Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 397 records · Page 22Linked to original sources

PubMed1998

Visualization of the information flow through human oculomotor cortical regions by transcranial magnetic stimulation.

We investigated the topography of human cortical activation during an antisaccade task by focal transcranial magnetic stimulation (TMS). We used a figure-eight shaped coil, with the stimulus intensity set just above the threshold for activation of the hand motor areas but weak enough not to elicit blinks. TMS was delivered at various time intervals (80, 100, and 120 ms) after target presentation over various sites on the scalp while the subjects performed the antisaccade task. It was possible to elicit a mild but significant delay in saccade onset over 1) the frontal regions (a region 2-4 cm anterior and 2-4 cm lateral to hand motor area) and 2) posterior parietal regions (6-8 cm posterior and 0-4 cm lateral to hand motor area) regardless of which hemisphere was stimulated. The frontal regions were assumed to correspond to a cortical region including the frontal eye fields (FEFs), whereas the parietal regions were assumed to represent a wide region that includes the posterior parietal cortices (PPCs). The regions inducing the delay shifted from the posterior parietal regions at an earlier interval (80 ms) to the frontal regions at a later interval (100 ms), which suggested an information flow from posterior to anterior cortical regions during the presaccadic period. At 120 ms, the effect of TMS over the frontal regions still persisted but was greatly diminished. Erroneous prosaccades to the presented target were elicited over a wide cortical region including the frontal and posterior parietal regions, which again showed a forward shift with time. However, the distribution of effective regions exhibited a clear contralateral predominance in terms of saccade direction. Our technique provides a useful method not only for detecting the topography of cortical regions active during saccadic eye movement, but also for constructing a physiological map to visualize the temporal evolution of functional activities in the relevant cortical regions.

Adult↗

PubMed1998

Neuronal activity in medial frontal cortex during learning of sequential procedures.

To study the role of medial frontal cortex in learning and memory of sequential procedures, we examined neuronal activity of the presupplementary motor area (pre-SMA) and supplementary motor area (SMA) while monkeys (n = 2) performed a sequential button press task, "2 x 5 task." In this paradigm, 2 of 16 (4 x 4 matrix) light-emitting diode buttons (called "set") were illuminated simultaneously and the monkey had to press them in a predetermined order. A total of five sets (called "hyperset") was presented in a fixed order for completion of a trial. We examined the neuronal activity of each cell using two kinds of hypersets: new hypersets that the monkey experienced for the first time for which he had to find the correct orders of button presses by trial-and-error and learned hypersets that the monkey had learned with extensive practice (n = 16 and 10 for each monkey). To investigate whether cells in medial frontal cortex are involved in the acquisition of new sequences or execution of well-learned procedures, we examined three to five new hypersets and three to five learned hypersets for each cell. Among 345 task-related cells, we found 78 cells that were more active during performance of new hypersets than learned hypersets (new-preferring cells) and 18 cells that were more active for learned hypersets (learned-preferring cells). Among new-preferring cells, 33 cells showed a learning-dependent decrease of cell activity: their activity was highest at the beginning of learning and decreased as the animal acquired the correct response for each set with increasing reliability. In contrast, 11 learned-preferring cells showed a learning-dependent increase of neuronal activity. We found a difference in the anatomic distribution of new-preferring cells. The proportion of new-preferring cells was greater in the rostral part of the medial frontal cortex, corresponding to the pre-SMA, than the posterior part, the SMA. There was some trend that learned-preferring cells were more abundant in the SMA. These results suggest that the pre-SMA, rather than SMA, is more involved in the acquisition of new sequential procedures.

Animals↗

PubMed1998

Efficacy of coronary artery bypass grafting in patients with a dilated left ventricle due to myocardial infarction.

