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Biomedical subjects

K Shindo

Publications and source records attributed to K Shindo.

At least 19 recordsLinked to original sources

In vivo effect of prednisolone on release of leukotriene C4 in eosinophils obtained from asthmatic patients.

We investigated the release of leukotriene C4 from eosinophils of asthmatic patients who were treated with or without intravenous prednisolone. The mean level of LTC4 in the supernatant of A23187-stimulated eosinophils obtained from asthmatic patients during an attack was significantly lower with intravenous prednisolone than without prednisolone treatment. Findings suggest that intravenous prednisolone inhibits the release of LTC4 from the eosinophils of asthmatic patients by acting on these cells in vivo.

Adult

Spatial distribution of thalamic projections to the supplementary motor area and the primary motor cortex: a retrograde multiple labeling study in the macaque monkey.

The exact knowledge on spatial organization of information sources from the thalamus to the supplementary motor area (SMA) and to the primary motor cortex (MI) has not been established. We investigated the distribution of thalamocortical neurons projecting to forelimb representations of the SMA and the MI using a multiple retrograde labeling technique in the monkey. The forelimb area of the SMA, and the distal and proximal forelimb areas of the MI were identified by electrophysiological techniques of intracortical microstimulation and single neuron recording. Injections were made into these three representations with three different dyes in the same animal (horseradish peroxidase conjugated to wheat germ agglutinin, diamidino yellow, and fast blue), and the thalamic neurons were retrogradely labeled. Injections into the SMA densely labeled thalamic neurons in nuclei ventralis lateralis pars oralis (VLo), ventralis lateralis pars medialis (VLm) and ventralis lateralis pars caudalis (VLc), but not in nucleus ventralis posterior lateralis pars oralis (VPLo). Injections into the MI labeled thalamic neurons primarily in VLo, VLc, and VPLo. We found that the distribution of projection neurons to the three areas was largely separate in the thalamus. However, in the middle part of VLo, and in a limited portion of VLc, thalamic neurons projecting to the SMA partially overlapped with those to the distal forelimb area of the MI. They overlapped little with those to the proximal forelimb area of the MI. We noted no overlap between the distributions of thalamic projection neurons to the distal and proximal forelimb areas of the MI. These findings suggest that the SMA and MI receive separate information from the thalamus, while sharing minor sources of common inputs.

Animals

Localization of oncofetal and normal fibronectin in colorectal cancer. Correlation with histologic grade, liver metastasis, and prognosis.

BACKGROUND: Expression of oncofetal fibronectin (oncFN) and normal fibronectin (norFN) in colorectal cancer specimens was examined to investigate the correlation between fibronectin localization and histologic grade, liver metastasis, and prognosis. METHODS: Immunohistochemical staining of oncFN and norFN was performed on 99 primary lesions and 12 liver metastases of colorectal cancer. The expression of norFN and oncFN was evaluated by grading the intensity of staining as negative, positive, or strongly positive. RESULTS: Positive staining for oncFN correlated positively with increasing stage. The rate of strongly positive staining for oncFN was 53% for primary lesions with liver metastasis, significantly higher than the oncFN-positive rate of 13% for metastasis free cases (P < 0.05). Liver lesions had an oncFN-positive rate of 92%. The postoperative 5-year survival rate for 51 cases classified as Dukes Stage C was 77.8% for oncFN-negative cases, 36.5% for oncFN-positive cases, and 22.2% for oncFN-strongly positive cases; these rates were significantly different (P < 0.01). Conversely, there was no correlation between norFN and any clinical variable. CONCLUSION: Expression of oncFN is correlated with a poor prognosis of Dukes C colorectal cancer and may serve as a useful postoperative prognostic sign.

Antigens, Neoplasm

Selective inhibition of myosin phosphorylation and tension of hyperplastic arteries by the kinase inhibitor HA1077.

To examine possible alterations in myosin light chain phosphorylation in hyperplastic arteries, rabbit strips from right hyperplastic and left normal control carotid arteries were used for experiments 6 weeks after the ballooning procedure. When the hyperplastic artery was stimulated with various concentrations of K+ (10, 20, 30, 40 and 60 mM), the maximal tension in response to each concentration was significantly higher (P < 0.05) than that in the control artery. The maximal extent of myosin light chain phosphorylation induced by 60 mM K+ in the hyperplastic artery was also significantly higher than that in the control (55.1 +/- 4.1 vs. 45.1 +/- 3.2%, mean +/- S.D.). However, the [Ca2+]i response to elevated K+ in hyperplastic arteries was much the same as that in control arteries, when measured with fura-PE3. HA1077 (1-5-(isoquinolinesulfonyl)-homopiperazine), a protein kinase inhibitor, was about 3-5 times more effective in inhibiting the tension and myosin light chain phosphorylation induced by 60 mM K+ in the hyperplastic artery than in the control artery. Nifedipine inhibited the tension and myosin light chain phosphorylation to the same extent in control and hyperplastic arteries. Thus, an alteration of the myosin light chain phosphorylation system, but not an alteration of Ca2+ mobilization, may be involved in the enhanced contraction of the hyperplastic artery. The enhanced phosphorylation of myosin light chain may be sensitive to HA1077.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Pain-related somatosensory evoked potentials following CO2 laser stimulation of foot in man.

