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Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 397 records · Page 22Linked to original sources
PubMed1999

Expression of cholecystokinin in the pancreas during development.

We have reported that cholecystokinin-like immunoreactivity (CCK-LI) and its transcripts are expressed in rat pancreatic islets (Endocrinology 1998;139:389-96). The purpose of this study was to elucidate the ontogeny of CCK during pancreatic development in the rat. Fetal rats from day 13 (E13) to 20 (E20) and postnatal (P) rats from day 1 to adulthood were used in this study. Immunohistochemical studies of rat pancreas were carried out with rabbit antisera against CCK-8 and gastrin-17. The absorption studies were performed by using CCK-8 antiserum incubated with excess CCK-8 or gastrin-17. In situ hybridization was performed to demonstrate the CCK and gastrin transcripts in the pancreas. CCK and gastrin were first detected at E15, and they were distributed in the periphery of the islets in the fetal and neonatal pancreas. The mirror sections for CCK revealed positive cells with characteristics identical to those that stained positive for gastrin. The CCK-LI in early development was completely abolished by preabsorption with excess gastrin but not with CCK-8. These findings indicated that the CCK-LI in the fetal and neonatal pancreas was crossreacting gastrin rather than CCK-8. From weaning (P21) through adulthood, on the other hand, CCK-LI was expressed diffusely in pancreatic islets, but there were no gastrin-positive cells after weaning. In situ hybridization showed that CCK messenger RNA (mRNA) was present in rat pancreatic islets in adults but not in early development. Although CCK-positive cells were not detected in fetal and neonatal pancreatic islets, CCK was expressed in islets during and after weaning through adulthood, indicating that CCK in pancreatic islets might be developmentally regulated.

Animals↗
PubMed1999

Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy.

BACKGROUND: To clarify the role of choroidal vascular abnormalities in central serous chorioretinopathy (CSC) in active stage, remission, and recurrence. METHODS: Indocyanine green angiography and fluorescein angiography were performed in 105 eyes (104 patients) with active CSC. Forty-six patients were followed up for 6 to 48 months (mean +/- standard deviation, 22.5 +/- 8.9 months) with repeated angiography (mean +/- standard deviation, 3.5 +/- 1.5 times). Indocyanine green angiography and fluorescein angiography also were performed during remission in all 46 eyes with CSC and during recurrent CSC in 6 eyes. Unaffected fellow eyes underwent angiographic examinations in all patients. RESULTS: In active CSC, indocyanine green angiography showed a choroidal filling delay (71%), venous dilation (61%), and focal choroidal hyperfluorescence (96%) surrounding leakage from the retinal pigment epithelium. Focal choroidal hyperfluorescence was present in unaffected areas of affected eyes (55%). The choroidal venous dilation (36%) and choroidal hyperfluorescence (62%) were noted even in unaffected fellow eyes. These choroidal abnormalities persisted during remission after leakage ceased throughout the follow-up period. In the six patients with recurrent CSC, new leakage developed in the areas of persistent choroidal hyperfluorescence. Central serous chorioretinopathy developed in the unaffected fellow eye in one of these six patients. CONCLUSION: Choroidal vascular abnormalities persist in both eyes even after leakage from the retinal pigment epithelium ceases. Central serous chorioretinopathy may recur in areas of choroidal vascular abnormalities.

Adult↗
PubMed1999

Low-dose intramuscular polymyxin B improves survival of septic rats.

UNLABELLED: Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neutralizes the lipid A moiety of endotoxin. We examined effects of a small dose of PLB on the mortality of rats with cecal ligation and puncture, on LPS-stimulated nitric oxide (NO) production, and on tumor necrosis factor alpha (TNF alpha) production by isolated rat Kupffer cells. MATERIALS AND METHODS: In vivo studies: Cecal ligation and puncture (CLP) was performed under anesthesia in 28 rats. One hour after CLP, either 600 U/kg of PLB or saline was administered intramuscularly every 6 h (PLB group: n = 12; control group: n = 16). Plasma endotoxin was measured at 3 and 24 h after the CLP by the Endospecy test. This was compared with survival. IN VITRO STUDIES: Kupffer cells were isolated from the normal rat liver. The cells were incubated with LPS or LPS + PLB. After 24 h, NO and TNF alpha content were measured using the Griess and ELISA methods, respectively. RESULTS: Low dose PLB significantly decreased the endotoxin levels at both 3 and 24 h (5.5 +/- 2.1 pg/mL vs. 32.8 +/- 3.6 at 3 h; 26.1 +/- 6.1 vs. 49.1 +/- 5.6 at 24 h (p < .05) after CLP. PLB significantly improved survival of CLP rats (68.8% in the control group vs. 100% in the PLB treated group on 3 days after CLP, p < .001). PLB also attenuated NO and TNF alpha production from the Kupffer cells. CONCLUSION: Intramuscular PLB administered in low doses may improve the mortality of sepsis.

