PubMed Health⌕ Search

Biomedical subjects

Y Totsuka

Publications and source records attributed to Y Totsuka.

At least 73 records · Page 4Linked to original sources
PubMed1997

Comparison between submucosal (extra-nodal) and nodal non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial region.

Fifty-two cases of non-Hodgkin's lymphoma (NHL) in the oral and maxillofacial region, comprising 31 submucosal (extra-nodal) and 21 cervical node NHLs, were investigated. The patients' ages ranged from 5 to 86 years, with a bimodal age distribution among young people below 12 years of age (average 8 years) and in those aged 30 years or older (average 60.3 years). The male-to-female gender difference ratio was 1.3:1. Patients presented with swelling as the major symptom. Histologically, diffuse, large cell malignant lymphoma was the most frequent type and 67.9% of lymphomas were of intermediate malignancy as defined by the Working Formulation for Clinical Usage. All submucosal lymphomas showed diffuse proliferation patterns, although follicular proliferation was identified in 5 of the 21 nodal lymphomas. Immunohistochemistry showed that the B-cell type was predominant, especially in nodal lymphomas.

Adolescent↗
PubMed1997

Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover.

Patients with poorly controlled noninsulin dependent diabetes mellitus (NIDDM) are shown to have higher bone mass. However, the influence of changes in glycemic control on bone turnover is not known. To clarify whether metabolic improvement of poorly controlled NIDDM affects bone turnover, markers for glucose, mineral, and bone metabolism were assessed before and after glycemic control for 3 weeks in 78 poorly controlled NIDDM patients with initial hemoglobin A1c over 8%. Metabolic improvement caused a reduction in urinary calcium (Ca) and phosphate (Pi) and serum 1,25(OH)2D levels, and an increase in serum Pi without changes in serum Ca or parathyroid hormone levels. Bone resorption markers, urinary deoxypyridinoline (Dpd) and type I collagen carboxy-terminal telopeptide (CTx), as well as a bone formation marker, serum bone type alkaline phosphatase (BALP), were reduced. However, another bone formation marker, serum osteocalcin (OC), was low before treatment and was elevated after treatment. The decrease in Dpd, CTx and BALP, but not the increase in OC, correlated with each other and with the improvement in glycemic indices. In conclusion, metabolic improvement of poorly controlled NIDDM decreases bone turnover within a short period. Thus, glycemic control may protect NIDDM patients from bone loss. It is possible that serum OC is affected by hyperglycemia per se, and may not correctly reflect bone turnover.

Adult↗
PubMed1997

Cyanamide-induced granulocytopenia.

We report a 64-year-old male with granulocytopenia and dermatitis due to cyanamide treatment. We administered cyanamide for alcoholism. After about one month he suffered from scaly erythema over his whole body and granulocytopenia (granulocyte; 140/microliter) with maturation arrest in bone marrow. After cessation of cyanamide and the start of granulocyte colony-stimulating factor administration, the skin eruption ameliorated gradually, and the peripheral blood granulocyte counts increased. Cyanamide showed positive results in the drug lymphocyte stimulation test (198%) and the patch test led to the diagnosis of granulocytopenia and dermatitis induced by cyanamide. After restarting glibenclamide and diazepam administration, his granulocytopenia did not reoccur. To our knowledge, this is the first report of a case with granulocytopenia induced by cyanamide.

Agranulocytosis↗
PubMed1997

Antisense E1AF transfection restrains oral cancer invasion by reducing matrix metalloproteinase activities.

E1AF is a newly identified human ets-family transcription factor. We have reported that E1AF can up-regulate transcription of matrix metalloproteinase (MMP) genes and confers invasive phenotype on human cancer cells. HSC3 is an oral squamous-cell-carcinoma-derived cell line, and it manifests high levels of E1AF and MMP-1 and -9 gene expression that are associated with invasive potential. We reconstructed an E1AF antisense expression vector, transfected HSC3 cells with the vector, and obtained HSC3AS cells that express E1AF antisense RNA. HSC3AS showed decreasing mRNA and protein levels of MMP-1, -3, and -9. Moreover, HSC3AS showed lower invasive potential in vitro three-dimensional raft culture and in vivo implantation into nude mice. These results imply that transfection of antisense E1AF inhibits tumor invasion by down-regulating MMP genes.

