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M Daimon

Publications and source records attributed to M Daimon.

At least 73 records · Page 4Linked to original sources
PubMed1995

A point mutation, C to T, in exon 8 of the porphobilinogen deaminase gene in a Japanese family with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a deficiency of porphobilinogen deaminase (PBGD). To date, only two mutations have been reported in Japanese patients. We report here another mutation of the gene in a Japanese patient. Analysis of the PCR amplified DNA fragments of the gene by direct-sequencing method revealed the gene abnormality responsible for the disease. The mutation found was a point mutation, C to T, in exon 8 of the gene at position 346 of the housekeeping cDNA from the translation codon ATG. This mutation resulted in an Arg116 to Trp substitution. Four carriers in the family were successfully diagnosed by detecting the mutation using restriction analysis of PCR products.

Adult↗
PubMed1995

Insulin-like growth factor I resistance in peripheral tissue but not in liver in streptozotocin-induced diabetic rats.

The metabolic effect of recombinant human insulin-like growth factor I (IGF-I) was investigated by the glucose clamp technique in normal rats and streptozotocin-induced diabetic rats, a model of insulin-dependent diabetes mellitus (IDDM), and compared with that of insulin. Glucose uptake by peripheral tissues was stimulated by intravenous administration of IGF-I at rates of from 0.369 to 3.690 nmol/kg/min in a dose dependent manner, with a potency of 1/52 that of insulin estimated on the basis of the ED50 molar ratio in normal rats. In streptozotocin-induced diabetic rats, the maximum effects of IGF-I and insulin were reduced to 72% and 70% of those in normal rats, respectively, indicating the presence of both IGF-I and insulin resistance. Hepatic glucose output in normal rats was suppressed by IGF-I in a dose dependent manner with a weaker potency of 1/99 that of insulin assessed on the basis of the ED50 values. In streptozotocin-induced diabetic rats, a dose-response curve of the suppressive effect of insulin on hepatic glucose output shifted to the right, indicating the presence of hepatic insulin resistance, but a leftward shifting of the suppressive effect of IGF-I on hepatic glucose output was observed. We concluded that the IGF-I effect on peripheral tissue was decreased but that on the liver was rather increased in streptozotocin-induced diabetic rats, in contrast to the resistance of both peripheral tissues and liver to insulin.

Animals↗
PubMed1995

[Procedure to identify gene abnormalities responsible for genetically inherited disease such as porphyrias].

Some genetically inherited diseases such as mitochondrial encephalomyopathies are caused by the very few mutations in the mitochondrial gene, but the diseases such as porphyrias are caused by many different mutations in the gene responsible for the disease. So, determining the genetical status of each individuals belonging to a family suffering from the diseases requires the detection of the gene mutation in the family, since the mutations found in other families can not be easily expected to be found in the family. We report in this manuscript the general procedure how to identify mutations of the genes. The methods involved in the procedure reported were PCR-SSCP, PCR-DGGE, PCR-cloning, PCR-direct sequencing, Allele discrimination hybridization, Allele specific amplification and PCR restriction analysis.

Alleles↗
PubMed1994

Acute intermittent porphyria caused by a single base insertion of C in exon 15 of the porphobilinogen deaminase gene that results in a frame shift and premature stopping of translation.

A single base insertion of C in exon 15 of the porphobilinogen deaminase (PBG-D) gene was observed in a patient with acute intermittent porphyria (AIP) by polymerase chain reaction (PCR)-direct sequencing analysis. The insertion locates between positions -22 and -21 from the translation termination codon TAA, causes a frame shift, and results in a stop codon located 4 codons downstream from the insertion (premature stopping of translation). The mutation generates an MspI recognition site, which can be used, in turn, to detect the mutant allele. Analysis of the cDNA fragments amplified by PCR revealed the existence of the abnormal PBG-D mRNA from the mutant allele in the patient.

Amino Acid Sequence↗
PubMed1993

Acute intermittent porphyria caused by a G to C mutation in exon 12 of the porphobilinogen deaminase gene that results in exon skipping.

Genomic DNA from a patient with acute intermittent porphyria were analyzed by the polymerase chain reaction (PCR)-direct sequencing method. The patient was heterozygote for a point mutation G to C at the last position of exon 12 of the porphobilinogen deaminase (PBG-D) gene. Analysis of the cDNA fragments amplified by PCR revealed that the patient has the abnormal PBG-D mRNA, which does not have exon 12 and exists in an approximately equal amount to the normal mRNA.

