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Biomedical subjects

M Kaneko

Publications and source records attributed to M Kaneko.

At least 217 records · Page 12Linked to original sources

Complete resection is not required in patients with neuroblastoma under 1 year of age.

BACKGROUND/PURPOSE: The prognosis of neuroblastoma (NB) patients when detected before 1 year of age is excellent, particularly in patients whose disease is detected by screening. In some institutions patients with stage I or II NB detected by screening have been observed closely without any treatment. Most showed tumor regression or maturation and are surviving without tumor resection. Resection of infantile NB sometimes is complicated by vascular accidents resulting in vanishing kidney or intestinal infarction. The role of surgery in the treatment of infantile NB therefore is becoming controversial. The authors have treated infants who have easily resectable primary tumors with resection and sampling for lymph node metastases. If the resection of the primary tumor seemed difficult, only biopsy was performed initially followed by chemotherapy with or without resection. The authors analyzed the clinical outcome of the infantile NB in their institution to elucidate the role of surgery in this particular group of patients. METHODS: Thirty-six patients less than 12 months of age were treated between 1982 and 1997. Twenty-five patients who showed no symptoms had NB detected by screening at 6 months. Five patients had stage IVS disease in early infancy. No patients had bone or remote lymph node metastases. N-mycamplification was not detected in any of the 28 tumors examined. There were four diploid and 12 near-triploid tumors. RESULTS: Complete resection was possible in 13 stage I and II patients without any complications. Obvious lymph node metastases were not resected in 13 patients with stage II or III NB. Partial resection leaving gross residual disease was accomplished in three patients with stage III NB. Surgical resection was not attempted in four patients because of unresectability in three patients with stage III or IVS disease and because of marked tumor shrinkage after a short course of chemotherapy in one patient with stage III NB involving the celiac axis. A neonatal cervicomediastinal stage III NB recurred very rapidly after partial resection but started to regress spontaneously 2 months postoperatively. Another neonatal stage II cervical NB progressed to stage IVS with hepatomegaly causing respiratory distress but regressed spontaneously. All the patients are alive and disease free without surgical morbidity. CONCLUSION: All of the 21 patients who underwent partial tumor resection with or without chemotherapy are alive and doing well without tumor, indicating that complete resection is not required in this particular group of patients.

Age Factors↗

Inhibitory effects of tyrosine kinase inhibitors on capacitative Ca2+ entry in rat glioma C6 cells.

The effects of genistein and erbstatin analogue, inhibitors of tyrosine kinase, on Ca2+ mobilization evoked by thapsigargin (TG) were examined in rat glioma C6 cells. Genistein and erbstatin analogue inhibited the Ca2+ release from intracellular pools as well as Ca2+ entry from extracellular medium evoked by TG in a dose-dependent manner. However, they did not affect a Ca2+ entry due to leakage of Ca2+ from extracellular medium into cells. The present results suggest that tyrosine kinase inhibitors inhibit capacitative Ca2+ entry due to the inhibition of both Ca2+ entry itself and Ca2+ release in rat glioma C6 cells.

Animals↗

Switch of osteonectin and osteopontin mRNA expression in the process of cartilage-to-bone transition during fracture repair.

The process of cartilage-to-bone transition (CBT) is a key event for the achievement of rigid bone healing during fracture repair. Since mineralization of cartilaginous matrix is a prerequisite for the initiation of CBT, the genetic localization of mineralization-related bone matrix proteins in CBT was examined in this study. An in situ hybridization method used on decalcified sections with digoxigenin-11-UTP labelled probes identified the cellular localizations of these genes in CBT. Cessation of osteonectin mRNA together with induction of osteopontin mRNA in chondrocyte maturation was observed during the process of CBT in the fracture callus on day 12 after fracture; osteocalcin mRNA was absent in chondrocytes of the CBT area. Induction of osteopontin mRNA in maturated chondrocytes was followed by the expression of mRNAs for osteonectin, osteopontin and osteocalcin in osteogenic cells in the ossification front of CBT. The data suggest that the switch from osteonectin to osteopontin mRNA expression in chondrocyte maturation is one of the key events during CBT. Transcriptional disorders of the expression of these molecules may be linked to the failure of fracture repair, i.e. delayed or prevented hypertrophic osteosynthesis.

