Search PubMed⌕ Search

Biomedical subjects

K Sakuma

Publications and source records attributed to K Sakuma.

At least 37 records · Page 2Linked to original sources

The adaptive response of transforming growth factor-beta 2 and -beta RII in the overloaded, regenerating and denervated muscles of rats.

Using a muscle cell line and satellite cell cultures, it has been shown that transforming growth factor-beta (TGF-beta) has a powerful inhibitory effect on myoblast replication and differentiation. However, little work has been done on the possible role of TGF-beta in adult muscle in vivo. Using Western blot and immunohistochemical analyses, we investigated normal distribution of TGF-beta 2 and TGF-beta RII proteins between slow and fast-type muscles, and the adaptive response of these proteins in the mechanically overloaded muscles, in the regenerating muscles following bupivacaine injection and in the denervated muscle after section of sciatic nerve. Slight TGF-beta 2 immunoreactivity was detected both in slow- and fast-type muscles of mature rat. The amount of TGF-beta RII protein was markedly greater in fast-type muscles. In the overloaded muscle, immunohistochemical analysis showed a marked increase in TGF-beta 2 immunoreactivity in the mononuclear cells (probably endothelial and perithelial or smooth muscle cells of endomysial capillaries) of the extracellular space at 3 and 6 days post surgery. Rapid increase of TGF-beta 2 protein and concomitant decrease of the receptor (TGF-beta RII) were observed in the mechanically overloaded and regenerating muscles. On the other hand, denervation of slow- and fast-type muscles showed a rapid increase in TGF-beta 2 protein, but did not elicit a concomitant decrease of TGF-beta RII. These results indicate that TGF-beta RII is preferentially distributed in fast-type muscles. Furthermore, TGF-beta 2 may play an important role in muscle hypertrophy and regeneration by the usage of TGF-beta RII.

Animals↗

Dietary short-chain fructooligosaccharides increase calbindin-D9k levels only in the large intestine in rats independent of dietary calcium deficiency or serum 1,25 dihydroxy vitamin D levels.

Dietary short-chain fructooligosaccharides (Sc-FOS) increase mucosal calbindin-D9k (CaBP) levels in the large intestine whereas levels in the small intestine are decreased in rats. In the present study, we investigated the mechanism by which Sc-FOS induce this increase in CaBP in the large intestine by measuring intestinal CaBP levels in rats fed normal and calcium-deficient diets. Dietary groups included a calcium-containing (0.5%) diet with or without Sc-FOS (100 g/kg diet) and a calcium-deficient (abt. 0.01%) diet with or without Sc-FOS (100 g/kg diet). The rats were fed these diets for 10 days following which they were killed and the intestine removed for collection of the entire mucosa which was divided into four segments, i.e., proximal and distal segments of the small intestine, the cecum and the colorectum. Mucosal CaBP and plasma calcium (Ca), 1,25-dihydroxycholecalciferol (1,25(OH)2D3), 25-hydroxycholecalciferol (25(OH)D3), parathyroid hormone (PTH) and calcitonin levels were measured. Feeding of calcium deficient diet resulted in an increase in CaBP levels in the small intestine, but did not influence levels in the large intestine. Moreover, a significant positive correlation between plasma 1,25(OH)2D3 and CaBP levels in the case of both small intestinal segments (proximal, r = 0.77012, p < 0.00007; distal, r = 0.75056, p < 0.00014) was observed, but not in the case of the large intestinal segments. Sc-FOS increased CaBP levels in the large intestine. These results suggest that the large intestinal CaBP levels do not change in response to dietary calcium conditions and are not regulated by circulating 1,25(OH)2D3 indicating that the effect of Sc-FOS on CaBP levels in the large intestine is independent of the action of 1,25(OH)2D3.

Animals↗

Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers.