This study was designed to clarify the efficacy of coronary artery bypass grafting (CABG) on left ventricular (LV) function in 16 patients with a dilated LV due to myocardial infarction (LV end-systolic volume index: LVESVI >60 ml/m2). All had attained complete revascularization. To estimate the LV wall motion quantitatively using echocardiography, a wall motion score (WMS) was used (LV was divided into 17 segments with a four-point scale: akinesis=3, severe hypokinesis=2, hypokinesis=1, normal=0 and then summed). Exercise stress tests were performed after surgery, revealing that anginal symptoms had vanished in all the patients. In 5 patients with a preoperative end-systolic volume index (ESVI) >100 ml/m2, the ejection fraction (EF) did not change, and both were under 30% (before to after: 26+/-4 to 26+/-4%). Neither the ESVI (148+/-50 to 133+/-39 ml/m2) nor the end-diastolic volume index (end-diastolic volume index (EDVI): 198+/-62 to 180+/-37 ml/m2) changed; the WMS did not change (33+/-2 to 33+/-3). During exercise, in spite of the increase in heart rate (HR) (at rest, 81+/-20; HR during exercise, 111+/-21 beats/min, p<0.005) and LV end-diastolic pressure (EDP) (22+/-9; 35+/-13 mmHg, p<0.02), both cardiac index (CI) (2.4+/-0.3; 2.6+/-0.4 L/min x m2) and minute work (MW: 4.0+/-1.1; 4.1+/-0.4 kg x M/min) did not increase. In 11 patients with a preoperative ESVI <100 ml/m2, EF was extremely increased in 5 patients (more than 10%, 35+/-4 to 60+/-6%, p<0.005=improved subgroup) in whom the EDVI (130+/-16 to 120+/-13 ml/m2) did not change whereas the ESVI (82+/-14 to 48+/-7 ml/m2) was reduced. However, in the 6 remaining patients (ie nonimproved subgroup), neither ESVI (78+/-8 to 74+/-12 ml/m2), EDVI (115+/-10 to 115+/-20 ml/m2) nor EF (31+/-7 to 35+/-3%) changed. During exercise, HR (at rest, 88+/-13; during exercise, 108+/-11 beats/min, p<0.005), LVEDP (20+/-6; 29+/-7 mmHg, p<0.01), CI (2.5+/-0.6; 3.3+/-0.5 L/min x m2, p<0.05), MW (4.6+/-1.0; 6.5+/-1.5 kg x M/min, p<0.05) increased. The WMS in the nonimproved subgroup did not change (29+/-6 to 27+/-2), but in the improved subgroup it reduced after surgery (27+/-3 to 19+/-4, p<0.01). These data suggested that CABG in patients with a dilated LV was effective against anginal symptoms, but was restricted to left ventricular function. It may be possible to estimate postoperative LV function, including exercise tolerance, from the preoperative LVESVI.

Aged↗

PubMed1998

Possible involvement of K(ATP) channel activation in depressor responses to vasoactive neuropeptides in rats.

I.v. bolus injections of vasoactive intestinal polypeptide (VIP) (0.3 or 1 microg/kg), calcitonin gene-related peptide (CGRP) (0.3 microg/kg) or substance P (0.1 microg/kg) to anesthetized rats reduced blood pressure, accompanied by slight increases in heart rate. Cromakalim (0.3 microg/kg/min) infused i.v. significantly potentiated the depressor responses to VIP and CGRP, but not those to substance P and acetylcholine (ACh) (0.1 microg/kg). Glibenclamide (20 mg/kg, i.v.) significantly inhibited not only the depressor responses to VIP and CGRP, but also the augmentation of the effects of the two agents by cromakalim. These results suggest that the depressor responses to VIP and CGRP are mediated in part through K(ATP) channel activation.

ATP-Binding Cassette Transporters↗

PubMed1998

Purification and characterization of an esterase involved in poly(vinyl alcohol) degradation by Pseudomonas vesicularis PD.

An esterase catalyzing the hydrolysis of acetyl ester moieties in poly(vinyl alcohol) was purified 400-fold to electrophoretic homogeneity from the cytoplasmic fraction of Pseudomonas vesicularis PD, which was capable of assimilating poly(vinyl alcohol) as the sole carbon and energy source. The purified enzyme was a homodimeric protein with a molecular mass of 80 kDa and the isoelectric point was 6.8. The pH and temperature optima of the enzyme were 8.0 and 45 degrees C. The enzyme catalyzed the hydrolysis of side chains of poly(vinyl alcohol), short-chain p-nitrophenyl esters, 2-naphthyl acetate, and phenyl acetate, and was slightly active toward aliphatic esters. The enzyme was also active toward the enzymatic degradation products, acetoxy hydroxy fatty acids, of poly(vinyl alcohol). The K(m) and Vmax of poly(vinyl alcohol) (degree of polymerization, 500; saponification degree, 86.5-89.0 mol%) and p-nitrophenyl acetate were 0.381% (10.6 mM as acetyl content in the polymer) and 2.56 microM, and 6.52 and 12.6 mumol/min/mg, respectively. The enzyme was strongly inhibited by phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate at a concentration of 5 mM, which indicated that the enzyme was a serine esterase. The pathway for the metabolism of poly(vinyl alcohol) is also discussed.

