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Biomedical subjects

N Takada

Publications and source records attributed to N Takada.

At least 19 recordsLinked to original sources
PubMed1992

Allelotype analysis in osteosarcomas: frequent allele loss on 3q, 13q, 17p, and 18q.

We have investigated the involvement of tumor suppressor genes in the genesis of osteosarcoma by analyzing allele losses at polymorphic loci in tumor tissues. Genotypes of DNA from primary osteosarcoma tissue and corresponding normal cells from 37 patients were analyzed at 58 polymorphic loci representing each autosomal chromosome arm except 5p and 20q. Allele losses were found at polymorphic loci on 36 of 37 chromosome arms analyzed. In particular, four of them showed frequencies of allele loss higher than 60%: 3q (75%); 13q (68%); 17p (72%); and 18q (64%). This result suggests that, in addition to the RB (retinoblastoma) gene on 13q and the p53 gene on 17p, at least two more tumor suppressor genes located on 3q and 18q are frequently involved in the development of osteosarcoma. The extent of allele losses as defined by fractional allelic loss among 36 tumors was diverse, from 0 to 0.64. The median fractional allelic loss value of 0.32 was much higher than those previously reported in colorectal carcinoma and breast carcinoma. Although no definite association of fractional allelic loss value to clinical prognosis of each case was found in osteosarcoma, tumors with 17p loss were more prone to the early onset of lung metastasis than tumors without 17p loss, indicating that allele loss on chromosome 17p can be a useful measure of prognosis.

Adolescent↗
PubMed1992

Clinical backgrounds of the patients having different types of hepatitis C virus genomes.

Hepatitis C virus (HCV) genomes were recently detected in biological materials, and variations of nucleotide sequences were reported. In the present study, typing of the HCV genomes was performed in 91 HCV-RNA-positive patients and the clinical features of patients with different types of HCV were compared. From the nucleotide sequences of the cDNA fragments, HCV can be divided into at least two types: HCV-K1-PT and HCV-K2. All cDNAs amplified from 91 patients were hybridized with cDNA probes of either HCV-K1-PT or HCV-K2. HCV-K1-PT was found in about 80% of the patients, and HCV-K2 was found in about 20% of the patients. These results indicate that types of HCV are limited to two types, i.e., K1-PT and K2, and the major type is HCV-K1-PT, at least in Japan. Detection rate of antibodies to C-100-3 protein were not different between the patients having HCV-K1-PT and HCV-K2, indicating that the antibodies may develop in HCV-related patients without relation to the types of the HCV genomes. Prevalence of the two types of HCV were nearly the same in various forms of NANB-related liver disease. However, the prevalence was somewhat different in alcoholic liver disease. HCV-K2 was found in patients younger than the patients with HCV-K1-PT. Frequency of a history of blood transfusion tended to be lower and the initial response to interferon treatment was clearly better in patients having HCV-K2 versus patients having HCV-K1-PT. These results suggest the possibility that clinical features due to HCV-K1 may be somewhat different from those due to HCV-K1-PT. However, the number of patients examined was too small to allow a definite conclusion, indicating a necessity for further study with a larger number of patients.

DNA, Viral↗
PubMed1992

Immunotargeting chemotherapy for AFP-producing pediatric liver cancer using the conjugates of anti-AFP antibody and anti-tumor agents.

The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.

Adolescent↗
PubMed1992

Spermidine/spermine N1-acetyltransferase, a new biochemical marker for epithelial proliferation in rat bladder.

We examined the activity of spermidine/spermine N1-acetyltransferase (SAT), a rate-limiting enzyme of the biodegradation of polyamines, in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced transitional cell carcinoma (TCC) and melamine-induced papillomatosis of rat bladder, and compared the activity to that of ornithine decarboxylase (ODC). Both activities were higher in both lesions than in control rats. The difference between SAT and ODC activities in cancerous tissue and papillomatosis was not significant. Cells stained for proliferating cell nuclear antigen (PCNA) were abundant in papillomatosis. TCC had areas with much PCNA. The results indicated that an elevation of SAT activity occurs in both reversible and irreversible proliferation of bladder epithelium and could be important in bladder carcinogenesis.

Acetyltransferases↗
PubMed1992

[Vectors of Japanese spotted fever].

