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Biomedical subjects

S Takada

Publications and source records attributed to S Takada.

At least 217 records · Page 12Linked to original sources

[Oral etoposide therapy in stage III-IV ovarian carcinoma].

Seven patients with Stage III-IV ovarian carcinoma were treated with oral etoposide. The patients received a dose of 25 or 50 mg/day/body for every day or 21 consecutive days every one months. Four patients received this treatment as second line chemotherapy, two as initial chemotherapy and one as maintenance chemotherapy. One of 6 patients with measurable tumor had complete response, one had partial response and four had no changes. One patient with embryonal carcinoma, who received this treatment as maintenance chemotherapy is in no relapse for 2 years and 2 months. Leucopenia with a WBC under 3,000/mm3 was seen in 3 cases. Oral mucositis occurred in 2 cases, hair loss and gastrointestinal toxicities in 1 case. This method of oral administration is effective, tolerated and convenient for advanced ovarian carcinoma and recurrence following prior, vigorous chemotherapy in a outpatient clinic.

Administration, Oral↗

Antisense RNA of the latent period gene (MER5) inhibits the differentiation of murine erythroleukemia cells.

The MER5 cDNA was cloned from RNA preferentially synthesized in murine erythroleukemia (MEL) cells during the early period of MEL cell differentiation. To understand the role of the MER5 gene in the differentiation, we have transferred the MER5 cDNA into MEL cells in both sense and antisense orientations under control of the promoter of the human metallothionein gene. Only in the transformants with the antisense MER5 cDNA, did their elevated expression inhibit differentiation. The result suggests that the MER5 gene product may promote early events in the differentiation of MEL cells.

Amino Acid Sequence↗

Microtubule translocation caused by three subspecies of inner-arm dynein from Chlamydomonas flagella.

To help understand the function of inner-arm dynein in flagellar motility, dynein samples from an outer arm-missing mutant of Chlamydomonas (oda1) were examined for the ability to translocate microtubules in vitro. High-salt extract of axonemes containing inner-arm dynein was separated by ion-exchange chromatography into 7 peak fractions with ATPase activities. Of these, three fractions containing different sets of dynein heavy chains translocated microtubules. The maximal velocities were all between 3 and 5 microns/s, which were comparable to the microtubule sliding rate in disintegrating oda axonemes.

Adenosine Triphosphatases↗

Integrated structures of HBV DNA in chronic hepatitis and hepatoma tissues.

Cellular DNAs of chronically hepatitis B virus (HBV)-infected human livers were analysed by Southern blot hybridization for the presence of integrated HBV DNA. In 15 out of 16 tissue samples, random HBV DNA integration was evident. By molecular cloning and structural analyses of 19 integrants from 3 chronic hepatitis tissues, rearrangement of HBV DNA with inverted duplication or translocation of cellular flanking DNA at the virus-cell junction was noted. Thus, the rearrangement of HBV DNA or cellular flanking DNA not to be a specific incident of HCC formation. Analyses of various integrants bearing HBV DNA rearrangement and their cellular counterpart DNAs failed to indicate any gross structural alteration in cellular DNA except for a small deletion at the integration sites, indicating HBV DNA rearrangement with inverted duplication to possibly occur prior to integration. Based on nucleotide sequencing analyses of virus-virus junctions, a mechanism of this inverted duplication of HBV DNA is proposed, in which an illegitimate recombination may take place by means of a patchy homology on one side of adjoining viral sequences.

Base Sequence↗

Trans-activation function of a 3' truncated X gene-cell fusion product from integrated hepatitis B virus DNA in chronic hepatitis tissues.

