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Biomedical subjects

K Yoshikawa

Publications and source records attributed to K Yoshikawa.

At least 271 records · Page 15Linked to original sources

Occurrence of toxicity and cell proliferation after a single gavage administration of chloroform to male F344 rats.

Chloroform, an industrial solvent and one of the most common environmental contaminants which produces carcinogenic effects in the liver and kidney of rodents, is not genotoxic in most traditional bacterial and mammalian test systems. Its carcinogenic potential appears attributable to the sustained cell turnover (regenerative hyperplasia) which results from chronic chloroform toxicity. In this present study, cell proliferation (replicative DNA synthesis, RDS) and histopathological changes in hepatocytes and renal tubular epithelial cells were assessed in male F344 rats following a single gavage chloroform exposure (50, 150 or 500 mg/kg). In addition, biochemical parameters (BUN, GOT, LDH and NAG) were examined using plasma and urine samples. Cell proliferation and histopathological changes (e.g. hypertrophy, necrosis, vacuolation) were only seen at the dose of 500 mg/kg in the liver and kidney. At the same dose, all biochemical markers were increased at the 24 to 48 hr time points. These results obtained are thus in line with earlier findings pointing to epigenetic carcinogenicity.

Administration, Oral↗

[Enterohemorrhagic Escherichia coli O157 infection in an elderly patient with secondary hemolytic uremic syndrome who developed recurrent acute exacerbation of chronic cholecystitis].

We encountered a patient with enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection and secondary hemolytic uremic syndrome (HUS). The patient was a 79-year-old woman with hypertension, constipation, and asymptomatic cholelithiasis. She complained of nausea and abdominal pain, and had bloody stool EHEC O157 was detected by fecal culture. The bloody stool resolved after treatment with antibiotics, but the patient was hospitalized on July 23, 1996 because of abdominal distention. HUS was diagnosed because of proteinuria, hematuria, thrombocytopenia, hemolytic anemia, fragmentation of red blood cells, and increased serum LDH. Treatment was focused on plasma exchange, administration of antibiotics, large doses of gamma-globulin, haptoglobin replacement, and anticoagulation. Within about 2 weeks, the level of hemoglobin, the number of platelets, and the serum LDH had normalized, and the patient recovered from HUS. The decreased intestinal movement continued. On August 23, acute cholecystitis was diagnosed, and percutaneous transhepatic gall bladder drainage was done. Another exacerbation was noted on October 13, and cholecystectomy was done on November 12, when the patient's status had improved after instillation of antibiotics. Macroscopically, the gallbladder wall was thickened. Histopathological examination showed diffuse infiltration of lymphocytes into the mucosa, chronic cholecystitis was diagnosed. Because the postoperative course was satisfactory, the patient was discharged from the hospital on December 15. Acute exacerbation of chronic cholecystitis might have been caused by decreased cholic excretion after the marked decrease in intestinal movement due to O157 infection and secondary HUS. Because elderly people frequently have anamnesis of the digestive system, considerably attention should be paid to the management of anamnesis, as well as O157 infection and secondary HUS.

Aged↗

[Auditory evoked magnetic fields in patients of pure word deafness].

Auditory evoked magnetic fields (AEF) were recorded in 2 cases with pure word deafness. AEF examination were performed with a novel 129-channel vector neuromagnetic imaging system (SBI 100). The latency and the location of equivalent current dipole (ECD) of N100 m after 1,000 Hz tone burst stimulation, one of the most prominent peak of AEF, were evaluated. One patient, 59-year-old man, suffered from left putaminal hemorrhage and the other, 59-year-old man, had a history of bilateral putaminal hemorrhage. There was no N100 m detected in the left temporal lobe with the right ear stimulation in both patients. However normal N100 m was obtained in the right hemisphere with the left ear stimulation in both cases. And the position of ECD of N100 m in the right hemisphere were correctly superimposed on the Heschl gyrus in brain MRI. The pathophysiology of pure word deafness has been postulated that a disconnection between Wernicke area and bilateral auditory inputs played one of important roles in progression of pure word deafness. Because there was no pathological lesion in temporal lobe verified by MRI study in both patients, N100 m in the left could not be evoked due to interception of the auditory pathway to the Heschl gyrus, but not due to destruction of Heschl gyrus. AEF test is one of the most useful tools in order to estimate central auditory function in patients with pure word deafness.

