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Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 865 records · Page 48Linked to original sources

Aromatase activity and progesterone metabolism in ovaries of scorbutic mutant rats unable to synthesize ascorbic acid.

Aromatase activity and progesterone metabolism were studied in ovaries of scorbutic ODS rats hereditarily unable to synthesize ascorbic acid (AsA). When ODS rats were kept on an AsA-deficient diet for 23 days, the scurvy developed with undetectable levels of AsA in ovaries. A significant increase in ovarian aromatase activity was observed in scorbutic ODS rats. However, there was no difference in the production of testosterone from progesterone between ovaries of scorbutic and ascorbutic ODS rats. These data suggest that AsA may play a role as a modulator of aromatase activity in vivo.

Animals↗

[Long-term stability of Kallidinogenase Reference Standard].

The long-term stability of Kallidinogenase Reference Standard of National Institutes of Hygienic Sciences was studied. The standard was kept for a long term (60 months) at -5 degrees C, 20 degrees C, 37 degrees C and 50 degrees C. No decrease in kallidinogenase activity was observed at 60 months at -5 degrees C and 28 months at 20 degrees C. The decrease in the activity of the standard kept at 37 degrees C was only 7% at 10 months. The standard kept at 50 degrees C had lost nearly all activity at 4 months. Therefore, "Kallidinogenase Standard" was stable for prolonged storage (about 5 years) at -5 degrees C.

Drug Stability↗

[Studies on the quality of enzyme preparations (IX)--kallidinogenase preparations].

Kallidinogenase preparations were investigated with a view of comparing their quality by the enzymological method. These studies were carried out on 13 types of preparations (tablet: 7 kinds, capsule: 3 kinds, ampoule: 3 kinds) of commercially available kalliginogenase preparations. The kinin-liberating activity per one international unit (IU) of kallidinogenase was approximately 400 ng bradykinin/min/IU. The contents of other enzymes, i.e., kininase, trypsin and protease, were determined as the impurities. Kininase, trypsin and protease activities in the preparations for injection were very low. However, one preparation for internal use contained large amounts of these enzyme as impurities. It was presumed that contamination with large amounts of kininase, trypsin and protease have an adverse influence upon the assay and stability and efficacy of these preparations.

Dosage Forms↗

[Effect of trihexyphenidyl-HCL on posttraumatic prolonged disturbance of consciousness: report of two cases].

Cases involving two patients who presented post-traumatic prolonged disturbance of consciousness (PTPDC), namely akinetic mutism, and recovered from it after treatment with trihexyphenidyl were reported. Case 1: A seventy-one-year-old farmer. Five months after head injury, when he was first admitted to us, he was stable with signs of oligokinesia, katatonic posture, speechlessness, rigid muscle tones and positive cog-wheel phenomenon. One week after administration of the drug, his speech and voluntary movement improved remarkably. Two months after the treatment, he was able to walk, and was discharged from the hospital. Case 2: A forty-six-year-old man sustained major head trauma. In the acute stage, he was comatose with decerebrate posture. On the 15th hospital day, he showed a state of akinetic mutism with normal sleep - wakefulness cycle. Evacuation of the collected subdural fluid was done one month after the injury, which resulted in no change in his clinical state. Five months after the injury, trihexyphenidyl treatment was begun. A few days after the treatment, his motor activity and his facial expression obviously improved. One week after, he mimicked the word 'o-ha-yo (good morning)' after the physician's greeting. CT scan and magnetic resonance imaging in the chronic state of these patients showed bifrontal cerebral white matter lesions, which indicated old cerebral contusion. No brain stem lesions were detected with these examinations. Our two cases clearly did not belong to the category of post-traumatic parkinsonism because of their clinical courses, and their features shown in radiological examinations. However the anti-parkinsonian drug, trihexyphenidyl was effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Long-term results of intra-arterial infusion therapy using cis-DDP (CDDP) in thoracic esophageal cancer].

