Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 469 records · Page 26Linked to original sources

PubMed1999

Effects of itraconazole on the steady-state plasma concentrations of bromperidol and reduced bromperidol in schizophrenic patients.

RATIONALE: A previously reported pharmacokinetic interaction between bromperidol and carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, suggests possible involvement of CYP3A4 in the metabolism of bromperidol. OBJECTIVE: We investigated pharmacokinetic interaction between bromperidol and itraconazole, a potent inhibitor of CYP3A4, to clarify the involvement of CYP3A4 in the metabolism of bromperidol and its reduced metabolite. METHODS: Itraconazole 200 mg/day for 7 days was coadministered to eight schizophrenic patients treated with a fixed dose of bromperidol 12 or 24 mg/day for at least 2 weeks. Blood samples were taken before and 1 week after itraconazole coadministration and 1 week after its discontinuation, together with clinical assessments using the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale. RESULTS: Plasma concentrations of bromperidol during itraconazole coadministration (16.7+/-4.9 ng/ml) were significantly higher (P<0.01) than before itraconazole coadministration (8.9+/-4.4 ng/ml) and 1 week after its discontinuation (9.9+/-4.3 ng/ml). Plasma concentrations of reduced bromperidol during itraconazole coadministration (3.6+/-2.9 ng/ml) were significantly higher (P<0.01) than before itraconazole coadministration (1.8+/-1.3 ng/ml). No changes were observed in BPRS and UKU scores throughout the study. CONCLUSIONS: The pharmacokinetic interaction between bromperidol and itraconazole is probably due to the inhibitory effect of itraconazole on the metabolism of bromperidol. This study provides in vivo evidence of involvement of CYP3A4 in the metabolism of bromperidol and reduced bromperidol.

Adult↗

PubMed1999

Evaluation of flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells.

The estimation of intralesional haemodynamics is crucial in determining appropriate treatment for soft-tissue vascular malformations. The aim of this study was to develop a method to evaluate the flow characteristics of soft-tissue vascular malformations using technetium-99m labelled red blood cells (99mTc-RBCs). Seventy-nine soft-tissue vascular malformations, including 20 arteriovenous malformations and 59 venous malformations, in 57 patients were examined. Following the intravenous injection of 99mTc-RBCs, dynamic imaging was performed for 30 min with the lesion in the field of view (99mTc-RBC flow study). A time-activity curve was generated for the lesion, and the lesion was categorized as a high-flow or low-flow lesion by visual inspection of the curve. In low-flow lesions, mean vascular transit time (MTT) was calculated by curve fitting based on a two-compartment model. Twenty-nine lesions in 19 patients were examined twice, and reproducibility was assessed. In 23 venous malformations in 16 patients, 99mTc-Sn colloid was percutaneously injected into the intravascular space of the lesion, and dynamic data of 5-min duration were acquired (direct puncture scintigraphy). MTT was estimated from the washout curve and compared with MTT estimated by 99mTc-RBC flow study. 99mTc-RBC flow study classified all 20 arteriovenous malformations as high-flow lesions and all 59 venous malformations as low-flow lesions. In the low-flow lesions, MTT estimated by 99mTc-RBC flow study ranged from 61.2 to 2174.9 s. In the reproducibility study, complete concordance in classification and high correlation in MTT were shown between the first and second examinations. MTT estimated by 99mTc-RBC flow study was significantly correlated with that estimated by direct puncture scintigraphy. In summary, 99mTc-RBC flow study provides a quantitative indicator of intralesional haemodynamics in low-flow lesions in addition to accurate distinction between high-flow and low-flow lesions. The results of this study suggest the feasibility of detailed evaluation of flow characteristics in soft-tissue vascular malformations using 99mTc-RBCs.

Adolescent↗

PubMed1999

Mechanisms underlying the age-related decrement in the human sweating response.