Since our previous study of pain somatosensory evoked potentials (SEPs) following CO2 laser stimulation of the hand dorsum could not clarify whether the early cortical component N1 was generated from the primary somatosensory cortex (SI) or the secondary somatosensory cortex (SII) or both, the scalp topography of SEPs following CO2 laser stimulation of the foot dorsum was studied in 10 normal subjects and was compared with that of the hand pain SEPs and the conventional SEPs following electrical stimulation of the posterior tibial nerve recorded in 8 and 6 of the 10 subjects, respectively. Three components (N1, N2 and P2) were recorded for both foot and hand pain SEPs. N1 of the foot pain SEPs was maximal at the midline electrodes (Cz or CPz) in all data where that potential was recognized, but the potential field distribution was variable among subjects and even between two sides within the same subject. N1 of the hand pain SEPs was maximal at the contralateral central or midtemporal electrode. The scalp distribution of N2 and P2, however, was not different between the foot and hand pain SEPs. The mean peak latency of N1 following stimulation of foot and hand was found to be 191 msec and 150 msec, respectively, but there was no significant difference in the interpeak latency of N1-N2 between foot and hand stimulation. It is therefore concluded that N1 of the foot pain SEPs is generated mainly from the foot area of SI. The variable scalp distribution of the N1 component of the foot pain SEPs is likely due to an anatomical variability among subjects and even between sides.

Adult

Effects of semotiadil fumarate (SD-3211) and its enantiomer, SD-3212, on the changes in cytosolic Ca2+ and tension caused by KCl and norepinephrine in isolated rat aortas.

Semotiadil fumarate (SD-3211), a Ca2+ channel blocker of benzothiazine derivative and its (S)-(-)-enantiomer (SD-3212), inhibited K(+)- and norepinephrine (NE)-induced contractions in isolated rat aortas. Inhibition of NE contraction induced by both drugs was greater than that induced by diltiazem or bepridil, whereas inhibition of K(+)-contraction was similar to that induced by diltiazem or bepridil. Semotiadil and SD-3212 (10 microM) inhibited the increase in cytosolic Ca2+ ([Ca2+]i) induced by 65.4 mM K+ in fura-2-loaded preparations as well as diltiazem and bepridil (10 microM). On the other hand, semotiadil and SD-3212 (10 microM) inhibited only the early phase of increase in [Ca2+]i induced by 1 microM NE. After 5 min, no significant effect on [Ca2+]i was observed with these compounds despite the significant decrease in the contraction. In contrast to these compounds, diltiazem and bepridil 10 microM affected neither the increase in [Ca2+]i nor the contraction induced by NE. Semotiadil and SD-3212 inhibited the transient contraction induced by 1 microM NE in the absence of external Ca2+. Both compounds partially but significantly inhibited the NE-induced contraction in nifedipine-treated muscles. These results suggest that semotiadil and SD-3212 inhibit contractions of vascular smooth muscle (VSM) not only through blockade of voltage-dependent Ca2+ channels but also through other mechanisms, such as inhibition of Ca2+ release from Ca2+ stores or decrease in sensitivity of the contractile elements to Ca2+.

Animals

[Analysis of malignant potential on colorectal carcinoma utilizing expression of epidermal growth factor and DNA ploidy patterns].

Human epidermal growth factor (EGF) and DNA ploidy patterns were investigated in order to elucidate malignant potential of 216 surgically resected colorectal carcinomas. EGF positive was detected in 140 out of 216 (64.8%) cases and DNA aneuploidy was found in 137 out of 216 (63.4%). No significant correlations were recognized between EGF expressions and DNA ploidy patterns. We subclassified the cases into four groups according to their histological EGF expressions and DNA ploidy patterns. In these groups, the relationship among EGF expressions, DNA ploidy patterns and clinicopathological findings was studied. Subgroups had a significant relation to depth of invasion, lymph node metastasis, lymphatic invasion and clinical stage. In patients with curative operation, the prognosis was significantly lower in EGF-positive-DNA aneuploidy group than in EGF-negative-DNA diploidy group. In DNA diploidy, the prognosis of EGF-positive group was poorer than in the EGF-negative group. In conclusion, the EGF expression as well as DNA ploidy patterns may be useful to assess malignant potential in colorectal carcinoma.