The effects of intra arterial infusion therapy using CDDP for patients with thoracic esophageal cancer were investigated. From June 1984 to December 1988, 25 of 146 resected patients with thoracic esophageal cancer underwent preoperative therapy in our institute. All of these patients it was suspected preoperatively that their chief lesion had invaded to the aorta, trachea or main bronchi. Preoperative radio-chemotherapy with intra arterial infusion therapy was given to 10 of 25 patients (A group), and without intra arterial infusion therapy to 15 of 25 patients (B group). CDDP 75 mg was infused into the proper esophageal artery. In A group, 7 of 10 (70%) showed moderately or marked effects in histologic study, although in B group, only 4 of 15 (27%) did so. As for long-term results, the 2-year survival rates were 50% in A group and 13% in B group (Kaplan-Meier method. Preoperative intra arterial infusion therapy using CDDP with radio-chemotherapy showed markedly better effects in histologic study and survival rates than preoperative radio-chemotherapy without intra arterial infusion therapy. We consider that this therapy is very useful for controlling the local lesion in advanced esophageal cancer.

Cisplatin↗

Measurement of regional myocardial blood flow in hypertrophic cardiomyopathy: application of the first-pass flow model using [13N]ammonia and PET.

Positron emission tomography (PET) has become an important tool in the study of regional myocardial blood flow. The purpose of the present study was to measure regional myocardial blood flow using dynamic [13N]ammonia PET and the first-pass flow model. Thirteen patients with hypertrophic cardiomyopathy, and with a considerably thickened ventricular wall (25 mm or greater), were selected for the study in order to minimize errors due to spillover of radioactivity from blood to the myocardium and to the underestimation of myocardial activity caused by the partial volume effect. Arterial input function was determined by assigning a region of interest to the left atrial cavity on the PET images. Using left atrial and myocardial time-activity curves, regional myocardial blood flow was calculated using the first-pass flow model. Mean myocardial blood flow ranged from 47.8 to 76.5 ml/min per 100 g (63.0 +/- 9.4). Regional myocardial blood flow in the septum was significantly lower than in the anterior and lateral walls of the left ventricle (P less than .01). These results indicate the potential usefulness of dynamic PET in the measurement of regional myocardial blood flow in man.

Adult↗

[The clinical study of 23 cases in patients with bladder cancer over 85 years old].

We treated 23 patients with bladder cancer over 85 years old. The male to female ratio was 3.6. Six cases (26%) were of low grade (G1) cancer and 16 (70%) were of high grade (G2, G3), and the other one was of unknown grade. Superficial cancer (less than or equal to pT1) was seen in 11 cases (48%), and invasive cancer (greater than or equal to pT2) was 12 cases (52%). The 3-year survival rate was 38% for all, that for superficial cancer 55%, and that for invasive cancer 0%. Fifteen cases (65%) were treated by TUR and the prognosis of invasive cases in this group was poor.

Aged↗

Effects of corn oil- and fish oil-supplemented diets on phospholipid fatty acid composition of rat liver nuclei.

The effects of dietary fat on fatty acid compositions of phospholipids in liver nuclei were investigated. By feeding a diet containing 5% corn oil or fish oil to rats, the proportions of n -6 or n -3 polyunsaturated fatty acids (PUFA), respectively, were increased in phospholipids of the liver nuclei. By feeding a fat-free diet, endogenous PUFA were increased. Even after feeding the fat-free diet for 40 weeks, the n - 6 still remained at about 10% in both phosphatidylcholine (PC) and phosphatidylethanolamine (PE), while the n -3 PUFA remained at about 5 and 16% in PC and PE, respectively. The fatty acid compositions of phospholipids in the liver nuclei were influenced by dietary fat and were roughly similar to those in the microsomes. The proportion of n - 3 PUFA was high in PE of both the nuclear membrane and matrix. The proportion of n - 6 was higher in both PC and PE of the nuclear matrix than in those of the membrane.

Animals↗

Unit activity of ventral horn cells in spinal cord slices isolated from adult rats.