To investigate the expression and transactivation function of the X gene in integrated hepatitis B virus (HBV) DNA from chronic hepatitis tissues, a series of transfectants containing cloned integrated HBV DNAs was made and analyzed for X mRNA expression and trans-activation activity by using a chloramphenicol acetyltransferase assay. Most of the integrated HBV DNAs expressed X mRNA and encoded a product with trans-activation activity in spite of the loss of the 3' end region of the X gene due to integration. From cDNA cloning and sequence analysis of X mRNA transcribed from native or integrated HBV DNA, the X protein was found to be translated from the X open reading frame without splicing. For integrated HBV DNA, transcription was extended to a cellular flanking DNA and an X gene-cell fusion transcript was terminated by using a cellular poly(A) signal. The amino acid sequence deduced from an X-cell fusion transcript indicated truncation of the carboxyl-terminal five amino acids, but the upstream region of seven amino acids conserved among hepadnaviruses was retained in the integrated HBV DNA, suggesting that this conserved region is essential for the transactivation function of the X protein. These findings support the following explanation for hepatocarcinogenesis by HBV DNA integration: the expression of a cellular oncogene(s) is transactivated at the time of chronic infection by the increasing amounts of the integrated HBV gene product(s), such as the X-cell fusion product.

Amino Acid Sequence↗

X protein of hepatitis B virus resembles a serine protease inhibitor.

The X protein of hepatitis B virus (HBV) has been shown to be a trans-activator for viral and cellular genes. Amino acid sequences in X protein were found to be highly homologous to functionally essential sequences in the "Kunitz domain," characteristic of Kunitz-type serine protease inhibitors. Mutations at these sequences completely abolished trans-activation. Consequently, HBV X protein resembles a serine protease inhibitor or its analogue, and may bring about trans-activation by activating certain transcriptional factors through proteolytic cleavage alteration.

Amino Acid Sequence↗

Structural rearrangement of integrated hepatitis B virus DNA as well as cellular flanking DNA is present in chronically infected hepatic tissues.

Cellular DNAs from human livers chronically infected with hepatitis B virus (HBV) were analyzed by Southern blot hybridization for the presence of integrated HBV DNA. In 15 of 16 chronically infected hepatic tissues, random HBV DNA integration was evident. By molecular cloning and structural analyses of 19 integrants from three chronically infected hepatic tissues, deletion of cellular flanking DNA in all cases and rearrangement of HBV DNA with inverted duplication or translocation of cellular flanking DNA at the virus-cell junction in some cases were noted. Thus, the rearrangement of HBV DNA or cellular flanking DNA is not a specific incident of hepatocellular carcinoma formation. Detailed analyses of various integrants bearing rearranged viral DNA failed to indicate any gross structural alteration in cellular DNA, except for a small deletion at the integration site, indicating that viral DNA rearrangement with inverted duplication possibly occurs before integration of HBV DNA. Based on nucleotide sequencing analyses of virus-virus junctions, a one- to three-nucleotide identity was found. A mechanism for this inverted duplication of HBV DNA is proposed in which illegitimate recombination between two complementary viral strands may take place by means of a nucleotide identity at the junction site in a weakly homologous region (patchy homology) on one side of adjoining viral sequences. For virus-cell junctions, the mechanism may be basically similar to that for virus-virus junctions.

Adolescent↗

Structure of a Plasmodium yoelii gene-encoded protein homologous to the Ca(2+)-ATPase of rabbit skeletal muscle sarcoplasmic reticulum.

A cation-transporting ATPase gene of Plasmodium yoelii was cloned from the parasite genomic library using an oligonucleotide probe derived from a conserved amino acid sequence of the phosphorylation domain of the aspartyl phosphate family of ATPases. The complete nucleotide sequence was determined and it predicts a 126,717 Mr encoded protein composed of 1115 amino acids. Northern blot analysis revealed that the gene is transcribed during the asexual stages of parasite development. The P. yoelii protein contains functional and structural features common to the family of aspartyl phosphate cation-transporting ATPases. The parasite protein shows the highest overall homology in amino acid sequence (42%) to the Ca2(+)-ATPase of rabbit skeletal muscle sarcoplasmic reticulum. Homologies to other aspartyl phosphate cation-transporting ATPases including a plasma membrane Ca2(+)-ATPase were between 13 and 24%. The structure predicted from a hydropathy plot also shows 10 transmembrane domains, the number and location of which correlated well with the sarcoplasmic reticulum Ca2(+)-ATPase. On the basis of these results, we conclude that the parasite gene encodes an organellar, but not plasma membrane, Ca2(+)-ATPase. The P. yoelii protein, furthermore, contains all six amino acid residues in the transmembrane domains that were recently identified as comprising a high-affinity Ca2(+)-binding site. It follows that organellar Ca2(+)-ATPases of rabbit and Plasmodium conserve functionally important amino acid residues, even though they are remote from each other phylogenetically.