Adenovirus E1A Proteins↗
PubMed1997

Effect of a low-calcium environment on EGF inducible AP-1 binding activity in osteoblastic MC3T3-E1 cells.

In the mouse osteoblastic cell line MC3T3-E1, the signaling response of DNA-binding protein induced by the treatment of epidermal growth factor (EGF) was examined using electrophoretic mobility shift assay. EGF increased the binding activity in nuclear extracts of MC3T3-E1 cells to TPA-responsive element (TRE). Competition experiments revealed that the binding activity to AP-1 site in the nuclear extracts of EGF treated MC3T3-E1 cells was entirely inhibited by unlabeled AP-1 consensus oligonucleotide. The DNA-binding activity of AP-1 by EGF in nuclear extracts of MC3T3-E1 cells cultured under a low calcium environment was more increased.

Animals↗
PubMed1996

High-risk HPV-positive human cancer cell lines show different sensitivity to cisplatin-induced apoptosis correlated with the p21Waf1/Cip1 level.

We investigated the sensitivity and cell-cycle inhibitory gene expression of human papillomavirus (HPV) 16- and 18-positive human cancer cell lines after DNA damage induced by treatment with the anti-cancer drug cisplatin. Four HPV-positive cell lines (Caski, SiHa, HeLa and KB) were treated with cisplatin at various concentrations. Apoptotic cell death was observed in a dose-dependent manner in all cell lines treated with cisplatin; however, colony assay for chemosensitivity revealed that HeLa and KB cells (HPV 18-positive cell lines) were more sensitive than SiHa and Caski cells (HPV 16-positive cell lines). Northern blot analyses showed that p53 and p21Waf1/Cip1 mRNA were detectable in all untreated cells, and increasing amounts of these transcripts were identified in all cell lines treated with cisplatin. However, signals were more prominent in HeLa and KB, HPV 18-positive-cells. Immunohistochemical detection of p21Waf1/Cip1 protein showed that the p21-positive cells with apoptotic features were more distinct in KB and HeLa cells (HPV 18-positive) than in SiHa and Caski cells (HPV 16-positive). Our results show that there were differences in sensitivity to cisplatin among four types of high risk HPV-positive cells, possibly due to different levels of p21Waf1/Cip1 up-regulation by functional p53.

Apoptosis↗
PubMed1996

32P-Postlabeling analysis of a DNA adduct, an N2-acetyl derivative of guanine, formed in vitro by methylglyoxal and hydrogen peroxide in combination.

Methylglyoxal is a direct-acting mutagen in Salmonella typhimurium TA100 and its mutagenicity is markedly enhanced in the presence of hydrogen peroxide. In addition, a mixture of methylglyoxal and hydrogen peroxide reacts with 2'-deoxyguanosine to form N2-acetyl-2'-deoxyguanosine. We examined whether the guanine residues in DNA were acetylated by methylglyoxal in the presence of hydrogen peroxide using the 32P-postlabeling method. First, N2-acetyl-2'-deoxyguanosine 3'-monophosphate and N2-acetyl-2'-deoxyguanosine 3,5'-diphosphate were chemically synthesized as standard compounds for the analysis. Then calf thymus DNA (3.24 micromol) was treated with methylglyoxal (64.8 micromol) at pH 7.4 for 3 h at 37 degrees C, and subsequently with hydrogen peroxide (64.8 micromol) at 37 degrees C for 2 h. The adduct formation was analyzed using HPLC in combination with the 32P-postlabeling method under the standard conditions. N2-Acetyl-2'-deoxyguanosine was detected at levels of 2/10(6) nucleotides in double-stranded DNA and 1/10(5) nucleotides in single-stranded DNA. The estimated limit of detection by our method was 3 per 10(8) nucleotides.

