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Biomedical subjects

R Hayashi

Publications and source records attributed to R Hayashi.

At least 181 records · Page 10Linked to original sources
PubMed1993

Optically active antifungal azoles. I. Synthesis and antifungal activity of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-b utanol and its stereoisomers.

(2R,3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butano l [(2R,3R)-7] and its stereoisomers [(2S,3R)-, (2S,3S)- and (2R,3S)-7] were prepared from the optically active oxiranes 6 by a newly developed ring-opening reaction and evaluated for antifungal activity. The thiol (2R,3R)-7 showed extremely potent antifungal activity in vitro and in vivo. The optically active oxirane (2R,3S)-6, a useful intermediate for the synthesis of sulfur-containing antifungal azoles 5, was synthesized from methyl (R)-lactate [(R)-8] via eight steps in a stereocontrolled manner. The key step in the synthesis is the Grignard reaction of an amide derivative [(R)-12a] of (R)-lactic acid with 2,4-difluorophenyl-magnesium bromide (13).

Animals↗
PubMed1993

Optically active antifungal azoles. II. Synthesis and antifungal activity of polysulfide derivatives of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H- 1,2,4-triazol-1-yl)-2-butanol.

In an effort to find potent antifungal agents, a variety of optically active triazole derivatives with a polysulfide structure, 3, 4 and 5, were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The symmetrical polysulfides 3 (m = 2-4) were obtained by an oxidative coupling reaction of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butanol (1) or by the treatment of its thiocarbonate derivative 8 with potassium tert-butoxide. The unsymmetrical disulfides 5 were synthesized by the reaction of the thiol 1 with Bunte salts 11 or the thiosulfinate 12 or by the reaction of the thiocarbonate 8 with various thiols 13. All of these polysulfides showed potent antifungal activity against candidosis in mice.

Animals↗
PubMed1993

[Apraxia of gait and disorders in posture and locomotion].

Apraxia of gait is a unique disorder of locomotion characterized by inability in lifting the feet from the floor despite alternating stepping action (frozen gait), and disequilibrium. Responsible site of lesions are in the frontal lobe and/or the basal ganglia. It is observed in an advanced stage of Parkinson's (PD) or vascular parkinsonism with multiple cerebral infarction (MCI). Studies on equilibrium and natural gait have disclosed unique features in this condition. Records of floor reaction forces in forward locomotion showed that vertical-foreaft vector angles at kick-off phase is small in both PD and MCI with frozen gait. EMG of antagonists in leg muscles were either reciprocal or coincided in frozen gait, and rhythm of stepping was crucial for development of freezing. Center of foot pressure (CFP) in forward-bent natural posture in PD still locates behind that of normals. For voluntary forward bending, maximal shift of CFP was smaller, and increase in EMG was larger in PD subjects. Pushing chest backward results in step-out or fall in parkinsonians. In this response, EMG in the pretibial muscles were the same amount in both PD and normals. However, velocity in hip extension and amount of knee and ankle displacement were smaller in PD.

Apraxias↗
PubMed1993

Event-related potentials, reaction time, and cognitive state in patients with Parkinson's disease.

ERPs, RT, and cognitive state in 53 patients with PD were studied. The peak latency of P300 and the RT in PD patients were significantly prolonged in the advanced stage of illness. The cognitive state in PD patients was characterized by impairment of attention, recent memory, and constructional ability in categories of the Folstein Mini-Mental State Examination. The significant association between neurophysiological and neuropsychological measurements suggests that these measurements reflect a disrupted aspect of cognitive function in PD patients.

Aged↗
PubMed1992

Formation of glycine conjugate and (-)-(R)-enantiomer from (+)-(S)-2-phenylpropionic acid suggesting the formation of the CoA thioester intermediate of (+)-(S)-enantiomer in dogs.

