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Biomedical subjects

A Sano

Publications and source records attributed to A Sano.

At least 127 records · Page 7Linked to original sources
PubMed1995

Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA).

An unstable expansion of CAG repeat in the coding region of the DRPLA gene on chromosome 12p is the mutation specific for hereditary dentatorubral-pallidoluysian atrophy (DRPLA). We studied the CAG expansion in brain and other tissues from six unrelated DRPLA patients. The CAG repeat lengths showed distinct differences between tissues. The sizes of the CAG expansion in various regions of the brain except the cerebellum were generally larger by several repeats than in other peripheral tissues. Brain samples showed greater variation of the expansion compared with other tissues, but neither the size of the CAG expansion nor the degree of CAG repeat variation parallels the detailed findings of neuropathological involvement. We conclude that somatic instabilities of the CAG repeat cause tissue variability of the CAG repeat size in DRPLA but other region or cell type-specific factors would be involved to explain the selectivity of cell damage in DRPLA.

Adult↗
PubMed1995

The effect of pentobarbital on the electrical activity of LHRH pulse generator in the ovariectomized rat with or without estrogen priming.

Effects of pentobarbital sodium (PB) on the electrical activity of LHRH pulse generator were investigated in the ovariectomized (OVX) rat fitted with chronically implanted electrode arrays in the arcuate-median eminence region of the hypothalamus. PB was injected intraperitoneally (i.p.) at a dose of 32 mg/kg bw, which has blocked the surge of LH secretion when injected at 13.45 on the day of proestrus, presumably by blocking the activity of the LHRH surge generator. After i.p. injection of PB, the first characteristic increase (volley) in the hypothalamic multiunit activity (MUA), each of which was associated with the initiation of an LH pulse, appeared at the mean interval of 42 min, which was significantly greater than the value, 30 min, in the rat given i.p. injection of saline. The second and third MUA volleys appeared, however, at similar intervals to those in rats given saline. There were no significant changes in the amplitude of LH pulses which followed. In the OVX rat implanted with a silastic tube packed with estradiol-benzoate (E2) for 1 day, MUA volleys were unclear, mingled with high background activities, but clear volleys appeared after PB injection. The mean interval of LH pulses in the rat given i.p. injection of saline was 51 min, by 24 min longer than the value in the E2-unimplanted OVX rat. But, after PB injection, the 1st LH pulse appeared at the interval of 37 min, which was by 25 min smaller than that after saline and the overall mean of 3 intervals was 34 min, showing a significant shortage. No PB effect was seen in the LH pulse amplitude in the E2-implanted OVX rat. The presults show that the LHRH pulse generator is much more resistant to PB than the surge generator in the OVX rat either with or without estrogen priming, and in the rat with estrogen priming, the pulse generator is rather activated by PB.

Animals↗
PubMed1995

LHRH pulse generator is stimulated by naloxone in the pentobarbital-blocked proestrous rat.

Previous studies by us and others led us to hypothesize that there are separate LHRH pulse and surge generators in the rat brain. The present study was designed to detect the activity of LHRH pulse generator by checking changes in LH secretion and the multiunit activity (MUA) of the arcuate-median eminence region of the hypothalamus during infusions of naloxone (NAL, 2 mg/h) in the proestrous rat in which the LHRH surge generator activity was blocked by pentobarbital sodium (PB, 32 mg/kg bw, ip). The animals were subjected to blood sampling in the morning (1000-1300 h) or afternoon (1400-1700), and injected with PB at 09.45 or 13.45, respectively. During saline infusions in the rat given PB injection at either 09.45 or 13.45, serum LH levels were low but fluctuated significantly, suggesting a pulsatile secretion in either the morning or the afternoon period. The pulse intervals were an average 28.2 min in the morning and 42.2 min in the afternoon. NAL infusions decreased the pulse interval significantly, to 22.0 min in the morning and to 27.0 min in the afternoon. In the electrophysiological experiment, characteristic increases in the MUA (volleys), which occur in association with the initiation of an LH pulse and therefore are considered to represent an increased activity of the LHRH pulse generator, appeared during NAL (5 mg/h) infusions in either the morning or the afternoon. These results strongly suggest that separate LHRH pulse and surge generators exist in the brain, and that, even during the critical period of proestrus, the activity of LHRH pulse generator is disclosed by PB, which, on the other hand, arrests the surge generator.

