Biomedical subjects
T Noguchi
Publications and source records attributed to T Noguchi.
[Resectability of primary carcinoma of the liver and pancreas, with special reference to radicality and functional reserve].
Resectability was studied in relation to both the functional reserve of the liver or pancreas and radicality in 112 cases of primary liver cancer and 34 cases of pancreatic head cancer resected in our department over an 11-year period. 1. Primary liver cancer: In extended hepatectomy including one segment beyond the tumor-bearing area, recurrence rate was low with a high long-term survival rate of more than 3 years, although hepatic insufficiency occurred frequently. In limited resection of the segment of the tumor or enucleation, many patients died due to recurrence within 2 years, except for those with small liver cancers. 2. Pancreatic head cancer: Extended surgery especially total pancreatectomy, had higher radicality with a higher 3-year survival rate than for the standard operation, even in case of advanced stage III or IV cancer. However, extended surgery produced a high incidence of postoperative fatty liver due to disturbance of pancreatic exo- and endocrine function, and severe diarrhea following dissection of the nerve plexus. Therefore, it is necessary to select a suitable operative method upon consideration of both radicality and functional reserve of the liver or the pancreas.
[A therapeutic trial with low-dose Ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes: a study of 15 cases].
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Influence of diet on the transcriptional and post-transcriptional regulation of malic enzyme induction in the rat liver.
Fasted rats were refed a carbohydrate/protein diet, a carbohydrate diet (without protein) or a protein diet (without carbohydrate) to investigate, using a cDNA cloned in our laboratory, the regulatory mechanisms involved in hepatic malic enzyme induction. In the carbohydrate/protein diet, although the enzyme activity and the mRNA concentration of malic enzyme were increased about 7-fold above the levels in the fasted rat, the rate of transcription was increased only 2-fold. In the carbohydrate diet group the rate of transcription and the concentration of mRNA were increased to the levels in the carbohydrate/protein diet group, whereas the enzyme activity increased only to 60% of those levels. Protein appears to contribute to an increase in the translation of malic enzyme mRNA. In the protein diet group the transcriptional rate was not low, but the mRNA concentration was about half in comparison with the level of the carbohydrate/protein diet group. Further, dietary fat did not reduce the transcriptional activity, but reduced the mRNA concentration and the enzyme activity to half of the basal levels. Therefore, it is suggested that fat stimulates the degradation of the mRNA in liver cytosol, whereas carbohydrate tends to stabilize the mRNA. On the other hand 3,5,3'-triiodothyronine treatment increased the transcriptional activity by 1.5-2-fold above the basal values on all the diets and even on fasting. Thus, it is suggested that 3,5,3'-triiodothyronine increases the transcriptional activity of malic enzyme independently from nutritional regulation, while the nutrients are predominantly involved in the post-transcriptional steps.
Cloning of human muscle phosphofructokinase cDNA.
Three overlapping cDNA clones for human muscle phosphofructokinase (HMPFK) covering the complete coding sequence were isolated. The sequence included a poly(A) tail, a 399 bp 3'-untranslated region, a 2337 bp coding region for 779 amino acid residues and a part of the 5'-untranslated region. Homologies between HMPFK and rabbit muscle phosphofructokinase (RMPFK) were 96% of the amino acids and 89% of the nucleotides in the coding region. Like RMPFK, HMPFK also possessed the internal homology between C- and N-halves in its primary structure. Cloning of HMPFK cDNA will help to identify the molecular defect in patients with glycogenosis type VII (HMPFK deficiency).
The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters.
cDNA clones for rat R-type pyruvate kinase and a genomic clone encoding both L- and R-type isozyme mRNAs were isolated. Their sequences were compared with that of the L-type isozyme cDNA to determine the sequences of mRNA and protein of the R-type isozyme and the organizations of the L- and R-type genes. Results showed that the R-type isozyme mRNA had an identical nucleotide sequence to that of the L-type except in the 5'-terminal region including the coding sequence and the length of the 3'-untranslated region. The sequence upstream of the 5th coding residue of the L-type was replaced by a 98-nucleotide coding sequence plus a 5'-untranslated region in the R-type isozyme. Therefore, the R-type subunit consists of 574 amino acids, which is 31 residues longer than the L-type at the amino terminus. The pyruvate kinase L gene is present as a single copy per haploid genome and is composed of 12 exons and 11 introns with a length of about 9.3 kilobase pairs. The first (exon R) and second (exon L) exons encode the 5'-terminal sequences specific for the R- and L-types, respectively. The remaining downstream exons encode a sequence common to both isozymes. The last exon contains the entire 3'-untranslated region, including several putative polyadenylation signals. Alternative use of these signals is reported to be responsible for generation of multiple mRNA species for the L-type, whereas the R-type uses only the first signal. The cap site is mapped 16 nucleotides upstream from the translation initiation site for the L-type, whereas multiple cap sites were suggested for the R-type. The canonical promoter of the TATA box was identified in the upstream sequence of exon L, but not in that of exon R. Instead, the 5'-flanking region of exon R contained another promoter sequence of the CAT box. Thus, we conclude that the L- and R-type isozymes of pyruvate kinase are produced from a single gene by use of different promoters.