A positive association between hyperuricemia and cardiovascular disease has been reported, but no study has evidenced yet the precise role of serum uric acid in the development of cardiovascular disease. In addition, no epidemiological studies have so far documented a decreased risk of cancer among people with hyperuricemia, even though the antioxidant action of uric acid has recently been stressed to inhibit DNA damage. The present prospective cohort study investigates the relationship between hyperuricemia and health hazards in a Japanese working population. The subjects were 49,413 Japanese male railroad workers, aged 25-60 years at enrollment. Serum uric acid and other baseline data were provided by annual health-survey records from 1975 to 1982. The vital status of the subjects was traced until the end of 1985 for those who remained alive. During an average 5.4-year study period, 984 deaths were recorded. Those with serum uric acid over 8.5 mg/dl showed elevated relative risks (RRs) of death in all causes (RR 1.62, p<0.01), coronary heart disease ( RR 1.52), stroke (RR 2.33, p<0.01), hepatic disease (RR 3.58, p<0.01), and renal failure ( RR 8.52, p<0.01), as compared with those with serum uric acid levels of 5.0-6.4mg/dl. The RR of death in all causes still remains statistically significant when adjusted by age and serum total cholesterol (2.00, p<0.01), age and alcohol intake (1.85, p<0.001), age and smoking (1.69, p<0.001), age and gout treatment (1.61, p<0.05), and also age and BMI (1.50, p< 0.05). On the other hand, the RR of all causes decreased but was still above 1.0 when adjusted by age and blood glucose (1.62), age and systolic blood pressure (1.32), age and GOT (1.23), and also age and history of cardiovascular disease (1.17). These results showed that hyperuricemia has a strong association with the RRs of death in all causes, coronary heart disease, stroke, hepatic disease and renal failure, and indicated that serum uric acid seems to be a considerable risk factor for reduced life expectancy.

Adult↗

[Recent surgical treatment for patients with true aortic arch aneurysm].

From december 1996 to april 1999, 25 patients with true aortic arch aneurysm underwent aortic arch aneurysm repair using selective cerebral perfusion. There were 17 males and 8 females ranging in age from 62 to 79 years (mean 71 years). Orikaesi method was used in the procedure of distal anastomosis for complete aortic arch replacement with a prosthetic graft. This technique allowed us a simple approach to the lesion and the easy additional stitch. The average duration of extracorporeal circulation, aortic crossclamping, selective cerebral perfusion were 269 minutes, 140 minutes, and 122 minutes, respectively, under 19.3 degrees C of lowest esophageal temperature. There were no cases complicated with postoperative low output syndrome and cerebrovascular accident, and no hospital mortality. Replacement of the aortic arch using selective cerebral perfusion is a safe procedure with acceptable hospital mortality.

Aged↗

The adaptive response of MyoD family proteins in overloaded, regenerating and denervated rat muscles.

Using Western blot analysis, we investigated whether the amount of myogenic regulatory factors differs in slow-type and fast-type muscles. In addition, we examined the adaptive response of myogenic regulatory factor protein in the overloaded rat muscles by the ablation of synergists, in the regenerating muscles following bupivacaine injection and in the denervated muscle. The amount of myogenin protein in the slow-type muscle was markedly greater. In contrast, the proteins MyoD and Myf-5 were selectively accumulated in the fast-type muscles. A gradual down-regulation of MyoD and Myf-5 proteins was detected in the denervated fast-type muscles, but not in the myogenin protein content. A rapid down-regulation of myogenic regulatory factor protein was observed both of the mechanically overloaded and in the regenerating muscles. These results indicate that the fast-type-specific gene expression in muscle is modulated by MyoD and Myf-5 proteins and suggest that myogenin protein plays an important role in the reconstruction of damaged neuromuscular connections.

Adaptation, Physiological↗

Frequency representation in the human hand somatosensory cortex: a reappraisal.

Frequency organization in the human primary somatosensory cortex (SI) was re-examined. Somatosensory evoked magnetic fields (SEFs) were measured with a 37 channel first-order axial gradiometer system. Sensory stimuli comprising a 20ms vibration at frequencies of 50, 100, 200 and 400 Hz were delivered to the volar surface of the tip of the right index finger. Using a single dipole model, the sources of the first main peak (M50) of SEFs were estimated. All of the sources were located in the 3b area. There were no statistically significant differences between the locations of the dipoles evoked by different frequency stimulations. These results support our previous study using a 122 channel whole head planar gradiometer system that systematic frequency organization at the hand area of SI cortex may not be present in humans.

Adult↗

High-frequency magnetic oscillations evoked by posterior tibial nerve stimulation.

