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Biomedical subjects

H Toyoshima

Publications and source records attributed to H Toyoshima.

At least 19 recordsLinked to original sources

Malignant lymphoma of the stomach associated with systemic sarcoidosis.

The case of a patient with gastric malignant lymphoma associated with systemic sarcoidosis is reported. The patient's sarcoidosis was identified by the findings of bilateral hilar lymphadenopathy and secondary glaucoma. Biopsy of a cervical lymph node showed epithelioid cell granuloma; the sarcoidosis was diagnosed 15 years previously. She had been treated with prednisolone for 5 years until 1979. Proximal gastrectomy, splenectomy, and lymph node dissection were done in 1989. The tumor was diagnosed as malignant lymphoma of the diffuse large cell type according to the Working Formulation. There was no infiltration of lymphoma cell in the 45 dissected lymph nodes, but sarcoid nodules were observed in all nodes. Only three cases of gastric malignant lymphoma complicating sarcoidosis have been reported to the authors' knowledge. Further study should be done in support of the concept of a sarcoidosis-lymphoma syndrome.

Aged

Frequent mutations in the p53 gene in human myeloid leukemia cell lines.

The p53 gene is currently considered to function as a tumor-suppressor gene in various human malignancies. In hematologic malignancies, alterations in the p53 gene have been shown in some human leukemias and lymphomas. Although mutations in the p53 gene are infrequent in acute myelogenous leukemia (AML) patients, we show in this report that alterations in the p53 gene are frequent in myeloid leukemia cell lines. We studied alterations of the p53 gene in nine human myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR), single-strand conformation polymorphism (SSCP) analysis, and direct sequencing. Expression of the p53 gene was not detected at all by RT-PCR in two of the nine cell lines. In these two cell lines, Southern blot analysis showed gross rearrangements and deletions in both of the p53 alleles. Six of the nine cell lines were found to express only mutant p53 mRNA by RT-PCR/SSCP analysis and direct sequencing, and wild-type p53 mRNA was not detected. Two of the mutant p53 mRNAs were shown to be products of abnormal splicing events induced by intronic point mutations. Taken together, eight of nine human myeloid leukemia cell lines expressed no or an undetectable amount of wild-type p53 mRNA. Three of the eight cell lines were growth factor-dependent. Our results suggest that inactivation of the p53 gene may be a common feature in myeloid leukemia cell lines and may play an important role in the establishment of these cell lines.

Base Sequence

[Effects of smoking and drinking habits and vitamin A intake on serum concentrations of beta-carotene and retinol].

Serum samples from 341 males aged 10 to 59 years were obtained and stored at -40 degrees C until examined for retinol and beta-carotene concentrations by HPLC, and their relationships to smoking habit, alcohol drinking habit and vitamin A intake were studied. In univariate analysis the serum beta-carotene level was significantly lower in the smokers than in the non-smokers (smokers: 4.6 micrograms/dl, non-smokers: 7.1 micrograms/dl, p less than 0.01) and lower in the drinkers than in the non-drinkers (drinkers: 4.6 micrograms/dl, non-drinkers: 7.3 micrograms/dl, p less than 0.01). The serum retinol level was not different by smoking habit but was higher in the drinkers than in the non-drinkers (drinkers: 80.4 micrograms/dl, non-drinkers: 67.0 micrograms/dl, p less than 0.01). Serum beta-carotene was higher in the group with a greater intake of vitamin A of vegetable origin (6.1 micrograms/dl) than in the group with a smaller intake of it (4.7 micrograms/dl) (p less than 0.01), but serum retinol was not different by the amount of vitamin A intake of animal food origin. To estimate the respective effects and interactions of the above factors on serum beta-carotene and retinol levels by adjusting for the confounding effects of age, serum total cholesterol, HDL-cholesterol and triglyceride, analysis of covariance was performed. For serum beta-carotene, smoking habit (p less than 0.01), drinking habit (p less than 0.01) and the amount of vitamin A intake of vegetable food origin (p less than 0.05) had significant main effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Circadian variations of sudden death].