To examine the mechanisms underlying the age-related decrement in the ability to sweat, seven older (64-76 years) and seven younger (20-24 years) men participated in a 60-min sweating test. The test consisted of placing the subject's lower legs in a water bath at 42 degrees C while sitting in a controlled environment of 35 degrees C ambient temperature and 45% relative humidity. The rectal (Trc) and skin temperatures, local sweating rates (m(sw): on the forehead, chest, back, forearm and thigh) and the frequency of sweat expulsion (f(sw)) were measured during the test. No group difference was observed in the mean body temperature (Tb) throughout the passive heating, although the older men had a higher Tre and a lower mean skin temperature during the last half of the 60-min test. There were no group differences in the Tb threshold for sweating, although the time to the onset of sweating tended to be longer for the older men regardless of body site. The m(sw) increased gradually for approximately 35 min after the start of heat exposure in the older men and for 30 min in the younger men and then reached a steady state. During the first half of the test, the older men had a significantly lower m(sw) at all sites. During the last half of the test, only m(sw) on the thigh was significantly lower in the older men than in the younger men. There was no group difference in the slope of f(sw) versus Tb (an indicator of the change in the central sudomotor response to thermal input). The slope of m(sw) versus f(sw) (an indicator of the change in peripheral activity in response to central sudomotor changes) was significantly lower on the thigh in the older men, but there were no differences for the other sites. These results suggest that in older men the lower thigh m(sw) observed during the last half of the heat test was possibly due to age-related modifications of peripheral mechanisms involving the sweat glands and surrounding tissues. It was not due to a change in the central drive to sudomotor function. Furthermore, the sluggish m(sw) responses in the older men appear to have been related to age-related modifications of the sensitivity of thermoreceptors in various body regions to thermal stimuli. They may also involve lower sweat glands' sensitivity to cholinergic stimulus or sluggish vasodilatation, and do not reflect age-related changes in the central drive.

Adult↗

PubMed1999

Physiological significance of hyperpolarization-activated inward currents (Ih) in smooth muscle cells from the circular layers of pregnant rat myometrium.

The properties of hyperpolarization-activated current in pregnant rat uterus (17-19 days gestation) were investigated using microelectrode and patch-clamp techniques, and isometric tension recording. The resting membrane potentials were -58.4 mV and -48.5 mV in longitudinal and circular muscle cells, respectively. Application of hyperpolarizing current pulses produced a time-dependent anomalous inward rectification of membrane potential only in circular muscle cells. Under voltage-clamp conditions, inward currents (Ih) were activated by long hyperpolarizing pulses below -60 mV in circular but not in longitudinal muscle cells. Application of extracellular but not intracellular Cs+ reduced the amplitude of I(h) in a concentration-dependent manner (an IC50( of 0.15 mM). The reversal potential for Ih was -26.2 mV and the slope conductance was 5 nS/pF. Changes in [K+]o and [Na+]o shifted the reversal potential, and Ih amplitude increased with excess [K+]o and decreased with low [Na+]o. The steady-state activation of Ih was well fitted by a Boltzmann equation with a half-activation potential of -84.3 mV and a slope factor of 9.6 mV. Time courses of activation and deactivation of the current strongly depended on membrane potential, and were well fitted by a single exponential function. The activation time constant of Ih was dependent on temperature. In isometric tension recording, application of extracellular Cs+ to the circular muscles reduced the frequency, but not the amplitude, of spontaneous contractions in a concentration-dependent manner. It is concluded that in pregnant rat uterus Ih channels are predominantly distributed in smooth muscle cells from the circular layer. Since Ih is activated at the resting membrane potential, it is likely that this current contributes to the maintenance of resting membrane potential and spontaneous activity in circular smooth muscle cells of late pregnant rats.

Algorithms↗

PubMed1999

Two-year cyclosporin treatment in children with steroid-dependent nephrotic syndrome.

We describe a prospective study of 2-year moderate-dose cyclosporin (CS) treatment in 13 children with steroid-dependent minimal change nephrotic syndrome (MCNS). CS treatment was commenced at 100-150 mg/m2 per day after remission was attained with prednisolone therapy, was adjusted to a target trough level of 100 ng/ml, and was administered for 2 years. The number of relapses during CS treatment significantly decreased compared with before CS treatment, all patients were able to discontinue prednisolone therapy, and steroid toxicity was reduced; 54% of patients remained in remission during CS treatment. Renal biopsies performed before CS treatment all showed MCNS without tubulointerstitial lesions. Creatinine clearance and urinary beta 2-microglobulin levels during CS treatment were normal in all patients, but renal biopsies performed after CS treatment revealed chronic CS nephrotoxicity in 7 patients. Clinical data, including CS dose and CS trough blood levels, were not significantly different between patients with and without nephrotoxicity. In conclusion, 2-year moderate-dose CS treatment in children with steroid-dependent MCNS is effective in preventing relapse and decreasing steroid toxicity. This treatment can, however, result in a high incidence of chronic nephrotoxicity. Renal function is not a reliable indicator of chronic CS nephrotoxicity. Renal biopsy is therefore necessary to monitor chronic CS nephrotoxicity.