Animals↗
PubMed1999

Analysis of a chronic myelogenous leukemia patient vaccinated with leukemic dendritic cells following autologous peripheral blood stem cell transplantation.

Dendritic cells (DCs) are believed to be the most potent antigen-presenting cells and may be important in the induction of anti-leukemia specific T cell responses. In this preliminary clinical study, a patient with chronic phase chronic myelogenous leukemia (CML) was vaccinated with autologous leukemic DCs following autologous peripheral blood stem cell transplantation (PBSCT). In an in vitro study, leukemic DCs were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha, and interleukin-4 from granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC fraction of this patient, and were found to be Ph1+, and to possess the morphologic and phenotypic characteristics of mature DCs. These cells could also elicit antigen specific immune responses, including a vigorous cytotoxicity specific to CML cells. In the clinical experiment, we obtained evidence that infused leukemic DCs could induce T cell clones expressing the same T cell receptor usage as a cytotoxic T cell line, suggesting that the immune repertoire includes tumor-reactive T cells. These cytotoxic T lymphocytes are activated in vivo. The vaccination of leukemic DC caused a decrease in the number of Ph1+ cells in the peripheral blood and bone marrow. These results indicate that the activity is an immunologically mediated phenomenon and vaccination therapy with leukemic DC following autologous PBSCT may be effective in treating CML.

Amino Acid Sequence↗
PubMed1999

Posttreatment M-protein nadir level is a significant prognostic factor associated with survival in multiple myeloma. Nagoya Myeloma Cooperative Study Group.

In the present study 142 patients with myeloma (102 with IgG M-protein and 40 with IgA) treated with either VMCP (65 patients) or MMCP (77 patients) as remission induction therapy were retrospectively analyzed. Response to treatment was evaluated in terms of a more-than-50% fall of pretreatment M-protein and the posttreatment M-protein nadir. Though significantly more patients treated with MMCP achieved partial response (PR) as compared with those treated with VMCP (P=0.019) and though patients achieving PR showed a significantly longer survival than those with less responsiveness (P=0.0091), the difference in survival curves between the two treatment groups was not significant (P=0.1871). The difference in response between the treatment groups evaluated in terms of posttreatment nadir was not significant (P=0.507). Multivariate analysis identified posttreatment M-protein nadir as a significant prognostic factor associated with survival, along with 3 other factors: sex, performance status, and hemoglobin. The lack of difference between the survival curves for patients treated with the 2 regimens despite the significantly different response rates evaluated in terms of percent fall of pretreatment M-protein levels was considered to be due to the lack of a difference in the ability to induce a deep posttreatment nadir between the regimens. Posttreatment M-protein nadir is an important prognostic factor associated with survival and should be included in the evaluation of the efficacy of chemotherapy.

Aged↗
PubMed1999

Circadian heart rate rhythms in Japanese centenarians.

OBJECTIVE: To investigate age-associated changes in the circadian rhythm of the heart rate. DESIGN: The circadian rhythm was extracted from diurnal heart rate (HR) variations, and patterns of HR rhythm were compared in centenarians and controls. SETTING: Centenarians living in the metropolitan area of Tokyo and in Aichi prefecture in 1992. PARTICIPANTS: Fifty centenarians underwent 24-hour ambulatory electrocardiogram (Holter) monitoring. The control group, comprised of 100 clinically healthy subjects who underwent similar Holter monitoring, was subdivided, by age, into two groups: the younger controls (age range 23 to 54 years, mean age 41) and the older controls (age range 55 to 82 years, mean age 69). MEASUREMENTS: Harmonic analysis was used to approximate the 24-hour RR interval (the interval between two neighboring R waves on the electrocardiogram) data obtained by Holter monitoring to a summation of three cosine waves with 24-hour, 12-hour, and 8-hour periods. The power of the period was adjusted for the goodness of curve-fit. The power of each period and the circadian acrophase (the timing of the peak in a 24-hour rhythm) were compared among the centenarians, older controls, and younger controls. HR rhythms were classified by k-means cluster analysis based on the power of the period. The prevalence of each pattern was compared among the three age groups. In the centenarians, the relationship between clinical parameters (activities of daily living, cognitive function, nutritional status, and present illness) and patterns of HR rhythm was investigated. RESULTS: The power of the 24-hour period in the centenarians was significantly smaller than that in the older (P < .05) and younger (P < .001) controls. The power of the 8-hour period in the centenarians was significantly larger than that in the younger controls (P < .05). Advances or delays in the circadian acrophase were frequently observed in the centenarians compared with the younger controls. The power of each period did not differ between centenarians with (n = 11) and without (n = 39) overt diseases capable of altering HR rhythms. Five patterns of HR rhythm were identified: 24-hour period dominant (n = 84), 24-hour+12-hour period (n = 18), 12-hour period dominant (n = 11), 8-hour period dominant (n = 7), and low goodness of curve-fit (n = 30). The 8-hour period dominant pattern and the low goodness of curve-fit pattern were observed commonly in the centenarians, whereas the 24-hour period dominant pattern and the 24-hour+12-hour period pattern were observed frequently in the younger controls. Patterns of HR rhythm were not related to clinical parameters in the centenarians. CONCLUSIONS: The circadian rhythm of HR changed with aging: there was reduction in the power of the 24-hour period, augmentation in the power of the 8-hour period, and a shift in the circadian acrophase.