Magnetocephalographic recordings of the primary somatosensory response (P37m) and high-frequency oscillations (HFOs) evoked by posterior tibial nerve stimulation were obtained in normal subjects. Electrical stimuli were delivered to the posterior tibial nerve and magnetic recordings were taken over the superior aspect of the left hemisphere with a 37-channel biomagnetometer. In order to separate the high-frequency oscillations from the underlying P37m, the wide-band (0.1-1200 Hz) recorded responses were digitally filtered with a 500-800 Hz band-pass filter. The localization of the HFOs were estimated to be in somatosensory area 3b, very close to the P37m source. Our data suggest that the HFOs are somatotopically arranged in the primary somatosensory cortex, and are a ubiquitous phenomenon of the primary somatosensory cortex.

Adult↗

Preoperative chemotherapy for advanced esophageal cancer and relation with histological effect.

The results of surgical treatment for advanced esophageal cancer remain extremely poor. Irradiation and chemotherapy are not superior to surgery. Perioperative morbidity and the influence on long-term survival of a combination of surgery and preoperative chemotherapy were investigated in patients with advanced esophageal cancer. Forty-nine patients with advanced esophageal squamous cell carcinoma were subjected to preoperative chemotherapy of cisplatin-5-fluorouracil. Fifty-seven patients were chosen as a historical control group who had not undergone chemotherapy before surgery but had the same histological stages as the chemotherapy group. The response to chemotherapy was assessed by histological studies of surgical specimens. The survival rates noted no significant difference between preoperative chemotherapy plus surgery and a resection alone. However, subclassification according to the grading of chemotherapeutic effectiveness showed that, compared with control, preoperative chemotherapy was beneficial to high responders (P = 0.01), ineffective in low responders (P = 0.61), and detrimental to nonresponders (P = 0.03). Postoperative morbidity was significantly higher in the chemotherapy group than in the control group (P = 0.02). These findings suggest that preoperative chemotherapy is necessary only for high responders and we therefore need to reliably identify non-, low, and high responders before chemotherapy to improve the survival and quality of life of patients with advanced esophageal cancer.

Actuarial Analysis↗

Relationship between tyrosinase inhibitory action and oxidation-reduction potential of cosmetic whitening ingredients and phenol derivatives.

The oxidation-reduction potentials of cosmetic raw materials, showing tyrosinase inhibitory action, and phenolic compounds structurally similar to L-tyrosine were determined by cyclic voltammetry. The voltammograms obtained could be classified into 4 patterns (patterns 1-4). Pattern 1, characterized by oxidation and reduction peaks as a pair, was observed with catechol, hydroquinone or phenol, and pattern 2 exhibiting another oxidation peak in addition to oxidation and reduction peaks as a pair was found with arbutin, kojic acid, resorcinol, methyl p-hydroxybenzoate and L-tyrosine as the substrate of tyrosinase. Pattern 3 with an independent oxidation peak only was expressed by L-ascorbic acid, and pattern 4 with a reduction peak only at high potentials, by hinokitiol. The tyrosinase inhibitory activity of these compounds was also evaluated using the 50% inhibitory concentration (IC50) and the inhibition constant (Ki) as parameters. Hinokitiol, classified as pattern 4, showed the highest inhibitory activity (lowest IC50 and Ki). Hydroquinone showing the second highest activity belonged to pattern 1, which also included compounds showing no inhibition of tyrosinase activity. The inhibitory activity of compounds exhibiting pattern 2 was relatively low with Ki values being in the order of 10(-4) M. Although there was no consistent relationship between oxidation-reduction potentials and tyrosinase inhibitory action, the voltammetry data can be used as an additional index to establish the relationship between the structure and the tyrosine inhibitory activity.

Cosmetics↗

Distal-proximal somatotopy in the human hand somatosensory cortex: a reappraisal.

