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Biomedical subjects

K Shindo

Publications and source records attributed to K Shindo.

At least 109 records · Page 6Linked to original sources

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↗

Increased sympathetic outflow to muscles in patients with amyotrophic lateral sclerosis: a comparison with other neuromuscular patients.

We investigated the effects of muscle loss and limitation of daily activities on sympathetic outflow to muscles by measuring muscle sympathetic nerve activity (MSNA) in 12 patients with amyotrophic lateral sclerosis (ALS) as compared with other 15 neuromuscular patients (controls). The burst incidence of MSNA at rest was significantly higher in patients with ALS, even in elderly patients, compared with controls (p < 0.01). There were no differences in the level of disability, heart rate or blood pressure at rest between two groups. Blood pressure and MSNA were less changed by head-up tilting in patients with ALS compared with controls. MSNA of ALS was not correlated with the disability score, PaO2, PaCO2, forced vital capacity, the disease duration or prognosis. MSNA at rest was increased in ALS patients, regardless of the severity of muscle loss or disability. It might be suggested that autonomic motor neurons seem to become affected by the same pathologic process that kills motor neurons.

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↗

[A case of chronic progressive radiation myelopathy with cavity formation in the thoracic spinal cord].

A 70-year-old man was admitted to our hospital in March 1994 because of subacute progressive paraparesis and sensory impairment below the level of the second thoracic (TH 2) spinal cord on the right side. He had received radiation therapy (48 Gy) on his neck and mediastinum eight years previously due to adenocarcinoma of the right upper lung. Blood chemistry, CT of the spine, bone and gallium scintigraphy were unremarkable. In magnetic resonance imaging (MRI) of the thoracic cord, the gadolinium (Gd)-enhanced T1-weighted image showed abnormal signal intensities from Th 3 to Th 4 of the spine. Myelography revealed no abnormalities. Three months later, the patient became a complete spinal man below the level of Th 4. Gd-enhanced MRI of the thoracic cord, performed eleven months later, showed formation of a spindle-shaped cavity from Th 2 to Th 5 of the spine surrounded by a ring-shaped enhanced cord. Chronic progressive radiation myelopathy (CPRM) was diagnosed based on these clinical and MRI findings. This was a rare case in which MRI-confirmed cavity formation in the spinal cord appeared in a patient with CPRM.

Aged↗

[Muscle sympathetic nerve activity in patients with spinocerebellar degeneration without orthostatic hypotension].

Muscle sympathetic nerve activity (MSNA) was compared in 6 patients (age; 45-76 years old, 3 males and 3 females) with spinocerebellar degeneration (SCD) without orthostatic hypotension (OH) and in 10 (age; 38-78 years old, 3 males and 7 females) with other neurologic disorders (controls). MSNA was elicited from the peroneal nerve at the resting recumbent position by using a microneurographic method. MSNA, heart rate (HR) from the electrocardiogram and mean blood pressure (MBP) measured by Finapres were recorded simultaneously at rest and during the head-up tilting at 45 degrees. Although there were no significant differences in MBP and HR between both groups, burst rate (bursts per minute) and burst incidence (bursts per 100 heart beats) of MSNA in SCD patients were significantly decreased as compared with controls (p < 0.01). During the head-up tilting, responses in MBP and MSNA showed a tendency to decrease in SCD patients. We concluded that the sympathetic noradrenergic system might be potentially impaired in SCD patients without OH.

Aged↗

Captopril inhibits neutrophil synthesis of leukotriene B4 in vitro and in vivo.

The aim of this investigation was to determine the effects of metalloproteinase inhibitors on leukotriene (LT) A4 hydrolase in human neutrophil cytosol and to examine the effects of captopril on intact neutrophils in vitro and in vivo. Cytosolic fractions were assayed for LTA4 hydrolase and 5-lipoxygenase activity in the presence or absence of inhibitors. Only bestatin, 1,10-O-phenanthroline, captopril and fosinoprilat demonstrated significant effects. The IC50 of captopril and fosinoprilat for LTA4 hydrolase activity were 500 microM and 1 mM, respectively. No inhibition of 5-lipoxygenase activity in cytosolic fractions was detected. The effect of captopril was only minimally reversed by ZnSO4. The IC50 of captopril for inhibition of LTB4 synthesis in intact neutrophils was 63 microM. Furthermore, 5-HETE production in intact cells was diminished 25.3 +/- 8.5% in the presence of 1 mM captopril. Oral captopril inhibited stimulated LTB4 release by subsequently isolated neutrophils by 48.1 +/- 5.6% and 5-HETE release by 43.2 +/- 5.5%. Thus, captopril is an inhibitor of LTB4 synthesis in neutrophils in vitro and in vivo. However, there are differences between the potency of this drug as assessed in cytosol and intact cell studies. This study significantly extends previous reports in that it demonstrates that captopril is a more potent inhibitor of LTB4 synthesis in intact neutrophils than in cytosol and in that it demonstrates an inhibitory effect of captopril on synthesis of LTB4 by neutrophils exposed to captopril in vivo.

