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Biomedical subjects

M Kihara

Publications and source records attributed to M Kihara.

At least 91 records · Page 5Linked to original sources
PubMed1998

Mechanism of angiotensin II-mediated regulation of fibronectin gene in rat vascular smooth muscle cells.

This study was performed to investigate a mechanism of angiotensin II (Ang II)-mediated activation of the fibronectin (FN) gene in rat vascular smooth muscle cells. Actinomycin D and CV11974 completely inhibited Ang II-mediated increase in FN mRNA levels. Inhibitors of protein kinase C (PKC), protein-tyrosine kinase (PTK), phosphatidylinositol-specific phospholipase C, Ras, phosphatidylinositol 3-kinase, p70 S6 kinase, and Ca2+/calmodulin kinase also decreased Ang II-induced activation of FN mRNA. In contrast, cycloheximide; PD123319; or inhibitors of Gi, protein kinase A, or mitogen-activated protein kinase kinase did not affect the induction. FN promoter contained a putative AP-1 binding site (rFN/AP-1; -463 to -437), and the results of a transient transfection and electrophoretic mobility shift assay showed that Ang II enhanced rFN/AP-1 activity. CV11974 and inhibitors of PKC or PTK suppressed Ang II-mediated increases in rFN/AP-1 activity, although neither PD123319 nor a protein kinase A inhibitor affected the induction. Furthermore, mutation of rFN/AP-1 that disrupted nuclear binding suppressed Ang II-induced transcription in the native FN promoter (-1908 to +136) context. Thus, Ang II activates transcription of the FN gene through the Ang II type 1 receptor in vascular smooth muscle cells, at least in part, via the activation of AP-1 by a signaling mechanism dependent on PKC and PTK.

Angiotensin II↗
PubMed1998

Development of synchrotron radiation storage rings.

Many third-generation light sources have been commissioned over the past ten years, and the soundness of the principal design concepts has been well recognized through experiences at these facilities. Also, technological developments concerning third-generation light sources have been remarkable. With the emittance and current of the beams far exceeding the previous levels, stability requirements of the beams have become much more stringent. In this report the present status of light sources, operational and projected, is summarized, and developments and future prospects of synchrotron radiation storage rings in view of accelerator physics and technology are reviewed.

Journal Article↗
PubMed1998

gp130 is involved in stretch-induced MAP kinase activation in cardiac myocytes.

We have recently reported that mitogen activated protein kinase (MAP kinase) is activated by the stretch of the cultured cardiac myocytes in the angiotensin II deficient state in the angiotensinogen-deficient mice (Atg-/-), suggesting that factors other than the cardiac renin-angiotensin system are involved in the stretch-induced MAP kinase activation. We examined the contribution of cytokines using RX435, an anti-gp130 antibody. Leukemia inhibitory factor, which is one of the cytokines and has the common receptor subunit gp130, activated MAP kinase and the response was completely blocked by pretreatment of the Atg-/- cardiac myocytes with RX435. RX435 pretreatment greatly reduced stretch-induced activation of MAP kinase in Atg-/- cardiac myocytes. Interestingly, the same results were obtained in the cardiac myocytes of control mice. These results suggest that cytokine-gp130 may play a role in the stretch-induced MAP kinase activation independently of Ang II in cardiac myocytes.

Angiotensinogen↗
PubMed1998

Cough-challenge trial with a new angiotensin-converting enzyme inhibitor, imidapril.