The distal-proximal representation of the finger and palm in the first somatosensory cortex was reexamined. Somatosensory evoked magnetic fields (SEFs) were measured with a 37-channel first-order axial gradiometer system. Sensory stimulus comprising a 20-ms vibration at a frequency of 200 Hz was delivered to five successive sites in 3-cm increments along the distal-proximal direction over the volar surface of the right index finger and palm. Using a single dipole model, the sources and the signal strengths of the main peak (M50) of the SEFs were estimated. All of the sources were located in the 3b area. There were no statistically significant differences between the locations of dipoles evoked by stimulation of different sites. The results support those of our previous study using a 122-channel whole-head planar gradiometer system that orderly distal-proximal representation of the hand, as described in monkeys, is blurred in the adult human somatosensory cortex.

Adult↗

Cyclooxygenase (COX)-2 immunoreactivity and relationship to p53 and Ki-67 expression in colorectal cancer.

The tumor-suppressive effects of nonsteroidal antiinflammatory drugs (NSAIDs) have been suggested to be due to a reduction in cyclooxygenase (COX)-2 activity, although the effects of COX-2 in the colonic mucosa and in colorectal cancer have not been determined. Ki-67 immunoreactivity in cancers is also attracting attention, as Ki-67 reflects cell proliferation, while p53 immunoreactivity is also of interest, as it reflects the malignancy of colorectal lesions. Accordingly, to determine these correlation, we investigated the distribution and intensity of COX-2, p53 and Ki-67 expression in both cancerous and non-cancerous tissues from patients with sporadic and ulcerative colitis (UC)-associated colorectal cancer. We selected 21 colorectal cancer specimens, obtained by surgical resection or colonoscopic biopsy, from 21 patients, including 3 with UC (13 men and 8 women; aged 42-78 years). Histological examination of hematoxylin and eosin-stained specimens revealed that 9 were well differentiated; 11. moderately differentiated: and 1 was a poorly differentiated adenocarcinoma. We used anti-COX-2, p53, and Ki-67 antisera to perform immunohistochemical staining by the labelled streptavidin biotin method and then assessed and graded the staining intensity and distribution. COX-2 staining was more intense in cancer tissue than in non-cancerous areas. Colorectal cancers associated with UC were not stained intensely. COX-2, p53, and Ki-67 positivity rates in were 38.1%, 38.1%, and 47.6%, respectively. There were no relationships among the distributions or intensities of COX-2, p53, and Ki-67 expression. Our results indicate that colorectal cancer tissues overexpress COX-2, but that there are no relationships between COX-2, p53, and Ki-67 expression, suggesting that COX-2 expression may not be related to cell proliferation or to the grade of malignancy. However, it is necessary to determine whether COX-2 in cancer tissue is involved in carcinogenesis or whether it is simply a product of cancer.

Adult↗

Perforation of the sigmoid colon with ischemic change due to polyarteritis nodosa.

A 60-year-old man who developed a perforation of the sigmoid colon with ischemic change due to polyarteritis nodosa is described. Histological examination of the resected colon led to the diagnosis of polyarteritis nodosa. Although the gastrointestinal tract is frequently involved with polyarteritis nodosa, it is extremely rare for polyarteritis nodosa to be accompanied by a perforation of the colon, particularly at the initial presentation.

Adrenal Cortex Hormones↗

Reciprocal modulation of somatosensory evoked N20m primary response and high-frequency oscillations by interference stimulation.

OBJECTIVES: We examined whether the inverse relation between somatic evoked N20m primary response and high-frequency oscillations during a wake-sleep cycle (Hashimoto, I., Mashiko, T., Imada, T., Somatic evoked high-frequency magnetic oscillations reflect activity of inhibitory interneurons in the human somatosensory cortex, Electroenceph clin Neurophysiol 1996;100:189-203) holds for interference stimulation. METHODS: Somatosensory evoked fields (SEFs) from 14 subjects were measured following electric median nerve stimulation at the wrist with, and without, concurrent brushing of the palm and fingers. SEFs were recorded with a wide bandpass (0.1-1200 Hz) and then N20m and high-frequency oscillations were separated by subsequent low-pass (< 300 Hz) and high-pass (> 300 Hz) filtering. RESULTS: The N20m decreased dramatically in amplitude during interference stimulation. In contrast, the high-frequency oscillations moderately increased in number of peaks. CONCLUSIONS: These results demonstrate the presence of an inverse relation between N20m and high-frequency oscillations for interference stimulation. We speculate that the high-frequency oscillations represent a localized activity of GABAergic inhibitory interneurons of layer 4, characterized by a high-frequency spike burst (200-1000 Hz) without adaptation, and that the continuous interference stimulation induces tonic excitation of the interneurons, leading to a facilitation of responses to the coherent afferent volley elicited by the median nerve stimulation (bottom-up mechanism). On the other hand, refractoriness of the pyramidal neurons caused directly by interference stimulation along with an enhanced feed-forward inhibition from the interneurons will lead to a decrease of N20m amplitude.