Using spinal cord slices isolated from adult rats, unitary action potentials were recorded extracellularly in the motor nuclei of the ventral horn following local stimulation of the adjacent site. Generation of these spikes was blocked by perfusion with artificial cerebrospinal fluid containing low Ca2+ and high Mg2+ and by increasing the frequency of electrical stimulation. Generation of unitary action potentials was very sensitive to hypoxia or anesthesia. In some cells, burst spikes similar to those of Renshaw cells were also observed. Physostigmine increased the firing rate of spike discharges, whereas mecamylamine decreased it. These results suggest that the former unitary action potentials were evoked transsynaptically in motoneurons by excitation of adjacent afferent fibers and that the latter burst potentials were evoked in Renshaw cells.

Action Potentials↗

Benzodiazepine receptors studied in living primates by positron emission tomography: antagonist interactions.

After labelling the brain benzodiazepine receptors of sub-human primates with [11C]RO15-1788, the interactions of different benzodiazepine receptor antagonist ligands were studied by positron emission tomography (PET). Various doses of either RO15-1788, RO15-3505 or propyl beta-carboline-3-carboxylate were injected intravenously 20 min after the radiotracer, and induced an immediate and specific dose-dependent displacement of the brain radioactivity. However, a comparison of the dose-receptor occupancy patterns of these three antagonists established from the displacement experiments revealed that only propyl beta-carboline-3-carboxylate displayed clear biphasic dose-receptor occupancy curves. This indicates that, in the living primate brain, there are two different benzodiazepine receptor subpopulations (which can be either different benzodiazepine receptor subtypes or distinct conformational states of a single receptor).

Animals↗

Transcriptional and posttranscriptional regulation of malic enzyme synthesis by insulin and triiodothyronine.

To investigate the transcriptional and posttranscriptional regulation of malate dehydrogenase (EC 1.1.1.40) induction by insulin, the transcriptional rate, mRNA concentration and enzyme induction of malic enzyme were compared in livers of normal and diabetic rats fed a high-carbohydrate diet. When rats were fed the diet for 4 days, the enzyme induction and mRNA concentration in livers of diabetic rats were only about 10% and 39%, respectively, of the values of normal rats, and the transcriptional rate was about 64%. Insulin treatment restored the transcriptional rate and mRNA concentration in 8 h and the enzyme induction in 4 days. Thus, it is suggested that insulin is involved in malic enzyme transcription of the gene and also possibly in the translation of the cytoplasm. On the other hand, by giving triiodothyronine treatment, the transcriptional rate and mRNA concentration were increased about twice and the enzyme induction, about 10-times in the diabetic animals. Triiodothyronine appears to stimulate malic enzyme transcription and possibly post-transcriptional steps even at a very low insulin level.

Animals↗

Discharges of bulbar respiratory neurons during rhythmic straining evoked by activation of pelvic afferent fibers in dogs.

Each cycle of rhythmic straining evoked through the reflex center in the Kölliker-Fuse nucleus by stimulation of pelvic afferents in decerebrate dogs usually began in early expiration. During the rhythmic straining cycle, postinspiratory discharges of the phrenic nerve increased simultaneously with a burst of discharges of the nerves innervating the rectus abdominis and adductors of the glottis. While about half of the bulbar expiratory units discharged concurrently with the rhythmic straining, almost none of the inspiratory units examined did so. Nearly all expiratory bulbospinal units discharged concurrently, but none of the inspiratory bulbospinal units did so. These results show that expiratory neurons in the caudal bulb relay commands for rhythmic straining from the pontine reflex center to motor neurons of expiratory muscles, but that bulbar inspiratory neurons do not relay the commands to inspiratory motor neurons. Discharges concurrent with rhythmic straining were also evoked in all 4 postinspiratory units of the ventral group, 3 very early onset expiratory units and all 9 inspiratory-expiratory units of the dorsal group. Possible roles played by these respiratory neurons in the organization of rhythmic straining were discussed.

Afferent Pathways↗

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) enhances tryptophan hydroxylase activity in mouse striatum, but not in the frontal cortex.

We measured serotonin (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) contents and tryptophan hydroxylase (TPH) activity in mouse striatum and frontal cortex after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (7 daily injections of 30 mg/kg). In the striatum, TPH activity was increased for at least 4 weeks after injection of MPTP, along with an increase in 5-HIAA. However, no significant change was observed in 5-HT, 5-HIAA or TPH activity in the frontal cortex. These results suggest that MPTP affects 5-HT through a change in TPH activity, specifically at nerve terminals in the striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The spinal reflex of chronic spinal rats is supersensitive to 5-HTP but not to TRH or 5-HT agonists.