Animals↗
PubMed1995

DNA analysis in hereditary dentatorubral-pallidoluysian atrophy: correlation between CAG repeat length and phenotypic variation and the molecular basis of anticipation.

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease with variable clinical phenotypes. Progressive ataxia, choreoathetosis, and dementia are the main clinical features of adult-onset cases, whereas the main feature in juvenile-onset DRPLA is progressive myoclonus epilepsy. Earlier onset is apparent in successive generations (anticipation). The molecular abnormality underlying DRPLA is an expanded, unstable CAG trinucleotide repeat on chromosome 12p. We analyzed 71 DNA samples obtained from 12 Japanese DRPLA pedigrees that included 38 affected individuals. Normal alleles had 7 to 23 repeats, DRPLA alleles 53 to 88 repeats. DRPLA alleles also were detected in five asymptomatic family members. Patients with juvenile onset had significantly larger repeats than did those with adult onset, and there was a significant negative correlation between CAG repeat length and age at onset. In 80% of the paternal transmissions, there was an increase of more than five repeats, whereas all the maternal transmissions showed either a decrease or an increase of fewer than five repeats. There was a significant correlation between father-child differences in repeat length and differences in age at onset. The analysis of CAG repeat length is a reliable diagnostic test for DRPLA and is of value for the presymptomatic detection of individuals at risk. The expansion of CAG repeats is important in phenotypic variation and anticipation. In addition, the sex of the transmitting parent has a significant effect on the molecular mechanism of anticipation.

Adolescent↗
PubMed1995

Cerebral local blood flow with a laser-Doppler flowmetry in rat sleep.

We preliminary examined whether or not laser-Doppler flowmetry was suitable for recording cerebral local blood flow (CLBF) continuously during the sleep-wakefulness cycle in the rat. As a result, this method of flowmetry led to succeed in the real-time monitoring of CLBF on the sleep-wakefulness cycle in a freely moving rat, except for the period of gross body movements. Moreover, it was proved that CLBF in the hippocampus during paradoxical sleep was significantly higher than that during slow-wave sleep. CLBF in the prefrontal cortex was a little different from that in the hippocampus.

Animals↗
PubMed1995

[Two diabetics with hemichorea-hemiballism and striatal lesions].

We report two diabetic patients with hemichorea-hemiballism associated with striatal lesions detected by MRI. Case 1 was a 57-year-old woman. On May 5, 1990, hemichorea-hemiballism of the right upper extremity developed suddenly. The blood glucose level at the time of onset was 695 mg/dl. Plain cranial CT scanning revealed a small high-density lesion in the left putamen. On MRI, this lesion showed a high signal intensity on T1-weighted images, while it showed as an irregular low-intensity area on T2-weighted images. Three and a half months later, the high intensity lesion on MRI decreased gradually and almost disappeared. Case 2 was a 68-year-old woman. In late August 1992, hemichorea-hemiballism of the right upper and lower extremities developed suddenly. The blood glucose level at the time of onset was 365 mg/dl. Plain cranial CT scanning was normal. MRI revealed a high signal intensity lesion involving the left putamen, globus pallidus and head of the caudate nucleus on T1-weighted images, while the lesion was almost isointense on T2-weighted images. The high-intensity lesion on MRI thereafter decreased gradually and disappeared almost completely one year after the onset. It is characteristic that the lesions responsible for hemichorea-hemiballism showed high-intensity areas on T1-weighted MRI in these two diabetics. In the hyperglycemic state, the Krebs cycle is inhibited and GABA is utilized as an energy source. The possibility has been suggested that striatal ischemia is likely to occur in diabetics because the GABA content of the corpus striatum is decreased by hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

[Therapeutic results of non-small cell lung cancer in stage III: combined synchronous irradiation with bronchial artery infusion of CDDP].