This study was conducted to examine whether imidaprilat, an active diacid of the angiotensin-converting enzyme (ACE) inhibitor imidapril, preferentially inhibits angiotensin I degradation rather than bradykinin degradation, and whether imidapril is less active than other ACE inhibitors in inducing cough in patients with hypertension. The effect of imidaprilat on the inhibition of pressor response to angiotensin I and augmentation of depressor response to bradykinin was compared with that of enalaprilat and captopril in anesthetized rats. To determine the incidence of cough associated with imidapril, patients with a history of ACE inhibitor-induced dry cough were enrolled in a randomized, open-labeled, crossover trial with two 6-week periods to be treated with imidapril or amlodipine, a calcium-channel blocker. The recurrence of cough was assessed during both treatments. In the animal study, there were no significant differences in the ratio of inhibition of pressor response to angiotensin I and the augmentation of depressor response to bradykinin among the ACE inhibitors. In the cough-challenge trial, a total of 60 patients with hypertension were enrolled in the study. Cough and cough related symptoms recurred in 98.3% of the patients (59/ 60) during imidapril therapy. In contrast, only two patients reported cough during treatment with amlodipine. These results indicate that imidapril has no selectivity in inhibiting angiotensin I- and bradykinin-degradation in rats, and that clinically it is not different from other ACE inhibitors in inducing cough in patients with hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Inhibitory effects of modified oligonucleotides complementary to the leader RNA on the multiplication of mouse hepatitis virus.

Phosphorothioate oligonucleotides (PS-oligo) and PS-oligos with cholesterol conjugates (ChPS-oligo) complementary to the leader RNA of strain JHM of mouse hepatitis virus (JHMV) were more effective inhibitors of viral multiplication than natural oligodeoxynucleotides (PO-oligo) in JHMV-infected DBT cells. PS- and ChPS-oligos were 1,000 times more potent than unmodified PO-oligo. No significant difference was observed in the inhibitory efficiency between PS-oligo and ChPS-oligo. Sequence-dependent inhibition of viral multiplication was shown at low concentrations (0.001-0.1 M) of antisense PS-oligo and ChPS-oligo. Phosphorothioate oligodeoxycytidine, PS-(dC)20, and PS-(dC)20 with cholesterol conjugates, and PS- and ChPS-oligo which have no significant homology to the JHMV sequences, showed inhibitory effects on JHMV multiplication at concentrations higher than 0.5 M. These results showed that PS-oligo and ChPS-oligo were more potent than PO-oligo in the inhibition of JHMV multiplication, and that PS-oligo and ChPS-oligo may inhibit JHMV multiplication by two different mechanisms, that is by sequence-dependent and sequence-independent manners.

5' Untranslated Regions↗
PubMed1998

Comparison of electrophysiologic and autonomic tests in sensory diabetic neuropathy.

We examined autonomic function in 46 patients with symmetric sensory non-insulin dependent diabetic neuropathy without autonomic symptoms and 31 age-matched control patients using the composite autonomic scoring scale (CASS) and electrophysiologic examination. The patients were divided into three groups by subjective severity of pain or numbness; 17 had slight pain or numbness, 15 had mild pain or numbness, and 14 had moderate pain or numbness. The patients in the moderate group had the following: a mild reduction in systolic and mean blood pressure (BP) within 1 minute of head-up tilt and a partial recovery after 5 minutes; an excessive fall in early phase II (IIe), an absence of late phase II (IIl) and reduced phase IV beat-to-beat BP responses to Valsalva maneuver (VM); a poor heart rate response to deep breathing; a reduced quantitative sudomotor axon reflex test (QSART) response in distal leg and foot; the highest CASS among the 3 groups; and reduced conduction velocity and amplitude in post-tibial nerve and sural nerve. The mild group had a mild reduction in BP during phase IIe and an absent phase IIl but normal phase IV overshoot during VM; a reduced QSART in the foot; a CASS between the moderate and slight groups; and reduced conduction velocity and amplitude in post-tibial nerve and reduced amplitude in sural nerve. The slight pain group had no abnormalities except for mild cardiovagal dysfunction. CASS gathered from all cases had a significant correlation with amplitude of sural nerve. These results suggest that the patients with symmetric sensory diabetic neuropathy may also have autonomic dysfunction, although they did not have any obvious autonomic symptoms, and that abnormalities in autonomic function parallel changes in somatic function in peripheral nerve. The CASS may be a sensitive tool, similar to the neurophysiologic test, for assessing diabetic neuropathy.

Autonomic Nervous System↗
PubMed1998

Quadriplegia caused by cervical hyperextension injury and intramedullary spinal cord tumour: a case report of autopsy.