Adolescent↗

PubMed1999

Exercise- and methylcholine-induced sweating responses in older and younger men: effect of heat acclimation and aerobic fitness.

The purpose of this investigation was to examine the effects of aging and aerobic fitness on exercise- and methylcholine-induced sweating responses during heat acclimation. Five younger [Y group-age: 23 +/- 1 (SEM) years; maximal oxygen consumption (VO2max): 47 +/- 3 ml.kg-1.min-1], four highly fit older (HO group- 63 +/- 3 years; 48 +/- 4 ml.kg-1.min-1) and five normally fit older men (NO group -67 +/- 3 years; 30 +/- 1 ml.kg-1.min-1) who were matched for height, body mass and percentage fat, were heat acclimated by daily cycle exercise (approximately 35% VO2max for 90 min) in a hot (43 degrees C, 30% RH) environment for 8 days. The heat acclimation regimen increased performance time, lowered final rectal temperature (Tre) and percentage maximal heart rate (%HRmax), improved thermal comfort and decreased sweat sodium concentration similarly in all groups. Although total body sweating rates (Msw) during acclimation were significantly greater in the Y and HO groups than in the NO group (P < 0.01) (because of the lower absolute workload in the NO group), the Msw did not change in all groups with the acclimation sessions. Neither were local sweating rates (msw) on chest, back, forearm and thigh changed in all groups by the acclimation. The HO group presented greater forearm msw (30-90 min) values and the Y group had greater back and thigh msw (early in exercise) values, compared to the other groups (P < 0.001). In a methylcholine injection test on days immediately before and after the acclimation, the order of sweat output per gland (SGO) on chest, back and thigh was Y > HO > NO, and on the forearm Y = HO > NO. No group differences were observed for activated sweat gland density at any site. The SGO at the respective sites increased in the post-acclimation test regardless of group (P < 0.01), but on the thigh the magnitude of the increase was lower in the NO (P < 0.02) and HO (P = 0.07) groups than in the Y group. These findings suggest that heat tolerance and the improvement with acclimation are little impaired not only in highly fit older but also normally fit older men, when the subjects exercised at the same relative exercise intensity. Furthermore, the changes induced by acclimation appear associated with an age-related decrease in VO2max. However methylcholine-activated SGO and the magnitude of improvement of SGO with acclimation are related not only to VO2max but also to aging, suggesting that sensitivity to cholinergic stimulation decreases with aging.

Adaptation, Physiological↗

PubMed1999

Erythropoietic protoporphyria with fatal liver failure.

A 33-year-old woman with a history of photosensitivity, persistent abdominal pain, and liver dysfunction was admitted to our department because of abdominal pain and progression of liver dysfunction. On admission, levels of protoporphyrin and coproporphyrin within erythrocytes were markedly increased. Autofluorescent erythrocytes were also detected, leading to a diagnosis of erythropoietic protoporphyria. A liver biopsy specimen revealed cirrhosis with dark brown granules filling hepatocytes, bile canaliculi, and bile ductules. Transfusion of washed erythrocytes, hemodialysis, and administration of cholestyramine and beta-carotene transiently improved levels of porphyrins and liver function. The patient died of rupture of esophageal varices followed by multiple organ failure. However, the treatments were believed to have extended survival.

Adult↗

PubMed1999

Surgical outcome of intramedullary spinal cord ependymoma.

Surgical outcome of intramedullary spinal cord ependymoma was investigated in order to define the treatment strategy. We have operated on 18 cases of intramedullary spinal cord ependymoma based on the principle of radical resection. The follow-up periods ranged from 10 months to 249 months with an average of 86.2 months. Postoperative neurological status in the long follow-up periods was compared to the pre-operative status and was correlated with the histological grade of malignancy. Total removal of the tumour was achieved in 17 cases, and subtotal removal followed by radiation therapy was conducted in 1 case. There was neither surgical mortality nor radiological evidence of recurrence in the long-term follow-up periods. The final outcome of the neurological condition was improved in 1 case, unchanged in 15 cases (including a case of subtotal removal) and deteriorated in 2 cases. The deterioration was in the form of gait disturbance due to the worsening of proprioception in 2 cases and dysaethesia in 1 case. Histological examination showed no evidence of anaplasia in 6 cases, evidence of early anaplasia in 10 cases, and moderate evidence of anaplasia in 2 cases. No relationship between the histological malignancy and clinical course was found. Intramedullary spinal cord ependymoma should be removed radically as early as possible while taking great care to avoid posterior column injury. Histologically malignant ependymoma might be a clinical exception.