Adult↗
PubMed1993

Thiazolidinediones (AD-4833 and CS-045) improve hepatic insulin resistance in streptozotocin-induced diabetic rats.

To investigate whether thiazolidinediones (AD-4833 and CS-045), new oral antidiabetic agents, are effective in insulin-dependent diabetes mellitus, the effect of thiazolidinediones on streptozotocin-induced diabetic rats was studied by the glucose clamp technique. Diabetic rats were divided into five groups: (1) intensively insulin treated group given a daily injection of 4-6 units Ultralente insulin, (2) AD-4833 group treated with a daily injection of 2 units Ultralente insulin, the minimal dose to make urinary ketones negative, and ingestion of 10 mg/kg of AD-4833 suspended in 5% gum arabic, (3) gum arabic group treated in the same way as the AD-4833 group except for the active drug, (4) CS-045 group treated with the same insulin injection and ingestion of 200 mg/kg CS-045 suspended in 0.5% chlormethyl cellulose, (5) chlormethyl cellulose group treated as the control for the CS-045 group. Seven days after these treatments, all five groups of diabetic rats and normal control rats were subjected to the glucose clamp study in which 3 mU.kg-1.min-1 porcine insulin was continuously infused. Glucose infusion rates (GIR) for the gum arabic and chlormethyl cellulose groups were significantly lower than in control rats, and the rates of hepatic glucose output (HGO) of these two groups were not suppressed, indicating the presence of hepatic insulin resistance. Intensive insulin treatment as well as administration of AD-4833 and CS-045 with a minimal dose of insulin restored both GIR and HGO towards normal levels. It is concluded that thiazolidinediones improved hepatic insulin resistance in the presence of a minimal dose of insulin.

Animals↗
PubMed1993

Effect of acidosis on insulin binding and glucose uptake in isolated rat adipocytes.

To assess the mechanism of insulin resistance in metabolic acidosis, we investigated insulin receptor binding and glucose uptake in isolated rat epididymal adipocytes at three pHs, acidic (pH 6.8), neutral (pH 7.4) and alkaline (pH 8.0) groups. After male Sprague-Dawley rats weighing 220-240 g were submitted under chloral hydrate anesthesia, epididymal fat pads were dissected and isolated. [125I]-insulin binding rate was not different between alkaline and neutral groups, but that of acidic group was markedly decreased to approximately 30% of neutral group at maximum specific insulin binding rate. Scatchard analysis showed that numbers of insulin receptors were not different among three groups, but values of binding affinity in acidic group was significantly lower than those of the others. 2-[3H]deoxy-D-glucose uptake of alkaline and neutral groups were increased to reach steady state immediately, but that of acidic group increased slowly and reached at maximum which was lower than the other two groups. Furthermore, 2-deoxy-D-glucose uptake against amount of bound insulin was lower in acidic group than other two groups. From these results, it is suggested that insulin resistance in metabolic acidosis resulted from the combined defects in binding affinity and post-binding process in the insulin receptor.

Acidosis↗
PubMed1992

The third IGF-II promoter specifies transcription of three transcripts out of five in human placenta.

Insulin-like growth factor-II (IGF-II) mRNA exists as multiple transcript size classes, such as 6.0, 5.3, 4.9, 3.2, and 2.2 kb mRNAs in various human tissues. Three different promoters, 2 different polyadenylation sites, and alternative splicing are involved in producing these multiple transcripts. Initiation of transcription at the 3 different promoters results in multiple mRNAs which contain identical coding regions but different 5'-untranslated regions (5'-UTRs). The first promoter is thought to direct expression of 5.3 kb mRNA in adult human liver. The second promoter region directs expression of 6.0, 3.2, and 2.2 kb mRNAs in human fetal tissues and several adult nonliver tissues. The third promoter specifies transcription of a 4.9 kb mRNA in various tissues. We isolated and sequenced a cDNA clone (pIGF-II-1-70) from a human placental cDNA library, which contains the IGF-II coding region and the 5'-UTR associated with the third promoter. By using a 5'-UTR-specific probe from the clone, we found that this third 5'-UTR is contained in the IGF-II mRNA of 2.2 kb and is absent in the 3.2 kb IGF-II mRNA. We also found an 0.9 kb transcript expressed in placenta, which hybridized strongly to the third 5'-UTR specific probe but not to IGF-II coding region probes. This finding might indicate the existence of an mRNA encoding an IGF-II-associated peptide.