Acetylation↗
PubMed1996

Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) in 23 cases of ameloblastoma.

Ameloblastoma is the most frequent odontogenic tumour. It occurs mainly in the mandible and grows expansively. The treatment of ameloblastoma, which influences the prognosis, is decided in consideration of many factors, especially the age and size of the tumour. Conservative treatment sometimes leads to the recurrence of tumours and poor prognosis, but the relationships between the prognosis and the cytological features of tumour cells are still unclear. In the present study, we examined the immunohistochemical detection of proliferating cell nuclear antigen (PCNA) in 23 cases of ameloblastoma and evaluated the correlation between the positive index of PCNA and the clinical and histological character. Our results revealed the higher the age of the patient the greater was the incidence of a positive index of PCNA. It was also shown that the mean positive PCNA index in the follicular type (34.56 +/- 14.00 S.D.) was higher than that of the plexiform type (24.436 +/- 15.74 S.D., P < 0.10). The cystic type showed a low positive PCNA index (14.75 +/- 8.41 S.D.). In the follicular type, the localisation of PCNA-positive cells was different according to the histological patterns of tumours. Additionally, the positive indices of the same patient differed at different periods of treatment.

Adult↗
PubMed1996

Presence of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (dG-C8-MeIQx) in human tissues.

One of the mutagenic and carcinogenic heterocyclic amines (HCAs), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), is present in cooked foods and we are chronically exposed to this compound in our daily life. To study the role of HCAs in human carcinogenesis, we analyzed MeIQx-DNA adducts in 38 DNA samples obtained from surgical and autopsy specimens by the 32P-postlabeling method under adduct-intensification conditions with the modification of additional digestion with nuclease P1 and phosphodiesterase I after 32P-labeling at 5'-hydroxyl termini. This modified 32P-postlabeling method can detect N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo- [4,5-f]quinoxaline 5'-monophosphate (5'-pdG-C8-MeIQx) at levels down to 1/10(10) nucleotides. The DNA samples from colon and rectum surgical specimens and a kidney taken at autopsy were found to contain an adduct spot corresponding to that of standard 5'-pdG-C8-MeIQx on TLC at levels of 14,18 and 1.8 per 10(10) nucleotides, respectively. Each adduct spot was extracted from TLC and identified to be 5'-pdG-C8-MeIQx by HPLC. Thus, MeIQx-DNA adducts actually exist in human tissues and this adduct formation may be involved in human cancer development.

Aged↗
PubMed1996

Formation of DNA adducts by the co-mutagen norharman with aromatic amines.

Norharman, widely distributed in our environment, is alone not mutagenic to Salmonella typhimurium TA98 and TA100 either with or without S9 mix, but becomes mutagenic to S.typhimurium TA98 with S9 mix when non-mutagenic aromatic amines like aniline or o- or m-toluidine are added. Thus norharman has been called a 'co-mutagen'. In the present study we examined whether or not DNA adducts are formed in DNA of S.typhimurium TA98 by treatment with norharman and aromatic amines using 32P-post-labeling analysis under modified adduct intensification conditions. When a sample of norharman (8 mg) and aniline (4 mg) was incubated with 4 ml of overnight culture of S.typhimurium TA98 in the presence of 20 ml S9 mix for 6 h at 37 degrees C, three adduct spots were detected at a total relative adduct labeling (RAL) of 10.8 +/- 2.27/10(8) nucleotides. Under the same conditions, a mixture of norharman (8 mg) and o-toluidine (4 mg) yielded three adduct spots at a RAL of 3.74 +/- 1.71/10(8) nucleotides. With a combination of norharman and m-toluidine, a single adduct spot was seen at a RAL of 0.04 +/- 0.01/10(8) nucleotides. In contrast, norharman with p-toluidine did not produce adduct spots. Furthermore, neither norharman nor the aromatic amines themselves gave any evidence of adducts. Thus DNA adduct formation by norharman with aromatic amines correlates with the co-mutagenic action of norharman in S.typhimurium TA98.