Adenosine Triphosphatases↗

Clinicopathological differences between early-onset and late-onset sepsis and pneumonia in very low birth weight infants.

We performed clinicopathological studies on early-onset sepsis (5 infants, less than 72 hours of life, EOS) and late-onset sepsis (15 infants, greater than 72 hours, LOS) of very low birth weight, less than 1500 g (VLBW). In EOS, the clinical features mimic the respiratory distress syndrome and hematological changes were not observed. The lungs showed slight interstitial pneumonia with structural immaturity, hyaline membranes, hemorrhage, and minimal infiltration by polymorphonuclear neutrophils (PMNs). The pathogen was group B streptococcus or weakly gram-negative bacilli. In LOS, pneumonia proceeded to sepsis and neutropenia with elevated numbers of circulating immature neutrophils, and increased levels of C-reactive protein were observed at the onset of sepsis. Severe pneumonia with infiltration of numerous PMNs and bacterial colonies and polymicrobial infection by nosocomial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were common. The thymus and spleen weights varied but retained normal structure in EOS. The thymus was depleted of lymphocytes, and the spleen was hypertrophic but poorly reactive against infection in LOS. The pathogenesis of EOS is regarded as being more closely correlated with lung immaturity and circulatory disorder in early life, whereas that of LOS is associated with immunological defenses of the host, potency of the pathogens, and terminal multiple organ failure.

Blood Cell Count↗

Regulation of DNA primase activity by phosphorylation of histone-H1 in regenerating rat liver.

The biological importance of histone H1 was investigated in relation to the cell cycle using liver regeneration in rat. Histone H1 was extracted from the regenerating rat liver at various intervals after partial hepatectomy and the number of phosphate residues was measured. The inhibitory effect of the extracted histone H1 on DNA primase was assayed. The activities of DNA polymerase-alpha, DNA primase and DNA synthesis were also determined in the regenerating rat liver. It was found that: 1) phosphate residue in histone H1 from normal rat liver was between 2-3 mol/mol of histone H1. 2) The number of phosphate residues did not change for the first 16h after partial hepatectomy. 3) A dramatic sudden increase of phosphate residues was detected at 18h after partial hepatectomy. 4) The high levels of phosphate residues remained constant thereafter up to 50h. 5) DNA primase activity was less inhibited by highly phosphorylated than by slightly phosphorylated histone H1. It seems probable that phosphorylation of histone H1 is needed for the releasing of DNA primase activity from its inhibited state, which would start DNA synthesis together with DNA polymerase-alpha.

Animals↗

[Frozen blood from one closely related donor reduced complications of blood transfusion without adverse effects in the open-heart surgery].

We used frozen blood from one closely related donor in 24 patients (group I) who underwent open heart surgery for congenital heart disease, in order to reduce of complications from a large quantity of blood transfusion. Blood of 600-2200 ml was collected from the single donor and was kept frozen until the operation. Two conditions of the patients were instituted, (1) body weight less than or equal to 40 kg (2) the single donor is father or mother or a close relative. The group of these patients was compared with patients using frozen autologous blood (group II) and patients using banked blood (group III). In group I patients two times of decline of red blood cell counts (RBC), hematocrit (Ht), hemoglobin (Hb) and total protein (TP) were noticed. The first was the period during the cardio-pulmonary bypass. The second was the time about one week after the transfusion of frozen red cells. But degree of the decline was uneventful clinically. The increment of complications induced from the use of frozen red cells was not noticed, and there was no case of serum hepatitis in group I patients. We concluded that the open-heart surgery using frozen blood cells (single donor), if the application was appropriate, could be undergone safely and would be effective on reducing infection and reaction induced from blood transfusion.