In the southeast coast of Shikoku, most of the Japanese spotted fever (JSF) patients were found to be infected with the rickettsial pathogen through bamboo plantation, and also the eschar was frequently noticed in skin inspection, so that it was clinically speculated to be caused by ticks. According to out field research, the tick fauna was very rich throughout that area, and it was permissible enough to determine ticks as the vectors, based on arising of anti-SF group rickettsiae (SFGR) antibody in mice inoculated with some tick emulsions, findings of rickettsiae reactive to patient sera or a species-specific monoclonal antibody to JSFR in the hemolymph cells of some ticks, and electron microscopical observations of SFGR in various internal organs including the salivary gland of ticks. Also the transovarial and transstadial transmission of SFGR in ticks were supposed. Our results suggest that common species (adult/nymph) of the genus Haemaphysalis may be the most related vectors to man, based on their dominances, SFGR-prevalences, behavior and incidences of infestation but also indicate that various genera and species should be kept as the potential vectors, in spite of JSFR isolation from a restricted species of ticks in the future.

Animals↗
PubMed1992

[Tsutsugamushi disease found in Haruna District, Gunma Prefecture--evaluations of the clinical features and the outbreak pattern].

From November to December in 1990, 7 cases of tsutsugamushi disease were found first in the southern foot of Mt. Haruna of Gunma Pref., Japan. The present study was conducted to clarify the clinical features and the outbreak pattern of rickettsial infection in this area. All the patients consisting of 6 males and 1 female farmers were admitted to our hospital, complaining of high fever, chills and skin rash on 5-12 days after working in the field. Based on laboratory examinations and one (or two) typical eschar, a tentative diagnosis of tsutsugamushi disease was made and all patients became better soon after the therapy with intravenous administration of minocyclin (200 mg/day). The high titer of serum antibody to Karp type Rickettsia (Orientia?) tsustugamushi was detected by an immunoperoxidase test (IP) in most of the patients, and also a Karp-like strain was isolated from only one patient, probably due to low virulence to mice. The agricultural areas along the Agatuma and Nakuta rivers in the northern foot of Mt. Haruna have been well known as the most endemic foci of the disease in Gunma Pref. Nevertheless, it was suggested that outbreaks of the disease might be potentially wide-spread throughout this Pref., when the prevalences of the disease were evaluated as incidences to a hundred thousand inhabitants or adjusted by the density of agricultural populations of each administrative divisions. As most of the patients in Gunma Pref. have been officially reported in autumn, a statistical trial indicates that there is a significant correlation between the levels of temperature and outbreaks of the disease in autumn.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Lung cancer accompanied by erythema.

Skin manifestations associated with malignant diseases are designated syndroma dermatotumorale. A case of lung cancer combined with atypical erythema is reported. A 70-year-old man was admitted to hospital because of a 4-month history of atypical erythema of unknown origin. A nodule in the right lung was revealed on chest roentgenogram which was diagnosed as lung cancer. After right upper lobectomy, the erythema regressed gradually and disappeared completely in 7 days. It is suggested that the erythema was a manifestation associated with the lung cancer.

Adenocarcinoma↗
PubMed1992

[Prediction of nocturnal desaturation in elderly patients with chronic respiratory disease].

Previous reports suggest that nocturnal disorders of sleep and breathing have increased prevalence among the elderly, and episodic nocturnal oxygen desaturation (NOD) has an increased incidence in patients with chronic respiratory disease. Current Japanese criteria for home low flow oxygen therapy (LFOT), recommend LFOT for patients with daytime PaO2 < 55 torr or with daytime PaO2 < or = 60 torr who have significant NOD. Strict adherence to these LFOT criteria requries full overnight monitoring of arterial oxygen saturation (SaO2) in all patients with daytime PaO2 < or = 60 torr. Since widespread nocturnal oximetry involves significant expenditure of time and resources, it is important among patients with chronic respiratory diseases to predict those who will have significant NOD. The aim of the present study was to formulate criteria for identification of patients who are most likely to demonstrate significant NOD based upon daytime respiratory function data. Subjects included 34 elderly patients with daytime PaO2 > or = 55 torr, who had stable severe chronic respiratory disease (15 chronic emphysema, 6 chronic bronchitis, 12 post-tuberculosis, and 1 kyphoscoliosis). Study data included medical history, assessment of dyspnea by Hugh-Jones classification, and measurement of daytime, awake arterial blood gases and spirometry. Each subject underwent full overnight oximetry monitoring. The percentage of total sleep time recorded with SaO2 < or = 85% was noted (DST85), and NOD was defined as DST85 > or = 1%. Of the 34 patients, 11 were identified as NOD, and 23 as non-NOD patients. Duration and severity of dyspnea were not different between NOD and non-NOD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Atypical lymphocytes with a multilobated nucleus from a patient with tsutsugamushi disease (scrub typhus) in Japan.