The carcinoembryonic antigen (CEA) contains multiple immunoglobulin-like domains.
The amino acid sequences of human carcinoembryonic antigen deduced from the cDNA sequences have been analysed. This antigen contains seven extracellular domains (previously recognized three highly repetitive domains are further divided into A and B subdomains each) which are strikingly homologous to each other and to immunoglobulin variable regions, poly-Ig receptor and Thy 1.1. The N-terminal domain lacks immunoglobulin-like fold but the other six domains have, suggesting that the CEA belongs to immunoglobulin superfamily.
Colchicine lesions in the rat hippocampus mimic the alterations of several markers in Alzheimer's disease.
An infusion of colchicine into the hippocampi of rats resulted in destruction of hippocampal cells. Twelve days after infusion, preoperative trained colchicine-treated rats showed a significant decrease in choice accuracy in a T-maze learning task. There was also local reduction in choline acetyltransferase (ChAT) activity and significant losses of 55-kDa protein in the soluble fraction and of 50-kDa protein in myelin and synaptosomal fractions in the hippocampi of colchicine-lesioned rats. There was a marked increase in [3H]glutamate binding in the hippocampus and cortex. In contrast, [3H]quinuclidinyl benzilate binding in the hippocampus was slightly reduced, whereas [3H]dihydroalprenolol binding was not affected by the colchicine treatment. Scatchard analysis revealed that the increase in glutamate binding is due to an increase in the number of glutamate receptors without significant change in their affinity. Some of the changes caused by hippocampal infusion of colchicine resemble those seen in Alzheimer's disease suggesting the use of such rats as one model for the disease.
Human liver type pyruvate kinase: cDNA cloning and chromosomal assignment.
Pyruvate kinase (PK) has four isozymes (L,R,M1,M2) that are encoded mainly by two different genes. We isolated a cDNA clone from a Japanese adult liver lambda gt10 cDNA library by using a rat liver(L)-type PK cDNA probe. One positively hybridizing clone, hlPK-1, which contained a 1,049-base pair cDNA insert, was subjected to DNA sequence analysis. Comparisons of the sequence data with the rat PK cDNAs indicated that the cDNA encoded information for the carboxyl terminal 105 amino acids of a human L-type PK and a 3' untranslated region of 734 nucleotides. Furthermore, the karyotype analysis of several human-mouse hybrid cells and Southern blot analysis of DNAs of the hybrids with a hlPK-1 indicated that the human L-type PK gene is located on chromosome 1.
The rabbit differs from other mammalian in the tissue distribution of alkaline phosphatase isoenzymes.
There are only two gene loci code for alkaline phosphatase of mammalian other than human and great apes: one for the intestinal form and other for the liver/kidney/bone form. The former form is present only in the intestine and the latter form occurs in other tissues such as liver, kidney and bone. In the present study, the rabbit was found to be different from other mammalian in the tissue distribution of alkaline phosphatase isoenzymes: only in the rabbit, most of the enzyme in the kidney and liver was the third form which differs from the liver/kidney/bone form, and this form was enzymatically and immunologically similar to the intestinal form of ALPase.
Localization of the mcf.2 transforming sequence to the X chromosome.
A transforming sequence was identified using co-transfection of DNA from the human mammary carcinoma cell line MCF-7 and of a G418 resistance gene into NIH 3T3 cells, followed by tumor formation in athymic mice. This sequence, named mcf.2, was molecularly cloned. A transforming activity resides in a cosmid clone of 42 kb. mcf.2 did not cross-hybridize with the known oncogenes tested. In situ hybridization localized it on the X chromosome, probably at q27. This localization was confirmed by hybridization to a panel of human--rodent cell line DNAs.
The role of mediastinal and multi-organ CT scans in staging presumable surgical candidates with non-small-cell lung cancer.
In order to evaluate the role of CT scan and bone scan in staging patients with non-small-cell lung cancer presumably indicated for surgery, 70 consecutive patients who underwent thoracotomy were reviewed. Most of them received mediastinal and multi-organ (brain, liver and adrenal) CT scans and a bone scan. In the most recent 40 of the 70 patients, CT findings of the mediastinal lymph nodes were compared to the pathology following complete sampling. The overall accuracy of the mediastinal CT was 60.0 per cent (12 true positive and 12 true negative), but the negative predictable value was 12/(12 + 3) or 80.0 per cent, whereas 3 were false negatives though they showed an acceptable postoperative course. Sixteen out of 21 patients with one, or at the most, three enlarged nodes detected on CT also did well postoperatively and retrospectively, were considered not to have required mediastinoscopy. A group of patients showing no, or at the most, three enlarged mediastinal lymph nodes on CT may be considered as candidates for surgery even without mediastinoscopy. Multi-organ survey by means of CT was believed cost-ineffective and omittable. Bone scan however, retrospectively detected three true positives among 20 patients with a positive uptake, so that it cannot be omitted out of hand, though further examination of this point is required.
