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At least 1,369 records · Page 76Linked to original sources
PubMed1994

[Selective effectiveness of galactose-containing liposome IL-2 on liver lymphocytes].

We have performed immunochemical intraarterial infusion immunochemotherapy containing IL-2, mitomycin C and 5-FU as the main active ingredient for metastatic liver tumor and obtained favorable results. However, we are obliged to perform intra-hepatic arterial infusion once or twice a week, because of the short half-life of IL-2. Thus, we are using a drug delivery system to activate lymphocytes of the liver. We noticed many galactose-receptors in the liver and prepared galactose-containing liposome preparations using various carriers/bases. As a result, galactose-containing liposome preparations showed the highest accumulation and the highest localized enhancing effect on the antitumor activity of lymphocytes in the liver sites.

Animals↗
PubMed1976

Effect of galactose and sugar substitutes on blood insulin levels in normal and obese individuals.

Eighteen male patients between the ages of 25 and 50 were given on a double blind randomized basis (A) 40 gms. galactose (B) 50 gms. arabinogalactan and 0.11 gm. sodium saccharin (C) 2 gm. methyl cellulose and 0.083 gm. sodium saccharin and (D) 4 gm. galactose, all in 200 ml water. Blood glucose, galactose and insulin levels were determined during a six hour period before and after ingestion. The three first mentioned solutions tasted equally sweet, the fourth was essentially tasteless. None of these feedings altered plasma insulin or glucose levels. It appears that in contrast to other conclusions reached by earlier investigators sweet taste is unable to induce insulin secretion through neurogenic pathways.

Adult↗
PubMed1996

Galactose-modified streptavidin-GC4 antifibrin monoclonal antibody conjugates: application for two-step thrombus/embolus imaging.

Diagnostic and therapeutic procedures utilizing the high affinity streptavidin (SA)/biotin system are being investigated for in vivo use. We are developing a rapid two-step imaging technique for the diagnosis of deep venous thrombosis and pulmonary embolism. The optimal SA-bound targeting moiety would circulate adequately for sufficient lesion accumulation, but nonbound reagent would clear in a reasonably short time before the injection of radiolabeled biotin. The objective of this study was to cross-link SA and galactose-modified SA to GC4 antifibrin monoclonal antibody and to study the pharmacokinetics and biodistribution of the radiolabeled GC4-SA conjugates after injection into rabbits. A cross-linking method was developed for the synthesis of the GC4-SA conjugates via the addition reaction of sulfhydryl containing SA derivatives with maleimide-GC4. In vivo, radiolabeled trigalactose modified SA-GC4 exhibited a much faster blood clearance compared to mono-galactose modified GC4-SA or GC4-SA containing no galactose.

Animals↗
PubMed1996

Structural basis of galactose recognition by C-type animal lectins.

The asialoglycoprotein receptors and many other C-type (Ca2+-dependent) animal lectins specifically recognize galactose- or N-acetylgalactosamine-terminated oligosaccharides. Analogous binding specificity can be engineered into the homologous rat mannose-binding protein A by changing three amino acids and inserting a glycine-rich loop (Iobst, S. T., and Drickamer, K. (1994) J. Biol. Chem. 269, 15512-15519). Crystal structures of this mutant complexed with beta-methyl galactoside and N-acetylgalactosamine (GalNAc) reveal that as with wild-type mannose-binding proteins, the 3- and 4-OH groups of the sugar directly coordinate Ca2+ and form hydrogen bonds with amino acids that also serve as Ca2+ ligands. The different stereochemistry of the 3- and 4-OH groups in mannose and galactose, combined with a fixed Ca2+ coordination geometry, leads to different pyranose ring locations in the two cases. The glycine-rich loop provides selectivity against mannose by holding a critical tryptophan in a position optimal for packing with the apolar face of galactose but incompatible with mannose binding. The 2-acetamido substituent of GalNAc is in the vicinity of amino acid positions identified by site-directed mutagenesis (Iobst, S. T., and Drickamer, K. (1996) J. Biol. Chem. 271, 6686-6693) as being important for the formation of a GalNAc-selective binding site.