Aphasia, Wernicke↗

[Clinical manifestations and diagnosis of patients with sarcoidosis].

We reviewed the records of new patients with uveitis who visited the Hokkaido University Hospital between 1991 and 1994. For the diagnosis of sarcoidosis, we used the criteria revised by the Diffuse Pulmonary Disease Research Committee of Japan in 1989. The total number of patients was 374, and 61 cases were diagnosed as sarcoidosis. Of 61 patients with sarcoidosis, 58 cases were diagnosed histologically. Transbronchial lung biopsy was the basis for 70% of the histological diagnosis. After the revision of the criteria of sarcoidosis, the percentage of histological diagnosis increased. The Diffuse Pulmonary Disease Research Committee of Japan also proposed guidelines for the diagnosis of ocular sarcoidosis in 1990. We applied these guidelines to our uveitis patients. Most of the patients (77.1%) with sarcoidosis were included in the group of probable sarcoidosis, but 20% of patients with uveitis who were not diagnosed as having sarcoidosis were also included in this group. These guidelines are not yet adequate.

Adult↗

Expression of intercellular adhesion molecule-1 in invasive breast cancer reflects low growth potential, negative lymph node involvement, and good prognosis.

To understand the role of intercellular adhesion molecule-1 (ICAM-1) in tumor progression in the host, we examined ICAM-1 expression in breast cancer by immunohistochemistry. This study included 274 female patients with invasive breast cancer, with a median follow-up of 98 months. The molecule was identified in formalin-fixed, paraffin-embedded primary tumors, and the relationship to clinicopathological factors and prognosis was analyzed. ICAM-1 expression occurred in 50.3% of patients. ICAM-1 expression had negative correlation to tumor size (P = 0.003), lymph node metastasis (P < 0.0001), tumor infiltration (P = 0.003), nuclear pleomorphism (P = 0.004), and nuclear grade (P = 0.042). Patients with ICAM-1-positive tumors had better relapse-free and overall survival than those with negative tumors (P < 0.0001 and P = 0.0003, respectively). These results suggest that expression of ICAM-1 on cancer cells might have a role as a suppressor of tumor progression under the host immune surveillance system.

Breast Neoplasms↗

Expression of the 150-kd oxygen-regulated protein in human breast cancer.

Tumor cells subjected to environmental stress, such as oxygen deprivation followed by reoxygenation, redirect biosynthetic pathways to express oxygen-regulated proteins (ORPs) and heat-shock proteins (HSPs). The 150-kd oxygen-regulated protein (ORP150) is a novel endoplasmic reticulum-associated polypeptide in the HSP70 family. In view of links between expression of HSPs/ORPs and tumor properties, especially tumor invasiveness and resistance to therapeutic regimens, expression of ORP150 in human breast cancers was examined. Western and Northern blotting demonstrated elevated expression of ORP150 in breast cancer, regardless of estrogen receptor status, compared with normal breast tissue. Immunohistochemical and in situ hybridization techniques revealed that infiltrating cancer cells in the stroma expressed ORP150 more strongly than large nests of cancer cells. Furthermore, pancreatic and thyroid carcinomas also displayed greater ORP150 expression. These results suggest that ORP150 is up-regulated in tumors and, in breast tumors, may be associated with tumor invasiveness.

Adenocarcinoma, Mucinous↗

Evaluation of glomerular filtration rate by camera-based method in both children and adults.

UNLABELLED: We describe a method to evaluate glomerular filtration rate (GFR) in both children and adults using 99mTc-diethylenetriamine pentaacetic acid (DTPA) and a gamma camera. METHODS: Renal scintigraphy with 99mTc-DTPA was performed in 40 children and 92 adults with various degrees of renal function. The percent renal uptake at 2-2.5 min after tracer arrival in the kidney was determined with background subtraction and correction for soft-tissue attenuation and was correlated by linear regression analysis with GFR measured from two blood samples. A perirenal region of interest was used for background subtraction. Renal depth was computed using the equations determined or validated on the basis of CT measurements, and the attenuation coefficient was set at 0.12. The obtained regression equation was used to predict GFR. Renal function was also assessed by the Gates' method. RESULTS: Percent renal uptake was closely correlated with GFR normalized for body surface area in all patients (y = 15.958x - 2.94; r = 0.939). GFR was successfully predicted using the regression equation in both children and adults. Gates' method severely overestimated GFR in children and provided less accurate values even in adults than our method. CONCLUSION: The method presented here requires neither blood sampling nor additional imaging and allows estimation of GFR in both children and adults.

