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Biomedical subjects

H Sugihara

Publications and source records attributed to H Sugihara.

At least 127 records · Page 7Linked to original sources

Vertical gaze palsy induced by midbrain lesions and its structural imaging.

We experienced four cases of vertical gaze palsy induced by midbrain lesions. Lesions commonly covered the rostral midbrain, including the rostral interstitial nucleus, dorsomedial to the red nucleus. Two of the four cases resulted from vascular insult, in which a single, unpaired perforator is supposed to innervate the rostral midbrain and medial thalamus bilaterally. One case showed vertical gaze palsy accompanied by bilateral ptosis. The findings agree with recent experimental evidence that a neural substrate in eyelid control lies in the supraoculomotor area immediately dorsal to the oculomotor nucleus. The remaining two cases, a brain hemorrhage and an inflammatory tumor, showed unilateral lesions of the rostral midbrain. In these cases, vertical gazes were not abolished, but were limited in an incomplete way. This may be explained by partial damages of the descending fibers, some of which decussate through the posterior commissure before it reaches the oculomotor nucleus. Thus, clinical signs and symptoms were clarified based on anatomical and physiological points of view.

Adult↗

Three-month effects of candesartan cilexetil, an angiotensin II type 1 (AT1) receptor antagonist, on left ventricular mass and hemodynamics in patients with essential hypertension.

Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2-8 mg/day orally for 8-12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 +/- 17.2 mmHg (mean +/- SD) to 150.2 +/- 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 +/- 6.5 mmHg to 87.8 +/- 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 +/- 31.3 g/m2 to 102.6 +/- 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 +/- 31.1 g/m2 to 115.8 +/- 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 +/- 636.3 dynes.s.cm-5 to 1540.4 +/- 432.0 dynes.s.cm-5 (P = 0.0034) on MRI and from 1820.4 +/- 318.8 dynes.s.cm-5 to 1659.0 +/- 317.7 dynes.s.cm-5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2-8 mg/day orally for 8-12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.

Adult↗

Proliferation and differentiation of organoid hair follicle cells co-cultured with fat cells in collagen gel matrix culture.

Using rat skin, we studied the influence of fat cells on the proliferation and differentiation of organoid hair follicle cells in a three-dimensional collagen gel matrix culture system. We cultured organoid hair follicles embedded in collagen gel under each of the following three conditions: cell-free collagen gel for control experiments (condition 1); co-culture with fat cells in close apposition (condition 2); and co-culture with fat cells in spatial separation (condition 3). Outgrowths of epithelial cells from the organoid hair follicles associated with perifollicular proliferation of fibroblasts were observed under conditions 1 and 3. Under condition 2, proliferation of both organoid hair follicle cells and fibroblasts was inhibited, but differentiation of the hair follicle cells appeared to be accelerated. Fat cells are considered to have an inhibitory effect on the proliferation of perifollicular fibroblasts, which might have resulted in the inhibition of hair follicle cell proliferation and also in the better maintenance of normal follicular structure and integrity, allowing for hair-type differentiation to proceed. A direct accelerating effect of fat cells on hair follicle differentiation may also have been responsible. In a physiological state (co-culture with keratinocytes on the collagen gel), similar results were observed under conditions 1 and 2. The different findings under conditions 2 and 3 may be due to either of two possibilities: either the concentration gradient of the soluble factors released from fat cells, acting on either the hair follicle cells or the perifollicular fibroblasts as an inhibitor of proliferation, caused the difference in the results, or direct contact between the organoid hair follicle cells and fat cells may have influenced the accelerating effect of fat cells on the differentiation of hair follicle cells.

Adipocytes↗

Study of the pharmacokinetics of cefpirome sulphate in the elderly.

OBJECTIVE: To determine the appropriate method of administration of the cephem antibiotic cefpirome sulphate in elderly patients. METHOD: We studied cefpirome's pharmacokinetics in patients with urinary tract infections. Patients received cefpirome sulphate 0.5 g by intravenous drip infusion over 30 mins. RESULTS: Patients with a creatinine clearance rate (Ccr) of 80 ml/min had an AUC of 96.7 microg.h/ml and a T1/2 of 2.36 h, whereas those with Ccr of 40-80 ml/min had an AUC of 172.0 microg.h/ml and a T1/2 of 3.45 h and those with Ccr of < 40 ml/min had an AUC of 152 microg.h/ ml and a T1/2 of 4.86 h. CONCLUSION: These results indicate that decreased kidney function can cause increases in the AUC and T1/2 of cefpirome. Thus in elderly patients and perhaps also in other patients with decreased kidney function, cefpirome should be administered at an initial dose of 0.5 g.

Aged↗

Fibroblast growth factor-2 free from extracellular matrix is increased in papillary thyroid carcinomas and Graves' thyroids.

Fibroblast growth factor (FGF)-2 is stored in the extracellular matrix (ECM). We hypothesized that FGF-2 is mobilized from the ECM and binds to receptors on the surface of FGF-2 responsive cells during thyroid enlargement. To test this hypothesis, we estimated levels of FGF-2 free from ECM in thyroids by comparing the efficiency of two methods for FGF-2 extraction (low salt and high salt). Because the high salt concentration (more than 1.5 M NaCl) is necessary to release FGF-2 from the normal ECM, FGF-2 extracted by low salt is indicative of ECM-free FGF-2. Human papillary thyroid carcinomas, normal part thyroid, and Graves' thyroid tissues were homogenized separately in an extraction buffer containing either 0 M NaCl (low salt) or 2.0 M NaCl (high salt), and the concentration of FGF-2 in the extracts was measured by enzyme-linked immunosorbent assay (ELISA). The yields of low and high salt extracts of immunoreactive (ir)FGF-2 from papillary carcinomas (low salt: 40.0 +/- 7.5, high salt: 233 +/- 53 ng/g tissue, mean +/- SE) were significantly higher than those of normal thyroid tissues extracted by the corresponding salt concentration (low salt: 14.6 +/- 1.8, high salt: 123 +/- 12 ng/g tissue). On the other hand, the extractable irFGF-2 from Graves' thyroid tissues (low salt: 25.2 +/- 2.5, high salt: 135 +/- 24 ng/g tissue) were not significantly different from that of normal thyroid tissues. However, the ratio of the extractable irFGF from carcinomas and Graves' thyroids by low salt to that by high salt (0 M/2 M ratio = 0.206 +/- 0.051, 0.209 +/- 0.025) were significantly higher than that of normal thyroids (0.120 +/- 0.014) (p < 0.05). These results suggest that intratissue ECM-free FGF-2 is increased in papillary thyroid carcinomas and Graves' thyroid tissues, and therefore a greater amount of FGF-2 may be available for stimulation of FGF-2 responsive cells.

Blotting, Western↗

Prognostic value of 1-day stress/rest electrocardiogram-gated single-photon emission computed tomography using Tc-99m-labeled methoxy-isobutyl isonitrile.

To evaluate the prognostic value of the simultaneous assessment of perfusion and left ventricular wall motion, exercise non-gated/rest electrocardiogram (ECG)-gated 99mTc methoxy-isobutyl isonitrile (MIBI) single-photon emission computed tomography (SPECT) was performed in 182 patients suspected of having coronary artery disease. After injection of 250 MBq of 99mTc-MIBI at peak exercise, stress perfusion images were classified into 3 groups: normal, equivocal, and abnormal. Normal subjects completed the 1-day protocol but not the resting study, whereas patients with abnormal or equivocal perfusion images underwent ECG-gated SPECT study with injection of 750 MBq of 99mTc-MIBI 3 h later. Patients with normal perfusion during this protocol had a benign prognosis. Only 4 soft events occurred in the normal group (4.8%). In contrast, patients with both myocardial infarction and abnormal wall motion at rest experienced more cardiac events (7 cardiac events including 1 cardiac death among a total of 45 patients; 15.6%, p<0.05 compared with normal subjects). In addition, ischemic patients also experienced more cardiac events (7 events including 2 cardiac deaths among a total of 25 subjects; 28.0%, p<0.01 compared with normal patients). Our data suggest that the simultaneous assessment of perfusion and wall motion by stress/rest ECG-gated 99mTc-MIBI SPECT is a reliable indicator of prognosis in patients suspected of having coronary artery disease.

Aged↗

Growth hormone inhibits its own secretion by acting on the hypothalamus through its receptors on neuropeptide Y neurons in the arcuate nucleus and somatostatin neurons in the periventricular nucleus.

GH secretion is regulated by hypothalamic somatostatin and GH-releasing factor. It has been postulated that GH feeds back on the hypothalamus and regulates its own secretion. We focused our attention on the action of GH in the hypothalamus in relation to GH secretion. Adult male rats were used throughout the studies, and the observation was made in conscious rats. Systemic administration of human GH induced c-fos gene expression, a marker of neuronal activity, in the hypothalamic arcuate nucleus (ARC) and the periventricular nucleus (PeV) in hypophysectomized male rats. The major cells in which c-fos gene expression was induced were neuropeptide Y (NPY) neurons in the ARC and somatostatin neurons in the PeV. GH receptor mRNA was demonstrated to be present in these neurons by in situ hybridization. The injection of a small dose of rat GH into the ARC or PeV inhibited GH secretion, whereas microinjection of IGF-I into these nuclei did not. Intracerebroventricular injection of NPY suppressed GH secretion, and this effect was abolished by anterolateral deafferentation of the medial basal hypothalamus (MBH), a procedure which disrupts the somatostatinergic input to the MBH. Taken together, these findings suggest that GH acts on NPY neurons in the ARC and somatostatin neurons in the PeV through GH receptor, and the activation of these neurons augments somatostatin release and inhibits GH secretion.

Animals↗

[Assessment of localized hypertrophy in the basal part of the interventricular septum in the elderly].

The basal part of the interventricular septum (IVS) is known to show different hypertrophic features from those observed in the other parts of the left ventricular wall. These are considered to reflect physiological changes that occur with normal aging. However, these changes have not been carefully evaluated, and their clinical significance has not been defined. We assessed these changes echocardiographically. The subjects were patients at least 70 years of age in whom localized hypertrophy in the basal part of the IVS was seen during the whole cardiac cycle on echocardiography. The prevalence was 6.3% among 96 consecutively studied patients. All 6 patients had a history of hypertension. Echocardiographic findings were as follows: 1) the left atrium was mildly or moderately dilated, 2) there was no evidence of either dilatation or narrowing of the left ventricular cavity, 3) the left ventricular wall motion appeared normal and indices of systolic function were within normal limits in all subjects except one who had a history of myocardial infarction, 4) the angle formed by the aorta and the IVS averaged 106.7 degrees (range: 95 to 120 degrees), 5) Doppler examination showed increases in the ratio of the peak flow velocity during atrial systole to the peak flow velocity early in diastole, and 6) prolongation of the deceleration time of the flow velocity early in diastole. The last of these findings suggested left ventricular diastolic dysfunction, but peak flow velocity at the left ventricular outflow tract was normal. There was no evidence of stenosis of the left ventricular outflow tract. Localized hypertrophy in the basal part of the IVS in elderly patients could be a type of cardiac hypertrophy caused by hypertension. On echocardiography, the basal part of the IVS seemed to protrude toward the left ventricular cavity, but there was no evidence of stenosis in the left ventricular outflow tract.

Aged↗

Comparison of the lethal components in Vipera aspis aspis and Vipera aspis zinnikeri venom.

Biological activities in Vipera a. aspis and V. a. zinnikeri venom were investigated and compared. Phospholipase A2 and lethal activities were found to be much higher in V. a. zinnikeri venom; the LD50 values for V. a. aspis and V. a. zinnikeri crude venom were 0.55 and 0.35 microgram/g, while PLA2 activities were 25.4 and 41.8 unit/mg, respectively. Other enzymatic and pharmacological activities investigated were similar in both venoms, suggesting that PLA2s might be responsible for the higher toxicity of V. a. zinnikeri venom. PLA2s contained in both venoms were compared immunologically, and the highly lethal phospholipase A2 (PLA2-I) purified from V. a. zinnikeri venom was not found in V. a. aspis venom as determined by antiserum for purified PLA2-I. The toxic effect of V. a. zinnikeri venom was inhibited by anti-PLA2-I, while the same antiserum could not prevent lethality by V. a. aspis venom. These results indicate that PLA2-I in V. a. zinnikeri venom possesses an important role in the lethal activity of this venom. Although V. a. zinnikeri is found in a defined area of France, it is possible that its lethal venom component developed differently than that of V. a. aspis.

Animals↗

Biological properties of kinin-releasing enzyme from Trimeresurus okinavensis (himehabu) venom.

A kinin-releasing enzyme was isolated and characterized from the venom of Trimeresurus okinavensis (himehabu) using Sephadex G-100, DEAE-Cellulose, and CM-Cellulose column chromatographies. The kinin-releasing enzyme was homogeneous as demonstrated by a single band on polyacrylamide gel electrophoresis, and isoelectric focusing. The enzyme possesses a molecular weight of 31,000 Da and isoelectric point of 8.2 and consists of 312 total amino acid residues. Specific esterolytic activities of the kinin-releasing enzyme on N-tosyl-L-arginine methyl ester (TAME) and N-benzoyl-L-arginine ethylester (BAEE) were determined to be 235.3 and 111.3 mumol/min/mg, respectively. The enzyme was inhibited by p-APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and benzamidine. Additionally, the enzyme was found stable to heat treatment. The enzyme cleaved a kininogen analog with the release of bradykinin, resulting in an immediate drop in blood pressure, and contractions of the rat uterus were also observed.

Animals↗

[Measurement of coronary flow reserve using adenosine 5'-triphosphate in dogs].

Adenosine 5'-triphospate (ATP) was compared with adenosine and papaverine for the measurement of coronary flow reserve in 12 anesthetized dogs. Intracoronary bolus injection of ATP (1 ml, 1-500 microM) produced a dose dependent increase in the blood flow of the left anterior descending artery, which attained the plateau at the dose of 100 microM. The ratio of peak to resting coronary flow volume (coronary flow reserve) with 100 microM of ATP (3.5 +/- 0.5) was similar to that with 200 microM of adenosine (4.0 +/- 0.7) and 50 mM of papaverine (3.7 +/- 0.8). Hemodynamic variables did not change after administration of each drug, except left ventricular regional wall motion abnormality during papaverine injection. The coronary flow reserve as measured after intracoronary ATP administration (100 microM) decreased as the grade of stenosis of the left anterior descending artery progressed. In addition, the flow reserve was similar to that of adenosine or papaverine administration at each stenosis grade. Intravenous administration of ATP (1,000 micrograms/min) caused a similar increase in coronary blood flow as intracoronary ATP injection (100 microM). However, premedication with 8-phenyltheophylline, an adenosine receptor blocker, significantly suppressed the coronary dilatory effect of intravenous ATP and intracoronary adenosine but not the effect of intracoronary ATP. These results indicate that intracoronary ATP is useful for measuring coronary flow reserve and that its coronary dilatory effect is not mediated by metabolysis to adenosine.

Adenosine↗

Increased subglottic gallium uptake in relapsing polychondritis.

Gallium scintigraphy was performed on a 14-yr-old girl with subglottic airway narrowing that caused wheezing and dyspnea. The study showed increased gallium uptake in the neck. A biopsy was performed on the subglottic region, and the histology was compatible with relapsing polychondritis. After treatment with steroids, laboratory data that had indicated active inflammation soon normalized. Repeat gallium scintigraphy showed diminished uptake, although the subglottic stenosis did not improve. These results suggest that gallium scintigraphy is valuable for evaluating inflammatory activity in relapsing polychondritis.

Adolescent↗

[A survey of opioid use in preanesthetic medication].

A mailing survey was carried out to assess the current practice of sedative premedication in anesthesia. Questionnaires were sent by mail to 77 university hospitals. We especially evaluated use of opioids for premedication. Sixty-one percent (n = 47) of the hospitals answered these questionnaires and 31 percent (n = 15) of them were using opioids for the preanesthetic medication. Pethidine was used most frequently for premedication of all opioids, and morphine was often used for the premedication before cardiac surgery. All opioids were administrated intramusculary both in adults and children.

Adolescent↗

[123I-metaiodobenzylguanidine (MIBG) scintigraphy for the staging of neuroblastoma].

Nineteen children with neuroblastoma (aged 2 w.-7 y.o.) were studied to evaluate the optimal scan conditions for Iodine-123-Metaiodobenzylguanidine (MIBG) scintigraphy for accurate staging at the time of diagnosis. Six and 24 hours after an injection of 123I-MIBG, whole body image and truncal spot and SPECT images were obtained. Compared with other studies (CT or MRI and bone scintigraphy), each 123I-MIBG image was evaluated visually to investigate which image can demonstrate the extent of neuroblastoma most exactly. MIBG images demonstrated primary tumors in all patients, and metastatic lymphadenopathy in 8 of 9 patients. Twenty-four hour SPECT images gave us the most detailed information about the extent of abnormal accumulation. As to bone and bone marrow lesions, 6 hour images were superior to 24 hour images in detectability. Moreover, MIBG showed many more lesions and more extended accumulation than the bone scan. 123I-MIBG scintigraphy was very useful in detecting neuroblastomas. In order to get the most valuable information, both delayed SPECT and early whole body planar images should be obtained.

3-Iodobenzylguanidine↗

A late ON response remains in visual response of the mGluR6-deficient mouse.

In a previous study, we showed that the visual ON response recorded from the superior colliculus is absent in the metabotropic glutamate receptor subtype 6 (mGluR6) knockout mice. However, these mutant mice can respond to some visual inputs and are able to learn a light-dark discrimination task. Here, we systematically investigated the possibility that some ON responses could remain in the mutant mice. Recording light evoked field potentials from the superior colliculus of mGluR6-deficient mice at scotopic and mesopic backgrounds, we found a characteristic ON response that differs from the ON response of wild-type mice. The ON responses recorded from the mutant mice appeared with a latency (200-300 ms) longer than that of the wild-type mice (50-100 ms) and amplitudes of this late ON response decreased upon increase of the light intensity in most cases examined. The late ON response may contribute to the apparent normal behavior and some physiological responses to light stimuli in mGluR6-deficient mice.

Animals↗

Changes in extracellular nitrite and nitrate levels after inhibition of glial metabolism with fluorocitrate.

The role of glial cells in nitric oxide production in the cerebellum of conscious rats was investigated with a glial selective metabolic inhibitor, fluorocitrate. The levels of nitric oxide metabolites (nitrite plus nitrate) in the dialysate following in vivo microdialysis progressively increased to more than 2-fold the basal levels during a 2-h infusion of fluorocitrate (1 mM), and the increase persisted for more than 2 h after the treatment. Pretreatment with N(G)-nitro-L-arginine methyl ester attenuated the fluorocitrate-induced increase in nitric oxide metabolite levels. None of the glutamate receptor antagonists, including D(-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione, and (+/-)-alpha-methyl-4-carboxyphenylglycine, inhibited the fluorocitrate-induced increase. The L-arginine-induced increase was significantly reduced by fluorocitrate treatment, while N-methyl-D-aspartate, (+)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and trans-(+/-)-1-amino-(1S,3R)-cyclopentane-dicarboxylic acid increased nitric oxide metabolites levels in the fluorocitrate-treated rats, as much as in control animals. These results suggest that glial cells play an important role in modulating nitric oxide production in the cerebellum by regulating L-arginine availability.

Aconitate Hydratase↗

Developmental analysis of cardiovascular system of 45,X fetuses with cystic hygroma.

There have been few pathological investigations of 45,X embryos and fetuses from a developmental point of view. Since most 45,X embryos and fetuses are lost prenatally, it is important to investigate them morphologically in order to elucidate the pathogenesis of the abnormalities. In this study, 13 45,X fetuses with cervical cystic hygroma were examined between 12 and 23 weeks of pregnancy. Every case had a hypoplastic thymus. The aortic valve was bicuspid in 11 cases and unicuspid in 2 cases. The aortic arch showed tubular hypoplasia between the left carotid artery and the left subclavian artery in 12 cases and type B interruption in one case. Smooth muscle cells and elastic fibers were reduced in number in the hypoplastic aortic arch. These results suggest hypoplastic development of the fourth branchial arch. Combined abnormalities between the aortic arch and aortic valve are not infrequently observed in DiGeorge anomaly. A similar developmental mechanism apparently underlies the pathogenesis of 45,X embryos. Possible genes causing the abnormalities are discussed.

Aorta, Thoracic↗

Identification of host and donor cells in porcine homograft heart valve explants by fluorescence in situ hybridization.

The pathogenesis of the primary tissue degeneration that limits the life-span of aortic and pulmonary homografts has still not been revealed. Histopathological studies on homograft explants have not given definitive insight into the eventual fate of donor cells, nor have they demonstrated the assumed importance of host cell ingrowth into the graft tissue. In this experimental study, fluorescence in situ hybridization (FISH) is introduced as a new approach to examine the distribution of host and donor cells in homograft explants. Aortic valve replacement was performed with a cryopreserved porcine aortic homograft in three pigs; donor and recipient were of opposite sex. After 4 months, the grafts were explanted and examined by FISH using a biotinylated porcine Y-chromosome-specific library probe. Following probe detection with FITC-conjugated avidin, a clear distinction could be made between cells of host and donor origin without distorting the histological integrity of the explants. There was ingrowth of donor cells into the graft aortic wall and into the valve leaflet, to some extent. In all explants, remaining donor cells were present, though decreased in number. The introduction of FISH in homograft heart valve research provides a powerful tool to study the fate of recipient and donor cellular elements in situ, and may therefore contribute to a better understanding of the histopathological processes that take place in transplanted homograft valves.

Animals↗