Amino Acid Sequence↗

PubMed1998

Saireito (a Chinese herbal drug) decreases inhibitory effect of prednisolone and accelerates the recovery of rat hypothalamic-pituitary-adrenal axis.

Saireito, a saiko agent (a Chinese herbal drug), increases the synthesis and secretion of ACTH by stimulating hypothalamic CRH release. In the present study, we examined the effect of food containing saireito (1.5%) on the recovery of the hypothalamic-pituitary-adrenal axis after treating male rats with prednisolone (PSL, 200 microM) in drinking water for 14 days. Saireito was administered during and after PSL administration. The rats were decapitated at various times after PSL administration. Tail-pinch stress had been applied to some rats. The plasma ACTH response to tail-pinch stress in the PSL + saireito group recovered to the control level on day 1, but that in the group given PSL alone recovered on day 3. The ACTH level in the anterior pituitary and the CRH level in the median eminence of the PSL + saireito group returned to the control level on day 3, and that in the group given PSL alone returned to it on day 5. These results indicate that the administration of saireito reduces the negative feedback effect of PSL on the hypothalamus and pituitary and accelerates the recovery of the hypothalamic CRH and pituitary ACTH level after glucocorticoid treatment.

Adrenal Gland Diseases↗

PubMed1998

Outcome after external decompression for massive cerebral infarction.

Acute ischemic stroke involving the entire vascular distribution of a carotid or middle cerebral artery can cause massive cerebral edema. This study evaluated external decompression for the treatment of massive stroke and analyzed possible prognostic factors. Twenty-four patients with acute massive cerebral infarction, which had progressed to tentorial herniation and impending death, underwent external decompression after medical therapy failed to achieve an effective response. The neurological outcome 2 months after surgery using the Glasgow Outcome Scale was severe disability in 14 patients, vegetative state in two, and death in eight. The overall mortality was 33%. Various characteristics (age, sex, etiology, side of hemispheric infarction, pupillary asymmetry, Japan Coma Scale, distribution of infarction, hemorrhagic infarction, midline shift, tentorial herniation) were evaluated to determine the factors associated with high mortality after surgical intervention. There was no statistically significant relationship between any variable and mortality. Mortality was especially high in the patients with preoperative consciousness level of 200, anterior, middle, and posterior cerebral artery territory infarction, and stage III of tentorial herniation. Postoperatively, all patients with severe disability returned to a clear level of consciousness. Six patients with dominant hemisphere stroke had some measure of communicative skills in spite of aphasia. External decompression is a life-saving treatment for patients with massive cerebral infarction and can provide a reasonable quality of life even for those with dominant hemisphere strokes. Decompressive surgery should be considered and performed as soon as possible if computed tomography demonstrates signs of descending tentorial herniation.

Acute Disease↗

PubMed1998

Effect of pranlukast, a leukotriene receptor antagonist, in patients with severe asthma refractory to corticosteroids.

We investigated the effect of pranlukast (ONO-1078), a cysteinyl leukotriene receptor antagonist, in 11 patients with severe bronchial asthma. The patients had been treated with 1600 micrograms/day of beclomethasone or 800-1600 micrograms/day of beclomethasone plus 2.5-20 mg/day of prednisolone, but remained symptomatic. After a 2-week baseline period, the patients received 225 mg of pranlukast twice daily for 8 weeks. Morning and evening peak expiratory flow rate (PEF) and symptom scores (cough, dyspnea, sleep) were recorded in an asthma diary. Ten patients completed the study. Symptom scores, especially dyspnea and sleep scores, and the number of rescue beta 2-agonist inhalations were significantly decreased. The morning PEF significantly improved from a mean baseline value of 311 to 341 L/min by the end of the study period. The evening PEF also improved, from 328 to 348 L/min, although the difference was not significant. These results suggest that pranlukast may be effective in treating patients with severe asthma who are refractory to corticosteroid therapy.

Aged↗

PubMed1998

[The intrarenal distribution of prostaglandin E2 and thromboxane A2 in the rat with unilateral ureteral obstruction or unilateral nephrectomy].

BACKGROUND: We evaluated the intrarenal distribution of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) on the rats that underwent unilateral ureteral obstruction (UUO), unilateral nephrectomy (UNX) or sham operation. METHODS: Male Sprague-Dawley rats were divided into three groups; left ureteral obstruction (UUO), left nephrectomy (UNX) and sham-operation (Control). They were sacrificed at 1, 3, 6, 12, 24 hours and Day 2, Day 3, Day 5, Day 7 and Day 9 after surgery. Intrarenal distribution of eicosanoids were immunohistochemically detected on both kidneys of UUO rats, and on right kidneys of UNX and Control rats. RESULTS: PGE2: In the obstructed kidneys, immunostained PGE2 increased in medullary interstitium at one hour to 6 hours, and in glomeruli and cortical interstitium at 6 hours. An increase of immunostained PGE2 was observed again in cortical interstitium at Day 3 to 5, and in medullary interstitium at Day 2 to 5. In the intact opposite kidneys, expression of immunostained PGE2 increased in glomeruli at Day 5 to 7, and in medullary interstitium at Day 3 to 5. In UNX, immunostained PGE2 increased in the medullary interstitium of the remnant kidneys at 3 hours and Day 3 to 7. On the other hand, an increase of immunostained PGE2 observed in glomeruli and cortical interstitium of these kidneys at Day 5 to 7. TxB2: In the obstructed kidneys, immunostained TxB2 increased in glomeruli and cortical interstitium at 6 hours, and in medullary interstitium at 3 to 12 hours. Predominant expression of TxB2 was observed in medullary interstitium at 3 hours compared to PGE2. We also observed an increase of immunostained TxB2 in cortical interstitium at Day 3 to 5, and in medullary interstitium at Day 2 to 5. In the intact opposite kidneys, immunostained TxB2 increased in medullary interstitium at 3 hours and Day 3. In the remnant kidneys of UNX, an increase of immunostained TxB2 was demonstrated in glomeruli at 6 hours and Day 7, and in medullary interstitium at 3 to 6 hours and Day 3 to 7. CONCLUSION: In the obstructed kidneys, imbalance between PGE2 and TxA2 may contribute to the progression of renal injuries. The fact that expression patterns of these eicosanoids in the opposite kidneys of UUO different from that of the remnant kidneys of UNK, even though both were similarly associated with functional loss of contralateral kidneys, suggested that the opposite kidneys of UUO were affected by any additional factors different from that responsible for the remnant kidneys of UNK.

Animals↗

PubMed1998

[Neural mechanisms for sleep regulation].

The mesopontine tegmentum has a pivotal role for regulation of paradoxical sleep. Noradrenergic neurons in the locus coeruleus and serotonergic neurons in the dorsal raphe have similar firing properties during sleep-waking cycles (active in waking and silent during paradoxical sleep). However, several findings suggest that these two populations of neurons have different influences on sleep-waking regulation. A population of cholinergic neurons in the brainstem which are most active during paradoxical sleep (PS-on neuron) are inhibited by carbachol and excited by bicuculline, while those of another population, active both during waking and paradoxical sleep, are inhibited by carbachol and excited by noradrenaline and histamine. Non-cholinergic PS-on neurons are excited by carbachol and inhibited by noradrenaline. Slow wave sleep is thought to be generated by a neural mechanism in the preoptic area, but neurons in the preoptic area display several kinds of firing patterns in relation with sleep-waking cycles.

Acetylcholine↗

PubMed1998

[Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 Study Group].