Activities of Daily Living↗
PubMed1999

Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein conferred by two N-terminal domains of FUS (TLS).

The FUS (TLS)-ERG chimeric protein associated with t(16;21)(p11;q22) acute myeloid leukemia is structurally similar to the Ewing's sarcoma chimeric transcription factor EWS-ERG. We found that both FUS-ERG and EWS-ERG could induce anchorage-independent proliferation of the mouse fibroblast cell line NIH 3T3. However, only FUS-ERG was able to inhibit the differentiation into neutrophils of a mouse myeloid precursor cell line L-G and induce its granulocyte colony-stimulating factor-dependent growth. We constructed several deletion mutants of FUS-ERG lacking a part of the N-terminal FUS region. A deletion mutant lacking the region between amino acids 1 and 173 (exons 1 to 5) lost the NIH 3T3-transforming activity but retained the L-G-transforming activity. On the other hand, a mutant lacking the region between amino acids 174 and 265 (exons 6 and 7) lost the L-G-transforming activity but retained the NIH 3T3-transforming activity. These results indicate that the N-terminal region of FUS contains two independent functional domains required for the NIH 3T3 and L-G transformation, which we named TR1 and TR2, respectively. Although EWS intrinsically possessed the TR2 domain, the EWS-ERG construct employed lacked the EWS sequence containing this domain. Since the TR2 domain is always found in chimeric proteins identified from t(16;21) leukemia patients but not in chimeric proteins from Ewing's sarcoma patients, it seems that the TR2 function is required only for the leukemogenic potential. In addition, we identified three cellular genes whose expression was altered by ectopic expression of FUS-ERG and found that these are regulated in either a TR1-dependent or a TR2-dependent manner. These results suggest that FUS-ERG may activate two independent oncogenic pathways during the leukemogenic process by modulating the expression of two different groups of genes simultaneously.

3T3 Cells↗
PubMed1999

Incorporation of dietary docosahexaenoic acid into the central nervous system of the yellowtail Seriola quinqueradiata.

In order to show the involvement of docosahexaenoic acid (DHA) in the development of the central nervous system (CNS) in carangid fish, we conducted tracer experiments by feeding radioactive DHA to larval yellowtail (Seriola quinqueradiata). Artemia nauplii were enriched with 14C-labeled DHA and fed to larval yellowtail for eight or ten days. Autoradiography of frozen sections, using both electric imaging plates and X-ray sensitive film, clearly showed that DHA was incorporated into and retained in the brain, spinal cord, and eyes. The brain, eyes, gill raker, liver, guts, and other muscle and bone structures were dissected, and radioactivity was measured in each organ by liquid scintillation counter. The results of this study suggest the incorporation of DHA into the brain. Considering our previous results indicating that DHA-free fish cannot form schools, we conclude that the incorporation of DHA into the brain might be a critical factor in the ontogeny of schooling behavior.

Animals↗
PubMed1999

Peptide specificity, HLA class II restriction, and T-cell subsets of the T-cell clones specific to either Cry j 1 or Cry j 2, the major allergens of Japanese cedar (Cryptomeria japonica) pollen.

