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Biomedical subjects

T Funabashi

Publications and source records attributed to T Funabashi.

15 recordsLinked to original sources

Gene memory in neuroendocrine and behavioural systems.

Several examples of sex steroid hormone actions on rat brain and behaviour show that initial hormone exposures may be followed by enduring neuronal alterations, apparent long after the hormone itself has disappeared. Precedents from non-neuronal systems led to the concept of 'gene memory'. We are studying genomic structural alterations in rat hypothalamic neurons to account for these effects. The preproenkephalin gene is turned on by oestradiol in rat brain neurons in a tissue-specific and genetic sex-specific manner. Levels of preproenkephalin mRNA in the ventromedial hypothalamus correlate tightly with oestradiol-dependent reproductive behaviour. Our results indicate a tissue-specific pattern of DNA methylation in the enkephalin promoter. Putative binding sites for several transcription factors have been described in the preproenkephalin gene promoter; a role for some of these factors in regulating expression of the gene has been demonstrated.

Animals

Prolactin receptor messenger RNA is synthesized by the epithelial cells of the choroid plexus.

To identify cellular sites of prolactin receptor messenger RNA synthesis in the rat brain, we used a combined reverse transcriptase-polymerase chain reaction protocol to generate single stranded DNA probes for in situ hybridization. The results of these experiments identify the epithelial cells of the choroid plexus as a major site of prolactin receptor gene expression in the rat central nervous system.

Animals

Intraventricular injection of vasoactive intestinal polypeptide facilitates the development of amygdaloid kindling.

To determine the involvement of vasoactive intestinal polypeptide (VIP) in the development of kindling in rats, VIP or antibody to VIP (anti-VIP) was injected into the third ventricle after the daily stimulation of the basolateral amygdala. The number of stimulations required to reach full amygdaloid kindling was significantly smaller in rats treated with VIP than rats treated with saline, whereas it increased significantly in rats treated with anti-VIP compared to that in the rats treated with either saline or normal rabbit serum. The results suggest that VIP participates in the development of amygdaloid kindling as a facilitatory factor.

Amygdala

Naloxone increases the frequency of the electrical activity of luteinizing hormone-releasing hormone pulse generator in long-term ovariectomized rats.

Characteristic increases in neuronal activity accompanied by the initiation of each luteinizing hormone (LH) pulse have been successfully recorded in freely moving ovariectomized rats by means of multiunit activity (MUA) recording techniques. In the present study, the effect of the opioid receptor antagonist naloxone on this neuronal activity was examined in rats ovariectomized for 6-10 weeks. Electrodes were chronically implanted into the medial basal hypothalamus (n = 78) or the medial preoptic area (n = 29). During the MUA recording, blood samples were taken through an indwelling atrial cannula at 3- or 6-min intervals to determine the serum LH concentration. Naloxone was administered intravenously for 1 h by either intermittent injection every 6 min (0.05 mg/kg, 10 times) or continuous infusion (0.1, 0.2 and 0.5 mg/kg/h). Explosive rises in the MUA (volleys) associated with the initiation of LH pulse were recorded in 7 animals in which the tips of electrodes were located in the arcuate nucleus-median eminence region. In 5 animals studied, the mean (+/- SE) duration and interval of the MUA volleys were 2.1 +/- 0.1 and 22.1 +/- 0.9 min, respectively. Naloxone given every 6 min significantly increased the duration to 2.6 +/- 0.1 min, and decreased the interval to 9.5 +/- 0.9 min. This naloxone treatment disturbed the clear pulsatility of LH secretion observed in the pretreatment control period. Analysis of the effects of naloxone infused at 3 different doses revealed that the facilitatory effects of naloxone on the duration and frequency of the MUA volleys were dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Naloxone injected into the preoptic region has hypophysiotropic and seizurogenic actions in rats.