Phase I study of TAT-59 (Miproxifen), an antiestrogen developed in Japan for breast cancer, was conducted with the collaboration of 12 hospitals. A single dose of 1.25, 5, 10, 20, 40 and 80 mg, or 5 consecutive daily doses of 1.25, 5, 10, 20 and 40 mg/day, were given orally. After single dosing, no clinical adverse effects were found. Decrease of serum Na, Cl, Ca level and increase of serum LDH level were observed in one patient after a single dose of 5 mg of TAT. An increase in the serum LDH level was also observed in one patient after a single dose in the of 10 mg of TAT. An increase in the serum LDH level and total bilirubin, increase of eosinophil, K and milky serum were also observed in one patient after a single dose of 40 mg of TAT, respectively. All of these abnormal values returned to the normal level within 26 days after final administration of TAT. No adverse clinical findings nor abnormal laboratory findings were observed after consecutive administration of TAT. After postprandial single dosing, the time to reach the maximum serum concentration (Tmax) of DP-TAT, dephosphorylated metabolite of TAT, and its demethylated metabolite, DMDP, ranged from 5.0 to 7.3 hr and from 17.0 to 42.8 hr, respectively. The maximum serum concentration (Cmax) and AUC of DP and DMDP elevated in a dose-dependent manner. T1/2 of DP and DMDP ranged from 24.2 to 41.5, and from 91.9 to 214.7 hr, respectively. There were no significant differences between pharmacokinetics of TAT before and after food intake. Based on the above results, we concluded that a Phase II study should be conducted to evaluate the efficacy, safety and optimal dose of TAT.

Administration, Oral↗

PubMed1998

[Changes in the threshold values of lingua throughout aging].

The filter-paper-disk method was employed for measuring the threshold values of four basic taste on lingua-tip with 308 healthy females aged 20-79. Taste substance were sequentially diluted with distilluted water (30 stages from 80.0 g/dl for sucrose, 30 stages from 30.0 g/dl for NaCl, 30 stages from 8.0 g/dl for sodium tartrate, 30 stages from 4.0 g/dl for HCl quinine). The result was as follows. A sensibility of gustation decreased rapidly in accordance with aging. A decrease of bitterness sensibility was most remarkably with aging, succeeded sourness, sweetness, saltyness. Also, a decrease of a gustation sensibility is beginning in early twenties, especially the sensitivity to a sweetness and sour taste decreased conspicuously from twenties to thirties.

Adult↗

PubMed1998

Effect of thromboxane A2 inhibitors on allergic pulmonary inflammation in mice.

Thromboxane (Tx)A2 synthase inhibitors and thromboxane prostanoid (TP) receptor antagonists have been developed as anti-asthma drugs. TxA2 may contribute to airflow limitation and bronchial hyperresponsiveness, and these compounds have been demonstrated to improve them. However, it is not known whether TxA2 is involved in bronchial inflammation. To address this question, we explored the influences of OKY-046 (a TxA2 synthase inhibitor) and S-1452 (a TP receptor antagonist) on eosinophilic inflammation of the airways using a murine model. BALB/c mice sensitized with ovalbumin and challenged by repeated exposure to ovalbumin yielded marked eosinophilia in bronchoalveolar lavage fluid (BALF). Treatment with either compound significantly reduced the number of total cells and eosinophils in BALF in a dose-dependent manner. The production of interleukin (IL)-5, IL-2 and interferon (IFN)-gamma by antigen-stimulated splenic mononuclear cells (SMNC) was significantly decreased in mice treated with either compound compared to that in untreated mice. Furthermore, both compounds inhibited proliferation and cytokine production of SMNC in vitro. These results suggest that both OKY-046 and S-1452 are capable of inhibiting production of cytokines, which in turn inhibits eosinophil infiltration into the murine airway. Thus, both thromboxane A2 synthesis inhibitors and thromboxane prostanoid antagonists may be effective as anti-inflammatory drugs in the treatment of asthma.

Animals↗

PubMed1998

Time course of apoptosis in collagen-induced arthritis.

Recently, apoptotic cells were discovered in the synovial cells of rheumatoid arthritis patients. Their role, however, is unknown. We thus examined the time course of apoptosis in the synovium using an animal model of rheumatoid arthritis, in which arthritis was induced by intracutaneous injection of collagen. No apoptotic cells were detected before the onset of synovitis, but they increased in parallel with the progress of arthritis in its initial period, and decreased in the later chronic stages. Apoptotic cells appear to maintain the homeostasis of a joint when synovial proliferation occurs.