BACKGROUND: Cry j 1 and Cry j 2 are thought to be the major allergens of Japanese cedar pollen. HLA class II types capable of presenting T-cell epitopes in both allergens and their role in induction of T-cell subsets are not well known. METHODS: CD4+ T (Th)-cell clones (TCCs) specific to either Cry j 1 or Cry j 2 were generated. HLA class II restrictions were determined by their reactivity to the T-cell epitope in the presence of antigen presenting cells sharing matched types. Interleukin (IL)-2, interferon-gamma, IL-4, and IL-5 contents in the supernatants of TCCs were estimated using enzyme immunoassay. RESULTS: Peripheral blood mononuclear cells (PBMC) from patients induced proliferation with 100 microgram/ml Cry j 1 or 3-10 microgram/ml rCry j 2 stimulation. T-cell epitopes in Cry j 1 were presented to Th cells by the gene products of DRA1*01/DRB1*0901, DRA1*01/DRB5*0101, DQA1* 0102/DQB1*0602, and DPA1*01/DPB1*0501; those in Cry j 2 were restricted by DRA1*01/DRB1*0901, DRA1* 01/DRB1*1501, DRA1*01/DRB4*01, DRA1*01/DRB5* 0101, DQA1*0102/DQB1*0602, DPA1*01/DPB1*0201, and DPA1*01 and *0202/DPB1*0501. Type 2-like cells were preferentially induced in Cry j 1 stimulation, while an almost equal number of type 2- and type 1-like cells was induced in rCry j 2. CONCLUSIONS: No clear correlation existed between peptide specificity, HLA class II restriction and induction of Th-cell subsets, suggesting that the requirement of different dose of Cry j 1 or Cry j 2 to induce proliferation in PBMC may lead to distinguishable difference in induction of Th subsets between TCCs specific to Cry j 1 and Cry j 2.

Adult↗
PubMed1999

Immediate causes of death in thyroid carcinoma: clinicopathological analysis of 161 fatal cases.

Most patients with thyroid carcinoma have a good prognosis. Due to the small number of fatal cases, it has not been clarified what conditions result in death for patients with thyroid carcinoma. To provide appropriate management for advanced thyroid carcinoma patients, we analyzed causes of death in 161 fatal cases. Clinical characteristics and immediate (final) causes of death based on pathological conditions were analyzed in 62 anaplastic carcinomas and 99 fatal differentiated carcinomas. Single fatal conditions could not be specified in 55 patients. In the remaining 106 patients, respiratory insufficiency (43%) was the most common specific fatal condition, followed by circulatory failure (15%), hemorrhage (15%), and airway obstruction (13%). Respiratory insufficiency due to remarkable pulmonary metastasis replacing lung tissue, massive hemorrhage and airway obstruction due to uncontrolled local tumors, and circulatory failure resulting from compression of the vena cava by extensive mediastinal or sternal metastases were found to be the most important immediate causes of death. Based on this knowledge, several palliative procedures may be worth considering to improve survival and quality of life in patients with advanced thyroid carcinoma.

Adenocarcinoma, Follicular↗
PubMed1999

Single cells can sense their position in a morphogen gradient.

Xenopus blastula cells show a morphogen-like response to activin by expressing different genes according to the concentration of activin to which they are exposed. To understand how cells recognize their position in a concentration gradient, it is essential to know whether each cell responds individually to activin concentration. An alternative idea, proposed by previous work, is that cells need to interact with their neighbours to generate a concentration-related response. To distinguish between these ideas, we have cultured blastula cells under conditions which provide different degrees of contact with other cells, allowing nil to maximum communication with their neighbours. The cultures include cells attached to fibronectin and cells resting unattached on an agarose base. The cultures also include cells that have no contact with any cell except their clonal progeny, cells that have lateral contact to neighbouring cells, and cells that are completely enveloped by other cells in a reaggregate. We have used RNase protection and in situ hybridization to assay the expression of the activin-responsive Xenopus genes Xbra, Xgsc, Xeomes, Xapod, Xchordin, Mix1, Xlim1 and Cerberus. We find no difference in gene expression between cells attached to fibronectin and those unattached on agarose. Most importantly, we find that cells respond to activin in a concentration-related way irrespective of their degree of contact with other cells. Therefore interaction among cells is not required for the interpretation of morphogen concentration, at least in the case of the early genes studied here. We conclude that isolated blastula cells can sense and respond individually to activin by expressing genes in a concentration-dependent way.

Activins↗
PubMed1999

The influence of hypothyroidism on wound healing. An experimental study.

