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T Sonoda

Publications and source records attributed to T Sonoda.

At least 19 recordsLinked to original sources

Promoter regions of the human X-linked housekeeping genes PRPS1 and PRPS2 encoding phosphoribosylpyrophosphate synthetase subunit I and II isoforms.

The 5' regions of the human phosphoribosylpyrophosphate synthetase subunit I and II genes (PRPS1 and PRPS2, respectively) were isolated and sequenced. A comparison of the nucleotide sequences between human and rat PRPS1 genes revealed that the sequences around the transcription initiation sites were conserved over 56 nucleotides, and that a TATA-like sequence, a CCAAT box and three putative Sp1 binding sites were present at almost the same positions in the GC-rich sequences. Two major transcription initiation sites were localized in the human PRPS1, one of the two was located 27 nucleotides downstream from the TATA-like sequence, while the upstream initiation site was in the TATA-like sequence. The promoter region of the human PRPS2 gene was also GC-rich and contained a TATA-like sequence, four Sp1 binding sites and a homopyrimidine stretch. The initiation sites were localized at 90 nucleotides upstream from the ATG initiation codon. Chloramphenicol acetyltransferase (CAT)/promoter fusion assays showed that a 2.0 kb region (human PRPS1) and a 1.1 kb region (human PRPS2) possessed the promoter activities in four cell lines. The CAT activities in the three human cell lines tended to correlate with the steady-state mRNA levels of the PRPS1 and PRPS2 genes. These results suggest that the 5' flanking regions cloned contribute to the cell-differential expression of these two genes.

Amino Acid Sequence

Hepatic resection for a hepatocellular carcinoma larger than 10 cm.

Twenty-one patients with hepatocellular carcinoma (HCC) larger than 10 cm diameter were treated during the 18 year period from 1971 to 1988. The mean tumor size was 13 cm (range 10-18 cm). Nineteen patients (90.5%) had subjective symptoms. Eight patients (38.1%) had alpha-fetoprotein (AFP) levels over 10,000 ng/ml, and in 18 patients (85.7%) the levels were over 20 ng/ml. Nevertheless, only three (14.3%) were detected by AFP. Scintigraphy before 1981 and ultrasonography after 1982 appears to be most helpful for detection of HCC. Nineteen lesions (90.5%) were localized in the right hepatic lobe. Large HCC showed a low incidence of histologically verified concomitant cirrhosis (33%; 7 of 21) and a relatively well preserved hepatocellular function (indocyanine green test; 13.9 +/- 6.6%). Curative resection could be done for all 21 patients. There were three (14.3%) operative deaths. The 1-, 3-, and 5-year survival rates were 72.2, 32.9, and 8.2%, respectively. One patient who underwent a left hepatic lobectomy has survived for over 5 years, with recurrence. There were 14 recurrences (66.7%) in 21 patients: 11 were hepatic and three were in the lungs. In patients with large HCC, surgical resection should be done, provided the clinical status and hepatocellular reserves are adequate.

Carcinoma, Hepatocellular

DNA ploidy of primary hepatocellular carcinoma and pulmonary metastases.

To better comprehend the differences in deoxyribonucleic acid (DNA) content between a primary hepatocellular carcinoma (HCC) and pulmonary metastatic nodules, tissue specimens taken at autopsy of 25 patients who had not received any drugs to treat the malignancy were examined using microspectrophotometry. The DNA distribution patterns were classified into Types I-III, and low (Types I and II) or high (Type III) ploidies, according to DNA distribution. Changes in the DNA content from high to low ploidies, namely DNA ploidy reduction from the primary lesion to pulmonary metastatic lesions, was evident in 9 of the 25 patients (36%), and changes from low to high were noted in 2 of the 25 patients (8%). The remaining 14 (56%) showed no evidence of changes in the DNA ploidy pattern. Reduction of DNA ploidy seen in HCC and its metastatic lesions in the lung may be one of the aspects of clonal evolution or selection mechanisms during the progression of tumor growth and metastasis.

Autopsy

In vivo and in vitro mechanisms of cardiac allograft acceptance in the rat after short treatment with 15-deoxyspergualin.