The effects of microinjection of naloxone, an opiate receptor antagonist, into the medial preoptic area (MPO) and diagonal band of Broca (DBB) on luteinizing hormone (LH) and prolactin (PRL) secretion were examined in the intact male rat and female rat in diestrus 1. In both the male and female rats, the injection of 50 micrograms naloxone at 1300 h produced an acute, two- to three-fold increase in serum LH, attaining the peak at 20 min. The PRL concentration in the female 20 min-2 h after the injection was significantly lower than in the saline-injected rat. In the male rat, naloxone caused a decrease in the PRL concentration in the late afternoon when a small rise occurred in the saline-injected rat, although it caused no immediate changes. In addition to these hypophysiotropic effects, naloxone injected in the MPO and DBB unexpectedly had seizurogenic actions. More than 40% of the animals of both sexes given an injection of naloxone had behavioral seizures, which began after about 20 min and were repeated intermittently at 15-20 min intervals through the sampling period of 6 h. In the LH and PRL response to naloxone, there was no significant difference between animals with and without seizure response in both sexes. The results suggest that in the preoptic opioid system there is no difference according to sex in the control of LH, and only a small one, if any, in the control of PRL. Further, on the basis of previous reports, there is a GABAergic system in the preoptic region, that is antagonized by naloxone and causes the activation of cortical neuronal activity.

Animals

Naloxone affects the luteinizing hormone secretory pattern in the short- and long-term ovariectomized rat.

The effect of naloxone, an opiate receptor antagonist, on the secretory pattern of luteinizing hormone (LH) was evaluated in 4-, 16- and 32-week ovariectomized (OVX) rats. Freely moving rats bearing cardiac cannulae were bled every 6 min for 3 h. During the first 90 min of bleeding, an equal volume of saline was injected after withdrawal of each blood sample, while during the second 90 min the replacement was done with saline containing naloxone at a dose of 0.5 (lower dose) or 1.0 (higher dose) mg/kg/h; statistical comparison was done between both treatment periods. In 4-week OVX rats, a significant increase in the mean LH level was observed through the 90-min period of lower-dose naloxone treatment, without significant changes in the pulse frequency and amplitude. In 4-week OVX rats treated with the higher dose and in 16-week OVX rats treated with either the lower or the higher dose, a significant elevation in mean LH levels was observed only during the first 30 min of treatment, which was probably related to the first, large LH peak in the naloxone treatment period. However, together with pulses appearing later in the treatment period, no significant changes were found in the LH pulsatility except for a decrease in frequency in 4-week OVX rats. In 32-week OVX rats, even the lower-dose naloxone did not induce an elevation in mean LH levels. The results demonstrate that naloxone can increase the LH secretion in the absence of ovarian hormones, and further that the effect on LH changes depending upon the dose of naloxone and the time after ovariectomy.

Animals

Two cases of cystic fibrosis in Japanese children: studies on the essential fatty acid and prostaglandin metabolism.

We describe the fatty acid (FA) and prostaglandin (PG) metabolism in two Japanese cases of cystic fibrosis (CF) with or without pancreatic insufficiency (PI). The diagnosis of CF was based on the elevated sweat chloride concentration by pilocarpine iontophoresis. A 1-month-old boy (case 1) showed poor weight gain, steatorrhea and scaly dermatitis, but no respiratory symptoms were noted. He had decreased levels of serum linoleate and arachidonate, and increased palmitoleate and oleate levels, indicating essential fatty acid (EFA) deficiency. Supplementation of fat-emulsion improved his skin lesions and the altered FA pattern within a few months, associated with the definite reduction of the urinary PG F2 alpha levels. Until two years of age, he has been free from respiratory symptoms. A 12-year-old girl (case 2) had had recurrent respiratory tract infections due to Pseudomonas aeruginosa and Staphylococcus aureus for several years, and her pancreatic functions were preserved. The FA patterns of her serum lipid were almost within the normal range. These results indicate that 1) the altered FA composition appeared to be a secondary consequence of PI commonly complicating CF and 2) the correction of the altered FA and PG metabolism might have a beneficial effect on the respiratory function of CF patients with EFA deficiency.

Child

[Geographic localization of three variants of herpes simplex virus type 1 in Japan].