Adolescent↗

PubMed1999

Expansive suboccipital cranioplasty for the treatment of syringomyelia associated with Chiari malformation.

In order to treat syringomyelia associated with adult type Chiari malformation, the authors developed a method of expansive suboccipital cranioplasty (ESC) that involves enlarging the small posterior fossa to obtain a sufficient flow of cerebrospinal fluid (CSF). The relative effectiveness of ESC with the obex plugged and not plugged was also examined, as well as other factors influencing the operative results. Twenty patients without arachnoid adhesion at the major cistern underwent ESC without opening the arachnoid membrane at the major cistern. After surgery, all improved with no recurrence and CSF flow study using magnetic resonance (MR) imaging showed significant improvement of the flow at the major cistern. Another 20 patients without arachnoid adhesion also underwent ESC but with obex plugging. Sixteen improved and one displayed only temporary improvement with recurrent syringomyelia due to postoperative arachnoid adhesions. The remaining three showed no change in spite of shrinkage of the syrinx on postoperative MR imaging. These three patients had displayed pre-operative symptoms over an approximately 10-year period involving almost the entire axial plain of the spinal cord, and presented a large syrinx before surgery. In 4 patients with arachnoid adhesions, all required intra-arachnoid procedures in addition to ESC. Intra-arachnoid procedures are not necessary to facilitate restoration of CSF flow in patients without arachnoid adhesions, because ESC can release the CSF flow blockage in the major cistern even without plugging of the obex. An associated arachnoid adhesion at the major cistern or a long-standing syringomyelia with irreversible damage of the spinal cord results in a poor operative prognosis. When posterior fossa surgery fails, insufficient decompression or postoperative arachnoid adhesions at the major cistern as the cause of treatment's failure should be evaluated by CSF flow studies using phase contrast MR imaging.

Adult↗

PubMed1999

Rapid mass screening method and counseling for the 1555A-->G mitochondrial mutation.

The 1555A-->G point mutation is associated with a susceptibility to aminoglycoside antibiotics, and is of particular interest, as it may cause hearing loss even without aminoglycoside exposure. There may be a considerably large high-risk population in Japan, and to avoid possible side effects in this group, a rapid mass screening system and careful counseling are recommended. We are currently using the mutant allele specific amplification (MASA) method to detect the 1555A-->G mitochondrial mutation and we distribute a warning card to subjects found to bear this mutation.

Aminoglycosides↗

PubMed1999

Role of oxytocin in the initiation of term and preterm labor in rats: changes in oxytocin receptor density and plasma oxytocin concentration and the effect of an oxytocin antagonist, L-366,509.

OBJECTIVE: Our purpose was to compare the functional roles of oxytocin in term and preterm labor in rats by both biochemical and pharmacologic means. STUDY DESIGN: We determined the myometrial oxytocin receptor density and the maternal plasma concentrations of oxytocin and progesterone on gestational days 18, 20, and 22 (morning) and at the onset of delivery (day 22 afternoon) in rats with labor at term and at the onset of delivery (day 20 afternoon) in rats in preterm labor induced by the combined use of bilateral ovariectomy and estradiol injection. We also evaluated the effects of an oxytocin antagonist, L-366,509, on the initiation of both term and preterm labor. RESULTS: The number of tritiated oxytocin binding sites in myometrial membranes rapidly increased on gestational day 22 (morning) in rats with term labor. Plasma progesterone level decreased in an inverse fashion. A rapid increase in circulating oxytocin concentration was observed at the onset of delivery in rats in labor at term. Both the plasma oxytocin concentration and the receptor density had the same values in rats with preterm labor as in rats with term labor. L-366,509 delayed the initiation of labor in rats with term and preterm labor in a dose-dependent manner. CONCLUSION: It is confirmed biochemically and pharmacologically that oxytocin plays an important role in the initiation of both term and preterm labor in rats. The oxytocin antagonist examined was able to delay term and preterm labor, so it might prove useful in clinical practice for the treatment of preterm labor.

Animals↗

PubMed1999

Resection of anterior mediastinal masses through an infrasternal approach.