Colorectal Neoplasms

Leukotriene B4 levels in the arterial blood of asthmatic patients and the effects of prednisolone.

Prednisolone is very effective in controlling wheezing attacks of bronchial asthma, but its mechanism and the pathogenic role of leukotriene B4 remain unclear. We measured changes in plasma levels of leukotriene B4 in an open study during the clinical course of bronchial asthma, with or without water-soluble prednisolone treatment. Two millilitres of blood was drawn from the radial artery of patients on three occasions: 1) during remission; 2) on admission to hospital with an asthma attack; and 3) 2 days after admission and treatment with intravenous prednisolone (1,000 mg.day-1). Leukotriene B4 was detected by chromatographic fractionation and radioimmunoassay. In 11 asthmatic patients, leukotriene B4 levels on the three occasions were 26.8 (10.7), 106.0 (39.9) and 51.6 (20.2) pg.ml-1 (mean (SD)), respectively. In contrast, the mean leukotriene B4 level of 10 normal controls was 35.9 (10.5) pg.ml-1. Leukotriene B4 levels differed significantly between remission and attack treated without prednisolone, and between attacks treated with and without prednisolone. Mean arterial carbon dioxide (PaCO2) values were 4.8 (0.4) kPa (36.0 (3.0) mmHg), 6.1 (0.4) kPa (45.6 (2.9) mmHg), and 5.5 (0.3) kPa (41.6 (2.0) mmHg), respectively. There were significant differences between these mean PaCO2 values. The mean leukotriene B4 levels on the three occasions were correlated with the mean PaCO2 values. Thus, leukotriene B4 levels in arterial blood reflect the severity of asthmatic attacks and may be affected by intravenous prednisolone.

Adult

Effect of H2-receptor antagonists on bile acid metabolism.

BACKGROUND: Several reports have been presented concerning pronounced overgrowth of bacteria in gastric juices of patients treated with H2-receptor antagonists. However, there has been no report concerning influence of H2-receptor antagonists on jejunal flora. Thus, to investigate the influence and its effect on bile acid metabolism, this study was performed: 1) to examine whether patients with gastric ulcers who have been treated with H2-receptor antagonists have positive bile acid breath tests due to bacterial overgrowth in their jejuna; 2) to verify that these bacteria, isolated and identified, have deconjugation ability; and 3) to determine whether the changes in the gastric pH are related to bacterial overgrowth. METHODS: The methods used were detection of deconjugation of bile acids in early phase by a bile acid breath test using 5 muCi of oral glycine-1-14C labeled glycocholate, aspiration of jejunal fluids by a double lumen tube with a rubber cover on the tip, and examination of deconjugation ability by thin layer chromatography. RESULTS: Expired breath samples from all 18 patients after administration of H2-receptor antagonists showed a significant increase in 14CO2 specific activity compared with those before administration of H2-receptor antagonist and the normal controls, and bacterial overgrowth was found in the jejunal fluid of the patients after administration of H2-receptor antagonist. The administration of tetracycline to the 18 patients reduced the 14CO2 specific activity significantly. The following species were identified in the jejunal fluid samples obtained from the patients: Escherichia coli, Candida albicans, Pseudomonas aeruginosa, enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Eubacterium lentum, and Eubacterium parvum. All of the species identified except for Escherichia coli, Pseudomonas aeruginosa, and Candida albicans deconjugated bile acids. There were significant correlations between the 14CO2 activity and gastric pH before and after administration of H2-receptor antagonist, respectively. CONCLUSIONS: Patients with gastric ulcers who were treated with H2-receptor antagonists have increased bile acid deconjugation due to bacterial overgrowth in their jejuna containing species that can deconjugate bile acids. The bacterial overgrowth is probably associated with a shift to neutral pH in the gastric juice caused by the H2-receptor antagonists.

Adult

Muscle spasm induced sympathetic reflex bursts on microneurography in a case with pontine demyelination.

Microneurography was performed in a 39-year-old woman with demyelination of the pontine white matter associated with muscle spasms in the lower extremities. Single bursts on the microneurogram were observed immediately after cessation of the spasm with no systemic changes in the blood pressure or heart rate. Voluntary tonic flexion of the lower extremities induced similar bursts with small amplitudes. These reflex bursts possessed a characteristic of muscle sympathetic nerve activity, because the latency between the peak of each burst and the prior R-wave on the electrocardiograph was constant. The occurrence of these bursts suggests that a segmental compensatory mechanism in the spinal cord may stabilize the muscle blood flow influenced by muscle contraction.

Adult

[A case of central pontine myelinolysis and extrapontine myelinolysis during rapid correction of hypernatremia].