Base Sequence↗
PubMed1992

Differences in glucagon-like peptide-1 and GIP responses following sucrose ingestion.

To investigate the mechanism of oral carbohydrate-stimulated secretion of the two most potent incretin candidates, gastric inhibitory polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1), we studied the changes in the plasma levels of these peptides in five healthy men after sucrose ingestion with or without pretreatment with an alpha-D-glucosidase inhibitor (AO-128). After sucrose ingestion, plasma levels of GIP peaked at 15 min and remained high up to 120 min. Plasma levels of GLP-1 NT measured with antiserum R1043 (N-terminal specific) tended to decrease gradually and those of GLP-1 CT measured with antiserum R2337 (C-terminal specific) increased. Therefore, estimated plasma levels of tGLP-1 increased markedly within 30 min, then declined slightly over the next 60 min. After treatment with AO-128 (0.6 mg/day) for 1 week, increases in plasma glucose and insulin levels were attenuated and the increase in plasma GIP levels was diminished, while the increase in tGLP-1 levels was sustained much longer. It is concluded that GIP secretion is stimulated by glucose absorption and tGLP-1 secretion by the presence of sucrose in the gut.

Adult↗
PubMed1992

Sepsis inhibits insulin-stimulated glucose transport in isolated rat adipocytes.

To assess the mechanism of insulin resistance in sepsis, we investigated insulin receptor binding and glucose uptake in isolated rat epididymal adipocytes. Male Sprague-Dawley (SD) rats weighing 200-220 g were submitted to cecal ligation under chloral hydrate anesthesia, followed by double punctures with 18-G needle into the ligated portion to produce peritonitis. Age-matched SD rats without operation were used as the controls. After starvation for 16 h, blood samples were taken from the inferior vena cava for bacterial culture and assayed for plasma glucose and IRI levels, and then adipocytes were isolated from the dissected epididymal fat tissues. Plasma levels of both glucose and IRI in septic rats were higher than those in the controls. The [125I]-insulin binding rate of the adipocytes in septic rats was similar to that of the controls. However, [3H]-2-deoxy-D-glucose uptake by adipocytes was markedly decreased in the septic group (approximately 45% of the control group at the plateau). In conclusion, this study suggests that insulin resistance in the septic state results, at least partly, from impairment in the post-binding level of the insulin receptor.

Adipose Tissue↗
PubMed1991

Unique 3'-untranslated sequence of insulin-like growth factor-I isolated from human placenta.

A cDNA clone of 525 bp corresponding to the 3'-untranslated region of insulin-like growth factor-I was isolated from a human placenta library. The sequence of this clone extended 200 nucleotides downstream from the previously reported 3'-end of IGF-IA cDNA, indicating the existence of IGF-IA transcripts having an even larger 3'-untranslated region. By using this clone for RNA transfer blot hybridization, it was shown that this longer 3'-untranslated region is included in the 7.5- and 5.0-kb transcripts, but not in the 1.1- and 0.9-kb transcripts. It is also apparent that transcripts bearing the extended 3'-untranslated sequence are highly expressed in human placenta.

Base Sequence↗
PubMed1990

[Effects of experimental hepatic artery embolization with lipiodol and gelatin sponge on liver tissue].

The effect of hepatic artery embolization with Lipiodol (Lp) and Gelatin sponge particles (GSP) on liver tissue was evaluated in 17 dogs embolized with GSP, 12 dogs with Lp and 19 dogs with Lp + GSP. Survival rate and extent of liver damage were used as evaluation criteria. None of the dogs with GSP died during the 4 week period, two exhibited small liver infarctions. Of the dogs with 0.2 to 5 ml/kg Lp, two dogs with 4 ml/kg or 5 ml/kg Lp died of cardiac failure. Gross liver examination did not show any liver infarction. Eight of the 19 dogs with Lp + GSP died of liver failure. Gross examination of the surviving dogs demonstrated infarction in 9 of the 11 livers with 100% incidence in those with 0.2 ml/kg or 0.5 ml/kg Lp. Liver infarction increased in size with the increase of Lp volume. In combination with Lp + GSP, the Lp volume should be less than 0.1 ml/kg.