15-Deoxyspergualin (DSG) has been reported to be a useful immunosuppressive agent already used to inhibit acute rejection in clinical transplantation. In the present study, the survival of heart allograft in rats after a short course of DSG treatment and the mechanisms underlying DSG-induced heart allograft acceptance were studied. Male LEW rats were used as recipients. Male ACI and Wistar rats were used as donors and third-party donors, respectively. Survival of ACI heart grafts in LEW recipients treated with a short course of DSG starting on day 4 after grafting was markedly prolonged, with a mean survival time of 16.6 +/- 5.8 days and 29.8 +/- 3.0 days at doses of 2.5 mg/kg per day and 5 mg/kg per day, respectively. On day 20 after grafting, the mechanism of inducing allograft survival after DSG treatment at a dose of 5 mg/kg per day was analyzed by testing the activation of spleen cells or serum in several assay systems. Spleen cells from DSG-treated rats with surviving heart allografts showed almost no proliferative response against donor strain stimulator cells compared with controls. The cytotoxic activity towards donor strain target cells of spleen cells from DSG-treated rats with surviving heart allografts was lower than that of spleen cells from rats with rejected heart allografts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Independent association of antibodies against human papillomavirus type 16 E1/E4 and E7 proteins with cervical cancer.

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an E1/E4 fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac-E1/E4 and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti-E1/E4 antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti-E1/E4 and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.

Adenocarcinoma

Thermogenic, thermolytic and body temperature effects of fenfluramine, a 5-hydroxytryptamine agonist, in the domestic fowl (Gallus domesticus).

1. Intramuscular injection of the 5-HT agonist DL-fenfluramine increased the metabolic rate of mature cockerels by about 25% over the following 22 hr. The acute effect, over the 3 hr following injection, attained 40% at 10 degrees C, 35% at 20 degrees C and 25% at 32 degrees C. 2. Heat loss mechanisms (peripheral vasodilatation, postural change and panting) were also stimulated, to an extent which varied with ambient temperature. 3. Food intake, respiratory quotient and locomotor activity were significantly reduced by fenfluramine injection. 4. The opposing effects on heat production and heat loss had an influence on deep-body temperature which varied from a reduction of 0.5 degrees C at 10 degrees C ambient to an increase of about 0.5 degrees C at 32 degrees C. 5. The 5-HT blocker, methysergide, prevented the effects of fenfluramine on both heat production and heat loss for about 5 hr after injection. 6. The autonomic ganglion blocker, hexamethonium chloride, reduced the thermogenic but not the heat-loss effects of fenfluramine. 7. The results suggest that DL-fenfluramine has centrally-occurring but independent effects on heat production and a number of heat loss effectors, and that the heat production effect is mediated by the autonomic nervous system. The effect of fenfluramine on deep-body temperature appears to result from an altered equilibrium between heat production and heat loss.

Animals

Interleukin-6 activity in urine and serum in patients with bladder carcinoma.

To investigate the correlation between interleukin-6 and urothelial neoplasms, interleukin-6 activities in blood and urine samples of patients with bladder carcinoma were measured with a proliferation assay using an interleukin-6 dependent murine hybridoma clone, MH60.BSF2. A total of 43 patients and 15 normal volunteers were entered into this study. All of the patients were examined preoperatively and 26 were reexamined more than 6 days postoperatively to eliminate the effect of surgical injury on interleukin-6 secretion. The interleukin-6 titers in urine and serum increased in accordance with the progression of the tumor stage, and tumor removal induced a remarkable decrease in the titer of urinary interleukin-6. Although the interleukin-6-producing site has not been elucidated yet, our study suggests that interleukin-6 activity in bladder carcinoma patients may reflect the immunoreaction against the tumor in local urothelium.

Adult

A strategy of cystine stone management.