A 68-year-old male had neck pain and weakness of the left upper extremity after a fall. MRI showed severe cervical canal stenosis and a high signal intensity of the spinal cord on T2-weighted images extending from the medulla oblongata to the C7 level. Neurological examination showed left hemiparesis, bilateral sensory disturbance and a neurogenic bladder. He underwent expansive laminoplasty 5 weeks later. After the operation his neurological deficit improved and 6 weeks later he left the hospital. However, his neurological conditions became worse (quadriparesis) and he was admitted as an emergency 3 weeks later. Although MRI showed decompression of the spinal cord, the area of high signal intensity on T2-weighted images had extended. Quadriparesis was progressive and he died of dyspnea. Autopsy showed the presence of the intramedullary spinal cord tumor (anaplastic astrocytoma; C1-Th4). We could not detect the intramedullary spinal cord tumour on MRI before surgery because of severe canal stenosis and the history of trauma. The high spinal intensity on T2-weighted images was thought to be oedema or myelomalacia. This case illustrates the difficulty of correctly interpreting MRI in patients with severe canal stenosis.

Aged↗
PubMed1998

Immunoadsorption therapy in Guillain-Barré syndrome.

A 12-year-old boy rapidly developed Guillain-Barré syndrome (GBS) after Campylobacter jejuni enteritis. Electrophysiologic studies suggested that demyelination was dominant, and serum anti-C. jejuni and both IgG and IgM anti-GM1 antibodies were significantly elevated. The patient was treated three times with immunoadsorption therapy using a tryptophan-immobilized column. The volume of treated plasma in each session was about 2 L. His blood pressure was maintained within normal range with the use of 5% albumin preparations and etilefrine hydrochloride. His clinical and electrophysiologic findings began to recover shortly after therapy, with a decrease in the levels of serum IgG and IgM anti-GM1 antibodies. This immunoadsorption therapy should be considered for anti-GM1 antibody-associated GBS.

Antibodies, Bacterial↗
PubMed1998

Genetic deficiency of angiotensinogen produces an impaired urine concentrating ability in mice.

Angiotensinogen gene-knockout (Atg-/-) mice lacking angiotensin II exhibit chronic hypotension. The present study was designed to investigate pathophysiology of Atg-/- mice from the renal functional view. Wild-type (Atg+/+) and Atg-/- mice at 10 weeks of age were housed in metabolic cages for 24-hour urine collection. When provided free access to water, Atg-/- mice showed an increased urine output and a decreased urine osmolality compared with Atg+/+ mice. Urinary excretion and plasma levels of vasopressin were significantly higher in mutant mice than in wild-type mice. On the other hand, urinary excretion of aldosterone in mutant mice was suppressed to the levels under the detection limit of the assay system. The mean plasma aldosterone level of Atg-/- mice was suppressed to 30% of that of Atg+/+ mice. Plasma levels of creatinine, endogenous creatinine clearance, and urinary electrolyte excretion were not different between these mice. In Atg+/+ mice, urine osmolality was markedly increased from 1929 +/- 21 to 3314 +/- 402 mOsm/kg during water deprivation, whereas this parameter in Atg-/- mice did not change significantly (from 1413 +/- 121 to 1590 +/- 92 mOsm/kg). Urinary vasopressin excretion increased during water deprivation from 0.24 +/- 0.04 and 0.70 +/- 0.08 to 0.42 +/- 0.06 and 2.31 +/- 0.35 ng/mg creatinine in wild-type and mutant mice, respectively. Histologic study revealed interstitial inflammation, and atrophic changes in the tubules and papilla in Atg-/- mice. In conclusion, a genetic deficiency of angiotensinogen produced an impaired urine concentrating ability and tubulointerstitial lesions, indicating the critical role of angiotensinogen in developing normal tubular function and construction.

Aldosterone↗
PubMed1998

Expression of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice.