A 69-year-old woman was admitted because of severe dehydration due to anorexia. Consciousness disturbance was found to be due to severe abnormalities of serum electrolyte balance, but recovered quickly by correcting the hyperosmolality. While the initial serum sodium value of 186 mEq/L was corrected to 139 mEq/L in 5 days, locked-in syndrome, bilateral hand tremor and tetraparesis appeared. Brain magnetic resonance imaging (MRI) revealed symmetrically high signal intensity areas on T2-weighted images and low signal intensity areas on T1-weighted images in central part of pons and bilateral middle cerebellar peduncles. One and a half month later, these neurologic symptoms were improved and the MRI abnormalities also disappeared. Auditory brain stem responses which showed prolongations of III to V wave peak to peak latency at the onset returned to normal. It is noted in this case that central pontine myelinolysis (CPM) and extrapontine myelipolysis (EPM) appeared during the period of rapid correction of hypernatremia. Although it is known CPM and EPM are caused by hypernatremia or the rapid correction of hyponatremia, there has been reported only one case of CPM and EPM after rapid correction of hypernatremia. According to the hypothesis of Norenberg, rapid rise in serum sodium may cause CPM and EPM, but if CPM and EPM are caused by the rapid correction of hypernatremia in this case, CPM and EPM may be caused by another pathogenesis of the disorder.

Aged

Magnetic resonance imaging in kainic acid-induced limbic seizure status in cats.

Magnetic resonance imaging before, during, and after kainic acid (KA)-induced limbic seizure status in cats demonstrated the bilateral hippocampi as slightly high-intensity areas on the T2-weighted images during the limbic seizure status, and isointensity areas 1-2 weeks after KA injection when the limbic seizure status subsided. However, the hippocampi again became high-intense 1-3 months after KA injection. Histological study suggested that the high-intensity area during the limbic seizure status resulted from regional edema, and in the chronic period from marked gliosis and/or atrophic change as a consequence of tissue damage in the hippocampus.

Amygdala

Flumazenil does not antagonize halothane, thiamylal or propofol anaesthesia in rats.

We have studied the effects of flumazenil on sleep time and EEG in rats anaesthetized with 1.5% halothane, propofol 20 mg kg-1, thiamylal 30 mg kg-1, or combinations of diazepam 5 mg kg-1 and anaesthetic agents. We also studied the effects of flumazenil 0.3, 3 and 30 mg kg-1 on behaviour and EEG. Flumazenil 0.3 and 3 mg kg-1 alone had no effect on behaviour or EEG, but flumazenil 30 mg kg-1 had depressive effects similar to those of diazepam on behaviour and EEG. Flumazenil 0.3, 3 and 30 mg kg-1 i.v., antagonized the effects of diazepam 10 mg kg-1 i.v. on behaviour and EEG. Flumazenil had no antagonistic effect on sleep time induced by anaesthetic agents, but flumazenil 30 mg kg-1 potentiated propofol-induced anaesthesia. Flumazenil did not affect anaesthesia-induced EEG changes. Diazepam 5 mg kg-1 potentiated anaesthesia. Flumazenil antagonism of diazepam potentiation varied with anaesthetic agent: flumazenil 0.3 mg kg-1 antagonized diazepam action in halothane anaesthesia, but 30 mg kg-1 was required in propofol anaesthesia; this large dose was insufficient in thiamylal anaesthesia.

Anesthesia, Inhalation

Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery.

There is currently accumulating evidence for bidirectional communication between the neuroendocrine and immune systems. Various cytokines have been suggested to be involved in the stimulation of stress hormone secretion during the times of infection and inflammation. To assess the possible involvement and pathophysiologic significance of cytokines in the mechanisms responsible for the perioperative stress response of the hypothalamo-pituitary-adrenal axis, we observed the changes of plasma adrenocorticotropic hormone and cortisol levels together with those of plasma endotoxin and cytokine levels. In patients undergoing pancreatoduodenectomy, perioperative stimulation of adrenocorticotropic hormone and cortisol secretion was accompanied by a significant elevation of plasma cytokine levels. Application of epidural block up to the upper thoracic levels failed to suppress this stress response effectively. In patients undergoing unilateral total hip replacement, the response of plasma hormone levels was smaller and briefer with no significant increase of plasma cytokine levels. Application of epidural block up to the lower thoracic levels suppressed this hormonal response almost completely. In patients undergoing pancreatoduodenectomy, a significant elevation of plasma endotoxin level was followed by a gradual but significant elevation of plasma tumor necrosis factor alpha and interleukin-6 levels. It seems likely that the stimulatory effects of these cytokines on the secretion of adrenocorticotropic hormone and cortisol might be involved in the development of the greater and more prolonged stress response of hypothalamo-pituitary-adrenal axis. Our present study suggests that not only neural input from the surgical wound but also stimulation of cytokine production were responsible for the development of the stress response of the hypothalamo-pituitary-adrenal axis during and after upper abdominal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone