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K Takei

Publications and source records attributed to K Takei.

At least 19 recordsLinked to original sources
PubMed2000

A functional link between dynamin and the actin cytoskeleton at podosomes.

Cell transformation by Rous sarcoma virus results in a dramatic change of adhesion structures with the substratum. Adhesion plaques are replaced by dot-like attachment sites called podosomes. Podosomes are also found constitutively in motile nontransformed cells such as leukocytes, macrophages, and osteoclasts. They are represented by columnar arrays of actin which are perpendicular to the substratum and contain tubular invaginations of the plasma membrane. Given the similarity of these tubules to those generated by dynamin around a variety of membrane templates, we investigated whether dynamin is present at podosomes. Immunoreactivities for dynamin 2 and for the dynamin 2-binding protein endophilin 2 (SH3P8) were detected at podosomes of transformed cells and osteoclasts. Furthermore, GFP wild-type dynamin 2aa was targeted to podosomes. As shown by fluorescence recovery after photobleaching, GFP-dynamin 2aa and GFP-actin had a very rapid and similar turnover at podosomes. Expression of the GFP-dynamin 2aa(G273D) abolished podosomes while GFP-dynamin(K44A) was targeted to podosomes but delayed actin turnover. These data demonstrate a functional link between a member of the dynamin family and actin at attachment sites between cells and the substratum.

Actins↗
PubMed2000

Nuclear cyclin D1 overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis.

Cyclin D1 overexpression is remarkably frequent in several human carcinomas and is believed to be a critical event in oncogenesis. We examined cyclin D1 expression, p53 expression, and the Ki-67 labeling index by immunostaining in human gallbladder mucosa in conditions varying from normal to malignant tissue. We also examined K-ras codon 12 mutations in these tissues with a two-step polymerase chain reaction. Nuclear cyclin D1 overexpression was observed in 48% of carcinomas occurring independently of adenoma, but not in adenomas, carcinomas arising in adenomas, or nonneoplastic lesions. Cytoplasmic cyclin D1 overexpression was observed in about 15% of abnormal specimens, irrespective of the type of epithelial abnormality. Carcinomas showing nuclear cyclin D1 overexpression had significantly higher Ki-67 labeling indexes than those with no overexpression. Moderately to poorly differentiated adenocarcinomas showed a higher incidence of nuclear cyclin D1 overexpression than papillary to well differentiated carcinomas. Specimens with cyclin D1 overexpression showed a high incidence of lymph permeation, venous permeation, and lymph node metastasis. We conclude that nuclear cyclin D1 overexpression is a critical event importantly associated with cell proliferation and invasive growth in gallbladder carcinogenesis, and that cyclin D1 immunostaining may become a useful marker for evaluating gallbladder carcinomas.

Adenocarcinoma↗
PubMed2000

Videokeratography after excimer laser in situ keratomileusis for myopia.

OBJECTIVE: The purpose of this study was to define qualitative patterns of videokeratography after excimer laser in situ keratomileusis (LASIK) for myopia and to identify associations of videokeratography patterns with clinical variables. DESIGN: Single-center, retrospective, cohort study. PARTICIPANTS: One hundred twenty-six eyes of 68 patients with myopia who desired surgical correction of myopia ranging from -1.50 to -8.80 diopters. INTERVENTION: Myopia was corrected with LASIK using a Summit OmniMed/Apex excimer laser. Computer-assisted videokeratography data were acquired at 3 months after primary LASIK, and associations of videokeratography pattern with clinical variable were assessed. MAIN OUTCOME MEASURES: Seven subgroup ablation zone patterns were characterized using tangential curvature maps; these subgroups were combined into pooled symmetric and asymmetric groups. Associations with age, attempted correction, single-zone or multizone ablation, postoperative uncorrected and spectacle-corrected visual acuity, predictability, astigmatism, corneal uniformity, glare disability, and contrast sensitivity were analyzed. RESULTS: Thirty-two eyes (25.4%) showed a uniform pattern, 14 eyes (11.1%) showed a bow-tie pattern, 22 eyes (17.5%) showed a peninsula pattern, 22 eyes (17.5%) showed a semicircular pattern, 22 eyes (17.5%) showed an off-center blue spot pattern, 10 eyes (7.9%) showed an irregular pattern, and 4 eyes (3.2%) showed a central island pattern. Spectacle-corrected visual acuity, astigmatism, corneal uniformity, glare disability, and contrast sensitivity were significantly related to videokeratography pattern, although the difference among videokeratography groups was clinically small. Age, attempted correction, single- or multizone ablation, and postoperative uncorrected visual acuity and predictability were not predictive of videokeratography pattern. CONCLUSIONS: Most eyes in this study had an asymmetric videokeratography pattern 3 months after LASIK. Small but statistically significant differences were identified among the videokeratography patterns that potentially may affect postoperative quality of vision.