Angiotensin type-1a (AT1a) receptor gene-knockout (AT1a-/-) mice exhibit chronic hypotension and renin overproduction. In the kidneys of AT1a-/- mice, the activity of neuronal type nitric oxide synthase (N-NOS) was histochemically detected by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry. The localization of renin was detected by immunohistochemistry and the results were analyzed morphometrically. The levels of N-NOS and renin mRNA in the renal cortical tissue were determined by reverse transcription-PCR and Northern blot analysis, respectively. In the renal sections from wild-type mice, NADPHd activity and N-NOS immunoreactivity were localized to the discrete region of the macula densa in contact with the parent glomerulus. In contrast, N-NOS-positive macula densa cells were distributed beyond the original location of the macula densa, occasionally extending to the opposite side of the distal tubules. The mean number of N-NOS positive macula densa cells was significantly increased in AT1a-/- mice (186 per 100 glomeruli) compared with wild-type mice (65 per 100 glomeruli). AT1a-/- mice showed 1.4-times higher N-NOS mRNA levels in the renal cortical tissues than wild-type mice. The plasma renin activity was significantly higher in AT1a-/- mice (205.5 +/- 26.1 ng/ml/hr) than in wild-type mice (8.0 +/- 0.2 ng/ml/hr). The renin-positive areas per glomerulus and renal renin gene expression were 12-times and 2.6-times higher in AT1a-/- mice than in wild-type mice, respectively. These abnormalities, however, were less remarkable in AT1a-/- mice compared with angiotensinogen-knockout mice. When AT1a-/- mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively-stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. Dietary salt loading produced a parallel decrease in plasma renin activity, renal renin-immunoreactive areas, and the levels of renin mRNA without affecting systemic blood pressure. These results provide evidence for the possible involvement of N-NOS at the macula densa in the increased renin production in AT1a-/- mice.

Angiotensin I↗
PubMed1998

The role of ansa-to-recurrent-laryngeal nerve anastomosis in operations for thyroid cancer.

OBJECTIVE: To study the recovery in phonation after reconstruction of the recurrent laryngeal nerve (RLN) in patients whose thyroid cancer was invading the nerve, and to evaluate the role of ansa cervicalis to RLN anastomosis (ARA) in operations for thyroid cancer. DESIGN: Retrospective study. SETTING: University hospital and private thyroid clinic hospital, Japan. SUBJECTS: 34 patients with thyroid cancer who underwent reconstruction of unilateral RLN and 331 consecutive patients operated on for thyroid cancer. INTERVENTIONS: Reconstruction was direct anastomosis (DA), free nerve grafting (FNG), vagus-RLN anastomosis (VRA) or ARA, including anastomosis behind the thyroid cartilage. MAIN OUTCOME MEASURES: Maximum phonation time (34 normal subjects and 26 patients with vocal cord paralysis served as controls), laryngoscopic examination, and the ratio of reconstruction in patients who needed resection of the RLN. RESULTS: The maximum phonation time started to increase rapidly 2-5 months postoperatively in most cases as the patients' voices recovered, and 12 months after reconstruction was significantly longer than in those patients with vocal cord paralysis (P < 0.0001). It was comparable to that of the normal subjects, although the reinnervated cords were fixed in the median. The number of reconstructions in the series of 331 patients increased from 18% to 82% after we started doing ARA with the meticulous technique of anastomosis inside the thyroid cartilage. CONCLUSIONS: ARA is as effective as DA or FNG in improving phonation in patients who need resection of a unilateral RLN. As ARA has several advantages over FNG it has a definite place in operations for thyroid cancer.

Adult↗
PubMed1998

Autonomic dysfunction in elderly bedfast patients.

OBJECTIVE: to quantify autonomic function in bedfast elderly patients. PATIENTS AND METHODS: we analysed orthostatic blood pressure, heart rate response to tilt, heart rate response to deep breathing, quantitative sudomotor axon reflex test (QSART) and beat-to-beat blood pressure during phases II and IV of the Valsalva manoeuvre (VM) in 15 patients with (OH+) and without orthostatic hypotension (OH-) and 12 age-matched controls. RESULTS: all bedfast patients had a poor response in the late phase II of beat-to-beat blood pressure, while OH+ patients had an additional abnormality in phase IV. QSARTs in the distal leg and foot were decreased in both OH+ and OH- groups. There was no difference between the two groups in duration of being bedfast or in activities of daily living. CONCLUSIONS: (i) being bedfast results in postganglionic sympathetic dysfunction in the lower extremities; (ii) some patients who have beta-adrenergic dysfunction have OH and (iii) preventing patients from becoming being bedfast may be important for the maintenance of normal autonomic functions.