A video-assisted surgical technique for benign anterior mediastinal lesions is described. In 3 patients, the Laparolift system was used to lift the lower sternum before resection. This operation is less invasive and cosmetically more pleasing than median sternotomy. Unlike thoracoscopy, this procedure avoids opening the chest and can be performed in patients with pleural adhesions or pulmonary insufficiency in whom differential lung ventilation is impossible. At present, this technique is considered suitable only for benign lesions.

Choristoma↗

PubMed1999

Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia.

BACKGROUND: The CYP2D6*10 (*10) allele that causes decreased CYP2D6 activity is present in Asians with a high frequency of about 50%. In this study we studied the effects of the *10 allele on the steady-state plasma concentrations (Css) of haloperidol and reduced haloperidol. METHODS: The subjects were 67 Japanese inpatients with schizophrenia who had only the wild-type or *10 alleles. Thirty-four patients were homozygous for the wild-type allele, and 26 were heterozygous and 7 were homozygous for the *10 allele. All patients had been receiving 12 mg/day haloperidol for at least 2 weeks. Plasma concentrations of haloperidol and reduced haloperidol were measured by HPLC. RESULTS: The mean +/- SD values of haloperidol Css in the patients with 0, 1, and 2 *10 alleles were 22.8+/-11.0, 30.1+/-10.6, and 31.2+/-21.2 nmol/L, respectively, and those values for reduced haloperidol were 6.1+/-2.9, 9.5+/-3.7, and 9.9+/-6.2 nmol/L, respectively. The mean haloperidol Css was significantly (P < .05) higher in the patients with 1 *10 allele than in those with no *10 alleles. The mean Css of reduced haloperidol was significantly (P < .05) higher in the patients with 1 and 2 *10 alleles than in those with no *10 alleles. CONCLUSION: This study suggests that the *10 allele plays an important role in controlling the Css of both haloperidol and reduced haloperidol, especially in Asian subjects.

Adult↗

PubMed1999

Pharmacokinetics of exogenous gonadotropin and ovarian response in in vitro fertilization.

OBJECTIVE: To assess the diffusion of gonadotropin into the follicular fluid (FF) and its relation to the results achieved in a human IVF-ET program. DESIGN: Retrospective pharmacokinetic study. SETTING: Fukuoka University Hospital, Japan. PATIENT(S): Eighty-seven infertile patients underwent 137 cycles of IVF-ET. INTERVENTION(S): Serum and FF were collected at the time of oocyte recovery. The hCG ratio (between follicular hCG and serum hCG concentrations, measured by time-resolved fluoroimmunoassay) was evaluated as an index of the diffusion of exogenous gonadotropin. MAIN OUTCOME MEASURE(S): Relation between hCG ratio and the results and outcome of the IVF-ET program. RESULT(S): The hCG ratio decreased with the total dosage of hMG and increased with the serum E2 level, the number of oocytes recovered, and the number of oocytes fertilized. Patients with a poor response showed a low hCG ratio, which was associated with a complete lack of fertilization. The mean hCG ratio in the pregnant cycles was significantly higher than that in the nonpregnant cycles. An hCG ratio > 0.46 was seen in all pregnant cycles. CONCLUSION(S): The diffusion of exogenous gonadotropin into the FF may be an important predictor of IVF outcome.

Chorionic Gonadotropin↗

PubMed1999

Insulin secretion and biosynthesis by the perfused pancreas of spontaneously hypertensive rats.

Insulin secretory activity was compared in the spontaneously hypertensive rat (SHR) versus the normotensive Wistar-Kyoto (WKY) rat and Wistar rat. When the isolated pancreas was perfused with 16.7 mmol/L glucose, insulin release was significantly greater in the SHR versus the other groups. On the other hand, there was no difference in arginine (19 mmol/L)-induced insulin secretion among the three groups. To determine insulin biosynthesis during glucose stimulation, the pancreas was perfused with 16.7 mmol/L glucose for 180 minutes. Insulin secretion was greater in SHR versus WKY and Wistar rats, but the net increase in insulin content was not different between the three groups. These results strongly suggest that in vivo hyperinsulinemia in the SHR is associated with increased in vitro insulin secretion in response to glucose. The mechanisms by which enhanced glucose-induced insulin secretion is linked to hypertension in the SHR remain unclear.

Animals↗

PubMed1999

Methicillin-resistant Staphylococcus aureus infections after scleral buckling procedures for retinal detachments associated with atopic dermatitis.