Adolescent↗
PubMed2000

Allelic imbalance on chromosome 18 in neuroblastoma.

We previously demonstrated that chromosome 18 is frequently deleted in neuroblastoma. To further elucidate the role of chromosome 18 deletions in the development of neuroblastomas we examined 82 cases of neuroblastomas for allelic imbalance (AI) at 17 loci on chromosome 18 to define the common region of AI in neuroblastoma. AI at one or more loci on chromosome 18 was detected in 18/82 (22%) cases. AI on 18q was detected in 17/82 (21%) cases, whereas AI on 18p was detected in 4/82 (5%) cases. There was a distinct common region of AI at 18q21.1 between the D18S363 and D18S858 loci. In addition, cases 16 and 53, which did not show AI at 18q21.1, showed AI at 18pter-q12.3 between the D18S52 and D18S36 loci, indicating that another common region of AI may exist on chromosome 18. AI on chromosome 18 did not significantly correlate with any clinicopathological findings of patients with neuroblastoma. The common region of AI at 18q21.1 includes the DCC gene but not the Smad2 and Smad4 genes. However, our previous studies together with the present study indicated that the incidence of DCC mutation is much less than that of AI at 18q21.1 in neuroblastoma. These results indicate that novel tumour suppressor genes involved in the development of neuroblastoma are present at 18q21.1, and possibly at 18pter-q12.3.

Blotting, Southern↗
PubMed2000

Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders.

Omenn syndrome was recently found to be caused by missense mutations in RAG1 or RAG2 gene that result in partial V(D)J recombination activity. Although the clinical hallmarks of the disease are well defined, there have been several cases with clinical findings similar to, but distinct from Omenn syndrome. The data on immune functions and RAG gene mutations of such cases are limited. We described five Japanese infants from four unrelated families, including two cases of Omenn syndrome and three cases of related disorders. Sibling cases with typical Omenn phenotype were found to be compound heterozygotes of R396C and L885R mutations in RAG1. The former has been reported in European cases and may constitute a hot spot. The latter is a novel missense mutation. Infants with related disorders exhibited erythroderma, eosinophilia, hypogammaglobulinaemia, decreased number of B cells and skewing to Th2, and their lymph node specimens showed architectural effacement, lymphocyte depletion and histiocytic hyperplasia, each of which is seen characteristically in Omenn syndrome. However, in these cases serum IgE levels were low or undetectable. We found no mutation in RAG genes except for a K820R substitution in RAG1, which was regarded to be a functional polymorphism, in two of these cases. Our study suggests that RAG missense mutation may be a genetic abnormality unique to Omenn syndrome with characteristic clinical and laboratory findings. Variations of Omenn syndrome, or related disorders, may represent a different type of immunodeficiency, distinct from abnormalities in lymphoid-specific recombinase activity.

Apoptosis↗
PubMed2000

Detection of telomerase activity in biopsy specimens for diagnosis of biliary tract cancers.

BACKGROUND: Telomerase activity is detectable in more than 85% of primary cancers. We determined telomerase activity in biopsy specimens obtained from biliary tract cancers to evaluate the clinical application of telomerase activity detection in combination with p53 immunostaining and routine histologic examination. METHODS: Biopsy specimens obtained during percutaneous transhepatic cholangioscopy from 13 patients with cholangiocarcinoma, 3 patients with gallbladder carcinoma, and 4 patients with intrahepatic bile duct stones were evaluated by routine histologic examination, p53 immunostaining, and telomerase activity. Semiquantitative determination of telomerase activity was performed using a fluorescence-based telomeric repeat amplification protocol. RESULTS: Thirteen of 16 specimens of malignant tissue had detectable telomerase activity, whereas no specimen of nonmalignant tissue had detectable telomerase activity. A p53 overexpression was recognized by immunostaining in 9 of 16 samples with cancers. Combining both telomerase activity and p53 overexpression resulted in the detection of all cancer with a sensitivity of 100%. There were no false-positive results by either modality (specificity 100%). CONCLUSIONS: The detection of telomerase activity in biopsy specimens and p53 overexpression in combination with routine histologic examination may improve the diagnosis of biliary tract cancers. (Gastrointest Endosc 2000;52:380-6).

Aged↗
PubMed2000

Histopathologic and immunohistochemical studies on the mechanism of interlobular fibrosis of the pancreas.