The present series consisted of 55 patients with non-small cell lung cancer in stage III who underwent radiotherapy from 1986-1989. They were divided into two groups: 35 patients with combined concurrent bronchial artery infusion (BAI) of CDDP (50 mg) and unevenly fractionated radiotherapy (combined group) and 20 with evenly fractionated irradiation (radiation group). The combined therapy was expected to achieve higher local control of disease. The rationale for the combined regime was based on the effects of CDDP, which causes cytostasis following intra-arterial infusion, and increased radiosensitivity from unevenly fractionated irradiation just after BAI. The radiotherapy group was considered a control in this study. The results of the combined group were limited to no CR, PR in 33 patients and NC in two with a period of 30 +/- 13 days for 50% reduction of tumor, superior to the radiation group. There was no difference between the two groups in the rate of local recurrence (combined group: 63%). The combined group showed 28 months of MST in cause-specific survival, a significant difference. Survival rates were 71% at one year, 27% at three years, and 15% at five years, including three survivors without recurrence. Stage III a patients in the combined group showed a better outcome than stage III b patients in the same group, and stage III a patients in the radiation group. Although radiation pneumonitis as a fatal side effect was noted in one patient of the combined group, the combined therapy presented here seemed to improve the prognosis of locally advanced lung cancer if properly indicated.

Aged↗
PubMed1994

The 3'-untranslated region of mouse myelin basic protein gene increases the amount of mRNA in immortalized mouse oligodendrocytes.

The 3'-untranslated region (UTR) of the myelin basic protein (MBP) mRNA has been found previously to enhance the translational efficiency of the coding region by two-fold in cell-free translational systems. In this study, we transfected eukaryotic expression vectors containing the reporter cDNA for chloramphenicol acetyltransferase (CAT) with or without the mouse MBP cDNA 3'-UTR into cultured cells. CAT activity in the mouse oligodendrocyte cell line, N20.1, transfected with a CAT cDNA containing the MBP 3'-UTR [CAT-MBP 3'-UTR], was twice as high as that of the CAT cDNA without the 3'-UTR; CAT activities for the two constructs were the same in the mouse fibroblast cell line, NIH 3T3. Using reverse transcriptase PCR quantitative analysis, the expression of mRNA was determined. The level of the [CAT-MBP 3'-UTR] mRNA was about ten times higher than CAT mRNA in N20.1 cells but they were the same in NIH 3T3 cells. We conclude that the 3'-UTR of MBP gene increases gene expression at both the mRNA and protein levels in oligodrocyte cell lines, probably through a post-transcriptional mechanism such a message stabilization.

3T3 Cells↗
PubMed1994

Protection by prosaposin against ischemia-induced learning disability and neuronal loss.

Prosaposin, the protein precursor of saposins A, B, C, and D which activate sphingolipid hydrolases, is abundant in several brain regions including the hippocampus. We infused prosaposin continuously for 7 days into the lateral ventricle of gerbils starting 3 hours before 3-min of forebrain ischemia. Using the step-down passive avoidance task, we demonstrated that ischemia-induced learning disability is prevented almost completely by prosaposin infusion. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 field of the hippocampus as well as synapses within the strata moleculare, lacunosum/radiatum and oriens of the field were significantly more numerous in gerbils infused with prosaposin infusion than in those receiving saline infusion. These findings suggest that prosaposin possesses neurotrotrophic activity to protect hippocampal CA1 neurons from lethal ischemic damage.

Animals↗
PubMed1994

Injection of bicuculline elicits firing of luteinizing hormone releasing hormone pulse generator in muscimol-treated ovariectomized rats.

We have already demonstrated that, although exogenous gamma-aminobutyric acidA (GABAA) receptor agonist is capable of inhibiting the activity of luteinizing hormone releasing hormone (LHRH) pulse generator, the reduction in the endogenous GABAA receptor activity does not have a significant effect in ovariectomized rats, suggesting a minor role of inhibitory GABA neurons in the control of pulsatile release of LHRH. In this study, we further analyzed the role of the GABAA receptor system in the regulation of LHRH pulse generator activity observed by recording the multiunit activity (MUA) in the hypothalamus of ovariectomized rats. An abrupt increase (volley) in the MUA in the arcuate nucleus (ARC)-median eminence region (ME) was accompanied by the initiation of a luteinizing hormone (LH) pulse, determined by measuring LH concentrations in blood sampled simultaneously. The injection of 1-3 mg/kg muscimol (MUS), a GABAA receptor agonist, decreased the basal MUA and delayed the occurrence of the next MUA volley, but it did not change the LH pulse amplitude. I.v. injection of 5 mg/kg bicuculline (BIC), a GABAA receptor antagonist, during continuous infusion of MUS (5 mg/kg/h) which decreased the basal MUA and prevented the MUA volley from occurring, evoked MUA volleys and LH pulses whose amplitudes were similar to those found before the MUS infusion. Injection of the same dose of BIC during the infusion of saline increased the MUA transiently, but this increase was not accompanied by an LH pulse and afterwards there occurred MUA volleys at ordinary intervals accompanied by LH pulses with unchanged pulse amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Anticipation in hereditary dentatorubral-pallidoluysian atrophy.