Amino Acid Sequence↗
PubMed1988

Prevention of pericyte ghost formation in retinal capillaries of galactose-fed dogs by aldose reductase inhibitors.

A distinguishing feature of early diabetic retinal vascular changes is the selective degeneration of pericytes (mural cells) from the retinal capillary vessels. Loss of these pericytes has been proposed to be associated with decreased capillary tonicity, the formation of microaneurysms, and vessel dilation. The role of aldose reductase in the progression of diabetic retinopathy has been investigated in age- and sex-matched beagles fed a 30% galactose diet with or without the aldose reductase inhibitors sorbinil or M79175. Eyes were periodically enucleated from dogs in each group and their retinal capillaries were examined as trypsin-digested flat preparations. Before the clinical appearance of retinal changes, pericyte ghost formation was observed in the eyes of three fourths of the dogs after 21 months and all of the dogs after 24 months of galactose feeding. Many of the capillaries containing pericyte ghosts demonstrated an apparent proliferation of endothelial cells and acellular vessels. No pericyte ghosts or abnormal findings were observed in retinas from either normal control (zero of nine) or galactose-fed dogs treated with aldose reductase inhibitors (zero of 16). These findings indicate that aldose reductase inhibitors can prevent the formation of pericyte ghosts and other subsequent capillary changes in experimental retinopathy.

Animals↗
PubMed1998

Mutation of galactose-1-phosphate uridyl transferase and its association with ovarian cancer and endometriosis.

Impaired galactose metabolism has been proposed as a risk factor for ovarian cancer and endometriosis, which is a putative precursor of endometrioid and clear cell histological sub-types of ovarian cancer. The prevalence of the most common galactose-I-phosphate uridyl transferase gene mutations, Q188R and N314D, was assessed in 206 women with ovarian cancer, 78 women with endometriosis and 248 controls. No Q188R mutations were found in any of the groups. A statistically significant increase in the frequency of N314D mutations was observed in women with serous and undifferentiated histological sub-types of ovarian cancer, but not mucinous, endometrioid or clear cell sub-types. There were no significant differences observed in the N314D mutation frequency between women with endometriosis (18%) and controls (17%). Our results support previous reports of an association of impaired galactose metabolism with serous and undifferentiated ovarian cancers but contradict previous findings of increased N314D mutation frequencies among women with endometriosis and endometrioid and clear cell sub-types ovarian cancer.

Adult↗
PubMed1998

Human UDP-galactose 4' epimerase (GALE) gene and identification of five missense mutations in patients with epimerase-deficiency galactosemia.

The galactosemias are a series of three inborn errors of metabolism caused by deficiency of any one of the three human galactose-metabolic enzymes: galactokinase (GALK), galactose-1-phosphate uridyl transferase (GALT), and UDP-galactose 4' epimerase (GALE). We report here the characterization of the entire coding sequence of the GALE gene and screening for mutations in epimerase-deficient individuals. The human GALE gene is about 4 kb in size and is divided into 11 exons on chromosome band 1p36. We have identified five mutations in the GALE gene of epimerase-deficient galactosemia patients. The patients were either homozygotes or compound heterozygotes for mutations. These results confirm that epimerase-deficiency galactosemia is the result of missense mutations in the GALE gene and indicate that the disease is characterized by extensive allelic heterogeneity.

Base Sequence↗
PubMed2000

Subcellular localization of galactose-1-phosphate uridylyltransferase in the yeast Saccharomyces cerevisiae.