Simple mechanical disintegration of cystine calculi by extracorporeal shock wave lithotripsy and/or percutaneous nephrolithotomy is being performed widely around the world. However, it cannot be denied that the cystine calculus is one of the most difficult stones for mechanical disintegration. We previously reported the oral medical chemolysis of cystine calculi in 1982 and a third of the patients became stone-free. In another third of the patients the cystine component was replaced by apatite during the medical treatment and apatite stones formed in this manner are easily disintegrated. In view of the complications of mechanical disintegration, oral medical treatment for chemolysis should be recommended before simple destruction of cystine calculi.

Adult

The in vitro immunosuppressive effect of deoxymethylspergualin in man as compared with FK506 and cyclosporine.

The effect of deoxymethylspergualin (MeDSG) on in vitro human lymphocyte response was assessed in comparison with FK506 and cyclosporine. Peripheral blood mononuclear cells from normal human volunteers were used for assay of mixed lymphocyte reaction, cell mediated lympholysis, and blastogenesis by PHA, IL-2, and OKT3. MeDSG suppressed only allogeneic stimulation (MLR and CML) and IL-2-induced blastogenesis, not PHA- or OKT3-induced blastogenesis, although the other immunosuppressive agents showed some suppressive effect for all assays. A kinetic study of MLR showed that the suppressive activity did not decrease even when MeDSG was added at day 3 or day 4. The other agents, however, showed a weak suppressive effect when added at a later phase of MLR.

Cyclosporine

FK506-induced kidney tubular cell injury.

Some renal changes associated with cyclosporine, such as tubular vacuolization and glomerular thrombosis, have also been reported with FK506. Furthermore, FK506 therapy is associated with a decrease in glomerular filtration rate and renal plasma flow and an increase in renal vascular resistance. We studied the in vitro tubular cell sensitivity to FK506 in comparison with CsA, the ultrastructural changes induced by FK506 and CsA, and the effect of both drugs on tubular cell growth in vitro. We also investigated whether FK506 and CsA induced endothelin-1 (ET-1) secretion of cultured tubular cells and whether this stimulatory effect coincided with a change in the endothelin systemic synthesis. Exposure of tubular cells to high concentrations of FK506 or CsA (10, 50, 100 microM) induced a time- and dose-dependent cell injury in vitro. The damage induced by FK506 and CsA was characterized by a direct cytotoxic effect on tubular cells, as expressed by release of 3H thymidine from prelabeled cells, N-acetyl-beta-D-glucosaminidase release, and cell detachment. Ultrastructural changes (vacuolizations, swelling, and mitochondrial enlargement) and inhibition of the growth of cultured tubular cells were also observed at high concentrations of FK506 and CsA. Low concentrations of FK506 and CsA (1, 0.1, 0.01, 0.001 microM) were not cytotoxic and induced only a minimal inhibitory effect on the growth of tubular cells in vitro. We demonstrated that FK506 (1, 0.1, 0.01 microM) time-dependently stimulated the secretion of endothelin by cultured tubular cells. CsA 10, 1, 0.1, 0.01 also exerted an enhancing effect on ET-1 secretion in cultured tubular cells. We observed that the concentration of CsA that induced the most important enhancing effect was 10 or 100 times higher than that required for FK506 to observe the same effect. The concentrations of FK506 or CsA that induced ET-1 secretion were not cytolytic for tubular cells in vitro. FK506- or CsA-treated rats showed an increase in serum level of ET-1 in comparison with the control. Through the stimulatory effect on endothelin secretion by tubular cells, FK506 and CsA may induce a perturbation of renal hemodynamics. Concentrations of FK506 and CsA, higher than established serum levels but close to those reached in tissues, are cytotoxic for tubular cells and induced ultrastructural changes and a significant delayed regeneration.

Acetylglucosaminidase

Etiologic and pathogenetic study of mental retardation with multiple congenital anomalies.

Etiology and pathogenesis of MCA/MR in 1,023 patients (618 male; 405 female) with mental retardation were studied. Of 1,023 patients, there were 563 cases (317 male; 246 female) with MCA (55%). Among the MCA patients, there were 303 (156 male; 147 female) whose primary etiology was clarified (53.8%). Among the 260 patients with MCA/MR of unknown etiology, there were 23 with recognizable syndromes of unknown etiology and 7 previously reported by us as possibly having a new malformation syndrome. We had 569 patients with mental retardation of unknown etiology including 263 (41.5%) who were involved with MCA.