Animals↗

PubMed1998

Mutation of the p53 gene in postradiation sarcoma.

Radiotherapy is known to cause secondary malignancies in the radiation field; postradiation sarcomas (PRS) are one example of such malignancies. Little is known about the genetic changes, including p53 gene alterations, that are thought to play a role in the tumorigenesis of human PRS. In the present study, p53 gene mutations were analyzed on paraffin-embedded specimens from 24 patients with PRS (4 men and 20 women) by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by direct sequencing. The primary tumors of these patients were uterine cervical cancers in 14, breast cancers in 3, malignant lymphomas in 2, and others in 5. Total radiation doses ranged from 36 to 300 Gy (median, 60 Gy). The latent period between completion of radiation therapy and development of PRS ranged from 3 to 34 years (median, 10 years). Malignant fibrous histiocytoma was the most common PRS, accounting for 12 cases. PCR-SSCP revealed the aberrant mobility shifts of bands in 24 cases: 21 shifts in exon 5, 18 in exon 7, and 12 in exon 8. Direct sequencing of the SSCP product revealed a total of 58 mutations in 21 (88%) of 24 cases: 4 cases had a single mutation, 5 had 2 mutations, 5 had 3 mutations, 6 had 4 mutations, and 1 had 5 mutations. Although 31% of the mutations did not change an amino acid, every tumor had at least one mutation that did, which may have provided the selection pressure for expansion. The frequency of p53 gene mutation in sporadic soft tissue sarcomas was 20%. These findings highlighted the extraordinarily high frequency of p53 gene mutations in PRS. G:C to A:T transition at dipyrimidine sites was found in 14 (58%) of 24 cases. Collectively, these findings indicate that radiation is causative for soft tissue sarcomas via p53 gene mutations.

Adolescent↗

PubMed1998

[Two patients with hypertrophic cardiomyopathy showing regionally increased washout of 123I-MIBG from the thick myocardium].

123I-MIBG scintigraphy was performed in two patients with hypertrophic cardiomyopathy. These patients showed marked asymmetrical wall thickening in the left ventricle. The findings of 123I-MIBG scintigraphy in the thickened wall were regional increased washout and defect in the delayed images with preserved 201Tl uptake. This mismatched finding, which is correlated with ventricular tachycardia, gives useful information for follow-up of the patients with HCM.

3-Iodobenzylguanidine↗

PubMed1998

[Non-Hodgkin's lymphoma of the spermatic cord: a case report].

A 77-year-old man presented with a 2-week history of a painless lump in the left groin. He underwent left radical orchiectomy under a diagnosis of left spermatic cord tumor. The specimen revealed a 5 x 3 cm solid tumor arising in the spermatic cord at the level of the symphysis pubis. On microscopic examination, the tumor was classified as a diffuse, large cell non-Hodgkin's malignant lymphoma in the Working Formulation, involving a small portion of the upper pole of the left testis. Immunohistochemical stains were positive for LCA and L26. Gallium scan showed increased activity along the left testicular artery in the abdomen. The patient underwent 6 cycles of chemotherapy consisting of cyclophosphamide, vindesine, pirarubicin, prednisone and subsequently the addition of etoposide, which resulted in only temporary improvement. He died with extensive disease 10 months after surgery.

Aged↗

PubMed1998

Reversible hyperintensity of the anterior pituitary gland on T1-weighted MR images in a patient receiving temporary parenteral nutrition.

We report a patient with severe anorexia nervosa, treated with temporary total parenteral nutrition (TPN), in whom reversible hyperintensity of the anterior pituitary gland was seen on T1-weighted MR images. The anterior pituitary was isointense with white matter before TPN therapy and became markedly hyperintense after 3 months of treatment. The intensity normalized after TPN therapy was discontinued. The transient hyperintensity was also seen in the basal ganglia and dorsal brain stem. We believe the hyperintensity of the anterior pituitary may be attributed to the TPN therapy.

Adolescent↗