Animals↗

Sensory impairments in spinal multiple sclerosis: a combined clinical, magnetic resonance imaging and somatosensory evoked potential study.

Thirty-one cases (26 patients) of clinically definite multiple sclerosis with predominant spinal cord involvement were studied retrospectively, focusing in particular on the results of sensory testings which were compared with the findings of spinal cord magnetic resonance imaging (MRI) and somatosensory evoked potentials (SEPs). Factor analysis of the sensory impairments showed two factors corresponding to superficial (pain and light-touch) and deep (position and 'thumb/big toe localizing') sensations. Vibratory sense depended on both factors, but more on deep sensations. Multiple regression analysis of the SEP abnormalities and sensory deficits showed that impaired deep sensations contributed to abnormal SEPs, but the results of clinical sensory testings and SEPs were dissociated in 31% of the extremities examined. The MRI sagittal images correlated well with the levels of sensory impairments, whereas the axial images showed a poor relationship to the extent of sensory impairments. We concluded that the use of SEPs as well as MRI is not always superior to such clinical sensory tests as the 'thumb/big toe localizing tests'.

Adolescent↗

Characterization of leukemic cells in CD2/CD19 double positive acute lymphoblastic leukemia.

In the diagnosis of leukemia, CD2 which is a T-cell associated marker and CD19 which is a B-cell associated marker are widely used to determine the lineage of leukemic cells. It is known that the cells of acute lymphoblastic leukemia (ALL) express both CD2 and CD19 in some cases. The origins of these cells are generally thought to be a common precursor for T- and B-lymphocytes. However, cytoplasmic staining of CD3 which is a more specific marker for T-lineage and cytoplasmic staining of mb-1 (CD79a) which is more specific for B-lineage were not performed in previous reports and the determination of the cell lineages of these cells was unclear. We had two cases of ALL whose blasts were CD2/CD19 double positive. The first case was assessed as B-lineage because the cells expressed cytoplasmic CD79a and lacked cytoplasmic CD3. The immunoglobulin (Ig) heavy chain gene was rearranged. The other cell surface markers including CD22 and HLA-DR also suggested that these cells were B-lineage. The CD2 expression may be a coincidence and should not be taken as a T-cell marker in this case. It was difficult to determine the lineage in the second case because both cytoplasmic CD79a and cytoplasmic CD3 were expressed and neither TCR beta chain nor Ig heavy chain genes were rearranged. The other surface markers were not useful to determine the lineage. We concluded that this case was really an unclassified ALL. Accordingly, cytoplasmic staining of CD3 and CD79a should be carried out in the diagnosis of leukemia when it is difficult to determine the cell lineage.

Adolescent↗

Neural substrates of Drosophila rhythms revealed by mutants and molecular manipulations.

In the fruit-fly Drosophila, rhythmic expression of the clock gene period is detected in cells throughout the body. Whereas these cells could be pacemakers for circadian rhythms of unknown physiological processes, the brain pacemakers are known to be responsible for circadian behavior. Recent progress in genetic and molecular studies of clock genes in Drosophila has permitted the identification of brain pacemakers at the cellular level and their output pathways to rhythmic behavior. Similar studies in other insect species have suggested considerable diversity in the anatomical and neurochemical properties of pacemaker cells, as well as in the mechanisms of clock-gene regulation.

Animals↗

Biologically active oligodeoxyribonucleotides. Part 11: The least phosphate-modification of quadruplex-forming hexadeoxyribonucleotide TGGGAG, bearing 3-and 5-end-modification, with anti-HIV-1 activity.

We have found that a hexadeoxyribonucleotide (5'TGGGAG3', R-95288), Koizumi, M. et al. Bioorganic & Medicinal Chemistry, 1997, 5, 2235, bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5'-end and a 2-hydroxyethylphosphate at the 3'-end, has high anti-HIV-1 activity and the least cytotoxicity in vitro and in vivo. In order to synthesize more potent hexadeoxyribonucleotides, we substituted phosphodiester (P-O) bonds in the 6-mer with the least phosphorothioate (P-S), phosphoramidate (P-N), or methylphosphonate (P-Me) bonds. When more than two P-N or P-Me bonds were introduced into a 6-mer, the phosphate-modified 6-mers had weak or no anti-HIV- activity, in spite of quadruplex structure formation. However, when P-S bonds were substituted for P-O bonds, anti-HIV-1 activity of their 6-mers did not dramatically decrease, compared with compounds substituted with P-N or P-Me bonds. The results suggest that the formation of a quadruplex structure is not always sufficient for anti-HIV-1 activity of the 6-mer, and that net negative charges derived from P-O or P-S bonds in the quadruplex are important for anti-HIV-1 activity. Moreover, among various phosphate-modified ODNs, we found that the anti-HIV-1 activity of ODN PS7 with only one P-S bond was the same as that of R-95288, both having a high stability in human plasma.

Anti-HIV Agents↗

Microradiographic and microscopic investigation of a rare case of complex odontoma.

An extremely rare case of odontoma that erupted into the oral cavity is presented. The lesion was surgically removed from a 14-year-old girl and examined by soft x-ray radiography, microradiography, and microscopy to determine whether the lesion was complex or compound. Macroscopically, the surface of the lesion was slightly lobular and solid, resembling the surface of an osteoma. The soft x-ray radiograph obtained from the surgical specimen showed radially arranged radiopaque spicules. Microradiographically, dentin was shown to be present in relatively large quantities and to form the bulk of the tumor, with irregular enamel and cementum in small quantities. There were numerous, comparatively well-formed, enamel-free, toothlike structures in the peripheral region of the tumor. Microscopically, the toothlike structures were seen to be arranged radially; this corresponded to the microradiographic findings. Each structure consisted of a central core of pulp tissue encased in a shell of dentin. In the central area of the mass, there was an irregular conglomerate of dentin, enamel, cementum, and pulp tissue. The findings showed that the lesion was a complex odontoma.

Adolescent↗

Scintigraphic evaluation of long-term salivary function after bilateral whole parotid gland irradiation in radiotherapy for head and neck tumour.

In 25 patients with head and neck tumour, in whom bilateral whole parotid glands were totally included in the irradiation volume, parotid gland function was estimated and compared with that of 58 non-irradiated parotid glands in 29 patients, by symptomatic grading and radioisotope (RI) sialography. Sequential follow-up by RI sialography has suggested that if the total dose to the parotid gland is less than 52 Gy or if the time-dose fractionation (TDF) value is less than 80, then partial recovery of salivary function can be expected 1 or 2 years after irradiation, even if patients show severe xerostomia during the first 6 months. Long-term recovery rarely occurs in parotid glands which have been irradiated at doses exceeding 55 Gy or with TDF values of 88 or higher. The 50% complication probability (ED50) was less than 33 Gy for subacute xerostomia during the first 6 months and 52.5 Gy for chronic xerostomia after 12 months, respectively. Although a prospective study will be required for confirmation, differences between the dose-response curves of xerostomia at subacute and chronic phases suggest a basis in different biological mechanisms.

Acute Disease↗

Moesin and CD44 expression in cutaneous melanocytic tumours.

The ERM (ezrin, radixin and moesin) family members, located just beneath the plasma membranes, are thought to be involved in the association of action filaments with the plasma membrane. One of the family members, moesin, is reported to bind to CD44. Splice variants of CD44 are thought to be associated with tumour progression or differentiation. Our aim was to investigate immunohistochemically the expression of moesin together with CD44 on paraffin tissue sections of a series of melanocytic tumours. The material included 12 ordinary melanocytic naevi, six Spitz naevi, eight dysplastic naevi, six blue naevi, seven malignant melanomas in situ, 15 primary malignant melanomas, five metastatic melanomas to the skin and five lymph node metastases. In the normal skin and the melanocytic tumours the expression of moesin was largely similar to that of CD44 standard. Strong moesin staining was observed in benign melanocytic lesions and melanomas in situ. However, the expression was decreased in advanced malignant melanomas. The moesin labelling in melanoma cells was downregulated with the depth of dermal invasion. The immunoreactivity was also diminished in the skin metastases and the lymph node metastases of melanoma. These results suggest that in melanocytic tumours, the alternation in the expression of moesin may be involved in the progression of malignancy.

Adult↗

Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts.

Pirfenidone has been shown to modify some cytokine regulatory actions and inhibit fibroblast biochemical reactions resulting in inhibition of proliferation and collagen matrix synthesis by fibroblast. We have investigated the effect of pirfenidone on the expression of cell adhesion molecules. The synovial fibroblasts were treated with IL-1alpha in the presence or absence of pirfenidone (range 0-1000 microM), and assayed for the expression of adhesion molecules such as ICAM-1 and endothelial-leucocyte adhesion molecule-1 (E-selectin) by cell ELISA. Pirfenidone significantly down-regulated the expression of ICAM-1 on cultured synovial fibroblasts in a dose-dependent manner. In contrast, expression of E-selectin was not affected. Furthermore, we examined whether pirfenidone affects the cellular binding between cultured lymphocytes and IL-1alpha-stimulated synovial fibroblasts by in vitro binding assay and found their mutual binding was significantly suppressed in a dose-dependent manner by pirfenidone. It is speculated that down-regulation of ICAM-1 might be one of the novel mechanisms of action of pirfenidone. These data indicate a novel mechanism of action for pirfenidone to reduce the activation of synovial fibroblasts.

Anti-Inflammatory Agents, Non-Steroidal↗

Genetic variation and population structure of the Japanese sika deer (Cervus nippon) in Hokkaido Island, based on mitochondrial D-loop sequences.

Mitochondrial DNA (mtDNA) D-loop region sequences (602 bp) from 141 samples of the sika deer Cervus nippon collected from Hokkaido Island of Japan were investigated to elucidate population genetic structure. All animals possessed seven repeat units (38 or 39 bp each) in the sequences. Comparison of the 602-bp sequences showed four sites of transitional mutations (A<-->G or C<-->T). Based on combination of the substitutions, six D-loop haplotypes (a-f types) were identified in the Hokkaido population, suggesting the occurrence of at least six maternal lineages. Distribution maps of the haplotypes constructed using the Geographic Information System showed that the distribution of the major three types differed from haplotype to haplotype. In particular, distribution of the major three types (a-, b-, and c-types) almost overlapped with three main areas of coniferous forests in Hokkaido. These results suggest that expansion of the sika deer population could have occurred through the habitat of coniferous forests after the historical bottleneck in Hokkaido.

Animals↗

Comparison of umbilical artery Doppler velocimetry between maternal supine position and complete left lateral position in predicting obstetric complications.

The aim of this study was to compare the predictive value of umbilical artery Doppler velocimetry in women in the supine position with that in women in the complete left lateral position as a screening test for abnormal obstetric outcomes. Umbilical artery resistance index (RI) was measured at 27-29 weeks and 35-37 weeks in 202 pregnant women. The measurements were performed with the mother in the supine position in 100 cases (supine group), and in the complete left lateral position in 102 cases (lateral group). Predictive values of the tests for abnormal outcomes (small for gestational age, fetal distress, pregnancy-induced hypertension) were compared between both groups. When abnormal RIs were defined as being greater than the 90th centile in the supine group, the sensitivities for any of the abnormal outcomes at 27-29 weeks were 18% in the supine group and 6% in the lateral group; the positive predictive values were 30% and 25%, respectively. For measurement at 35-37 weeks, the sensitivity and positive predictive value were 29% and 45%, respectively in the supine group, and 0% in both cases in the lateral group. When abnormal RIs were defined as being greater than the 90th centile in the lateral group, the sensitivities at 27-29 weeks were 41% in the supine group and 6% in the lateral group; the positive predictive values were 44% and 8%, respectively. At 35-37 weeks, the sensitivity and positive predictive value were 53% and 43% in the supine group, and 6% and 8% in the lateral group. Umbilical artery Doppler velocimetry when the mother was in the complete left lateral position was of little value as a screening test. However, when the mother is in the supine position, it may serve as a kind of stress test and disclose latent obstetric abnormalities in certain cases.

Adult↗

Therapeutic apheresis for septic patients with organ dysfunction: hemoperfusion using a polymyxin B immobilized column.

A prospective clinical study was performed to evaluate a new method of treatment of endotoxin shock, a column containing polystyrene fibers with covalently bound immobile polymyxin B. Direct hemoperfusion using the column removes circulating endotoxin by adsorption. All of the patients studied, 37 in the treatment group and 33 in the control group, had endotoxemia and failure of 1 or more organs. The perfusion was performed 1-7 times per patient, 2 h/session. The survival rate was significantly higher in the treatment group (54%) than in the controls (36.4%). The mean plasma endotoxin concentration was significantly lowered by the treatment from 83.7 pg/ml before perfusion to 56.4 pg/ml immediately after and 28.5 pg/ml the day after the treatment, and the posttreatment level was much lower in those who survived (mean, 18.8 pg/ml) compared to those who died (mean, 88 pg/ml). Various parameters of cardiac function also improved after the treatment.

Adolescent↗

MR and CT cholangiography in evaluation of the biliary tract.

OBJECTIVE: To compare MR and CT cholangiography (MRC and CTC) in evaluating the anatomy of the extrahepatic biliary tract and the pathology related to the gallbladder. MATERIAL AND METHODS: Twenty-three patients underwent MRC and CTC with a biliary contrast medium for investigation of biliary disease. 3D displays of both were also obtained. Endoscopic retrograde cholangiography was performed in 17 patients, and the pathology of all 23 was evaluated. RESULTS: Overall, the image quality was higher with CTC than with MRC (4.7 vs 3.9, p < 0.05). The cystic duct was demonstrated better by CTC than MRC (p < 0.05). Multiplanar reformation (MPR) and source images provided additional information to that obtained from 3D MRC and CTC images. Gallstones were revealed in 6 patients by CTC and in 5 of these 6 by MRC. In 2 patients with cholecystitis, CTC demonstrated gallbladder wall thickening but MRC did not. In 3 patients with adenomyomatosis. MRC demonstrated Rokitansky-Aschoff sinuses (RAS) while CTC demonstrated focal gallbladder wall thickening in all 3 and RAS in 1 of them. CONCLUSION: Both MRC and CTC provided anatomical and pathological information about the biliary system. With both techniques, however, either MPR or source images proved necessary in addition for evaluating the biliary system anatomy and pathology. The gallbladder wall was depicted clearly in source CTC, but MRC is recommended for the evaluation of adenomyomatosis because it depicts RAS clearly.

Adult↗

Interaction of intrathecally infused morphine and lidocaine in rats (part I): synergistic antinociceptive effects.

BACKGROUND: Synergistic antinociception of opioids and local anesthetics has been established in bolus injections but not in long-term use. The somatic and visceral antinociceptive effects of intrathecally infused morphine or lidocaine were characterized, and the nature of the interaction of those agents in rats was evaluated. METHODS: Intrathecal catheters were implanted in rats. Morphine (0.3 to 10 microg x kg(-1) x h(-1)), lidocaine (30-1,000 microg x kg(-1) x h(-1)), a combination of those, or saline was infused intrathecally at a constant rate of 1 microl/h for 6 days. The tail flick and colorectal distension tests were used to measure the somatic and visceral antinociceptive effects, respectively. Nociceptive tests and motor function tests were repeated on days 1, 2, 3, 4, and 6. Isobolographic analysis was performed on the results of the tail flick test to determine the magnitude of the interaction. RESULTS: Intrathecally infused morphine produced dose-dependent antinociceptive effects in both the tail flick and the colorectal distension tests. Morphine showed a lower peak percentage maximum possible effect (%MPE) in the colorectal distension test than in the tail flick test. Intrathecal lidocaine also produced dose-dependent antinociceptive effects. Lidocaine infusion at 1,000 microg x kg(-1) x h(-1) caused motor impairment. Coinfusion of morphine 0.3 microg x kg(-1) x h(-1) and lidocaine 200 microg x kg(-1) x h(-1), which had no effects by themselves, significantly increased the percentage maximum possible effects (P < 0.01). Coinfused lidocaine potentiated the duration and the magnitude of morphine antinociception. Isobolographic analysis of the tail flick test on day 1 showed a synergistic interaction between morphine and lidocaine. CONCLUSIONS: Morphine and lidocaine intrathecally coadministered synergistically potentiated the antinociceptive effects of each other. That coinfusion dramatically potentiated visceral antinociception, whereas the infusion of morphine alone showed little visceral antinociception.

Analgesics↗