Amines↗
PubMed1996

Time-dependent expression of bone sialoprotein fragments in osteogenesis induced by bone morphogenetic protein.

Bone sialoprotein is unique to bone and dentin, but its precise role in these tissues is still unknown, although several hypotheses have been presented. We chose ectopic chondro- and osteogenesis induced by bone morphogenetic protein (BMP) as a model system to examine the role of this protein. Partially purified bovine BMP obtained by a three-step chromatographic procedure contained all the active BMPs (natural BMP cocktail). It was combined with insoluble bone matrix and subcutaneously implanted into rats. Expression of bone sialoprotein (BSP) in the implants was followed by using a monoclonal antibody as previously reported. Immunostaining studies showed BSP in the osteoblasts lining the new bone surface at 5 weeks. Western blotting showed 53 and 30 kDa bands, instead of the 57 kDa band normally found in rat femur. These two fragments were metabolically labeled with [3H]proline. The total amount of the fragments rapidly increased after 3 weeks, and at 5 weeks was 3 times as high as that at 2 weeks and still increasing. This time-dependent change was almost parallel to that of osteocalcin. The amount of bone estimated in terms of calcium content increased until 3 weeks and was remained at a plateau thereafter. Alkaline phosphatase activity was prominent only in the first 3 weeks. It was concluded that the 53 and 30 kDa BSP fragments might contribute to maintenance or remodeling in BMP-induced ectopic bone formation.

Aging↗
PubMed1996

Human exposure to carcinogenic heterocyclic amines and their mutational fingerprints in experimental animals.

Heterocyclic amines (HCAs) are mutagens/carcinogens to which humans are exposed on almost a daily basis. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) is the most abundant of the various carcinogenic HCAs (present at a level of 0.56 to 69.2 ng/g of cooked meat or fish), with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) following it at 0.64 to 6.44 ng/g. HCAs have been found in the urine of healthy people who consume ordinary diets, while patients receiving parenteral alimentation lack, for example, PhlP and MelQx in their urine. Based on the concentrations of PhlP and MelQx in urine samples from 10 healthy volunteers, daily intake of MelQx in Japanese was calculated to be 0.3 to 3.9 micrograms/person, while that of PhlP was 0.005 to 0 micrograms. The Japanese consume more MelQx than Americans, whereas Japanese intake of PhlP was about one-third that of Americans. MelQx-DNA adducts have also detected in Japanese Kidney, colon, and rectum samples using the 32P-postlabeling method followed by identification using high-performance liquid chromatography (HPLC) analysis; the levels were 0.18, 1.8, and 1.4 per 10(9) nucleotides, respectively. In addition, we elucidated the mutational fingerprints of Phlp by analyzing Apc mutations in rat colon cancers induced by this carcinogen. Four of eight tumors had a total of five mutations in the Apc gene, four of which featured a guanine deletion from 5'-GTGGGAT-3' sequences. This specific mutation spectrum may be used as a fingerprint of PhlP in evaluating its risk potential for human colon carcinogenesis. Mutations were not found in similar 2-amino-3-methylimidazo[4,5-f]quinoline-induced colon lesions. Microsatellite instability was detected in both colon and mammary tumors induced by PhlP. The mechanisms involved in this development of microsatellite instability in PhlP. The mechanisms involved in this development of microsatellite instability in PhlP-induced cancers remain to be elucidated.

Amines↗
PubMed1996

Dose-dependent effect of niceritrol on plasma lipoprotein-a.