It has been proposed that the chiral inversion of the 2-arylpropionic acids is due to the stereospecific formation of the (-)-R-profenyl-CoA thioesters which are putative intermediates in the inversion. Accordingly, amino acid conjugation, for which the CoA thioesters are obligate intermediates, should be restricted to those optical forms which give rise to the (-)-R-profenyl-CoA, i.e., the racemates and the (-)-(R)-isomers. We have examined this problem in dogs with respect to 2-phenylpropionic acid(2-PPA). Regardless of the optical configuration of 2-phenylpropionic acid administered, the glycine conjugate was the major urinary metabolite and this was shown to be exclusively the (+)-(S)-enantiomer by chiral HPLC. Both (-)-(R)- and (+)-(S)-2-phenylpropionic acid were present in plasma after the administration of either antipode, and further evidence of the chiral inversion of both enantiomers was provided by the presence of some 25% of the opposite enantiomer in the free 2-phenylpropionic acid and its glucuronide excreted in urine after administration of (-)-(R)- and (+)-(S)-2-phenylpropionic acid. The (+)-(S)-enantiomer underwent chiral inversion to the (-)-(R)-antipode when incubated with dog hepatocytes. These data suggests that both enantiomers of 2-phenylpropionic acid are substrates for canine hepatic acyl CoA ligase(s) and thus undergo chiral inversion, but that the CoA thioester of only (+)-(S)-2-phenylpropionic acid is a substrate for the glycine N-acyl transferase. These studies are presently being extended to the structure and species specificity of the reverse inversion and amino acid conjugation of profen NSAIDs.

Animals↗
PubMed1992

Rescue therapy for acute rejection using 15-deoxyspergualin (DSG) in combination with superoxide dismutase (SOD) on cardiac allografts in rats.

This study was performed to investigate the effect of combination therapy using 15-deoxyspergualin (DSG) plus recombinant human superoxide dismutase (h-SOD) on acute graft rejection in heterotopic rat heart transplantation. DSG was intraperitoneally injected for 10 days at a dose of 5 mg/kg per day, and h-SOD (15,000 or 30,000 microm/kg per day) was continuously administered via external iliac vein for approximately 8 days with a mini-osmotic pump (Alzet model 2001). Administration of the drugs was started on the 4th day after grafting. The grafts treated with h-SOD alone survived slightly longer than the control allografts. The graft survival time was significantly prolonged in the groups treated with DSG alone or DSG plus h-SOD. A higher percentage of induction of immunological unresponsiveness was achieved in the group treated with DSG plus h-SOD at 30,000 microm/kg per day. The ratios of inorganic phosphate (Pi)/phosphocreatine (PCr) and PCr/ATP on the 31P nuclear magnetic resonance spectrogram are useful parameters for assessing the graft injury associated with acute rejection. The ratio of Pi/PCr and that of PCr/ATP were found to increase and decrease, respectively, in proportion to the progress in rejection. In the animals treated with DSG alone, the Pi/PCr ratio was significantly increased from the 4th day, and PCr/ATP ratio decreased from 10th day after grafting. These parameters were not improved during the observation period. However, these parameters were significantly recovered in the animals treated with DSG and h-SOD in combination. Improvement of the parameters seemed to be related to SOD dosage. These results clearly demonstrated that the oxygen free radical plays a toxic role in cardiac allografts with ongoing rejection and, therefore, the administration of h-SOD in combination with DSG can minimize the graft injury.

Acute Disease↗
PubMed1992

Myotonic and repetitive discharges in hypokalemic myopathy associated with glycyrrhizin-induced hypochloremia.

Electromyographic studies were performed in two patients with hypokalemic myopathy induced by the administration of glycyrrhizin, 270-273 mg per day for a period of two and eight months, respectively. Myotonic and repetitive discharges were observed when the serum chloride level fell below 90 mEq/l. Following the administration of potassium chloride, when the chloride level rose above 90 mEq/l, these discharges disappeared. These findings support the causal role of hypochloremia in myotonic discharges. A serum chloride level below 90 mEq/l appears to be critical in producing the myotonic and repetitive discharges.

Aged↗
PubMed1992

Comparison of amplitude of human soleus H-reflex during sitting and standing.