Adult↗

Neural source estimation from a time-frequency component of somatic evoked high-frequency magnetic oscillations to posterior tibial nerve stimulation.

OBJECTIVE: High frequency oscillations (HFOs) evoked by posterior tibial nerve stimulation were recorded using magnetoencephalography (MEG). Time-frequency domain multiple signal classification (TF-MUSIC) algorithm was applied, and the usefulness of this method was demonstrated. METHODS: Ten normal subjects were studied. To localize sources for the HFOs of those somatosensory evoked fields, we applied two kinds of methods: the single moving dipole (SMD) method and the TF-MUSIC method. The SMD method was applied after digitally band-pass filtering the somatosensory response with a bandwidth of 500-800 Hz. To estimate the locations of sources with the TF-MUSIC algorithm, we first set the target region on the spectrogram of the somatosensory responses. Then, the procedure described in Section 2.2 was applied with this target region. RESULTS: A clear, isolated region was detected in 6 out of 10 subjects using a time-frequency spectrogram. The averaged distance of the dipole sources between the HFOs and the underlying P37m using the TF-MUSIC algorithm was smaller than using the SMD method. CONCLUSIONS: The TF-MUSIC algorithm is suitable for extracting a target response whose spectrum changes significantly during the observation.

Adult↗

Human mannose-binding lectin preferentially binds to human colon adenocarcinoma cell lines expressing high amount of Lewis A and Lewis B antigens.

The binding of human mannose-binding lectin (MBL) to human colon adenocarcinoma cell lines and leukemia cell lines was analyzed by flow cytometry using specific antibodies against MBL. MBL binding was observed in 3 of 7 colon adenocarcinoma cell lines (Colo205, Colo201 and DLD-1), but not in any of 3 leukemia cell lines tested. The binding of MBL to these cell lines was sugar-specific and calcium-dependent, since it was almost completely inhibited in the presence of 10 mM EDTA or 50 mM mannose. The MBL binding to Colo205 cells was more strongly reduced by the pretreatment of the cells with an O-linked glycosylation inhibitor, benzyl-2-acetamide-2-deoxy-alpha-galactopyranoside (Bz-alpha-GalNAc), rather than an N-linked glycosylation inhibitor, tunicamycin. The degree of MBL binding was well correlated with the expression of Lewis A and Lewis B antigens on these cell lines. Moreover, MBL binding to Colo205 cells was inhibited by anti-Lewis A and anti-Lewis B antibodies. These results suggest that MBL could bind to some human colon adenocarcinoma cell lines through their Lewis A and Lewis B moieties.

Adenocarcinoma↗

[Effect of Helicobacter pylori eradication from patients with gastritis evaluated by the pathological grading and cell proliferation related factors].

We used Image Analysis Processor to clarify the relation ship between cell proliferation, apoptosis and inflammation before and after eradication in H. pylori gastritis. Fifty-two patients with H. pylori gastritis were diagnosed using the Rapid Urease Test under endoscopical and histological examination. The grading of gastritis was determined by the Updated Sydney System. While the effects of Ki-67 on epithelial cell proliferation were examined by immunohistochemistry using Image Analysis Processor, and apoptosis in epithelial cells was counted after staining by in situ TDT. H. pylori density, the number of neutrophils, mononuclear cell, and number of lymphoid follicles had significantly decreased after eradication. Ki-67 labeling index significantly decreased from 11.74 percent to 0.98 percent after eradication (p < 0.0001). The apoptotic index had also decreased after eradication, but with a lack of significant difference (p < 0.06). These data suggest that H. pylori gastritis was remarkably ameliorated by eradication, have led to being capable of improving epithelial cell damage, and activity of proliferative cells and apoptotic cells were becoming normalization.

Apoptosis↗