An experimental study was performed to investigate the influence of hypothyroidism on wound healing. A state of severe hypothyroidism was induced initially by performing a total thyroidectomy on rat models; subsequently wounds were made by making long midline abdominal incisions and then suturing them. The parameters used to evaluate the process of wound healing of these incisions were the assay of type-I collagen, type-III collagen (procollagen peptide PIPC and P III P, each being the precursor of collagen), type-IV collagen, and hydroxyproline. The assays were repeated at specific times and compared to assays of similar parameters taken from a control group. In the state of hypothyroidism, a decrease was observed in type-IV collagen and hydroxyproline during the proliferative phase of wound healing. This indicated that the state of hypothyroidism constitutes an important factor in delaying wound healing.

Animals↗
PubMed1999

Overexpression of fibroblast growth factor receptor 3 in a human thyroid carcinoma cell line results in overgrowth of the confluent cultures.

Recent reports indicate that a gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR-3) inhibits cell growth in the cartilaginous growth plates. These results suggest that FGFR-3 may be the receptor transducing growth inhibitory signals. Using reverse transcription-PCR we examined seven papillary thyroid carcinomas to determine FGFR-3 expression. Six out of the seven papillary carcinomas expressed FGFR-3. To clarify the role of FGFR-3 in thyroid carcinoma, FGFR-3 was overexpressed in an established human papillary thyroid carcinoma cell line. High levels of FGFR-3 protein were identified in cells stably transfected with the vector containing FGFR-3 cDNA. The specific binding of 125I-FGF-2 of these cells was threefold higher than that of control cells. Growth rates of cells overexpressing FGFR-3 were similar to those of control cells. However, cells overexpressing FGFR-3 continued to grow beyond the density at which control cells stopped proliferating. These results suggest that FGFR-3 in thyroid carcinoma is not involved strongly in the cell proliferation mechanism but may contribute to the malignant extension of some of the carcinomas by modifying cell contact signaling.

Carcinoma, Papillary↗
PubMed1999

Multiple endocrine neoplasia type 2A with the identical somatic mutation in medullary thyroid carcinoma and pheochromocytoma without germline mutation at the corresponding site in the RET proto-oncogene.

A germline mutation either in exon 10 or 11 of the RET proto-oncogene is found in the majority of patients with multiple endocrine neoplasia type 2A (MEN 2A). A 41-year-old female patient was referred for further evaluation of incidentally discovered right adrenal tumor. She had bilateral adrenal pheochromocytomas and medullary thyroid carcinomas detected by endocrinological and radiological examination, and diagnosed as MEN 2A. Molecular genetic testing of the RET exons 10 and 11 exhibited the identical somatic missense mutation at codon 634 in both tumors but did not confirm germline mutations in the corresponding sites. Possible mechanisms for tumorigenesis in this patient are discussed.

Adrenal Gland Neoplasms↗
PubMed1999

Intracerebral cystic meningioma--case report.

A 46-year-old female presented with persistent bifrontal headache. Computed tomography revealed a large cystic tumor in the right temporoparietal area, which included a solid component. The tumor had no attachment to the dura. There was no peritumoral edema or mass effect usually found around cystic meningiomas. The solid component was totally removed. Histological examination indicated that the tumor was a fibrous meningioma. Intracerebral meningioma with a large cystic component without dural attachment should be considered in the differential diagnosis of cystic cerebral tumors.

Arachnoid Cysts↗
PubMed1999

Cystic lesion at the foramen magnum disseminated from a pituitary adenoma--case report.

A 38-year-old male presented with a cystic lesion at the foramen magnum due to intracranial dissemination from a pituitary adenoma. The primary tumor had required reoperation for regrowth twice. The tumor at the foramen magnum was removed surgically. Two smaller solid tumors were located in the left parietal convexity and the right temporal lobe. The former tumor was also removed surgically and the latter was observed. Histological examination showed the typical characteristics of pituitary adenoma in both surgical specimens. Immunohistochemical staining with MIB-1 and p53 antibodies showed low (< 1%) and negative reaction. Patients with pituitary adenoma, even benign tumors, must be carefully followed up for signs of metastasis.

Adenoma↗
PubMed1999

Skull metastasis of Ewing's sarcoma--three case reports.

Three cases of skull metastasis of Ewing's sarcoma were treated. The metastatic lesion was located at the midline of the skull above the superior sagittal sinus in all cases. Surgery was performed in two patients with solitary skull lesions involving short segments of the superior sagittal sinus without remarkable systemic metastasis, resulting in good outcome. The third patient had extensive, multiple tumors involving the superior sagittal sinus which could not be excised, and died due to intracranial hypertension. The surgical indication for skull metastasis of Ewing's sarcoma depends on the location and length of the involved superior sagittal sinus, and general condition.

Adolescent↗