The modulation of the H-reflex in the human soleus muscle under conditions of different length or of background EMG activity was compared in 7 healthy subjects under three conditions: sitting, standing with support, and standing without support. The amplitude of the H-reflex increased when the muscle was shortened in both the sitting and standing conditions. The degree of increase in H-reflex was smaller during standing than sitting for the same change in muscle length. The H-reflex was augmented according to the increase of the background EMG. The "reflex gain", the ratio of the increase in amplitude of the H-reflex to soleus muscle EMG activity, decreased on sitting, standing with support and standing without support, ranked in that order. From these observations, it is concluded that the H-reflex is modulated by both muscle length and the degree of postural stability. The modulation of the reflex could be interpreted in terms of gain compensation and would serve to stabilize posture. A decrease in reflex gain may be appropriate in stabilizing the spinal reflex feedback loop during standing, especially without support.

Adult↗
PubMed1992

Four clinical types of panic disorders.

The authors attempted to classify panic disorders into four types according to a clinical course and accompanying neurotic or depressive symptoms. The characteristics of each type are as follows; type I: a single panic attack is the only symptom, type II: only panic attacks occur frequently without any accompanying neurotic or depressive symptoms, type III: a recurrence of panic attacks and the gradual development of neurotic symptoms, such as anticipatory anxiety, generalized anxiety, agoraphobia, or hypochondriasis, type IV: depressive symptoms develop in the course of recurring panic attacks. Type IV is further divided into three subtypes. Type IV-1: depressive symptoms develop secondary to panic attacks and major depression later coexists with panic disorder. Type IV-2: panic disorder continuously changed into major depression. Type IV-3: panic attacks and depressive symptoms are seen independently. The most common types are type III and type IV-1, and seem to be a core group of the panic disorder. Typical cases of each type are presented and underlying psychopathology is discussed.

Adult↗
PubMed1992

Serial computed tomographic and electroencephalographic studies in Creutzfeldt-Jakob disease.

The serial changes in computed tomography (CT) as correlated with the clinical and electroencephalographic findings were evaluated in 3 patients with Creutzfeldt-Jakob disease. The disease was subsequently confirmed histologically in 2. CT revealed that brain atrophy began in an early clinical stage and was prominent even before the state of akinetic mutism. Periodic synchronous discharges (PSDs) were observed either before or simultaneous with the observation of myoclonus. With progressive brain atrophy, the frequency of PSDs and the degree of myoclonus both decreased and disappeared 8 to 15 months after the onset of disease.

Aged↗
PubMed1992

Spinal cord sarcoidosis: MRI findings in response to treatment.

The unusual case of a 64-year-old female with sarcoidosis involving the spinal cord is reported. Diffuse swelling of the cord with nodular lesions was observed on MRI. The lesions showed a low intensity area on the T1-weighted image. Following the administration of gadolinium-diethylenetriamine pentaacetic acid, the spinal cord, especially the nodular lesions, was diffusely enhanced. Serum levels of anti-endothelial cell antibodies and antinuclear antibodies were elevated. The diagnosis was confirmed by transbronchial lung biopsy which revealed noncaseating granulomas with giant epithelioid cells. The administration of prednisolone, 40 mg/day for 4 weeks, induced a remission.

Autoantibodies↗
PubMed1992

Leukoencephalopathy induced by tegafur: serial studies of somatosensory evoked potentials and cerebrospinal fluid.

A case of leukoencephalopathy induced by tegafur, an antineoplastic derivative of 5-FU, is reported. The patient received 600 mg of tegafur p.o. for 16 days before excision of rectal cancer. After the operation, gait disturbance and mental abnormalities appeared. He became akinetic and mute within a few days following readministration of tegafur. Serial studies of brain CT, somatosensory evoked potentials (SEP) were made, and myelin basic proteins (MBP) in the cerebrospinal fluid were measured. The level of MBP was about twice the normal value and the central conduction time (CCT) of SEP was prolonged at admission. The value of MBP and CCT improved with recovery from akinetic mutism.

Akinetic Mutism↗
PubMed1992

[Experimental study on platelet activating factor and systemic circulatory failure caused by ischemic liver].

