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[The effect of hadacidin, ultraviolet irradiation of blood (UVB) and thiamine on the prenatal development of Uje:WIST rats: correlation with the hepatic activity of gamma-glutamyltranspeptidase (GGT)].

The influence of hadacidin, a model substance for induction of cheilognathouranoschisis in rat fetuses (2,550 mg/kg b.m. at gestation day 12), ultraviolet irradiation (UVB) of blood (1 week before gestation) and thiamine (25 mg/kg b.m. from gestation days 12 to 15) on the prenatal development of rats at the 20th day of gestation was investigated. Using the body mass and the hepatic GGT-activity as parameters. Hadacidin caused a distinct retardation of the fetal somatic development. Partially, the embryotoxic effect was compensated by UVB or thiamine. The combination of both procedures was more effective. There is a good correlation between the maturation grade of fetuses at day 20 of gestation and the hepatic GGT activity.

Animals↗

The influence of GGT, COHb% and body weight on the 2-h glucose and insulin response after a standardized oral glucose load.

Relative body weight (A/I weight) serum gamma-glutamyl-transferase (GGT) and carboxyhemoglobin (COHb%) were related to glucose and insulin values at 0 and 120 min in a sizable, consecutive series of oral glucose tolerance tests (OGTTs) in middle-aged males. Partial and multiple correlation coefficients were calculated, and the squared stepwise multiple correlation coefficient was used to estimate how much of the variability of glucose and insulin could be accounted for by the three factors. No less than 14% of the glucose variability and 25% of the insulin variability at 2 h could be attributed to them, emphasizing the importance of keeping these three factors in mind when interpreting the results of OGTTs.

Blood Glucose↗

NAG, GGT, creatinine, urea and creatinine clearance before and after ESWL.

N-acetyl-beta glucosaminidase (NAG) and gamma-glutamyltransferase (GGT) were measured in the urine and serum before, 24 hours and one week after extracorporeal shock wave lithotripsy in 25 patients. Although ESWL is the preferred method in the treatment of kidney stones, its effect on renal parenchymal cells has not been sufficiently elucidated. Since radiographic methods remain inadequate in the estimation and management of parenchymal damage, it is useful to establish the specific renal cell proteins in urine and serum, reflecting renal tubular cell destruction.

Acetylglucosaminidase↗

c-K-ras codon 12 GGT-CGT point mutation. An infrequent event in human lung cancer.

Hu-c-ras represent a family of oncogenes which are capable of inducing malignant transformation in the NIH/3T3 mouse cell line. Associated with this transformation are specific point mutations observed in the 12th and 61st codon of c-K-ras and N-ras and c-Ha-ras, respectively. These base changes generate, in some instances, a new restriction enzyme cleavage site and a restriction fragment length polymorphism (RFLP). One such RFLP has recently been reported for the mutation GGT-CGT at codon 12 of c-K-ras. Our data suggest that this point mutation is rarely present in human lung cancer and therefore is not likely to play a major role in cancer development.

Cell Transformation, Neoplastic↗

Study of the enzymatic activity of GGT, LDH, PAP and PSA in semen stains: application to age calculation.

The conditions under which semen stains are stored can markedly affect the stability of some of their biochemical parameters. Because of the resistance of semen to processes of degradation and denaturation, the age of the stain may, under optimum conditions, be calculated. We studied six series of semen stain placed on absorbent natural cloth under three different storage temperatures: 5 degrees C (refrigerator), 18-25 degrees C (room temperature), and 38 degrees C (incubator). Seminal fluid was obtained from nonvasectomized and vasectomized individuals aged 25-40 years (mean age 30 +/- 0.32 years, SD 3.06). A total of 240 strains were divided into groups depending on the duration of storage: 24, 48 or 72 h, 1 week, 1, 2, 4 or 6 months. Eluates were analyzed for gamma glutamyltransferase (GGT), lactate dehydrogenase (LDH), prostatic acid phosphatase (PAP), and p30 or prostate specific antigen (PSA). The results of regression analyses showed that a large proportion of the dependent variable (age of the stain) was explained by the rest of the biochemical markers tested. Calculation of the age of the semen stain thus requires consideration of several biochemical parameters.

Adult↗

Benign recurrent intrahepatic cholestasis progressing to progressive familial intrahepatic cholestasis: low GGT cholestasis is a clinical continuum.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disease, characterised by intermittent attacks of cholestasis, which can start at any age and last for several weeks to months. Characteristically serum GGT activity is low and normal liver structure is preserved. Progressive familial intrahepatic cholestasis (PFIC) is another liver disease, characterised by severe cholestasis, starting almost invariably before 6 months of age. All patients progress to cirrhosis, liver failure and death, unless a liver transplantation is performed. We now identified four patients who presented in childhood with recurrent attacks of cholestasis, while in the course of the disease the cholestasis gradually became permanent. Although liver biopsies performed in the early stages of the disease showed normal liver architecture, late stage biopsies revealed evident fibrosis with porto-portal septa formation. In conclusion, the disease of these patients started with the clinical and histopathological characteristics of BRIC but progressed to PFIC.