Confronting cisternae in pituitary gland thyrotrophs of congenitally hypothyroid mice.
Confronting cisternae were found in pituitary thyrotrophs of congenitally hypothyroid mice. These confronting cisternae rapidly reverted back to ordinary rough endoplasmic reticulum following thyroxine administration. Confronting cisternae were not observed in the thyrotrophs of euthyroid control mice. Our results strongly suggest that confronting cisternae are a peculiar form of rough endoplasmic reticulum which appears under certain conditions of enhanced cellular metabolism.
Alkaline phosphatase in the periodontal ligament of the rabbit and macaque monkey.
This enzyme's specific activity was high in the periodontal ligament with other tissues in both species, but much higher in the rabbit. The alkaline phosphatase in the rabbit ligament is a liver/kidney/bone form and not an intestinal one.
Mode of action of bestatin and leupeptin to induce the accumulation of acid soluble peptides in rat liver in vivo and the properties of the accumulated peptides. The important role of bestatin- and leupeptin-sensitive proteases in the protein degradation pathway in vivo.
The chemical properties of acid soluble peptides accumulated in liver or excreted into urine after administration of bestatin or leupeptin to rats were investigated extensively. At the same time, the effects of glucagon on the bestatin-induced accumulation of acid soluble peptides were studied. The results show the important role of bestatin- and leupeptin-sensitive proteases in the degradation pathway of intracellular proteins in vivo.
Effects of chronic renal failure on the regulation of pyruvate kinase.
The effects of chronic renal failure on the enzyme activity of pyruvate kinase and the mRNA level of this enzyme were studied in 7 out of 8 nephrectomized rats. The mRNA level was measured by RNA-DNA dot blot hybridization, using cloned pyruvate kinase cDNA as hybridized probe. Neither the activity of M1-type pyruvate kinase nor the level of this enzyme in rat gastrocnemius muscle was affected by chronic renal failure, whereas L-type pyruvate kinase enzyme activity in uremic rat liver was lower than that in control at both fasted and refed states. The levels of L-type pyruvate kinase mRNA were not different between two groups at the fasted state. Induction of L-type pyruvate kinase mRNA after high carbohydrate diet refeeding was suppressed proportionally to the severity of chronic renal failure, which was expressed by the serum creatinine concentrations (r = -.876, P less than .005). These results indicate that the suppression of L-type pyruvate kinase activity in uremia was partly reflected by the decreased accumulation of this enzyme mRNA. There was a significantly negative correlation between L-type pyruvate kinase mRNA levels and plasma glucagon/insulin ratios (r = -.719, P less than .05). Hyperglucagonemia in uremia might play a major role in this suppression.
Distribution of tritiated tetrodotoxin administered intraperitoneally to pufferfish.
Tetrodotoxin was recoil-tritiated by the 3He(n,p)3H reaction and purified by gel filtration. The [3H]tetrodotoxin gave only one spot in both cellulose acetate strip electrophoresis and thin layer chromatography. The specific toxicity of tetrodotoxin did not decrease during the recoil tritiation and the [3H]tetrodotoxin showed a specific radioactivity of 25 x 10(-6) Ci/mmole. In spite of the low specific radioactivity, the [3H]tetrodotoxin was able to be used to investigate the anatomical distribution of tetrodotoxin in pufferfish. When intraperitoneally injected into 'torafugu' puffer, [3H]tetrodotoxin accumulated in most tissues, the level being highest in the skin, followed by the liver, intestines and muscle. With time, the [3H]tetrodotoxin radioactivity level in the injected pufferfish decreased in most tissues, except for skin and gallbladder. Based on these results, the metabolism of tetrodotoxin in pufferfish is discussed.
Distribution of tetrodotoxin in the tissues of the flatworm Planocera multitentaculata (Platyhelminthes).
tetrodotoxin distribution in various tissues of the flatworm Planocera multitentaculata was examined. The oviduct was most toxic (2000-3240 MU/g), followed by digestive organs (900-1400 MU/g), oviduct-free genital organs (430-590 MU/g), etc. The mucus secreted also showed some lethal potency. On the other hand, the eggs laid, whether in laboratory aquarium or on coastal rocks, exhibited an extremely high potency up to 10,700 MU/g. It was suggested from these findings that flatworms possess tetrodotoxin as a defense or alarm substance against predators.