptyline.

Amitriptyline↗

Human penile hemodynamics studied by a polarographic method.

Observations of the tissue oxygen tension alteration were made using an open tip type oxygen electrode polarographic method as an index of blood flow change in the penile skin, corpus cavernosum and thigh skin of 16 males aged 20-26 years (average age: 20.5 years). In another five males aged 18-21 (average age: 19.8 years) the relationship between corpus cavernosum tissue oxygen tension alteration and penile circumference change in the erection process was observed. This relation was obtained in the penile circulation model, and penile hemodynamics were ascertained. In the flaccid penis the corpus cavernosum contains low-oxygen blood and there is a blockade at the vascular tree in the corpus cavernosum. In the tumescence phase the blood flow of the corpus cavernosum increased suddenly by the relief of cavernosum vascular blockade. During the penile tumescence phase the increased inflow and outflow persisted in corpus cavernosum, and in penile skin the blood also increased initially, but gradually decreased as penile circumference increased. After erection was attained it is thought that resistance to inflow occurred by outflow pathway contraction. In the detumescence phase, a decrease of inflow and a concomitant increase of outflow occurred and the reopening of outflow is thought to be necessary for prompt penile detumescence.

Adult↗

Biphasic actions of L-DOPA on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices.

Effects of L-DOPA on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices evoked by electrical field stimulation at 5 Hz were investigated in the absence and presence of p-bromobenzyloxyamine (NSD-1055), a DOPA-decarboxylase inhibitor. In the absence of NSD-1055, L-DOPA produced a facilitation of impulse-evoked release of noradrenaline at 0.1 microM but not at 1 and 10 microM, and had no effect on the spontaneous release. On the other hand, L-DOPA 0.1 to 10 microM dose-dependently increased the spontaneous release of dopamine and the highest concentration only increased the evoked release and tissue content of dopamine. In the presence of NSD-1055 10 microM, the increase in the spontaneous release of dopamine was prevented and L-DOPA produced biphasic regulatory effects on the evoked release of noradrenaline and dopamine, a facilitation at 0.1 microM and an inhibition at 1 microM. The facilitation was antagonized by (-)-propranolol 0.1 microM, but not by the (+)-isomer, whereas the inhibition was antagonized by S-sulpiride 1 nM, but not by the R-isomer. In conclusion, L-DOPA appears to produce biphasic actions on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices, not through its conversion to dopamine but through presynaptic regulatory mechanisms, an inhibition via dopamine receptors at a micromolar concentration and a facilitation via beta-adrenoceptors at the lower concentration.

Animals↗

Contribution of vasopressin to hypertension caused by baroreceptor denervation and nucleus tractus solitarius lesions in rats.

The purpose of this study was to examine, using pentobarbital-anesthetized rats, whether vasopressin contributes to hypertension caused by denervation of baroreceptors, in comparison to the contribution of vasopressin to hypertension caused by nucleus tractus solitarius (NTS) lesions. Bilateral baroreceptor denervation caused acute hypertension which was inhibited by intravenous injection of an antagonist of the vasoconstrictor action of vasopressin. Lesions of the NTS also produced an increased in blood pressure which was reduced by the vasopressin antagonist. The magnitude of the antagonist-induced hypotension was significantly greater in NTS hypertension than that in baroreceptor denervation hypertension. It is concluded, that in rats, vasopressin contributes to the neurogenic hypertension caused by baroreceptor denervation and NTS lesions. Thus, it appears that interruption of baroreceptor afferents at the NTS level is responsible for the vasopressin-mediated hypertension caused by NTS lesions but that it is not the only factor involved.

Animals↗

Pregnancy in cardiac patients: possible influence of volume overload by pregnancy on pulmonary circulation.

To evaluate the influence of volume overload by pregnancy on heart diseases, the relations between cardiac status before pregnancy and clinical courses during pregnancy were studied, especially from the viewpoint of pulmonary circulation. In 206 pregnant cardiac patients whose prepregnancy laboratory data were known, the deterioration (appearance or advance of heart failure) during pregnancy was prospectively related to: pulmonary congestion (p less than 0.05), enlarged left atrium (p less than 0.05), atrial fibrillation (p less than 0.01) and right ventricular hypertrophy (p less than 0.005) in mitral stenosis; cardiomegaly (p less than 0.05) and atrial fibrillation (p less than 0.005) in mitral regurgitation; cardiomegaly (p less than 0.005) in congenital heart diseases; and to previous congestive heart failure (p less than 0.005) in total cases. All of the cases with systolic pulmonary artery pressure higher than 50 mmHg deteriorated during pregnancy. Some cases with no deteriorating laboratory findings showed dyspnea suddenly at the end of pregnancy. In 1033 cardiac patients who had experienced pregnancy, deterioration during pregnancy was seen more frequently in cases with mitral valvular diseases that in those with aortic valvular diseases. No deterioration was seen in pulmonary stenosis patients. Abnormal status of pulmonary circulation may be one of the important determining factors of deterioration by pregnancy in cardiac patients. The criteria for permitting pregnancy in cardiac patients are proposed.