OBJECTIVE: To determine the incidence and the clinical course of methicillin-resistant Staphylococcus aureus as a cause of acute-onset infections in patients with atopic dermatitis after a scleral buckling procedures. DESIGN: A retrospective chart review. PARTICIPANTS: Two hundred eighty-seven patients (293 eyes) who underwent scleral buckling procedures to treat rhegmatogenous retinal detachments at either Osaka Rosai Hospital or Osaka University Medical School between July 1, 1995, and June 30, 1997, participated. Of these, 32 eyes (10.9%) were associated with atopic dermatitis. INTERVENTION: Demographic and clinical data were abstracted from patients' medical records. MAIN OUTCOME MEASURES: The incidence, clinical features, and management of postoperative infections associated with methicillin-resistant S. aureus were studied. RESULTS: Methicillin-resistant S. aureus infection after scleral buckling procedures was identified in 6 (18.8%) of 32 eyes of patients with atopic dermatitis but in only 1 (0.4%) of the other 261 cases without atopic dermatitis (P < 0.001). The average interval from the scleral buckling procedures to the initial onset of infection was 8.3 +/- 9.1 days (range, 2-28 days). Bacterial infection and inflammation were controlled in four eyes by prompt removal of the infected buckle in combination with vancomycin administration. In the other three eyes, however, repeat intravitreous injections of vancomycin or emergent vitrectomies were required because of the development of endophthalmitis. CONCLUSIONS: Methicillin-resistant S. aureus is an important causative pathogen of scleral buckling infections, particularly in patients with retinal detachment associated with atopic dermatitis. Preoperative evaluation and intraoperative attention to contamination are recommended to prevent methicillin-resistant S. aureus infections in these patients.

Acute Disease↗

PubMed1999

Early establishment of lesion-insensitive mature barrelettes corresponding to upper lip vibrissae in developing mice.

Vibrissae are tactile sense organs on the face of non-human mammals, and build up topographical representations in the brainstem trigeminal sensory nucleus called barrelettes. In the present study, we examined postnatal development of barrelettes corresponding to upper lip vibrissae by cytochrome oxidase (CO) histochemistry. At nuclear regions corresponding to upper lip vibrissae, a few segregated barrelettes first appeared at postnatal day 2 (P2), and segregation became clear for most upper lip barrelettes at P4. Compared with major barrelettes corresponding to mystacial vibrissae on the snout, the development of segregated pattern formation for upper lip barrelettes was retarded by 1-2 days. When vibrissa-related patterns were examined 5 days after infraorbital nerve transection, upper lip barrelettes became obscure in all mice lesioned at P1 and P2. Lesion-insensitive upper lip barrelettes first emerged in a few mice lesioned at P3 (33%), and the percentage attained 100% at P6. This temporal transition from lesion-sensitive to lesion-insensitive barrelettes was 3 days ahead of mystacial barrelettes. Therefore, upper lip barrelettes achieve rapid development within a narrow time frame during the first postnatal week. The early and rapid establishment of lesion-insensitive, mature barrelettes can be interpreted as suggesting the importance of oral sensory function in neonatal life.

Aging↗

PubMed1999

Distinct spatiotemporal expression of mRNAs for the PSD-95/SAP90 protein family in the mouse brain.

PSD-95 (SAP90), SAP102 and Chapsyn-110 (PSD-93) are members of the membrane-associated guanylate kinase family, and interact with N-methyl-D-aspartate (NMDA) receptor NR2A (GluRepsilon1) and NR2B (GluRepsilon2) subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. In the present study, we examined their expression in developing and adult mouse brains by in situ hybridization with antisense oligonucleotide probes. PSD-95 and SAP102 mRNAs were prominently expressed at embryonic day 13 (E13) in the mantle zone of various brain regions, where NMDA receptor NR2B subunit mRNA is expressed at high levels. In the early postnatal period when active synaptogenesis takes place, both mRNAs became elevated and concentrated in the telencephalon and cerebellar granular layer, where NR2A and/or NR2B subunit mRNAs are abundantly expressed. Chapsyn-110 mRNA was, though at low levels, found over the mantle zone of embryonic brains, and the level was progressively increased in the telencephalon starting at perinatal stages. The spatial and temporal correlations in the brain in vivo suggest that the PSD-95/SAP90 protein family can interact with NMDA receptor subunits to cluster them into channel complex at both synaptic and non-synaptic sites before, during and after synaptogenic stages.

Aging↗