The effects of thyrotropin-releasing hormone (TRH), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and L-5-hydroxytryptophan (5-HTP) were studied on the monosynaptic reflex (MSR) and the polysynaptic reflex (PSR) in acute and chronic spinal rats. Radioimmunoassay showed that while chronic spinal transection (for 2 weeks) caused the complete depletion of TRH in the ventral lumbar enlargement a certain level of TRH was maintained in the dorsal lumbar enlargement. This result suggested the existence of TRH-containing neurons in the dorsal horn other than the medullary raphe neurons descending to the spinal cord. The latency to the start of the MSR was shortened in chronic spinal rats and the amplitudes of the MSR and PSR were significantly greater than those in acute spinal rats. There was no obvious difference in the effects of TRH and 5-MeODMT on spinal reflexes of acute and of chronic spinal rats although marked supersensitivity to 5-HTP was observed in both the MSR and the PSR in chronic spinal rats. The supersensitivity to 5-HTP was considered to be due to a lack of 5-hydroxytryptamine (5-HT) uptake into 5-HT-containing nerve terminals rather than to a change in 5-HT receptors. It is suggested that TRH and 5-HT do not show any mutual requirement for each other in their effects on the spinal reflex since co-depletion of TRH and 5-HT did not change the effects of TRH and 5-MeODMT in chronic spinal rats. The coexistence of 5-HT and TRH in the descending spinal pathway is not considered to be significant for the control of spinal reflexes at the postsynaptic level.

5-Hydroxytryptophan↗

Lipogenic enzyme induction and incorporation of exogenous fatty acid into liver and liver nuclei.

The incorporation of exogenous fatty acid into lipids of liver and liver nuclei of rats fed diets with or without fat was compared. When [3H]palmitic acid was injected into rats, more radioactivity was incorporated into triacylglycerols and phospholipids of liver and liver nuclei from rats fed the fat-free diet than from those fed the fat diet. The results were supported further by an autoradiographic study. On the other hand, the enzyme induction and quantity of malic enzyme mRNA were decreased by fat feeding. Other lipogenic enzymes were also coordinately decreased. Thus, it may be possible that exogenous fatty acid is involved in nuclear regulation in addition to cytosolic regulation of lipogenic enzyme induction.

Animals↗

Status epilepticus induced by pentylenetetrazole modulates in vivo [11C]Ro 15-1788 binding to benzodiazepine receptors. Effects of ligands acting at the supramolecular receptor complex.

Positron emission tomography (PET) was used to investigate, in the living baboon, the in vivo modulation of [11C]Ro 15-1788 binding to benzodiazepine receptors in brain and the changes with ligands acting at the supramolecular complex during status epilepticus induced by pentylenetetrazole. The central type benzodiazepine receptors were labelled in vivo by intravenous injection of [11C]Ro 15-1788. Simultaneous positron emission tomography and electroencephalographic activity recording evidenced a modulation of the brain binding of [11C]Ro 15-1788 during pentylenetetrazole-induced status epilepticus. We investigated the changes in the modulation of radioligand kinetics and in seizure activity after intravenous administration of a benzodiazepine agonist (diazepam, 1.5 mg/kg), a benzodiazepine antagonist (Ro 15-1788, 2 mg/kg), a GABA agonist (progabide, 50 mg/kg) and a ligand of the picrotoxin/barbiturate binding sites (LY81067, 3.5 mg/kg). The results showed that there is an in vivo competitive interaction of pentylenetetrazole with the benzodiazepine receptors, as reflected by the low displacement of [11C]Ro 15-1788 in the first 10 min of the status epilepticus. However, in contrast to diazepam, progabide and LY81067, a dose (2 mg/kg) of Ro 15-1788 that saturates the benzodiazepine receptors was unable to block the seizures induced by pentylenetetrazole. This indicates that the benzodiazepine receptors play only a minor role in the status epilepticus induced by pentylenetetrazole. The contribution of other binding sites within the supramolecular complex is assessed.

Animals↗