Characteristics of the circadian variation for sudden death (SD), were studied by analyzing summary death certificates for the period of 1984 to 1986 in Niigata prefecture. SD was defined as death within 2 hours of onset of underlying cause (n = 4,362), and the time of onset of the cause was determined by subtracting the "time elapsed until death" from the "time of death." The periodicity for time of onset of the cause was analyzed in groups stratified by year, season, sex and age with Rogers' method utilized to check the statistical significance of the periodicity. SD, as a whole, showed a statistically significant circadian variation with a low incidence during 0 to 4 A.M. and a high incidence during 6 to 8 A.M. and 6 to 8 P.M. By season, no significant circadian variation was seen in the summer unlike for other seasons. When analyzed by age group, no significant circadian variation in SD was seen for the young to middle aged group (15-54 years old). On the other hand, there was a significant circadian variation for the senior (55 to 74 years old) and the elderly group (75 years old or older) with a low incidence during 0 to 4 A.M. and high incidence during 6 to 12 A.M. and 6 to 8 P.M.. For the old age group, the number of the cases increased so remarkably as to form an evening peak. The percentage of SD for young to middle cases was higher in the summer than in the other seasons which may be the reason for absence of significant circadian variation in the summer.

Adolescent

Emergent embolization for control of massive hemorrhage from a splanchnic artery with a new coaxial catheter system.

Emergent superselective embolization with a 3.0 F (1 mm) coaxial catheter and a steerable guidewire was performed in 27 patients with massive hemorrhage from a small-caliber splanchnic artery. Eight patients had intraperitoneal hemorrhage, 3 had hemobilia, 9 had gastric hemorrhage, and 7 had intestinal hemorrhage. Out of 27 patients, 7 had hemorrhage from a splanchnic artery pseudoaneurysm. Complete cessation of bleeding was obtained in all patients initially, but in 3 patients gastric hemorrhage recurred later. Otherwise, there was no rebleeding nor any major complication such as marked infarction of tissue or misplacement of embolic materials. This coaxial catheter system was highly reliable for achieving superselective catheterization in small-caliber arteries, minimizing the volume of infarcted tissue and allowing maximal preservation of splanchnic organic function. We conclude that this system represents a major advance in interventional radiology.

Adolescent

Mutations of the p53 gene in lymphoid leukemia.

p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase-polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenström's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias.

Base Sequence

[Past histories of sudden death without specific underlying disease].

To study past histories of patients who died suddenly, we selected cases from all the summary death certificates in which death occurred within 24 hours from the onset of symptoms spanning 1984 to 1986 in Niigata prefecture with a population of 2.5 million. We then re-examined all information on the death certificates to determine the underlying causes. Sudden deaths due to cardiovascular diseases other than acute myocardial infarction and cerebrovascular accident (OCD) accounted for the largest proportion (51.4%). The proportion of death of unknown etiology increased with the decrease in age in both sexes aged 15 to 54 years, accounting for 67.8% in males and 51.1% in females. The number of cases with histories of diseases related to atherosclerosis (e.g. hypertension, old cerebrovascular accident, etc) increased with age in both sexes, accounting for 38.5% in males and 36.4% in females, both aged 75 years old and over. Except diseases related to atherosclerosis, the past histories accounted for 2.5% or greater were as follows: alcoholism (4.1%), psychiatric disorder (PSY, 2.9%) and valvular heart diseases (VD, 2.6%) in 15-54-year-old males; ischemic heart diseases (IHD, 9.4%), arrhythmia without organic heart diseases (ARR, 2.5%) and VD (2.5%) in 55-74-year-old male; IHD (11.4%), bronchial asthma (3.7%), common cold within one month (CC, 3.6%), cor pulmonale or its related diseases (3.0%) and ARR (2.6%) in male of 75 years old and over; PSY (8.7%), IHD (5.8%), VD (5.1%), pregnancy, delivery or related diseases (4.4%), chronic renal failure (3.6%) and CC (2.9%) in 15-54-year-old females; IHD (10.2%), VD (3.2%) and ARR (2.6%) in 55-74-year-old females; and IHD (11.8%) in females of 75 years old and over. When diseases related to atherosclerosis were included, half of the sudden death cases due to OCD had past histories of underlying cause. As descriptions of past histories are often incomplete, there were probably more cases with past histories. The results of this study indicate that investigation of past histories may aid in elucidating and preventing sudden death.