Anticipation refers to the progressively earlier onset and increase in disease severity in successive generations. We studied four families with hereditary dentatorubral-pallidoluysian atrophy (DRPLA), a neurodegenerative disease, and anticipation was present in the mode of inheritance. In subsequent generations DRPLA shows an earlier onset and more severe as well as additional symptoms. Older onset patients suffer from cerebellar ataxia with or without dementia, whereas younger onset patients present as progressive myoclonus epilepsy syndrome, which consists of mental retardation, dementia, and cerebellar ataxia as well as epilepsy and myoclonus. Anticipation with paternal transmission was significantly greater than with maternal transmission.

Adult↗
PubMed1994

Postoperative changes of rat EEG variance.

Concerning an EEG parameter variance, the long-term postoperative changes were observed in rats chronically implanted with bipolar depth electrodes for EEG recordings. The cortico-hippocampal EEG signals were continuously digitized and their variances were computed for each 1 min in real time. Daily mean of the EEG variance gradually increased over 2 weeks after surgery for the implantation of chronic electrodes and, then, reached a plateau. To observe the absolute quantity of the depth EEG in the rat, at least 2 weeks are required before data collections.

Animals↗
PubMed1994

Cessation of the electrical activity of gonadotropin-releasing hormone pulse generator during the steroid-induced surge of luteinizing hormone in the rat.

Neuronal activity in the mediobasal hypothalamus was recorded during the steroid-induced surge of luteinizing hormone (LH) in ovariectomized female rats by means of multiunit activity (MUA) recording techniques. The day of subcutaneous implantation of estradiol-containing silastic tubing, which was done at 12.00 h, was designated as day 1, and progesterone (1 mg) dissolved in sesame oil was injected at 12.00 h on day 5. The hypothalamic MUA and serum LH level were monitored between 10.00 and 20.00 h on days 1, 4 and 5. All 5 animals examined showed characteristic increases (volleys) in MUA associated with pulsatile LH secretion. After implantation of estradiol on day 1, gradual and significant decreases in the serum LH level and in MUA volley frequency were observed. In the afternoon of both days 4 and 5, an LH surge occurred, though it was much greater on day 5 than day 4 due to progesterone injection on day 5. However, neither MUA volleys nor considerable changes in baseline MUA were discernible throughout the recording period on days 4 and 5. More than 5 days after the removal of estradiol-containing tubing, MUA volleys were found to reappear in all the animals. These results suggest that estradiol has an inhibitory effect on gonadotropin-releasing hormone (GnRH) pulse generator activity, and that the GnRH pulse generator is not involved in inducing the LH surge in the rat.

Animals↗
PubMed1994

[Partial purification and properties of deoxyribonucleases from eggs and liver of Xenopus laevis. Comparison with deoxyribonuclease II from bovine spleen].

Deoxyribonucleases from eggs and the liver of Xenopus laevis were partially purified by DEAE-cellulose and heparin-Sepharose affinity column chromatographies. The fractions having egg and liver DNase activities were eluted on high performance liquid chromatography through TSK gel G3000SW at the molecular weights of 41.5 and 45 kDa, respectively. The frog DNases hydrolyzed a native DNA over a heat-denatured DNA, and also formed double-strand cuts not only in linear lambda-DNA but also in closed circular pBR322DNA. The pH optimum of the DNases was 4.5-5.0 in 50 mM acetate buffer. These enzyme activities were abolished by treatment at 80 degrees C for 5 min and pH 2, 3 or 12 for 1 h. The enzymes act in such a manner as deoxyribonuclease II (from bovine spleen)-type nuclease with respect to substrate specificity, optimum pH and cation dependence.