We previously reported that a variant of herpes simplex virus type 1 (HSV-1) designated variant type A was isolated at a much higher frequency in Western Japan than in Eastern Japan. We examined the localization of two other variant types designated B and C. The proportion of the type B and type C variants among 553 fresh HSV-1 isolates from 10 areas in Japan were 5.4% and 1.3%, respectively. The isolation frequency of type B variant in Eastern Japan was 8.3%. It was as high as 20.5% in Iwate area. The frequency in Western Japan was only 3.0%. Type C variant showed no specific geographic localization. These results were discussed in terms of characteristic mode of HSV infection and the history of the Japanese nation.

Genetic Variation

LHRH injected into the medial preoptic area potentiates LH secretion in ovariectomized estrogen-primed and proestrous rats.

To determine if luteinizing hormone releasing hormone (LHRH) might act within the central nervous system to modulate its own secretion, microinjection of LHRH into the medial preoptic area (MPO) was performed at 13:00 h in both the ovariectomized estrogen-primed and proestrous rat, and the effects on the afternoon rise in the serum concentration of luteinizing hormone (LH) were studied. Microinjection of 5 ng LHRH into the MPO in the ovariectomized estrogen-primed rat resulted in a significant increase in serum LH from 16:00 to 19:00 h compared to the value in the saline-injected rat, whereas the injection at a dose of 2 ng did not induce a significant change. The injection of 5 ng LHRH into the third ventricle in the ovariectomized estrogen-primed rat induced a transient increase in serum LH immediately after the injection, followed by recovery to the preinjection concentration by 1 h, indicating that the potentiating effect of 5 ng LHRH in the MPO was not due to the LHRH leaked into the third ventricle. Finally, microinjection of 5 ng LHRH in the proestrous rat induced an early increase in serum LH, resulting in an advancement of the peak of the afternoon rise by 1 h. It is suggested that LHRH secreted in the MPO may, directly or indirectly, stimulate its own secretion in the median eminence to produce the surge of LH secretion.

Animals

Mucocutaneous lymph node syndrome. A cross-sectional echocardiographic diagnosis of coronary aneurysms.

The cross-sectional echocardiographic technique for detecting coronary artery aneurysms of mucocutaneous lymph node syndrome (MLNS) was examined. When cutting the aortic root in round slices by the echocardiographic scanner, each of the right and left coronary arteries was imaged as a linear echo-free structure arising from the aortic root. Of 22 normal subjects, the left main coronary artery was imaged in all, the anterior descending branch in 18, the circumflex branch in six, and the right coronary artery in 18. Of 41 patients with MLNS, coronary artery aneurysms were detected as large echo-free spaces in four patients who were proved later to have these lesions by coronary angiography or autopsy. In addition, in four patients, whose echocardiograms demonstrated the coronary arteries to be normal, the angiographic studies showed that the coronary arteries were intact. These results suggest that the cross-sectional echocardiographic technique is a useful noninvasive diagnostic method for imaging the coronary arteries and the aneurysms in MLNS.

Aneurysm

Cholesterol side-chain cleavage enzyme activity and cytochrome P-450 content in adrenal mitochondria of a patient with congenital lipoid adrenal hyperplasia (Prader disease).

An autopsied case with congenital lipoid adrenal hyperplasia (Prader disease) was presented. The cholesterol side-chain cleavage (SCC) enzyme activity in adrenal mitochondria of this case was assayed with [3H]cholesterol as substrate, combined with purified bovine adrenodoxin and adrenodoxin reductase, by measuring the amount of [3H]pregnenolone formed. The cytochrome P-450 content was also measured by recording the difference absorption spectra of carbon monoxide-complexed P-450. The cholesterol SCC enzyme activity in adrenal mitochondria of Prader disease was 0.81 nmol pregnenolone/nmol P-450 per min, which was approximately 10% of that in normal tissue. The content of cytochrome P-450 was 0.074 nmol/mg protein, which was about half of that in controls. These results indicate that there is a cholesterol SCC enzyme deficiency in adrenal mitochondria in this disease.

Adrenal Glands