The enzyme galactose-1-phosphate uridylyltransferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, following galactokinase (GALK) and preceding UDP-galactose-4-epimerase (GALE). Impairment of GALT in humans results in the potentially lethal disorder classic galactosemia. Standard lysis protocols of bacteria, yeast, or mammalian cells release all three Leloir enzymes in the soluble fraction, leading to the historical assumption that all three function as free cytosolic enzymes. We have tested this assumption with regard to GALT in vivo using the yeast Saccharomyces cerevisiae, by linking a GFP-tag onto the amino terminus of Gal7p, the endogenous yeast GALT. We find clear evidence of localization of the fusion protein to discrete spots in the cytoplasm of the majority of cells expressing all three Leloir enzymes, although GFP alone appears freely cytosolic. In contrast, yeast expressing GFP-Gal7p but lacking Gal1p (GALK), Gal10p (GALE), or both do not demonstrate spots in the majority of cells, implicating a role, either direct or indirect, for these other Leloir proteins in the Gal7p localization process. Preliminary truncation experiments reveal that amino acids 1-134 of Gal7p are sufficient to drive localization of the fusion protein, while amino acids 1-66 are not. Finally, GFP-tagged human GALT expressed in yeast also localizes to spots, demonstrating that at least some of the intrinsic determinants of localization have been conserved. These observations raise the intriguing possibility that GALT may function in a sequestered rather than a freely diffusible state, and that this subcellular organization may have been conserved through evolution.

Base Sequence↗
PubMed1979

Characteristics of galactokinase and galactose-1-phosphate uridyltransferase in cultivated fibroblasts and amniotic fluid cells.

The kinetic characteristics of galactose-1-phosphate uridyltransferase and galactokinase in cultivated fibroblasts and amniotic fluid cells were investigated. The Km values of galactokinase for galactose at 2.0 mM ATP are 0.34 mM in amniotic fluid cells and 0.48 mM in fibroblasts. The Km values for ATP at 0.5 mM galactose are 1.25 mM and 2.10 mM. Transferase and galactokinase activities and protein content increase logarithmically during the growth of cultivated cells. The specific activity of both enzymes also increases and reaches a maximum level 10--15 days after subculture. The specific activity of transferase increases faster than that of galactokinase in the case of amniotic fluid cells. In the case of fibroblasts the specific activity of galactokinase increases faster than that of transferase.

Amniotic Fluid↗
PubMed1976

A new genetic variant of galactose-1-phosphate uridyl transferase.

The enzyme galactose-1-phosphate uridyl transferase (E.C.2.7.7.12), which has an important function in the metabolism of galactose, exists in multiple molecular forms. The different phenotypes are genetically determined. They can be distinguished according to their electrophoretic mobility. The enzymatic activity of the different gene products varies within certain limits. A new phenotype of the enzyme has been detected in the red cells of a healthy individual. The electrophoretic migration of this phenotype is slower compared to the wild type and its enzymatic activity is lower, but still sufficient as not to cause galactosemia. An extensive family study revealed that the rare gene is inherited according to mendelian law. Independently the same gene product has been detected in two other, nonrelated individuals out of a total of 1668 samples tested. The gene frequency can therefore be estimated to 0.0009 in the Swiss population. We suggest that the new type be called Berne variant of galactose-1-phosphate uridyl transferase.

Adult↗
PubMed1993

Clinical and biochemical evidence of skeletal muscle involvement in galactose-1-phosphate uridyl transferase deficiency.

An 8-year-old boy with galactose-1-phosphate uridyl transferase (GALT) deficiency presented with hypotonia, muscle hypotrophy, hepatomegaly, bilateral cataract and mild mental retardation. Two brothers showed a GALT activity consistent with a homozygotic condition and both parents were found to be heterozygotes for this defect. Histological and ultrastructural examination of muscle biopsy specimens showed several necrotic fibres. GALT activity was undetectable in skeletal muscle and muscle tissue cultures; myotubes converted galactose to CO2 at a lower rate than controls. Galactose-1-phosphate was increased in the patient's red cells and muscle tissue. GALT deficiency, not previously described in muscle, may be of pathogenic relevance in determining the myopathic features present in GALT deficiency syndrome.

Biopsy↗
PubMed1996

Three missense mutations in the galactose-1-phosphate uridyltransferase gene of three families with mild galactosaemia.