OBJECTIVE: To elucidate the mechanism of interlobular fibrosis of the pancreas, which is categorized as chronic alcoholic pancreatitis. METHODS: Forty pancreatic tissue samples from patients with ampullary carcinomas, which cause various degrees of stricture of the main pancreatic duct, and 20 patients with chronic alcoholic pancreatitis were studied histopathologically and immunohistochemically. RESULTS: Fibrosis was observed in 23 of 40 patients with ampullary carcinomas and was classified into 3 categories: mild changes (10 cases), moderate changes (9 cases), and marked changes (4 cases). In the mild change cases, mild fibrosis was diffusely distributed in the interlobular areas, with scant immunoreactivity of anti-alpha-smooth muscle actin (alpha-SMA) and an expansive lobular appearance, whereas moderate and marked change cases showed interlobular and intralobular fibrosis with marked anti-alpha-SMA immunoreactivity and lobular atrophy. By quantitative analysis, the mild change cases showed both higher MIB1-positive and lower apoptotic acinar cell ratios than those of moderate and marked changes. Anti-alpha-SMA immunoreactivity in the patients with chronic alcoholic pancreatitis was found in interlobular fibrosis. Hence, mild changes in cases of ampullary carcinomas had histologic findings similar to chronic alcoholic pancreatitis, except for excessive fibrosis cases with patchy distribution. CONCLUSION: Incomplete obstruction of the main pancreatic duct caused the beginning of interlobular fibrosis, which is categorized as chronic alcoholic pancreatitis.

Actins↗
PubMed2000

[Acute myocardial infarction in elderly patients: medical and social problems].

The number of elderly patients with acute myocardial infarction has been increasing. However, the choice of treatment remains controversial. Medical records of 310 consecutive patients with acute myocardial infarction were reviewed. Two retrospective analyses were performed. 1) Patients were divided into the elderly group(70 years or more) and the younger group(under 70 years). In-hospital course and outcome were compared. 2) Pre-hospital performance status and living status were reviewed in the elderly group. Acute phase reperfusion therapy was performed in fewer patients in the elderly group(60.8% vs 71.9%, p < 0.01). The difference was most pronounced in cases of direct coronary angioplasty(28.6% vs 54.7%, p < 0.05). As a result, the rate of reperfusion success(74.8% vs 86.8%, p < 0.01) was lower in the elderly group. Moreover, the rates of in-hospital death(23.6% vs 6.8%, p < 0.005), pulmonary edema(20.3% vs 10.8%, p < 0.05), cardiogenic shock(11.9% vs 6.0%, p < 0.005), pneumonia(17.3% vs 3.0%, p < 0.005), and delirium(29.4% vs 12.0%, p < 0.001) were higher in the elderly group. Five patients in the elderly group and 3 patients in the younger group required rehabilitation because of worsened performance status. Six of them were non-reperfused patients. Elderly patients considered likely to become bed-ridden because of pre-existing physical disability at admission accounted for 28.9% of the total. Moreover, many elderly patients had poor support systems (8.4% were living alone, 21.0% were living only with their spouse or a child, 30.1% were widows or widowers). These results show that a lower acute phase reperfusion rate(especially angioplasty) resulted in a poor prognosis and worse performance status in elderly patients. Also 30% of patients were not good candidates for conventional treatment because of delirium, and that self-help in daily life is a fundamental goal for most elderly patients. Rapid and simple acute phase reperfusion, subsequent immediate mobilization, and early discharge are recommended for elderly patients with acute myocardial infarction.

Activities of Daily Living↗
PubMed2000

[A case of autosomal recessive juvenile parkinsonism (AR-JP) with onset at the age of 6 years].

We report a 26-year-old woman with autosomal recessive juvenile parkinsonism (AR-JP). Her parents made consanguineous marriage. The disease started with dystonic posture of legs 20 years prior to the admission (6 years old). The equinovarus foot appeared at 9 years old and parkinsonism gradually developed. These symptoms were remarkably improved after sleep. Levodopa was effective on her parkinsonian symptoms. However, the response to levodopa gradually reduced. On admission, she presented with a masked face, marked rigidity, moderate retropulsion, postural tremor in the upper limbs and mild hyperreflexia in the lower limbs. Mutational analysis revealed homozygous deletion of exon 4 in perkin gene. This patient has youngest age of onset for ARJP to our knowledge.

Adult↗
PubMed2000

Immunohistochemical and statistical studies on the islets of Langerhans pancreas in autopsied patients after gastrectomy.

We describe in detail the pathologic features of the islets of Langerhans in specimens of the pancreas from 75 autopsy specimens of patients who underwent gastrectomy and compare them with specimens from 22 patients not having gastrectomy with respect to the duration of the postoperative period and the operative procedure. In comparison with the control group, the islets of Langerhans from the gastrectomy patients showed hyperplasia and increased numbers of endocrine cells within 5 years of gastrectomy but atrophy and decreased numbers of endocrine cells thereafter. These changes are compatible with anti-insulin immunoreactivity (B-cells) in the islets of Langerhans, where B-cell counts correlated with the area of the islets. The proliferating cell nuclear antigen (PCNA)-positive cell ratio in the islets was higher during the early phase after gastrectomy, whereas the apoptotic cell ratio was not affected by the time after gastrectomy. Hyalinization of the islets of Langerhans was first recognized after 5 years postoperatively, and the percentage of hyalinization gradually increased. Amylin deposits, detected by immunostaining, increased progressively in the islets in relation to the duration of postoperative period, correlating inversely with B-cell count and PCNA positivity. These histologic changes suggest that B cells proliferated secondary to oxyhyperglycemia in the early phase after gastrectomy followed by the state of waste, finally resulting in atrophy and amylin deposits, which led to hypofunction of the islets of Langerhans with resultant glucose intolerance. HUM PATHOL 31:1368-1376.