Lipoprotein-a, Lp(a), is a variant form of low density lipoprotein (LDL) that contains apolipoprotein-a, whose structure has 75-85% homology with plasminogen. Elevated plasma levels of Lp(a) are considered to be one of the independent risk factors for cardiovascular disease. We studied the effects of niceritrol, a nicotinic acid derivative, on plasma Lp(a) levels in 72 patients with hypercholesterolaemia. The dose of niceritrol was increased every 4 weeks, from 750 to 1500 and then to 2250 mg day-1. The final dose was adjusted to obtain a plasma cholesterol level less than 5.69 mmol l-1. Niceritrol led to significant decreases in plasma levels of median Lp(a), from 16.1 mg dl-1 (interquartile intervals, 8.7 to 32.8) to 11.1 mg dl-1 (interquartile intervals, 6.6 to 21), the mean reduction rate being 17.6%. In the group with pretreatment Lp(a) levels of over 20 mg dl-1, Lp(a) decreased by 10.0, 22.0 and 31.8% at the doses of 750, 1500, and 2250 mg day-1, respectively. In the group with levels less than 20 mg dl-1, only the dose of 2250 mg day-1 was effective in the reduction of Lp(a). The results suggest that the reduction of Lp(a) was dependent on the dose of niceritrol and on the pretreatment level of Lp(a). In conclusion, niceritrol is effective, in a dose-dependent manner, for reducing Lp(a) levels.

Aged↗
PubMed1995

Anemia due to reduced serum erythropoietin concentration in non-uremic diabetic patients.

We encountered two patients with non-insulin-dependent diabetes mellitus (DM) who developed normocytic normochromic anemia. Routine hematological examinations revealed no specific causes except for the reduced serum levels of erythropoietin. Since their renal functions were preserved, the anemias may not have been due to chronic renal failure. Treatment with human recombinant erythropoietin (rHuEPO) improved anemia, ascribing the cause of anemia to low levels of erythropoietin in these patients. Underlying common clinical features of the two patients were longstanding poorly controlled diabetes mellitus accompanied with advanced neuropathy. Since erythropoietin production is regulated in part by autonomic nervous system, the results suggest that erythropoietin production could be prematurely impaired in patients with severe diabetic autonomic neuropathy.

Anemia↗
PubMed1995

Hepatocellular carcinoma metastatic to the mandible.

A case of hepatocellular carcinoma metastatic to the mandible is described. The patient reported swelling, pain, and trismus after a pathologic fracture. After a systematic examination with the use of 99mTc-methylene diphosphonate, 67Ga-citrate, and 99mTc-pyridoxyl-5-methyl triptophan scintigraphy the primary focus was discovered in the right lobe of the liver. The focus was confirmed by computed tomography and magnetic resonance imaging. The histopathologic diagnosis of hepatocellular carcinoma was made from a biopsy specimen of the mandibular lesion.

Carcinoma, Hepatocellular↗
PubMed1995

[Bladder tumor associated with von Recklinghausen's neurofibromatosis: a case report].

A 47-year-old female was admitted to our hospital complaining of macrohematuria. The patient had a history of von Recklinghausen's disease. Her skin showed multiple cafe-au-lait spots and neurofibromatosis. Thorough examinations were done. Urine cytology was positive. Intravenous pyelography and cystography demonstrated an irregular wall of the bladder. A computerized tomographic scan demonstrated a 7 cm nodular mass. Cystoscopy revealed a papillary tumor on the right lateral and anterior wall of the bladder. She was diagnosed as having a bladder tumor in von Recklinghausen's neurofibromatosis. Total cystectomy was performed. Histopathological diagnosis was transitional cell carcinoma with squamous cell carcinoma (Grade III, pT3N2N0). Fifty three cases of von Recklinghausen's disease in the literature were accompanied with malignancy.

Carcinoma, Squamous Cell↗
PubMed1995

[Change in serum prostate specific antigen values in men who had no evidence of prostate cancer on initial biopsy].

To determine the need for repeat prostatic biopsy, we retrospectively evaluated 19 men for longitudinal prostate specific antigen (PSA) for more than 20 weeks from initial biopsy. Their initial biopsy results revealed no evidence of prostatic cancer. They had no surgical therapy or hormone therapy after it. If they had a 50% increase in the PSA level from initial biopsy, we performed the second biopsy. Of the 5 men who had the second biopsy, 3 men had prostatic cancer.

Biopsy↗