UNLABELLED: Classical galactosaemia caused by deficiency of galactose-1-phosphate uridyltransferase (GALT) is characterized by acute symptoms of hepatocellular dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation reverses these complications immediately, however, most of these children have a long-term complication of verbal dyspraxia mental retardation and ovarian failure. The GALT gene was cloned and several mutations including the common Q188R have been reported. In this study the coding region of GALT was amplified by polymerase chain reaction from genomic DNA of classical galactosaemic individuals and characterized by direct sequencing of the products. Three missense mutations were identified in three patients with a mild galactosaemic variant: (1) replacement of threonine-138 by methionine (T138M); (2) replacement of arginine by tryptophan (R259W); and (3) replacement of threonine by alanine (T350A). All three galactosaemic individuals, one girl and two boys, have varying degrees of residual GALT activity in RBC and their galactose-1-phosphate levels decreased much faster than in other galactosaemic patients. These missense mutations occur in regions that are not highly conserved domains. CONCLUSION: The study of the molecular basis related to the phenotype variation may indeed help to prognosticate the outcome of patients with classical galactosaemia.

Amino Acid Sequence↗
PubMed1995

Mutations in the galactose-1-phosphate uridyltransferase gene of two families with mild galactosaemia variants.

Classical galactosaemia, deficiency of galactose-1-phosphate uridyltransferase (GALT), is characterized by acute symptoms of hepatomegaly, jaundice, sepsis, cataracts and growth retardation. Treatment with dietary galactose restriction corrects these complications immediately; however, most of these children develop long-term complications of verbal dyspraxia, mental retardation and ovarian failure. Our previous molecular study showed that the most common mutation of the GALT gene is a missense mutation of Q188R (replacement of glutamine-188 by arginine) in approximately 60-65% of the German galactosaemic population. The coding region of GALT was amplified by the polymerase chain reaction from genomic DNA of classical galactosaemic individuals, who are negative or heterozygous for Q188R, and was further characterized by direct sequencing. Three new disease-causing mutations, two missense and a stop codon mutation, were identified in three patients from two families with mild galactosaemic variants: firstly R67C, replacement of arginine-67 by cysteine and W316X, the stop codon at tryptophan-316 in one male; secondly A330V, replacement of alanine-330 by valine in two female siblings. In the first family the patient was also heterozygous for the polymorphism N314D and in the second family both girls were compound heterozygotes for Q188R and A330V. All three galactosaemic individuals have a considerable amount of the residual GALT activity in RBC and the galactose-1-phosphate (GALP) level decreased much faster on treatment than that of other galactosaemic patients with missense mutations such as Q188R. The clinical and biochemical data of these patients were much more favourable in comparison with those of two female galactosaemic individuals, one homozygous for L195P and the other compound heterozygous for Q188R and L195P. These three missense mutations (R67C, L195P and A330V) also occur in highly conserved regions. These observations suggest that the phenotypic variation in galactosaemic individuals may be due to different molecular aetiologies.

Adolescent↗
PubMed2000

Galactosaemia and allelic variation at the galactose-1-phosphate uridyltransferase gene: a complex relationship between genotype and phenotype.

UNLABELLED: More than 160 different base changes have been described at the galactose-1-phosphate uridyltransferase gene and most of these are associated with a disease phenotype. Q188R is the most common mutation in north European populations and those predominantly of European descent. K285N is much rarer but in some countries of east/central Europe it is the second most common mutation. In some populations of northern Europe these two mutations can be found on 70%-80% of mutant chromosomes. Both mutations appear to be associated with a complete loss in enzyme activity and thus, a more severe biochemical phenotype. A single amino acid substitution, N314D, is found on both Duarte 1 and Duarte 2 alleles. Additional base changes that are different on each distinguish D1 from D2 alleles. Whether the differences in galactose-1-phosphate uridyltransferase enzyme activities are associated with the additional molecular changes that distinguish D1 and D2 alleles remains unclear. S135L is found almost exclusively in galactosaemic individuals of African origin. Despite early diagnosis and treatment and adherence to a lactose free diet neurological complications, poor growth and reduced fertility are frequently observed in affected individuals. CONCLUSION: Allelic variation at the galactose-1-phosphate uridyltransferase gene undoubtedly plays a role in defining the biochemical and clinical phenotype. However, clinical galactosaemia is a complex trait in which multiple developmental and metabolic pathways are involved. Ultimately the phenotype is beyond the control of the single gene itself.