Adult↗

Cardiovascular effects of L-glutamate and gamma-aminobutyric acid injected into the rostral ventrolateral medulla in normotensive and spontaneously hypertensive rats.

We studied the responses to chemical stimulation of the ventrolateral medulla in pentobarbital-anaesthetized, paralyzed, normotensive and spontaneously hypertensive (SHR) rats. When unilaterally injected into a circumscribed region of the rostral ventrolateral medulla, L-glutamate (0.16-1.6 nmol) elicited a dose-dependent increase in arterial pressure and heart rate. Bilateral microinjections of L-glutamate diethylester (63 nmol), an antagonist of excitatory amino acids, into the glutamate-sensitive sites markedly reduced arterial pressure and heart rate. gamma-Aminobutyric acid (GABA) (0.3-3 nmol) injected into the glutamate-sensitive sites caused a dose-dependent decrease in arterial pressure and heart rate. The depressor response to GABA was smaller in SHR than that in normotensive Wistar Kyoto rats (WKY), while there were no differences between WKY and SHR in the pressor response to L-glutamate. Thus, a depressor function involving the ventrolateral medulla appears to be diminished in SHR.

Animals↗

Alterations of presynaptic and endothelial functions in SHR: effects of adenosine.

The effects of adenosine on stimulation-evoked 3H-efflux from perfused mesenteric arteries pretreated with 3H-norepinephrine and on norepinephrine-induced contractile responses of the thoracic aorta before and after mechanical removal of endothelial cells were examined in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Adenosine inhibited the stimulation-evoked 3H-efflux; this inhibitory effect was smaller in young and adult SHR than age-matched WKY. Mechanical removal of endothelial cells rendered the SHR aorta much less responsive to adenosine, while in the WKY aorta endothelial removal had no influence on the relaxation response to adenosine. These results support the hypothesis that pre-synaptic factors are contributory whereas endothelial factors are compensatory to hypertension in SHR.

Adenosine↗

Further evidence for tonically functioning presynaptic beta-adrenoceptors in guinea-pig pulmonary arteries.

Effects of dl- and d-carteolol alone on the release of tritium evoked by transmural field stimulation at 1 Hz were investigated in spirally cut guinea-pig pulmonary arteries preloaded with [3H]-norepinephrine. Cumulatively applied dl-carteolol 10(-8) M, 10(-7) M and 10(-6) M readily inhibited the release of tritium in a concentration-dependent manner, whereas the same concentrations of d-carteolol produced no effect. In conclusion, presynaptic beta-adrenoceptors in guinea-pig pulmonary arteries tonically function to facilitate the release of the transmitter norepinephrine.

Animals↗

[A case of primary ureteral carcinoma in the duplicated renal pelvis and ureter diagnosed by transurethral uretero-renoscopy].

We present a case of primary ureteral carcinoma in the duplicated renal pelvis and ureter diagnosed by transurethral uretero-renoscopy. The case was of a 78-year-old man with the complaint of sudden asymptomatic macrohematuria. An excretory urogram strongly suggested the presence of duplication of the right collecting system, and cystoscopy revealed a gross hematuria from the right ureteral orifice. A retrograde ureteropyelogram revealed incomplete duplication of the right renal pelvis and ureter fused at about the ureter crossing over the iliac vessels, and a polyp-like filling defect in the lower segment of duplicated ureter at about 4 cm from the fusion of the ureters. Transurethral uretero-renoscopy was employed to investigate the filling defect, and a papillary tumor extended into the lower segment of duplicated ureter was revealed. Tumor was resected by a rigid operating instrument under transurethral uretero-renoscopy. The pathological diagnosis was grade I-transitional cell carcinoma of the ureter, so that right total nephroureterectomy with partial cystectomy was carried out subsequently. Surgical specimen after right total nephroureterectomy with partial cystectomy showed no other tumor in the pelvis or ureter macroscopically, and histopathological studies of surgical specimens were no evidence of malignancy. We believe that transurethral uretero-renoscopy significantly increases the diagnostic accuracy in determining the nature of upper urinary tract lesions, and this procedure is indispensable in the diagnosis of ureteral tumors. The present case was the 7th case of primary ureteral carcinoma in the duplicated renal pelvis and ureter in the Japanese literature.

Aged↗

Canada-Cronkhite syndrome associated with systemic lupus erythematosus.

A 43-year-old woman with a history of systemic lupus erythematosus manifested severe diarrhea, generalized gastrointestinal polyposis, pigmentation, and onychodystrophy, which were typical of Canada-Cronkhite syndrome. The exacerbation of systemic lupus erythematosus, presenting with hemolytic anemia and subsequently with profound proteinuria, was seen during the course of this syndrome. The patient achieved complete symptomatic remissions of both entities for more than four years following prednisolone therapy; the resolution of the gastrointestinal polyps was confirmed histologically. This case showed that this syndrome could be completely reversible in its course and that it might have an exogenous cause, as previously suggested.

Adult↗

Distribution and fine structure of neuronal elements containing glutamate decarboxylase in the rat cochlear nucleus.