Animals↗
PubMed1990

Expression of the insulin-like and platelet-derived growth factor genes in human uterine tissues.

The human uterus repeatedly exhibits cyclic biochemical and cytological changes during the reproductive period of life. These changes are the result of a well-characterized endocrine network involving the hypothalamus, pituitary, and ovary. The exact nature of the mechanism(s) by which the sex steroids act on the uterus remains to be elucidated. Possible local mediators of hormonal action on the uterus include polypeptide growth factors. Using the method of RNA transfer blot hybridization, we have analyzed tissue samples from the cycling human endometrium and tissue samples of human myometrium and myometrial benign tumor (leiomyoma) for the presence of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF) RNA. All the uterine tissues examined possessed RNA for PDGF-B chain and IGF-I and -II. Two transcripts were observed for PDGF-B chain, four were observed for IGF-I, and eight were observed for IGF-II. Overall, the relative abundance of PDGF-B chain RNA was consistent in all of the uterine tissues examined. In contrast, IGF RNA relative abundance varied. IGF-I RNA was highest in late proliferative stage endometrium, and IGF-II RNA was highest in early proliferative stage endometrium. Both IGF-I and IGF-II RNAs were greater in amount of leiomyoma than in myometrium. The increased IGF-I RNA in late proliferative-stage human endometrium correlates with the known elevation of estradiol secretion by the ovary and the increased concentration of uterine estradiol receptors during this stage of the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrium↗
PubMed1988

Isolation of an insulin-like growth factor II cDNA with a unique 5' untranslated region from human placenta.

Human insulin-like growth factor II (IGF-II) cDNA from a placental library was isolated and sequenced. The 5' untranslated region (5'-UTR) sequence of this cDNA differs completely from that of adult human liver and has considerable base sequence identity to the same region of an IGF-II cDNA of a rat liver cell line, BRL-3A. Human placental poly(A)+ RNA was probed with either the 5'-UTR of the isolated human placental IGF-II cDNA or the 5'-UTR of the IGF-II cDNA obtained from adult human liver. No transcripts were detected by using the 5'-UTR of the adult liver IGF-II as the probe. In contrast, three transcripts of 6.0, 3.2, and 2.2 kilobases were detected by using the 5'-UTR of the placental IGF-II cDNA as the probe or the probe from the coding sequence. A fourth IGF-II transcript of 4.9 kilobases presumably containing a 5'-UTR consisting of a base sequence dissimilar to that of either IGF-II 5'-UTR was apparent. Therefore, IGF-II transcripts detected may be products of alternative splicing as their 5'-UTR sequence is contained within the human IGF-II gene or they may be a consequence of alternative promoter utilization in placenta.

Amino Acid Sequence↗
PubMed1988

Insulin-like growth factor-I messenger ribonucleic acid in the developing human placenta and in term placenta of diabetics.

Fetal growth and development are dependent upon the growth and development of the placenta. Control of placental growth and development is little understood. Immunoreactive insulin-like growth factor-I and -II (IGF-I and IGF-II) have been shown to be released by human placental tissue and human placental membranes have been observed to contain specific receptors for these growth factors. Furthermore, we have demonstrated the presence of IGF-II mRNA transcripts in the developing human placenta and at gestational term in placentae of diabetics. Thus, the IGFs may have a regulatory role in the growth and development of the placenta via autocrine and/or paracrine mechanism(s) of action. In this report we demonstrate the presence of four differing size species of placental poly(A)+ RNA which specifically hybridize to an IGF-I probe originally isolated from an adult human liver cDNA library and localize IGF-I and IGF-II mRNA to syncytiotrophoblasts and fibroblasts, respectively, of the placenta by in situ hybridization. The major transcript is 7500 bases in size and the remaining three transcripts are 5000, 1100, and 900 bases in length with no apparent changes from these sizes throughout gestation and at term in diabetics. Quantification by densitometry of placental IGF-I mRNA detected by dot blot hybridization indicated that first and second trimester placentae each express more IGF-I mRNA relative to that expressed in placenta at term. These results suggest that there are developmental changes in the relative amount of IGF-I mRNA expressed in the human placenta. IGF-I is, therefore, most likely important early in gestation as a placental growth factor. This time period is critical for fetal development and growth, when embryonic induction, organogenesis, and rapid cell proliferation occur.

Female↗