Adolescent

[Nuclear DNA analysis of benign skin tumor and carcinoma in site developed from keratinocyte].

To know the variation of DNA contents of seborrheic keratosis, keratoacanthoma, actinic keratosis, and Bowen's disease, cytophotometric assay was used. As the results, following findings were obtained. 1. DNA index of actinic keratosis was higher than those of seborrheic keratosis and keratoacanthoma. 2. DNA index of Bowen's disease was higher than that of seborrheic keratosis. 3. Polyploid cell population (greater than 6C) of keratoacanthoma was higher than that of seborrheic keratosis. 4. Polyploid cell populations (greater than GC) of carcinoma in site (actinic keratosis, Bowen's disease) were higher than that of keratoacanthoma . These date suggested that polyploid cell population and DNA index reflect grade of malignancy of tumor developed from keratinocytes. A clinic keratosis and Bowen's disease revealed almost the same DNA pattern. And the difference of polyploid cell population of keratoacanthoma++ ++ and seborrheic keratosis suggested the difference of the biological activity of them.

Aged

[Nuclear DNA contents in the cells of squamous cell carcinoma. III. Separation and analysis of polyploid cells].

In order to reveal the cytological nature of polyploid cells, the cell suspension of squamous cell carcinoma was separated into low density (1.050 greater than), intermediate density (1.050 to 1.088), and high density (1.988 greater than) fractions, by density gradient centrifugation. The DNA content of the tumor cells in each fraction were measured on the smear specimens prepared by Giemsa's staining and Feulgen's stainings. As the results, it was found that the cells showing high NC ratio and having high DNA content were observed in the high density fraction. However, there was no specific relationship between the nuclear contour index and density of the tumor cell.

Aged

[Influences of polychlorinated dibenzofuran on pUC18 plasmid DNA].

We investigated an effect of polychlorinated dibenzofuran (PCDF) on pUC18 plasmid DNA. The mixtures of pUC18 and PCDF were introduced into the competent cells derived from E. coli. The competent cells were cultured on Luria-Bertani agar plate containing ampicillin. The number of colonies was not decreased in compared with it of E. coli inserted non-treated pUC18. The pUC18 re-extracted from the E. coli with PCDF-treated pUC18 were digested with 15 kinds of restriction enzymes and agarose gell electrophoresed. As the results no changes were found in compared with non-treated pUC18. Those findings suggested that the PCDF did not react with pUC18.

Benzofurans

[A study of epidermal alterations induced by PCDF on experimental carcinogenesis].

An effect of 2,3,4,7,8-pentachlorodibenzofuran (PCDF) as a promoter on a course of experimental skin carcinogenesis in mice by chemicals 20-methylcholanthrene (MC) has been proved by our previous studies. Details of ultrastructural epidermal alterations induced by MC and PCDF were observed and an attempt to differentiate benign tumor from malignant one in which a combined application of MC and PCDF on mice skin resulted was done electron microscopically. Four significant findings as follows were detected. First of all even the epidermal cells without tumor had some atypicality. Secondly both of benign tumor and normal-appeared skin without tumor had giant and round-shaped keratohyalin granules (KHGs) which show a tendency of less keratinization. Thirdly cytoplasmic projections of epidermal cells increased in number and sparse tonofilaments scattered in the cytoplasm of benign tumor. This is also an appearance of mucous metaplasia of keratinocytes as well as the form of KHGs mentioned above. Finally benign tumor had thick horny cells including numerous lipid droplets, and that is a sign of acceleration of epidermal turn over. Since epidermal cells have little chance to be exposed to carcinogens when they quickly keratinize, they rarely form a cancer. When epidermal cells have such tendency as less keratinization or more keratinization, they are supposed to be less sensitive to any stimuli of carcinogens, and consequently they incline to be benign tumor instead of malignant one.

Animals

HTLV-1 Rex protein accumulates unspliced RNA in the nucleus as well as in cytoplasm.