Adolescent↗

Fibrinogens Kosai and Ogasa: Bbeta15Gly-->Cys (GGT-->TGT) substitution associated with impairment of fibrinopeptide B release and lateral aggregation.

We found two heterozygous dysfibrinogenemias, designated fibrinogen Kosai and fibrinogen Ogasa. Kosai was associated with arteriosclerosis obliterans but Ogasa showed no bleeding or thrombotic tendencies. The plasma fibrinogen concentrations from the two propositi (Ogasa and Kosai) were much lower when determined by the thrombin-time method (0.94 and 1.06 g L(-1), respectively) than when determined by the immunological method (2.87 and 2.72 g L(-1), respectively). We performed DNA sequencing and functional analyses to clarify the relationship between the structural and functional abnormalities. Genetic analysis of PCR-amplified DNA from the propositi identified the heterozygous substitution Bbeta15Gly-->Cys (GGT-->TGT). Western blotting analysis of purified fibrinogen revealed the existence of albumin-fibrinogen complexes. Functional analyses indicated that compared with the normal control, the propositi's fibrinogen released only half the normal amount of fibrinopeptide B and showed markedly impaired polymerization. In addition, the observation of thinner fibers in fibrin clots (by scanning electron microscopy) indicated markedly defective lateral aggregation in the variant fibrinogens. The impaired functions may be due to the substitution of Cys for Bbetao15Gly plus the existence of some additional disulfide-bonded forms.

Adult↗

Hb Hope [beta136(H14)Gly-->Asp (GGT-->GAT)]: interactions with Hb S [beta6(A3)Glu-->Val (GAG-->GTG)], other variant hemoglobins and thalassemia.

Hb Hope [beta136(H14)Gly-->Asp (GGT-->GAT)] was first described in an African-American family in 1965. Since then, it has been found in combination with several different globin gene mutations in many other families of divergent ethnic backgrounds. The basis for its relatively frequent occurrences remains unexplained. This variant hemoglobin (Hb) is mildly unstable and has reduced oxygen affinity, but is generally innocuous clinically. This variant Hb can present as a confounding factor in arriving at a correct diagnosis by either electrophoresis or high performance liquid chromatography (HPLC), particularly during the neonatal period. DNA-based diagnostics can help solve this potential problem.

Ethnicity↗

Human minisatellite loci composed of interspersed GGA-GGT triplet repeats.

We have isolated two tandemly repeated loci from human DNA which contain long blocks of GGA and GGT trinucleotide repeats. These two repeat unit types, together with other less common variants, are apparently irregularly interspersed along each repeat array. Genotyping methods have been developed for these highly polymorphic loci, including typing by polymerase chain reaction followed by Southern blot hybridization. Linkage analysis in Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees has been used to map the loci to chromosomes 15 and 22. In normal individuals, alleles at these loci can contain thousands of repeats, greatly exceeding repeat copy number at most trinucleotide and other simple repeat loci. No evidence for longer, higher-order repeats was observed among the limited number of repeats sequenced. These loci may represent a transitional state between simple repeat loci and some minisatellites.

Animals↗

DNA sequence of the Escherichia coli K-12 gamma-glutamyltranspeptidase gene, ggt.

The DNA sequence of ggt, the gene that codes for gamma-glutamyltranspeptidase (EC 2.3.2.2) of Escherichia coli K-12, has been determined. The sequence contains a single open reading frame encoding the signal peptide and large and small subunits, in that order. This result suggests that E. coli gamma-glutamyltranspeptidase is processed posttranslationally.

Amino Acid Sequence↗

Two elliptocytogenic alpha I/74 variants of the spectrin alpha I domain. Spectrin Culoz (GGT----GTT; alpha I 40 Gly----Val) and spectrin Lyon (CTT----TTT; alpha I 43 Leu---Phe).

Spectrin alpha I/74 elliptocytosis results from abnormalities involving the "head" region of spectrin dimer. Increased susceptibility to trypsin enhances cleavage of the alpha spectrin chain, yielding an increased amount of the alpha I 74-kD fragment at the expense of the alpha I 80-kD parent fragment. Recently we showed that the mutations causing the Sp alpha I/74 abnormality may lie in the alpha- or the beta-chain, and that spectrin Culoz and spectrin Lyon were two (alpha I/74) alpha-variants, respectively. We now show that the spectrin Culoz alpha I domain undergoes prominent tryptic cleavage after Lys 42, whereas cleavage prevails after Arg 39 in spectrin Lyon. Applying the polymerase chain reaction (PCR) technique to exon 2 of the spectrin alpha I domain, we have established that the mutation responsible for spectrin Culoz is alpha I 40 Gly----Val; GGT----GTT. Applying the PCR technique to the cDNA derived from reticulocyte mRNA, we have shown that the mutation responsible for spectrin Lyon is alpha I 43 Leu----Phe; CTT----TTT. Studies of normal controls and of family members using dot blot hybridization with allele-specific oligonucleotide probes confirmed these results. Variants such as spectrin Culoz and spectrin Lyon should provide insight into a region that participates in spectrin dimer self-association and whose susceptibility to proteolysis must reflect subtle conformational changes.