Aged↗
PubMed1998

Iodine-131 MIBG imaging in multiple endocrine neoplasia type 2B.

A 16-year-old boy had a swollen neck that was a result of multiple endocrine neoplasia Type 2B (MEN 2B). CT revealed bilateral thyroid tumors, swelling of right cervical lymph nodes, and slight enlargement of the right adrenal gland. I-131 metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased uptake in the right adrenal gland and the left thyroid tumor, but no abnormal uptake in the right thyroid tumor and the right cervical lymph nodes. Postoperative pathologic findings were consistent with the diagnosis of right adrenal medullary hyperplasia, which is a precursor of pheochromocytoma. In patients with MEN 2B, I-131 MIBG scintigraphy in conjunction with CT of the adrenal glands should be performed to determine the disease stage of the adrenal medullae. In the cervical region, the diagnosis was medullary thyroid carcinoma (MTC) in both thyroid tumors and metastases in the right cervical lymph nodes. The right MTC was more aggressive than the left MTC. It is interesting that not all sites of known MTC take up I-131 MIBG to the same degree.

3-Iodobenzylguanidine↗
PubMed1998

Endocrinological abnormalities in angiotensinogen-gene knockout mice: studies of hormonal responses to dietary salt loading.

OBJECTIVE: Physiological roles of the renin-angiotensin system in maintaining blood pressure and sodium-water balance in angiotensinogen gene-knockout mice were evaluated with special reference to endogenous pressor substances. METHODS: Angiotensinogen-gene knockout mice and control mice were fed a 0.3 or 4% NaCl diet for 2 weeks. Systolic blood pressure and urinary excretions of electrolytes, creatinine, aldosterone, adrenaline, noradrenaline, dopamine and vasopressin were measured. RESULTS: About 60% of our angiotensinogen-gene knockout mice did not survive until weaning. These mice presented with hypotension and polyuria. Urinary excretion of aldosterone from such mice was significantly lower (not detected) than that from control mice (2.0+/-0.3 pg/mg creatinine). In contrast, urinary excretion of vasopressin from angiotensinogen-gene knockout mice (0.7+/-0.1 ng/mg creatinine) was greater than that from control mice (0.3+/-0.1 ng/mg creatinine), and those of adrenaline and of noradrenaline were similar for knockout and control mice. After salt loading (a 4% NaCl diet), angiotensinogen-gene knockout mice exhibited a significant increase in systolic blood pressure (from 68.3+/-2.9 to 95.9+/-5.9 mmHg), significant decreases in urinary excretions of adrenaline (from 65+/-8 to 40+/-7 pg/mg creatinine) and noradrenaline (from 467+/-48 to 281+/-41 pg/mg creatinine) and no change in excretion of vasopressin compared with such mice fed a 0.3% NaCl diet CONCLUSION: The present results with angiotensinogen-gene knockout mice confirm that the renin-angiotensin system plays fundamental roles in maintaining the blood pressure and sodium-water balance. Because the vasopressin and catecholaminergic systems may be altered by lack of angiotensin in angiotensinogen-gene knockout mice, these systems perhaps are not able to restore blood pressure and sodium-water depletion to normal levels in these mice.

Aldosterone↗
PubMed1998

Translation of the flagellar gene fliO of Salmonella typhimurium from putative tandem starts.