Ischemic hepatic failure is often accompanied by systemic circulatory failure. In hepatic graft failure, this circulatory derangement is reported to be cured by retransplantation. This suggests that ischemic liver might release some substance which causes circulatory depression. In the present study, the role of platelet activating factor (PAF) in systemic circulatory failure after liver ischemia was investigated. Partial hepatic ischemia was induced in ten dogs by clamping the afferent vessels to almost 70% of the liver for 60 minutes, and non-ischemic lobes were resected after declamping. Five were pretreated with 3 mg/kg of PAF antagonist (CV6209) i.v. (PAF antagonist group), and the others were pretreated with saline (control group). The mean arterial pressure markedly decreased after declamping in control group (89 +/- 25mmHg 25 min after declamping), but it did not fall in PAF antagonist group (155 +/- 221mmHg). Three died from either shock or hepatic failure within a week in control group, but none died in PAF antagonist group. In conclusion, ischemic liver was suggested to release PAF and depress systemic circulation. And a PAF antagonist was expected to be an effective drug for the circulatory derangement caused by ischemic liver.

Animals↗
PubMed1992

[Analysis of the determinant factors for open heart surgery without blood transfusion by the quantification theory--possibility of application of maximum surgical blood order schedule for open heart surgery].

In order to complete operations without blood transfusion we have chosen means of preoperative autologous blood saving and intraoperative autotransfusion, but we have not always achieved our purpose. We examined 29 patients (13 patients without blood transfusion and 16 with blood transfusion) to analyze the determinant factors as to whether open heart surgery without blood transfusion may be indicated or not, according to the quantification theory (type II) and to examine the possibility to apply the maximum surgical blood order schedule (MSBOS) for the open heart surgery by the quantification theory (type I). The analysis of determinant factors revealed hematocrit (Ht) value before saving of blood (more than 40%) as the best contributor of possibility of non-blood transfusion surgery, followed by the amount of blood loss during operation (less than 600 ml), the amount of saving blood (more than 800 ml), body weight (less than 70 kg), calculated Ht value on the beginning of cardiopulmonary bypass (CPB) (more than 24%), CPB time (less than 120 minutes) and the amount of postoperative blood loss (less than 600 ml). The prospective using blood volume at the operation was precisely calculated by the values of 4 preoperative factors, that is, the amount of saving blood, calculated Ht value on the beginning of CPB, CPB time and body weight. Therefore it is important to increase the amount of preoperative saving blood and decrease the amount of surgical bleeding in order to perform operations without blood transfusion, and is possible to apply the MSBOS for the open heart surgery.

Adolescent↗
PubMed1991

Effects of hypothyroidism and high-fat feeding on mRNA concentrations for the low-density-lipoprotein receptor and on acyl-CoA:cholesterol acyltransferase activities in rat liver.

1. Induction of hypothyroidism in rats by feeding propylthiouracil (PTU) significantly increased serum cholesterol concentrations, and the effect was more pronounced for cholesterol in low-density lipoproteins (LDL) rather than high-density lipoproteins (HDL). The concentrations of serum triacylglycerol were decreased in hypothyroidism. These effects on serum lipids were also seen when the normal rats were pair-fed with the PTU-treated group. 2. Feeding a diet rich in saturated fat and cholesterol further increased cholesterol concentrations in LDL and also elevated that in very-low-density lipoprotein (VLDL) of hypothyroid rats. In euthyroid rats such a diet resulted in a relatively small increase in VLDL cholesterol, whereas LDL cholesterol was decreased. 3. Steady-state concentrations of mRNA for the hepatic LDL receptor were significantly decreased in the livers of hypothyroid rats, but were not significantly changed by high-fat feeding in euthyroid or hypothyroid rats. 4. The expression of the LDL receptor in hepatocytes cultured from hypothyroid rats was decreased relative to the euthyroid controls. 5. Whereas the esterification of cholesterol with oleate in hepatocytes cultured from hypothyroid rats was decreased, the activity of acyl-CoA:cholesterol acyltransferase (ACAT) in the livers of these animals was not changed. 6. High-fat feeding increased the hepatic ACAT activity in normal and hypothyroid rats. 7. Incubation of rat hepatocytes with 10 nM-tri-iodothyronine for 4 h increased the relative concentration of the mRNA for the LDL receptor by 25%. 8. It is therefore concluded that thyroid hormones stimulate the synthesis and expression of the hepatic LDL receptor. Elevated cholesterol concentrations in LDL in hypothyroidism probably result from a primary defect in the expression of the hepatic receptor, rather than indirectly via changes in ACAT activity.

Animals↗