Adult↗

[A case of asynchronous renal cell carcinoma, hepatocellular carcinoma and residual ureteral cancer].

A case of asynchronous triple cancer in an 88-year-old male is reported. Six years ago, he had received left radical nephrectomy for renal cell carcinoma, and 2 years ago partial hepatectomy for hepatocellular carcinoma detected by follow-up computed tomography (CT). During the post-operative follow-up, no metastasis of either the renal or hepatic carcinoma was detected. On February 12, 1997 he presented with macroscopic hematuria. Cystoscopy revealed a tumor emerging from the left ureteral orifice, while CT and magnetic resonance imaging (MRI) revealed a tumor mass in the left exterior of bladder. Diagnosis of residual ureter tumor, we performed both left ureterectomy and partial cystectomy. Histological diagnosis revealed transitional cell carcinoma of the residual ureter (G2 > G3, pT1, pV0, pL0, pR0). Convalescence was uneventful and 10 months after the operation, he is alive with no recurrence or metastasis. We stress the importance of careful follow-up not only to perceive the recurrence or metastasis of renal cancer but also to detect cancer in other parts of the body.

Aged↗

Serum protein determination by high-performance gel-permeation chromatography.

A general high-performance gel-permeation chromatography (HPGPC) method was developed to determine protein in human serum with improved sensitivity and speed. The optimum UV wavelength for protein detection was found to be 210 nm, by comparing the protein values obtained by varying the UV wavelength of the HPLC detection system with the protein values obtained from spectrophotometric protein assays, i.e., the bicinchoninic acid (BCA) method and the biuret method. The analysis time was less than 1 min. Since this HPGPC serum protein assay method is simple and rapid, it is expected to be particularly well adapted for use in clinical laboratories.

Adolescent↗

Tissue-specific knockout of the mouse Pig-a gene reveals important roles for GPI-anchored proteins in skin development.

Glycosylphosphatidylinositol (GPI)-anchored proteins are widely distributed on plasma membranes of eukaryotes. More than 50 GPI-anchored proteins have been shown to be spatiotemporally expressed in mice with a deficiency of GPI-anchor biosynthesis that causes embryonic lethality. Here, we examine the functional roles of GPI-anchored proteins in mouse skin using the Cre-loxP recombination system. We disrupted the Pig-a gene, an X-linked gene essential for GPI-anchor biosynthesis, in skin. The Cre-mediated Pig-a disruption occurred in skin at almost 100% efficiency in male mice bearing two identically orientated loxP sites within the Pig-a gene. Expression of GPI-anchored proteins was completely absent in the skin of these mice. The skin of such mutants looked wrinkled and more scaly than that of wild-type mice. Furthermore, histological examination of mutant mice showed that the epidermal horny layer was tightly packed and thickened. Electron microscopy showed that the intercellular space was narrow and there were many small vesicles embedded in the intercellular space that were not observed in equivalent wild-type mouse skin preparations. Mutant mice died within a few days after birth, suggesting that Pig-a function is essential for proper skin differentiation and maintenance.

Animals↗

Glutamate responsiveness enhanced in neurones expressing amyloid precursor protein.

Although the neurotoxicity of beta-amyloid peptide is well established, the cellular functions of amyloid precursor protein (APP) remain unclear. Using an adenoviral vector, we introduced cDNA encoding human APP holoprotein into rat hippocampal neurones in culture. Neurones expressing the membrane-bound form of APP showed greater responsiveness to applied glutamate than non-expressing control neurones, as revealed by Ca2+ fluorometry. This increased responsiveness was not the result of secreted APP, as confirmed by observations of closely spaced APP-expressing and non-expressing cells in the same culture dish. These data suggest that one function of APP may be the regulation of glutamate receptors in neurones.

Adenovirus Infections, Human↗

Gene transfer mediated by polyarginine requires a formation of big carrier-complex of DNA aggregate.