Distribution and fine structure of gamma-aminobutyric acid (GABA)-containing structures were examined in the rat cochlear nuclear complex by means of immunohistochemistry using glutamate decarboxylase (GAD) as a marker. GAD-like immunoreactive (GADI) terminals were diffusely distributed in the dorsal cochlear nucleus, while in the ventral cochlear nucleus numerous immunoreactive fibers were situated around the cell bodies. These light-microscopic observations were confirmed by electron microscopy. Evidence suggesting that many of GADI boutons in the cochlear nucleus are of intrinsic origin was also shown.

4-Aminobutyrate Transaminase↗

Peptidergic and aminergic innervation of the facial nucleus of the rat with special reference to ontogenetic development.

The distribution and ontogenetic development of several neuropeptides such as enkephalin, substance P, somatostatin, neuropeptide Y, and of monoamines such as serotonin and catecholamines in the facial nucleus of the rat were investigated with immunocytochemistry. The neuropeptides were concentrated in certain subnuclei. Enkephalin-immunoreactive fibers were distributed in the medial and dorsal subnuclei, substance P in the intermediate and dorsal subnuclei, somatostatin in the intermediate subnucleus, and neuropeptide Y in the dorsal subnucleus. The amines were distributed evenly throughout the nucleus. These distribution patterns suggest that peptidergic fibers are closely related to the functions of different subnuclei, while fibers containing monoamines are more basic--not specific to individual muscles. Few of these fibers were observed in the prenatal stage of the rat, but they increased markedly in number during the first postnatal week, and had established their innervation pattern by the tenth postnatal day, which coincides with the establishment of nerve-muscle innervation. The present study further showed that fibers containing serotonin are supplied mainly from the raphe nucleus, that catecholamine fibers are from neurons containing catecholamine surrounding the facial nucleus, and that fibers containing neuropeptide Y are from the lateral part of the caudal medullary reticular formation. These findings suggest that catecholamine and neuropeptide Y are not both present in the single neurons projecting to the facial nucleus.

Animals↗

Primary structure of delta subunit precursor of calf muscle acetylcholine receptor deduced from cDNA sequence.

Clones carrying cDNA sequences for the delta subunit precursor of the acetylcholine receptor from calf skeletal muscle have been isolated. Nucleotide sequence analysis of the cloned cDNA has indicated that this polypeptide consists of 516 amino acids including a hydrophobic prepeptide of 21 amino acids. The delta subunit of the calf muscle acetylcholine receptor, like the alpha, beta and gamma subunits of the same receptor as well as the alpha and gamma subunits of its human counterpart, exhibits structural features common to all four subunits of the Torpedo electroplax receptor, apparently being oriented across the membrane in the same manner as proposed for the fish receptor subunits. The degree of amino acid sequence homology between the calf and Torpedo delta subunits (60%) is comparable to that between the beta subunits (59%) and to that between the gamma subunits (56%), but is lower than that between the alpha subunits of the two species (81%). This suggests that the alpha subunit evolved more slowly than the three other subunits. A dendrogram representing the sequence relatedness among the four subunit precursors of the mammalian and fish acetylcholine receptors has been constructed. Some regions of the delta subunit molecule, including the region containing the putative disulphide bridge and that encompassing the clustered putative transmembrane segments M1, M2 and M3, are relatively well conserved between calf and Torpedo. The relative pattern of regional homology is similar for all four subunit precursors.

Amino Acid Sequence↗

Cloning and sequence analysis of human genomic DNA encoding gamma subunit precursor of muscle acetylcholine receptor.

Human genomic DNA encoding the gamma subunit precursor of the skeletal muscle acetylcholine receptor has been cloned by screening a gene library with a calf cDNA probe and has been subjected to nucleotide sequence analysis. Comparison of the nucleotide sequence of the cloned human genomic DNA with that of the calf cDNA has revealed that the protein-coding sequence of this gene is divided by 11 introns into 12 exons. Evidence is presented to suggest that the human muscle acetylcholine receptor gamma and delta subunit genes are juxtaposed. The primary structure of the gamma subunit precursor of the human muscle acetylcholine receptor has been deduced from the corresponding gene sequence. This polypeptide is composed of 517 amino acids including a hydrophobic prepeptide of 22 amino acids. The gamma subunit of the human muscle acetylcholine receptor, like the alpha subunit of the same receptor as well as the alpha, beta and gamma subunits of its calf counterpart, shares structural features common to all four subunits of the Torpedo electroplax receptor, such as the putative disulphide bridge corresponding to that in the alpha subunit proposed as being in close proximity to the acetylcholine binding site and the four putative, hydrophobic transmembrane segments M1-M4. Thus, the human gamma subunit molecule apparently exhibits the same transmembrane topology as proposed for the fish receptor subunits. The 12 exons seem to correspond to different structural and functional domains of the gamma subunit precursor molecule. Some exons and the protein regions encoded by them are more highly conserved between the mammalian and Torpedo sequences. The pattern of regional homology observed is consistent with the relatively high conservation of the region encompassing the putative disulphide bridge and of the region containing the putative transmembrane segments M1, M2 and M3.

Amino Acid Sequence↗