Brain

Cytogenetics of tumor cells from patients with nonfamilial renal cell carcinomas.

We analyzed cytogenetically 20 nonfamilial renal cell carcinomas, using a combined method of enzymatic technique and short-term culture with several passages. From 16 of the 20 patients, metaphase cells suitable for analysis were successfully obtained. Fourteen of the 16 patients demonstrated clonal chromosome aberrations which included missing Y chromosome in 8, gain of chromosome 7 in 7, an extra X chromosome in 4, translocation between chromosome 3 and other chromosomes in 4, deletion of the short arm of chromosome 3 in 2 and monosomy 3 in 2. Abnormalities of chromosome 7 and sex chromosomes were only numerical, and those are thought to be related to the neoplastic changes of various malignant tumors. Abnormalities of chromosome 3, however, were not only numerical but also structural, especially in the short arm, and those may be possibly associated with the genesis of renal cell carcinoma.

Adult

Epiderstatin induces the flat reversion of NRK cells transformed by temperature-sensitive Rous sarcoma virus.

Epiderstatin is a unique glutarimide antibiotic which was found by screening for inhibitors of the signal transduction of epidermal growth factor (EGF). The antibiotic (0.01 microM) was found to reverse the morphology of NRK cells that were infected with a temperature-sensitive mutant of Rous sarcoma virus (srcts-NRK) from the transformed phenotype to the normal phenotype at the permissive temperature (32 degrees C). Epiderstatin did not inhibit the protein kinase activity of p60v-src. The cell cycle progression of src(ts)-NRK cells was blocked at G0/G1 phase, which was caused by the inhibition of biosynthesis of p60v-src but not the transcription of v-src mRNA.

Animals

[The experience of administration of 15-deoxyspergualin on rejection in kidney transplant recipients].

We report here the favorable results of clinical application of 15-deoxyspergualin (DSG) as a rescue therapy for rejection episodes in kidney transplant recipients. DSG was discovered in Japan and was proved to be a novel immunosuppressant in various animal transplantation models. The immunosuppressive mechanism of DSG is unclear yet, but its point of action is supposed to be in the early immuno response to allogeneic stimulation without the regulation of cytokine production. We performed the administration of DSG in fifteen patients, who had rejection episodes, with a dosage of 3 mg/kg/day or 5 mg/kg/day for five days by drip infusion. In the group of recipients who had rejection episodes within six months after kidney transplantation, DSG proved effective on six out of seven acute rejection episodes and induced favorable remission. And in the group of recipients who had rejection episodes after six months since kidney transplantation, DSG proved effective on all of ten rejection episodes. There was not a difference of effectiveness in respect to the dosage of DSG. The side effect of DSG treatment was mainly leukopenia but in most cases these leukopenia was remitted just under careful observation. Some patients complained the sense of abdominal discomfort. But so far, we did not encounter serious or critical side effects and complications during all the time of progression. Another benefit was that DSG was able to reverse the rejection episode even in the patient who had already treated with anti lymphocyte globulin and/or anti CD3 monoclonal antibody OKT3. We concluded that the administration of DSG as a rescue therapy was not accompanied by the serious side effects and was most effective against acute rejection after kidney transplantation.

Adult

[Infantile spasms in monozygotic twins with Smith-Lemli-Opitz syndrome type I].

Monozygotic twins with Smith-Lemli-Opitz syndrome who developed infantile spasms were presented. They were the result of the first full-term pregnancy of non-consanguineous parents. They had following abnormalities: marked growth and developmental retardation, congenital heart disease, light brown hair which is rare in Japanese, small dolichocephaly, hypertelorism, anteverted nostrils, micrognathia, hypospadias and shawl scrotum. The cranial MRI showed the delayed myelination of occipital lobe. As far as we could review published reports, we were unable to find other report on monozygotic twins having the Smith-Lemli-Opitz syndrome.

Abnormalities, Multiple