A case of tsutsugamushi disease (scrub typhus) with atypical lymphocytes with a multilobated nucleus is reported. Although this type of atypical lymphocyte has been reported in patients with viral infections such as adult T-cell leukemia, infectious mononucleosis, human immunodeficiency virus (HIV) infection, this is the first reported case of atypical lymphocyte with a multilobated nucleus in a patient with rickettsial infection. This type of atypical lymphocyte seems to exist in a broad spectrum of infectious diseases.

Cell Nucleus↗
PubMed1991

Hepatitis C virus RNA genome in plasma of patients with non-A, non-B hepatitis.

Recently, the assay system of anti-hepatitis C virus antibody (HCV-Ab) was developed. However, there is no clinically useful method to detect hepatitis C virus (HCV) itself. The authors recently developed a method to detect the HCV-RNA genome in plasma using polymerase chain reaction (PCR). In the present study, the specificity of this assay in detecting HCV infection was investigated. Freshly obtained 1 ml plasma specimens from 100 patients with various liver diseases and from 11 control subjects were studied. In patients with non-A, non-B (NANB) hepatitis-related liver diseases, HCV-RNA was detected in 2 out of 7 cases of acute hepatitis, in 29 out of 31 cases of chronic hepatitis, in 17 out of 21 cases of cirrhosis and in 2 out of 6 cases of hepatocellular carcinoma. On the other hand, no HCV-RNA was detected in 15 cases of various types of alcoholic liver diseases, in 12 cases of hepatitis B related liver diseases, and in 11 controls. HCV-RNA was detected in 2 of 6 drinkers with chronic hepatitis. The prevalence of HCV-RNA was not closely related to a history of blood transfusions. These results suggest that our method for HCV-RNA is specific for HCV infection and HCV infection is the likely etiology of most chronic NANB hepatitis cases. The clinical usefulness of our method is illustrated by the fact that we were able to study 100 patients and needed only 1 ml plasma per HCV-RNA assay.

Electrophoresis, Polyacrylamide Gel↗
PubMed1991

Typing of hepatitis C virus genomes by restriction fragment length polymorphism.

Recently, we reported that hepatitis C virus (HCV) can be classified genetically into two types, HCV-K1 and HCV-K2, which show 67% and 71% identity at the nucleotide and amino acid sequence levels in a 340 bp region which encodes the NS5 gene Gly-Asp-Asp motif. To develop a rapid method to classify the genomes of HCV isolates, we identified restriction fragment length polymorphisms (RFLPs) in reverse transcriptase-polymerase chain reaction products encoding a portion of the NS5 gene. AluI and AccII enabled HCV to be classified into the K1 and K2 types, and Sau96I enabled classification into the K1 type, and the K2a and K2b subtypes. These RFLPs also generally allow Japanese isolates to be distinguished from the prototype (PT, an isolate from the U.S.A.), which is a K1 type. Sequence analysis of the 5'-untranslated regions of Japanese isolates revealed near identity between the K1 type and PT, and 93 to 94% identity between the K1 and K2 types, indicating that there are type K1- and K2-specific RFLPs in this region. Our results suggest that the nucleotide sequences of the K1 and K2 types are different throughout the HCV genome. The incidence of HCV types K1, K2a and K2b, and PT in 50 samples was 74%, 16%, 8% and 2%, respectively.

Base Sequence↗
PubMed1991

Morphological and cytogenetic characterization and N-myc oncogene analysis of a newly established neuroblastoma cell line.

A permanent cell line established from a xenograft of neuroblastoma which occurred in a 5-year-old girl was investigated for its morphological and biological characteristics. The cultured cells were tumorigenic in nude mice. Microscopically, each tumor consisted of small round to polygonal cells with irregular nuclei and prominent nucleoli, corresponding to the features of the primary and xenografted tumor cells. Electron microscopic examination revealed that both the transplanted tumor cells and the cultured cells contained scanty microtubules and dense-core neurosecretory granules. Chromosome analysis of this cell line showed monosomy for chromosomes 1, 10, 19 and X, and structural rearrangements involving chromosomes 8, 17 and 20, in addition to numerous double minutes. The N-myc oncogene was found to be amplified 40- to 80-fold in the transplanted and cultured tumor cells, as well as in the primary tumor cells. In situ hybridization with a digoxigenin-labeled uridine-triphosphate N-myc RNA probe detected abundant mRNA in the tumor cells. This neuroblastoma line may become a valuable in vitro experimental model system for studies aimed at better characterization of neuroblastoma.

Animals↗
PubMed1991

[Hospital spread of scabies from an immunocompromised patient with Norwegian scabies].