The flagellar gene fliO of Salmonella typhimurium can be translated from an AUG codon that overlaps the termination codon of fliN (K. Ohnishi et al., J. Bacteriol. 179:6092-6099, 1997). However, it had been concluded on the basis of complementation analysis that in Escherichia coli a second start codon 60 bp downstream was the authentic one (J. Malakooti et al., J. Bacteriol. 176:189-197, 1994). This raised the possibility of tandem translational starts, such as occur for the chemotaxis gene cheA; this possibility was increased by the existence of a stem-loop sequence covering the second start, a feature also found with cheA. Protein translated from the first start codon was detected regardless of whether the second start codon was present; it was also detected when the stem-loop structure was disrupted or deleted. Translation from the second start codon, either as the natural one (GUG) or as AUG, was not detected when the first start and intervening sequence were intact. Nor was it detected when the first codon was attenuated (by conversion of AUGAUG to AUAAUA; in S. typhimurium there is a second, adjacent, AUG) or eliminated (by conversion to CGCCGC); disruption of the stem-loop structure still did not yield detectable translation from the second start. When the entire sequence up to the second start was deleted, translation from the second start was detected provided the natural codon GUG had been converted to AUG. A fliO null mutant could be fully complemented in swarm assays whenever the first start and intervening sequence were present, regardless of the state of the second start. Reasonably good complementation occurred when the first start and intervening sequence were absent provided the second start was intact, either as AUG or as GUG; thus translation from the GUG codon must have been occurring even though protein levels were too low to be detected. The translated intervening sequence is rather divergent between S. typhimurium and E. coli and corresponds to a substantial cytoplasmic domain prior to the sole transmembrane segment, which is highly conserved; the sequence following the second start begins immediately prior to that transmembrane segment. The significance of the data for FliO is discussed and compared to the equivalent data for CheA. Attention is also drawn to the fact that given an optimal ribosome binding site, AUA can serve as a fairly efficient start codon even though it seldom if ever appears to be used in nature.

Amino Acid Sequence↗
PubMed1998

Activation of angiotensinogen gene in cardiac myocytes by angiotensin II and mechanical stretch.

Circulating and cardiac renin-angiotensin systems (RAS) play important roles in the development of cardiac hypertrophy. Mechanical stretch of cardiac myocytes induces secretion of ANG II and evokes hypertrophic responses. Angiotensinogen is a unique substrate of the RAS. This study was performed to examine the regulation of the angiotensinogen gene in cardiac myocytes in response to ANG II and stretch. ANG II and stretch significantly increased the levels of angiotensinogen mRNA in cardiac myocytes. Actinomycin D completely inhibited ANG II- and stretch-mediated increases in angiotensinogen mRNA. Although CV-11974 abolished ANG II-mediated increases in mRNA level and promoter activity of the angiotensinogen gene, the inhibition of stretch-mediated activation by CV-11974 was significant but not complete. These results indicate that ANG II activates transcription of the angiotensinogen gene exclusively via ANG II type 1-receptor pathway and that stretch activates such transcription mainly via the same pathway in cardiac myocytes. Furthermore, factors other than ANG II may also be involved in stretch-mediated activation of the angiotensinogen gene in cardiac myocytes.

Angiotensin II↗
PubMed1998

Increased cardiac angiotensin II receptors in angiotensinogen-deficient mice.

Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT1-R) and type 2 (AT2-R), have been identified in the heart. However, little is known about the regulation of cardiac AT1-R and AT2-R by Ang II in vivo. Thus, we examined cardiac AT1-R and AT2-R in angiotensinogen-deficient (Atg-/-) mice that are hypotensive and lack circulating Ang II. Cardiac Ang II receptors (Ang II-R) were assessed by radioligand binding with 125I-[Sar1,Ile8]-Ang II in plasma membrane fractions. AT1-R and AT2-R were distinguished using their specific antagonists CV-11974 and PD123319, respectively. Total densities of Ang II-R and AT1-R density were significantly greater in the Atg-/- mice than Atg+/+ mice (31.1+/-2.8 versus 18.8+/-2.1, 28.7+/-3.0 versus 16.9+/-2.3 fmol/mg protein, P<.01, respectively), and AT2-R showed a slight but not significant increase in Atg-/- mice relative to Atg+/+ control animals. Kd values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (AT1a-R) and AT2-R mRNA did not differ between Atg-/- and Atg+/+ mice. These results suggest that lack of Ang II may upregulate AT1-R through translational and/or posttranslational mechanisms in Atg-/- mice.

Angiotensin II↗