Amyloid↗
PubMed1999

The neural cell adhesion molecules L1 and NCAM-180 act in different steps of neurite outgrowth.

The formation of neurocircuitry depends on the control of neurite outgrowth that, in turn, can be divided into two processes: nerve growth cone protrusion and neurite extension. It has long been known that the neural cell adhesion molecules L1 and NCAM-180 promote neurite outgrowth, but how they function in growth cones is unclear. We addressed the roles of L1 and NCAM-180 in neurite outgrowth by using microscale chromophore-assisted laser inactivation (micro-CALI) of these proteins to perturb their functions at precise times in single growth cones of embryonic chick dorsal root ganglion neurons grown in culture. Micro-CALI of L1 causes neurite retraction after a 10 min lag period but does not affect growth cone protrusion. In contrast, micro-CALI of NCAM-180 causes rapid growth cone retraction but does not affect neurite extension. The simultaneous inactivation of both these molecules resulted in both distinct effects that were segregated in time. The behavior of growth cones after these micro-CALI treatments resemble the drug-induced perturbation of microtubules for L1 and F-actin for NCAM-180. These findings suggest distinct roles in the growth cone for L1 and NCAM-180 in different steps of neurite outgrowth: L1 functions in neurite extension,whereas NCAM-180 functions in growth cone protrusion.

Animals↗
PubMed1999

Essential role of phosphoinositide metabolism in synaptic vesicle recycling.

Growing evidence suggests that phosphoinositides play an important role in membrane traffic. A polyphosphoinositide phosphatase, synaptojanin 1, was identified as a major presynaptic protein associated with endocytic coated intermediates. We report here that synaptojanin 1-deficient mice exhibit neurological defects and die shortly after birth. In neurons of mutant animals, PI(4,5)P2 levels are increased, and clathrin-coated vesicles accumulate in the cytomatrix-rich area that surrounds the synaptic vesicle cluster in nerve endings. In cell-free assays, reduced phosphoinositide phosphatase activity correlated with increased association of clathrin coats with liposomes. Intracellular recording in hippocampal slices revealed enhanced synaptic depression during prolonged high-frequency stimulation followed by delayed recovery. These results provide genetic evidence for a crucial role of phosphoinositide metabolism in synaptic vesicle recycling.

Animals↗
PubMed1999

Radiotherapy following mastectomy: indication and contraindication of chest wall irradiation.

PURPOSE: To determine in which cases radiotherapy of the chest wall following mastectomy is indicated, based on the local recurrent rate in patients with locally advanced breast cancer. METHODS AND MATERIALS: From 1984 until 1994, 105 patients who had four or more histopathologically confirmed axillary nodes metastases, or T3-4Nany, were subjected to mastectomy and were administered radiotherapy postoperatively using the hockey-stick field, which included the ipsilateral supraclavicular fossa and internal mammary nodes, except the chest wall. Median age was 51 years old (range, 23 to 82 years old). Eighty-five patients underwent radical mastectomy, 18 modified radical mastectomy, and 2 extended radical mastectomy. Fraction size was 2 Gy/day, the weekly fraction size was 10 Gy and the total dose ranged from 44 Gy to 54 Gy (median 50 Gy). Seventy-four patients were administered adjuvant chemotherapy, and 61 patients were administered hormone therapy. RESULTS: The 5-year disease-free survival rates of the whole study population were 66%. The 5-year chest wall recurrence rates were 10%. The 5-year chest wall recurrence rates of the patients who had no vascular invasion (n = 19) and the patients who had definite vascular invasion (n = 38) were 0% and 24%, respectively (p = 0.036). All the patients who presented chest wall recurrence had four or more axillary nodes metastases. Nine of the 10 patients who presented chest wall recurrence had definite vascular invasion, while there was no information about vascular invasion for the remaining patient. Factors such as age, pathological subtypes, tumor location, estrogen receptors, extent of resection, chemotherapy, and hormone therapy did not influence the development of chest wall recurrence. CONCLUSION: Among patients with breast cancer who have four or more positive axillary nodes or T3-4Nany, those who have no vascular invasion or less than 4 axillary nodes metastases do not need to be subjected to chest wall irradiation after radical mastectomy.

Adult↗