The Rex protein of human T-cell leukemia viruses (HTLV) is a trans-acting regulator inducing the expression of gag and env mRNA containing the introns. The rex gene can also induce expression of unspliced RNA of human immunodeficiency viruses (HIV). We have analyzed the level of spliced and unspliced RNAs in nucleus and cytoplasm to understand the mechanism by which the Rex protein modulates RNA processing. With the gag gene of HTLV-1, the unspliced RNA was accumulated by Rex protein in both nucleus and cytoplasm. However, the apparent effects on nuclear unspliced RNA depended on the reporter genes: with the env gene of HTLV-1 as well as that of HIV-1, Rex did not accumulate the unspliced RNA in nucleus, but did so only in cytoplasm. These results clearly indicate that Rex protein not only activates the nuclear export of unspliced RNA, but also modulates some steps of RNA processing before the splicing, probably through stabilization of the precursor RNA.

Cell Nucleus

[Analysis of DNA synthetic activity of aged epidermis].

The basal cells of old and young guinea pigs were separated by use of density gradient centrifugation. DNA contents of basal cells were measured on the smear specimens prepared by Feulgen's stainings. DNA synthetic activities of old guinea pigs and those of young guinea pigs were almost the same. These date suggested that there was no specific relationship between the DNA synthetic activity and aging of epidermis.

Aging

Total gastrectomy for gastric cancer in the elderly.

Of 1070 patients with gastric cancers, 292 patients underwent total gastrectomy during 13 years. Sixty patients were more than 70 years of age and 232 were under 69 years. The incidence of well-differentiated carcinomas and poorly differentiated carcinomas was the same in the elderly patients, whereas the latter was dominant in the young patients. However, there was no significant difference between the two groups regarding location, size, macroscopic patterns, extent of lymph metastases, or stage classification. The rates of preoperative surgical risk factors were significantly different between the two groups (p less than 0.01): 90.0% for the elderly and 34.9% for the young patients. However, the rates of postoperative morbidity and mortality were 31.7% and 3.3% for the elderly and 24.1% and 1.3% for the young patients, respectively, with no significant difference. The 5- and 10-year survival rates after curative total gastrectomy were 48.6% and 23.2% for the elderly compared with 49.4% and 33.6% for the young patients, respectively, with no significant difference. A 5-year survival rate after noncurative operation was 0% for the elderly and 6.4% for the young patients. These results indicate that, when performed for cure, total gastrectomy with systematic lymphadenectomy can provide good long-term results for elderly, as well as young, patients.

Age Factors

Secondary structure of the human T-cell leukemia virus type 1 rex-responsive element is essential for rex regulation of RNA processing and transport of unspliced RNAs.

Rex protein of human T-cell leukemia virus type 1 (HTLV-1) induces cytoplasmic expression of unspliced gag/pol mRNA and singly spliced env mRNA and thus is essential for replication of the virus. This regulation requires a cis-acting rex-responsive element (RXE), located in the 3' region of the viral RNA. By external deletion, we have identified RXE composed of 205 nucleotides. The secondary structure of RXE was confirmed by studies on its susceptibility to nuclease digestions to consist of four stem-loops and a long stretch of stem structure. Substitution and deletion mutations revealed that two regions of the stem-loops and their secondary structures are essential for rex regulation. Similar secondary structures were found in the corresponding regions of HTLV-2, bovine leukemia virus and human immunodeficiency virus. Furthermore, a sequence of 11 nucleotides in the RXE was found to be conserved in the secondary structures of HTLV-1, HTLV-2, and bovine leukemia virus. These observations suggest that the secondary structure as well as the conserved sequence may be important in expression of unspliced RNA even with diverged sequences as observed in these viruses.

Base Sequence

[Detection of activated oncogenes in hematological malignancies using RT-PCR method and its clinical applications].

Recently, a new and simple method of PCR has been developed and its application is extending widely including clinical research. We are using this method to detect various activated oncogenes within clinical samples from hematological malignancies. We now attempt to use these results as supporting evidences in clinical diagnosis. Here we report several successful results we have obtained through the study of activated RAS oncogenes.

Adult