Animals↗
PubMed1994

Response of the sleep-wake rhythm to an 8-hour advance of the light-dark cycle in the rat.

We have studied the effects of an 8-h advance of the environmental light-dark (LD) cycle on the sleep-wake rhythm in the rat. Electroencephalograms and electromyograms were recorded simultaneously on chart paper through a two-channel telemetry system for 3 days before phase shift (baseline) and 8 days during and after phase shift. Phase advance of the LD cycle led to an increase in both non-rapid eye movement (NREM) and REM sleep. The amount of NREM sleep in the light period correlated positively with that in the preceding dark period for 4 days after phase advance. The duration of REM sleep in the light period correlated negatively with that in the preceding dark period. The results suggest that homeostatic control of the amount of NREM sleep between the preceding dark period and the following light period is disturbed by phase advance of the LD cycle.

Activity Cycles↗
PubMed1994

Fibrosis patterns of lesions developed by athymic and euthymic mice infected with Paracoccidioides brasiliensis.

Athymic and euthymic mice with BALB/c background were used to study the patterns of fibrosis during ip infection with a virulent isolate of Paracoccidioides brasiliensis. Specimens from various organs were collected from the animals at 1, 4 and 7 weeks after infection and observed under light microscopy using various histologic staining methods. Lesions from the first week of infection, in both animal groups, presented a predominance of collagen III over I, carboxylated proteoglycans, and a tendency to encapsulation. From 4 weeks onward, the lesions of nu/+ mice tended to involute to macrophage-pseudoxanthomatous aggregates or to encapsulation with an increase of collagen I and sulfated proteoglycans. On the contrary, with the evolution of the infection, the nu/nu mice displayed permanently active lesions, rich in reticular fibers and carboxylated proteoglycans, with varied amounts of collagens III and I, without or with minimal encapsulation. However, independent of the type of mice, or of the type of lesions, the minimal P. brasiliensis-ECM unit was formed by a fibrillar cocoon of reticular fibers that encloses an individual yeast or a "family" composed of a mother cell plus one or various peripheral daughter cells, alone or engulfed by macrophages or giant cells. The overall difference of the lesions of nude and normal mice was not in isolated aspects of their components, but in the general architecture of the lesions. Those of nu/+ mice were either of involutive or of encapsulated type (slightly active), and those of nu/nu mice were of the sustained-expansive type (very active), without or with minimal encapsulation.

Animals↗
PubMed1994

Relation between recurrence and expression of proliferating cell nuclear antigen, sialyl LewisX, and sialyl Lewis(a) in lung cancer.

Blood vessel invasion, recurrence rate, and time to recurrence were examined in relation to the immunohistochemical expression of proliferating cell nuclear antigen, sialyl LewisX, and sialyl Lewis(a) in 303 patients with lung cancer who had a curative resection from 1980 to 1991. Of these, 150 had adenocarcinoma, 117 had squamous, 21 had large-cell, and 15 had small-cell carcinoma. Significant differences were detected in the expression of proliferating cell nuclear antigen and sialyl LewisX between adenocarcinomas and the other histologic types; thus the subjects were divided into 150 with adenocarcinoma and 153 with non-adenocarcinoma. In those with adenocarcinoma, the frequency of blood vessel invasion was significantly higher in tumors with strong sialyl LewisX expression, and the disease-free survival of the patients with blood vessel invasion was significantly worse when their tumors strongly expressed both sialyl LewisX and proliferating cell nuclear antigen. In those with non-adenocarcinoma, on the other hand, tumors with strong expression of sialyl Lewis(a) and proliferating cell nuclear antigen showed significantly higher frequencies of blood vessel invasion and worse disease-free survival. In patients with recurrent tumors, those with strong proliferating cell nuclear antigen expression showed a significantly shorter time to recurrence. We conclude that sialyl LewisX and proliferating cell nuclear antigen expression in adenocarcinoma and sialyl Lewis(a) and proliferating cell nuclear antigen expression in non-adenocarcinoma may be an important determinant of recurrence.

Adenocarcinoma↗