Scabies was first found in a 71-year-old female who had been diagnosed as having leukemic transformation of primary myelofibrosis and had undergone treatment for the disease. She was admitted to the hospital in December 1986, because of abdominal fullness and a generalized subcutaneous tumor that proved to be myeloblastoma. For treatment of the underlying disease, the regimen of the combination of vindesine, cyclophosphamide, 6-mercaptopurine, and prednisolone was selected. She developed cardiac failure and fell into a coma one month after starting the anticancer therapy. She was put on artificial respiration and on additional steroid therapy as well. Dexamethasone was administrated at 16 mg/day. Since the myeloblastomas found on admission regressed, the steroid therapy was continued. She was in coma for a few days before her skin lesions turned red and formed a grayish crust in the lower abdominal region. Several days later, the doctor responsible for the treatment of this patient developed pruritus and exanthema on both arms, and soon many nurses in the same hospital-ward developed similar symptoms. At approximately the same time, the patient with myelofibrosis was diagnosed as having Norwegian scabies: the crusted skin lesions revealing many Sarcoptes scabiei mites. Two doctors (2/18), 17 nurses (17/19) and 3 other patients (3/51) were found to have contracted scabies, and we recognized the hospital spread of the infection. The first patient was isolated in a private room, and we avoided direct contact with her. The persons with scabies were treated with crotamiton liniment. The first scabies patient died of cardiac failure 1 month after falling into a coma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Different types of chronic hepatitis in alcoholic patients: does chronic hepatitis induced by alcohol exist?

To verify the existence of chronic hepatitis induced by alcohol, the clinicopathological features of chronic hepatitis in heavy drinkers were studied using various viral markers. Histological features of chronic active hepatitis were seen in 27 heavy drinkers. These patients were divided into four groups. The AL group (seven cases) consisted of alcoholics who were negative for both hepatitis C antibody and HBsAg; the HB group (four cases) was positive for HBsAg; the HC1 group (seven cases) was positive for hepatitis C antibody but negative for hepatitis C virus-RNA genome; and the HC2 group (nine cases) was positive both for hepatitis C antibody and hepatitis C virus-RNA genome. Serum AST and ALT activity declined during 4 wk of abstinence in most patients in the AL group and in the HC1 group. The response of serum AST and ALT to abstinence was poor in most patients in the HB group and the HC2 group. Serum desialo-transferrin and alcohol liver membrane antibodies were detected more frequently in the sera of patients in the AL group and HC1 group. A trend toward increased frequency of centrilobular ballooning existed in the AL group, but this did not reach statistical significance. These results suggest that chronic active hepatitis in patients in the AL group, in whom markers of HBV and hepatitis C virus were absent, may be caused by alcohol. Patients in the HC1 group who had hepatitis C antibody but not hepatitis C virus-RNA may represent cases where both alcohol and hepatitis C virus are involved.

Adult↗
PubMed1991

Alcoholic liver disease in heterozygotes of mutant and normal aldehyde dehydrogenase-2 genes.

To clarify the pathogenetic role of acetaldehyde in the development of alcoholic liver disease, genotyping of aldehyde dehydrogenase-2 genes was performed and the clinical features of the alcoholic liver disease patients with different genotypes were compared. Genotyping of aldehyde dehydrogenase-2 was performed in 47 patients with alcoholic liver disease using the polymerase chain reaction and slot-blot hybridization. Of the 47 patients with alcoholic liver disease, 40 were homozygous for the normal aldehyde dehydrogenase-2 gene and the remaining seven cases were heterozygous for the normal and mutant aldehyde dehydrogenase-2 genes. No homozygote was found for the mutant aldehyde dehydrogenase-2 genes. Daily alcohol intake was less than 100 gm in all heterozygotes without relation to the type of alcoholic liver disease. On the other hand, all but four patients homozygotic for the normal aldehyde dehydrogenase-2 gene drank more than 100 gm alcohol/day. The mean daily alcohol intake in the heterozygotes was significantly lower than that in the normal homozygotes. The incidence of alcoholic fibrosis tended to be lower in the heterozygotes than in the normal homozygotes (14.2% vs. 52.5%). On the other hand, the incidence of alcoholic hepatitis and/or cirrhosis tended to be higher in the heterozygotes than in the normal homozygotes. These results indicate that alcoholic liver disease develops even with moderate amounts of alcohol intake in heterozygotes of the aldehyde dehydrogenase-2 genes, in which acetaldehyde metabolism in the liver is impaired and liver damage in the heterozygotes is more severe than that in the normal homozygotes, suggesting that habitual drinkers who are heterozygotes of the aldehyde dehydrogenase-2 genes may be at high risk for alcoholic liver disease.

Alcohol Drinking↗