Adolescent↗

Lung lobe torsion following lobectomy.

Three cases of postoperative pulmonary lobe torsion were reported. Two of three showed hemorrhagic infarctions, and as a result underwent rethoracotomies and removal of the affected lobes. From these experiences, we consider that computed tomography (CT) and bronchofiberscopic examinations are useful for the diagnosis of advanced torsion.

Adenocarcinoma↗

[A case of stage III ovarian carcinoma successfully treated with oral etoposide].

A 49-year-old woman with stage III ovarian cancer (undifferentiated adenocarcinoma), who refused combination chemotherapy for postoperative residual tumor, were successfully treated with daily oral etoposide in the outpatient clinic. The etoposide (50 mg/day) was first given orally and then a dose of etoposide was decreased to 25 mg/day because of alopecia and gastrointestinal toxicity. After seven months of treatment, the complete remission was confirmed by the second look laparotomy, and cytology of peritoneal surface revealed no signs of adenocarcinoma. This case suggests that daily oral etoposide therapy might be the alternative as a first-line and second-line chemotherapy of ovarian cancer in the outpatient clinic.

Adenocarcinoma↗

Toxicity of vincristine overdose in a patient with invasive mole.

A few reports have documented overdoses of vincristine sulfate. The present report describes our experience with serious complications of a vincristine overdose in an 18-year-old female who had methotrexate-resistant invasive mole. The patient received VAC therapy as the second line chemotherapy after 2 courses of MTX therapy. In the 6th course of VAC therapy, she was given 5 consecutive daily doses of VCR by mistake. On the 5th day of this VAC therapy, she showed the following toxic symptoms: abdominal pain, lumbago, insomnia, bleeding tendency, absence of motor reflex, leukopenia, and paralytic ileus. These symptoms led to realization of the VCR overdose. Leucovorin calcium administration and supportive treatment were carried out. Although it was difficult to evaluate the efficacy of leucovorin calcium on the vincristine toxic symptoms, she recovered and was discharged on the 36th hospital day.

Adolescent↗

Differences in surface phenotype between cytolytic and non-cytolytic CD4+ T cells. MHC class II-specific cytotoxic T lymphocytes lack Leu 8 antigen and express CD2 in high density.

A number of cell surface molecules are differentially expressed on functionally distinct subsets of CD4+ T cells. However, to date CD4+ T cells capable of becoming CTL have not been shown to be phenotypically distinct from other CD4+ T cells, and in the current study we examined the ability of Leu 8+ and Leu 8- CD4+ subpopulations to become cytotoxic effectors after their stimulation with allogeneic lymphoblastoid cell lines. Although CD4+, Leu 8+ cells proliferated more vigorously than CD4+, Leu 8- cells in primary cultures stimulated with allogeneic LCL, the CD4+, Leu 8- population was the major source of cytotoxic effectors, killing targets with specificity for their class II MHC alloantigens. In most subjects, CD4+ precursors of CTL were distinguished not only by their lack of Leu 8 expression but also by their relatively high density of CD2, LFA-1, and LFA-3, molecules known to mediate non-specific cell-to-cell adhesion and postulated to be markers of immunologic memory. The absence of Leu 8 does not appear to be a reliable memory cell marker, however, because Leu 8+ as well as Leu 8-, CD4+ cells from PPD skin test positive subjects responded to the recall Ag, PPD. During 3 mo of continuous culture with allogeneic stimulators, Leu 8- cells retained their cytolytic activity and remained unreactive with anti-Leu 8 mAb, whereas Leu 8+ cells remained non-cytolytic and reactive with anti-Leu 8, suggesting that under the conditions used the Leu 8 phenotype is relatively stable. PHA or anti-CD3 mAb enhanced non-specific killing by alloantigen-stimulated CD4+,Leu 8- lines but failed to unmask any cytolytic potential in CD4+,Leu 8+ lines. We conclude that MHC class II-specific cytolytic CD4+ T cells can be distinguished from non-cytolytic CD4+ cells on the basis of their surface phenotype, and that most CD4+ CTL are contained within the Leu 8- subpopulation.

Animals↗