Arachidonate 5-Lipoxygenase↗

Complete remission of liver metastases from colorectal cancer by treatment with a hepatic artery infusion (HAI) of interleukin-2-based immunochemotherapy: reports of three cases.

In an attempt to improve the therapeutic efficacy against liver metastases, a hepatic arterial infusion (HAI) of interleukin-2 (IL-2)-based immunochemotherapy for anticipating the regional potentiation of hepatic lymphokine-activated killer (LAK)/tumor-infiltrating lymphocytes (TIL) was initiated. We present herein the cases of three patients with multiple liver metastases from colorectal cancer in whom complete remission was achieved by treatment with an HAI of IL-2 in combination with mitomycin C (MMC) and 5-fluorouracil (5-FU). These patients received an HAI of IL-2 at 8 x 10(5) JRU, 5-FU at 250 mg daily, and MMC at 4 mg once weekly for 3 weeks, being the induction regimen, after which they were discharged on maintenance therapy consisting of IL-2 at 2 x 10(6) JRU, 5-FU at 250 mg twice weekly, and MMC at 4 mg once weekly. It was evident from the liver CT scan taken after 2-3 months that the metastatic foci seen before therapy had clearly disappeared, while the serum carcinoembryonic antigen (CEA) had decreased to normal levels in all three patients. Pancytopenia was seen in one patient, but other laboratory studies of the hepatic and renal parameters were normal. The total lymphocyte count in the peripheral blood showed a mild decrease, while the lymphocyte phenotype study showed a notable increase in CD4+ cells and a decrease in CD8+ cells, with an elevation of a 4/8 ratio, in all cases during therapy. One patient relapsed with pelvic recurrence 14 months after the initiation of therapy, but the other two patients are still in remission 25 and 22 months after the initiation of therapy.

Antineoplastic Combined Chemotherapy Protocols↗

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↗

Generator mechanism of pain-related evoked potentials following CO2 laser stimulation of the hand: scalp topography and effect of predictive warning signal.

In order to clarify the generator mechanism of pain-related evoked potentials (pain EPs), we studied the scalp topography of the pain EPs following CO2 laser stimulation of hand dorsum by using balanced sternovertebral electrodes as the noncephalic reference in 11 normal volunteers. We also examined the effects of predictive warning signal (light-emitting diode) on the pain EPs. In both the warned and unwarned conditions, all of the 22 hand stimulations showed a large negative component (N2) at the peak latency of about 213 ms followed by a large positive component (P2) at the peak latency of about 329 ms. A preceding small negative component (N1) at the peak latency of about 148 ms was detected in 12 of the 22 hand stimulations in the warned condition and in 13 of the 22 hand stimulations in the unwarned condition. P2 was significantly larger and occurred earlier in the warned condition than in the unwarned condition, whereas other components did not differ between the two conditions, suggesting that an increased attention of the subject to the stimulus influenced the generator mechanism of the P2 component. With regards to the scalp topography, N2 was maximal at Cz and widespread transversely to both sides, whereas P2 was maximal at Cz or Pz and spread more posteriorly than N2. These findings suggest that P2 is generated by a different mechanism from N2 and is most likely associated with pain-related cognitive function. N1 was localized to the contralateral central and midtemporal areas, confirming that the nociceptive inputs are perceived in the sensory cortex in humans. The question as to whether the N1 component is generated in the hand area of the primary somatosensory cortex or in the secondary somatosensory cortex, or in both areas, remains to be solved.

Adult↗

Leukotriene A4 hydrolase in human bronchoalveolar lavage fluid.

We examined cell-free human bronchoalveolar lavage fluid (BALF) for enzymes of the 5-lipoxygenase pathway. BALF was obtained from six patients who were active smokers and six nonsmokers. Enzymatic activity in cell-free BALF was assessed by specific assays for leukotriene (LT) A4 hydrolase, 5-lipoxygenase, and LTC4 synthase using HPLC. Only LTA4 hydrolase enzymatic activity was found. This activity ranged from 101 to 667 when expressed as picomoles of LTB4 produced per milliliter BALF. Enzymatic activity in smokers vs nonsmokers was 484 +/- 120 vs 129 +/- 32 pmol LTB4/ml BALF (mean +/- SD, P < 0.0001). There were no leukotrienes found in BALF before assay. Immunoblot analysis revealed an immunoreactive band at a relative molecular mass of 69,000 D in all samples, consistent with LTA4 hydrolase, but no evidence of 5-lipoxygenase. BALF had greater LTA4 hydrolase activity per milligram of protein than neutrophil cytosol, epithelial cell cytosol, plasma, or serum. The synthesis of LTB4 was significantly increased when neutrophils were stimulated in BALF. These data indicate the selective presence of LTA4 hydrolase in BALF which is significantly increased in smokers. This enzyme in BALF may contribute to the inflammatory response in tobacco-related lung disease.

Adult↗