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Biomedical subjects

S Hashiguchi

Publications and source records attributed to S Hashiguchi.

At least 55 records · Page 3Linked to original sources

[Minimally invasive technique for mitral valve repair--the importance of intraoperative transesophageal echocardiography].

A 65-year-old male with mitral regurgitation was scheduled for the mitral valve repair by means of minimally invasive technique. The technique, which requires a 10-cm right parasternal incision, offers minimal discomfort, less postoperative pain, quick functional recovery and excellent cosmetic healing. However, the intraoperative monitoring by the transesophageal echocardiography was required to evaluate the mitral valve function and to confirm the complete removal of air from the apex of the left ventricle and right upper pulmonary vein due to the small operative field. In addition, the monitoring of the short-axis view of the left ventricle makes it possible to evaluate and to confirm the preload and the left ventricular contractility. We considered that the transesophageal echocardiography is essential and useful for the minimally invasive mitral valve repair.

Aged↗

[A case of Guillain-Barré syndrome with bulbar palsy and a high titer of anti-GT1a antibody].

We report a rare case of Guillain-Barré syndrome (GBS) in a patient with anti-GT1a antibody. A 42-year-old man was admitted with dysphagia, dysarthria and weakness in his neck and both upper limbs. Serial electrophysiological studies suggested that the predominant process was demyelination of the motor nerves. Thin-layer chromatography with immunostaining revealed that his serum IgG reacted strongly with GT1a and weakly with GQ1b. He recovered rapidly with plasmapheresis. These findings suggest that anti-GT1a IgG antibody might play an important role in the pathogenesis of bulbar palsy in GBS.

Adult↗

Th1/Th2 response profiles to the major allergens Cry j 1 and Cry j 2 of Japanese cedar pollen.

Cry j 1 and Cry j 2 are known to be the major allergens of Japanese cedar pollen. A comparative study was carried out on the immune responses to stimulation with Cry j 1 and Cry j 2 in 24 symptomatic patients and six nonallergic subjects. In T-cell proliferation assays, mean stimulation indexes (SI) were 10.6 for Cry j 1 and 11.7 for Cry j 2 stimulation, respectively, in the allergic patients. Two of the nonallergic subjects showed strong T-cell proliferation to both allergens, while the remainder did not. All the allergic subjects (17/17) showed high titers of anti-Cry j 1 IgE antibody at a mean value of 165 U/ml, whereas only 64% responded to Cry j 2 with low titers at a mean value of 26 U/ml. Nonallergic subjects did not respond with IgE production. Allergic subjects were further examined for their cytokine production profiles. All allergic subjects tested (16/16) produced high levels of interferon-gamma (IFN-gamma) in response to Cry j 1 with a mean value of 918 pg/ml, while only five subjects showed significant elevation of IFN-gamma production in response to Cry j 2 with a mean value of 679 pg/ml. The remainder produced small amounts of IFN-gamma. Cry j 1 induced higher levels of interleukin (IL)-10 gene expression than did Cry j 2 stimulation, while both allergens induced IL-4 expression at a similar level. The IL-12 p35 gene was constitutively expressed, whereas the IL-12 p40 gene expression in Cry j 1-stimulated cells was elevated eightfold over that of nonstimulated cells. Increased expression of the IL-12 p40 gene was negligible in Cry j 2-stimulated cells. Thus, Cry j 1 stimulated mixed features of Th1 and Th2-like responses, while Cry j 2 played a minor role in inducing IgE production and cytokine (IFN-gamma, IL-10, and IL-12) production, except for IL-2 production and strong T-cell proliferative activity. Therefore, it was concluded that Cry j 1 is the more important allergen, and that T-cell proliferation assays do not necessarily reflect the level of allergenicity.

Allergens↗

Immunodominance of seven regions of a major allergen, Cry j 2, of Japanese cedar pollen for T-cell immunity.

The immunodominant regions of the Japanese cedar pollen allergen Cry j 2 for T-cell immunity were determined with whole peripheral blood lymphocytes (PBL) derived from seven allergic patients and three nonallergic subjects. Cry j 2-stimulated T-cell proliferation was inhibited by anti-HLA-DR, but not by anti-HLA-DQ antibody, indicating that the responding T cells recognized the allergen peptides associated with HLA-DR molecules. It was found that seven regions of Cry j 2, i.e., regions corresponding to amino acid numbers 1-26, 70-84, 151-167, 187-203, 252-279, 283-314, and 345-362, were immunodominant for T-cell proliferation. Thus, Cry j 2 bears a limited number of immunodominant regions despite polymorphic features of HLA-DR in the immune system. This suggests the possibility of molecularly designing Cry j 2 antagonists that could downregulate allergic reactions to Japanese cedar pollen.

Case-Control Studies↗

Synthesis and biological activity of novel 1,3-benzoxazine derivatives as K+ channel openers.

A new series of 1,3-benzoxazine derivatives with a 2-pyridine 1-oxide group at C4 was designed to explore novel K+ channel openers. Synthesis was carried out by using a palladium(0)-catalyzed carbon-carbon bond formation reaction of imino-triflates with organozinc reagents and via a new one-pot 1,3-benzoxazine skeleton formation reaction of benzoylpyridines. The compounds were tested for vasorelaxant activity in tetraethylammonium chloride (TEA) and BaCl2-induced and high KCl-induced contraction of rat aorta to identify potential K+ channel openers, and also for oral hypotensive effects in spontaneously hypertensive rats. An electron-withdrawing group with the proper shape at C6 and a methyl or halogeno group at C7 of the 1,3-benzoxazine nucleus were required for the development of optimal vasorelaxant and hypotensive activity. In particular, 2-(6-bromo-7-chloro-2,2-dimethyl-2H-1,3-benzoxazin-4-yl)pyridine 1-oxide (71) showed more potent vasorelaxant activity (EC50 = 0.14 microM) against TEA and BaCl2-induced contraction and longer-lasting hypotensive effects than cromakalim (1).

Animals↗

[A case of conus syndrome following arteriogenic impotence].

A patient with conus syndrome following arteriogenic impotence is described. A 62-year-old man became impotent. 7 months after the onset, he was admitted because of a sudden left sensorimotor disturbance (L2 to S5 segments) when he awoke. A marked bilateral reduction of cutaneous sensation in the S2 to S5 dermatome distribution persisted. An MRI of the spinal cord demonstrated no abnormal lesion on T2-weighted and Gadolinium enhanced images. Angiography of the pelvic artery showed severe arteriosclerotic findings. We diagnosed this case as a conus syndrome due to ischemia in the conus medullaris. The impotence in our case was considered to be arteriogenic because there was no detection of the bilateral deep arteries of the penis on angiography after an intracorporeal PGE1 injection. In this case, arteriogenic impotence might be a prodrome of a conus medullaris infarction.

Humans↗

[Molecular immunology of Japanese cedar pollen allergens: analysis of T cell epitopes].

Recent studies demonstrated that partial alteration of the amino acid sequence of T cell epitopes induced a stimulatory signal that was qualitatively different. Therefore, it is conceivable that immunotherapy using peptides representing dominant T cell epitopes could modulate the T cell response of allergic patients and prevent the production of IgE antibodies. Accordingly, a number of allergens have been molecularly cloned to determine their amino acid sequences. In Japan, the number of patients suffering from Japanese cedar pollinosis is steadily increasing and it has become a serious social problem. In this paper, we review the recent advances on T cell epitope mapping of Japanese cedar pollen, Cry j 1 and Cry j 2 and immunomodulating trials based on the mechanisms of T cell antigen-recognition.

Allergens↗

[A case of myotonic dystrophy with impairment of smooth pursuit eye movement].

We reported a 36-year-old woman of myotonic dystrophy with impairment of smooth pursuit eye movement. The patient, whose mother was also affected, had psychomotor retardation from childhood. DNA analysis by Southern hybridization technique showed large DNA fragment (14/8.6 kb). Oculomotor limitation and gaze nystagmus were not observed, and saccadic eye movements were normal. In electrooculography, smooth pursuit eye movements were impaired toward both directions, and interrupted by saccades. The caloric test elicited a satisfactory response, but the visual suppression test produced no suppression. CT scan displayed paraventricular low density area, and MRI showed the multiple foci of high signal intensity in the white matter on T2-weighted images. No changes were detected on CT or MRI in the brainstem and cerebellum. The lesions in the brain are considered to be correlated with smooth pursuit impairment.

Adult↗

Antihypertensive and cardiovascular effects of a new potassium channel opener, TCV-295, in rats and dogs.

The antihypertensive and cardiovascular properties of a new potassium channel opener, TCV-295, were studied in rats and dogs. In conscious, spontaneously hypertensive rats (SHR), TCV-295 (0.03-1 mg/kg orally, p.o.) reduced blood pressure (BP) dose dependently with slow onset of action. The antihypertensive effects induced by TCV-295 lasted much longer than those of levcromakalim and nisoldipine, and the reflex tachycardia it evoked was less marked than that evoked by these drugs as compared at doses showing similar maximal hypotensive effects. Glibenclamide (30 mg/kg intravenously, i.v.) inhibited the TCV-295-induced BP decrease in anesthetized rats. In a 4-week chronic dosing study in SHR, TCV-295 (0.3 mg/kg/day p.o.) produced neither potentiation nor tolerance to its antihypertensive action and no rebound hypertension occurred when drug treatment was discontinued. In anesthetized normotensive dogs, TCV-295 (4.5 micrograms/kg/min i.v.) induced BP reductions accompanied by reductions in systemic vascular resistance. TCV-295 also reduced resistances of the coronary, vertebral, mesenteric, and renal vascular beds, and the most marked effect was observed in the coronary vasculature. Myocardial O2 consumption was reduced by TCV-295, possibly owing to afterload decrease. These results suggest that TCV-295 has a desirable profile for an antihypertensive agent.

Administration, Oral↗

[Persistent isolated abducens nerve palsy from pontine infarction confirmed by gadolinium-DTPA enhanced MRI].

An 80-year-old man had left isolated abducens nerve palsy after repeated conjugate deviation to the right without any other findings. MRI demonstrated no abnormal lesion of T2-weighted images, while left paramedian tegmentum pontis was enhanced as responsible lesion by gadolinium (Gd)-DTPA on the 13th hospital day when Foville syndrome lasted. On the 33rd hospital day when isolated abducens nerve palsy lasted, however, this lesion was not detected with Gd enhanced images. The diagnosis of abducens nerve palsy caused by pontine infarction was obtained. Our patient had a lesion involving the left PPRF and ipsilateral abducens nerve. We concluded that the complete damage of left abducens motoneuron may cause isolated abducens nerve palsy lasting more than one year after Foville syndrome due to the dysfunction of left PPRF. To our knowledge, this is the first report of the persistent isolated abducens nerve palsy resulting from a pontine miniature ischemic lesion speculated by Gd enhanced MRI.

Abducens Nerve↗

[Involvements of neuropeptides in pentylenetetrazol-induced convulsion in rats and effects of TRH and ceruletide on the convulsion].

To study the possible involvements of neuropeptides in the occurrence of convulsion, pentylenetetrazol (PTZ) was given to male Wistar rats weighing 250-350 g, and the concentration of neurotensin (NT), and the maximal number of binding sites (Bmax) and dissociation constant (Kd) of NT receptor in the frontal cortex were measured. The effect of the pretreatment of thyrotropin-releasing hormone (TRH) or ceruletide (CER) on the convulsion was also studied. NT was extracted from the homogenates of rat frontal cortex by boiling, and measured by radioimmunoassay. Membrane fractions were incubated with increasing concentrations of 125I-NT. Nonspecific binding was determined in the presence of unlabeled NT and subtracted from total binding to obtain the specific binding. The Bmax and Kd were calculated by Scatchard analysis. Generalized convulsion appeared after intraperitoneal administration of 50 mg/kg PTZ with a latency of 68.2 +/- 4.4 sec. One hour after the administration, neurotensin-like immunoreactivity (NTLI) concentration was reduced from 4.7 +/- 0.6 to 2.3 +/- 0.1 ng/g wet wt (p less than 0.01) and the Bmax of NT receptor from 17.2 +/- 2.8 to 10.8 +/- 1.1 fmol/mg protein (p less than 0.01). However no significant changes were observed in somatostatin-like immunoreactivity (SSLI) concentration and the Bmax and Kd of SS receptor. These facts indicate that PTZ stimulates the release of NT resulting in down regulation of NT receptor. Pretreatment with intracerebroventricular (icv) administration of 30 micrograms/10 microliters NT 30 min before the 50 mg/kg PTZ administration shortened the duration of the convulsion from 135.0 +/- 42.8 to 11.5 +/- 11.9 sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chemical modification of sulfazecin. Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives.

In expectation of improving the antibacterial activity of sulfazecin by chemical modification at the 3- and 4-positions, a number of 3-[2-(2-aminothiazol-4-yl)-(Z)-2-(substituted oxyimino)-acetamido]-4-(substituted methyl)-2-azetidinone-1-sulfonic acids were synthesized. Among various 4-substituents explored, the carbamoyloxymethyl group was found to provide a good effect to the antibacterial activity of these 2-azetidinone derivatives. An extensive study of structure-activity relationships led to selecting (3S,4S)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-carboxymethoxyiminoace tamido]-4- carbamoyloxymethyl-2-azetidinone-1-sulfonic acid, AMA-1080 (Ro 17-2301), which has highly potent antibacterial activity against Gram-negative bacteria including Pseudomonas aeruginosa, for further biological and subsequent clinical evaluation.

Anti-Bacterial Agents↗