Amino Acid Sequence↗

[One case of cholangiocarcinoma in hepatic hilium only connected to increase GGT].

This is the case of a patient 53 years old afflicted with cholangiocarcinoma infiltrated in the hepatic parenchyma and in soft tissues the of hepatic hilum. The patient was asymptomatic and objective examination was negative. The diagnostic suspicion was caused by the progressive increase of GGT, while the other indexes of hepatic functionality were normal. The diagnosis was confirmed by hepatic ultrasonography, abdominal TAC and, at last, by ERCP. The patient was operated by resection of bilious organs and multiple biliary-digestive anastomosis. Now he is in good health.

English Abstract↗

Peripartal gamma-glutamyltranspeptidase (GGT) activity in the mammary glands of pregnant Uje: WIST rats.

On Day 21 of gestation ( = expected day of delivery), GGT activity of the mammary gland is low 4-6 h before beginning of delivery. It is significantly higher immediately (up to 3 h) before delivery or after labor. The extent of prepartal increase is individually different. The activity measured early in the morning cannot be used to predict the remaining time to beginning of spontaneous parturition.

Animals↗

Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT----GGAG).

A frameshift mutation that causes a silent phenotype for human serum cholinesterase was identified in the DNA of seven individuals of two unrelated families. The mutation, identified using the polymerase chain reaction, causes a shift in the reading frame from Gly 117, where GGT (Gly)----GGAG (Gly+ 1 base) to a new stop codon created at position 129. This alteration is upstream of the active site (Ser 198), and, if any protein were made, it would represent only 22% of the mature enzyme found in normal serum. Results of analysis of the enzymatic activities in serum agreed with the genotypes inferred from the nucleotide sequence. Rocket immunoelectrophoresis using alpha-naphthyl acetate to detect enzymatic activity showed an absence of cross-reactive material, as expected. One additional individual with a silent phenotype did not show the same frameshift mutation. This was not unexpected, since there must be considerable molecular heterogeneity involved in causes for the silent cholinesterase phenotype. This is the first report of a molecular mechanism underlying the silent phenotype for serum cholinesterase. The analytical approach used was similar to the one we recently employed to identify the mutation that causes the atypical cholinesterase variant.

Amino Acid Sequence↗

Enhanced erythropoietin and suppression of gamma-glutamyl transpeptidase (GGT) activity in murine lymphoma following administration of vanadium.

Administration of vanadium as ammonium monovanadate (0.005 microgram/0.1 ml/mouse/day) was found to reduce the tumor cell proliferation in the host mice bearing Dalton's lymphoma. The high activity of gamma-glutamyl transpeptidase (GGT), a neoplastic marker, was seen in the host cells bearing lymphoma. Vanadium effectively prevented an increase in activity of gamma-glutamyl transpeptidase and maintained a sustained low activity of this enzyme. In addition, an improvement of the hematological aspects of the mice and almost fourfold elevation of erythropoietin (Epo) was obtained following vanadium treatment. This increase in Epo activity may play a vital role in regulating the growth of cellular neoplasia. The present study further confirms the antitumorigenic potential of vanadium in the control of tumor progression in lymphoma via modulating several factors involving erythropoiesis and may emerge as a new chemopreventive agent for the future.

Animals↗

The effects of D-fenfluramine on the development of aflatoxin-B1 induced GGT+ hepatic foci in F344 rats.

The role of total caloric intake and attained body weight in the carcinogenic process in rodents is controversial. In the present study we examined the development of hepatic pre-neoplastic foci in rats treated with aflatoxin-B1 (AFB) and given the drug D-fenfluramine (FEN). Ingestion of this drug leads to a reduction in body weight by increasing the thermogenic response to a meal and by transiently reducing food intake. Young male rats were dosed with AFB or vehicle alone and were then assigned to receive control diet (NO FEN) or control diet + FEN (FEN; 0.15 g/kg diet) for 12-14 weeks. Body weight gain and food intake were reduced among animals given FEN; brown adipose tissue weight (% body weight) was elevated in these groups. Indices of protein status, and concentrations of T3, T4 and insulin did not differ among the groups. All animals given FEN developed GGT+ hepatic foci. The number and volume fraction of foci were significantly larger in FEN relative to NO FEN animals. The mean diameter of foci was slightly enhanced among FEN animals. These results suggest that FEN promotes the development of AFB-induced hepatocellular foci, despite reduced food intake and lower body weight. Since FEN is widely used as a weight loss aid, these findings deserve further study.

Adipose Tissue↗