Cationic peptide, poly-arginine, promotes transfection efficiency under a proper concentration. Using fluorescence microscopy, we observed the structure of the DNA carrier-complex in solution directly. Under low concentration of poly-arginine, small complexes were observed with fluorescence images like a blight light spot. This small complex (sizes are c.a. 1 approximately 2 microns order) had no transfection ability. As the concentration of poly-arginine became high, the complex grew into a big one whose size reached to a degree of 10 microns. Transfection was succeeded under that condition. The relationship between transfection efficiency and higher-order structure of the DNA carrier-complex was discussed.

Amino Acid Sequence↗

First-order phase transition in large single duplex DNA induced by a nonionic surfactant.

The effect of the nonionic surfactant Triton X-100 on the conformational behavior of large T4DNA was studied. Through single-molecule observation using fluorescence microscopy, we found that T4DNA macromolecules exhibit a discrete coil-globule transition with an increase in the Triton X-100 concentration. At low surfactant concentrations, all of the DNAs exhibited an elongated coil state, whereas only compacted globular DNAs were observed at high molar fractions of Triton X-100. The formation of DNA globules was not detected at relatively low Triton X-100 concentrations, even above the CMC; DNA collapse occurred in 50-90% solutions of Triton X-100. The increase in osmotic pressure in concentrated Triton X-100 solutions is considered to be the driving force for the compaction of single T4DNAs.

Bacteriophage T4↗

Possible role of coexpression of CD9 with membrane-anchored heparin-binding EGF-like growth factor and amphiregulin in cultured human keratinocyte growth.

CD9 is a protein with 4 transmembrane domains, and functions as a cell surface antigen. We have previously reported that CD9 functions as an up-regulator of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) activity, which is a potent mitogen as well as a soluble HB-EGF. Anti-CD9 antibodies can neutralize the juxtacrine activity of proHB-EGF when both CD9 and proHB-EGF are coexpressed. We demonstrated here: (1) the CD9 gene was transcribed and translated in the cultured human keratinocytes; (2) anti-CD9 antibody inhibited the approximately 50% growth of human keratinocytes in culture; (3) CD9 was coprecipitated with proHB-EGF and membrane-anchored amphiregulin (proAR), and (4) the transient coexpression of CD9 with proHB-EGF or proAR in mouse L cells up-regulated their juxtacrine growth factor activities. These results suggest that CD9 would make a heterodimer and/or trimer complex with proHB-EGF and proAR, and might cooperate with proHB-EGF and proAR for human keratinocyte growth in a juxtacrine manner.

Amphiregulin↗

Reorientation of large DNA molecules in concentrated polyacrylamide solution during crossed-field electrophoresis.

Recently, we found that, in concentrated neutral solutions, DNA molecules migrate in linear conformation under steady electric field. In this paper, we report the conformational change of DNA during 120 degree crossed-field electrophoresis in the same polymer solution. We found that, in concentrated polyacrylamide solutions, the reorientation process of DNAs becomes simple: the DNA goes back along the previous track and the reorientation time is longer for larger DNA. Such a backtrack motion has been thought to be an essential motion for the separation of DNA fragments in pulsed field gel electrophoresis. We expect that this phenomenon is useful for a more efficient separation technique of large DNAs than the current pulsed field gel electrophoresis.

Acrylic Resins↗

Effects of electrochemotherapy on CaSki cells derived from a cervical squamous cell carcinoma.

Electrochemotherapy is a new approach to the treatment of tumors that takes advantage of the permeabilization of the cell membranes by electric pulses to facilitate the intracellular delivery of chemotherapeutic drugs into cells. Using the female genital squamous cell carcinoma cell line, CaSki, the antitumor effectiveness of electrochemotherapy was tested. In vitro studies showed that the cytotoxicity of some anticancer drugs, especially bleomycin, can be greatly enhanced by exposing cells to noncytotoxic electric pulses. This enhancement was significantly greater when the electric treatment was given after exposure to the drug than when applied preexposure. Treatment of nude mice bearing subcutaneous transplanted tumors with noneffective intraperitoneal doses of bleomycin followed by local delivery of electric pulses similar to those performed in vitro resulted in tumor reduction and complete disappearance after 12 days this electrochemotherapy. Histological changes in tumor tissue such as necrosis and degeneration were extensive even 6 hr after the electrochemotherapy. Thus the antitumor effects of bleomycin in mice can be considerably potentiated by local electric pulses, suggesting that electrochemotherapy with bleomycin may have promise for treatment of vulvar or ectocervical squamous cell carcinomas with early invasion.

Animals↗