Allelic Imbalance↗
PubMed1998

Characterization of a galactose-1-phosphate uridylyltransferase gene from the marine red alga Gracilaria gracilis.

The metabolism of D-galactose is a major feature of red-algal physiology. We have cloned and sequenced a gene from the red alga Gracilaria gracilis that encodes a key enzyme of D-galactose metabolism, galactose-1-phosphate uridylyltransferase (GALT). This gene, designated GgGALT1, is apparently devoid of introns. A potential TATA box, four potential CAAT boxes, and a repeated sequence occur in the 5'-flanking region. The predicted 369-aa peptide shares significant sequence similarity with GALTs from other organisms (human, 47%; Saccharomyces cerevisiae, 49%; Solanum tuberosum, 49%). Southern-hybridization analysis reveals two related, but apparently not identical, GALT genes in the nuclear genome of G. gracilis. Sequence analysis indicates that the GgGALT1 enzyme lacks a rubredoxin "knuckle" motif, which in bacterial and fungal GALTs is involved in binding zinc. An open reading frame encoding a potential peptidyl tRNA hydrolase occurs 179 bp downstream from the GgGALT1 gene.

Amino Acid Sequence↗
PubMed1975

Zero-trans and infinite-cis uptake of galactose in human erythrocytes.

1. The zero-trans and infinite-cis uptake of galactose into human erythrocytes was measured as a function of galactose concentration at 20 degrees C. 2. A special procedure, the "cis-trans test" has been developed to determine the directionality of an asymmetric transport carrier. 3. Using the "cis-trans test" and results obtained by phloretin inhibition, could show the existance of two sites mediating galactose uptake. The kinetic parameters of the high affinity site are K1 equals 11 mM; V1 equals 16 mmol - cell unit-1-min-1 and of the low affinity site: K2 equals 286 mM; V2 equals 21 mmol-cell unit-2-min-1. 4. The infinite-cis Km, using an intergrated rate equation treatment was 21 mM and that found by a direct preloading procedure was 25 mM. The existence of a high affnity site at the inner side of the membrane was thus confirmed.

Biological Transport, Active↗
PubMed1987

Fluorinated carbohydrates as potential plasma membrane modifiers and inhibitors. Synthesis of 2-acetamido-2,6-dideoxy-6-fluoro-D-galactose.

Reaction of benzyl 2-acetamido-3,4-di-O-benzyl-2-deoxy-6-O-mesyl-alpha-D-galactopyran oside with cesium floride gave benzyl 2-acetamido-3,6-anhydro-4-O-benzyl-2-deoxy-alpha-D-galactopyranoside instead of the desired 6-fluoro derivative. Acetonation of benzyl 2-acetamido-2-deoxy-6-O-mesyl-alpha-D-galactopyranoside gave the corresponding 3,4-O-isopropylidene derivative. The 6-O-mesyl group was displaced by fluorine with cesium fluoride in boiling 1,2-ethanediol, and hydrolysis and subsequent N-acetylation gave the target compound. In another procedure, treatment of 2-acetamido-1,3,4-tri-O-acetyl-2-deoxy-alpha-D-galactose with N-(diethylamino)sulfur trifluoride gave 2-acetamido-1,3,4-tri-O-acetyl-2,6-dideoxy-6-fluoro-D-galactose which, on acid hydrolysis followed by N-acetylation, gave 2-acetamido-2,6-dideoxy-6-fluoro-D-galactose.

Cell Membrane↗
PubMed1976

A method for galactose-1-phosphate uridyltransferase assay and the separation of its isozymes by DEAE-cellulose column chromatography.

A simplified radioactive assay for galactose-1-phosphate uridyltransferase (EC 2.7.7.12) using a small DEAE-cellulose column for the identification of the endproduct (uridine diphosphate galactose) is described. The enzyme activities in red blood cell hemolysates of normal subjects are in the range of 24 to 33 (average 30.3) mumol UDPgalactose produced per g hemoglobin per h and in fibroblasts 0.39 and 1.39 (average 0.71) nmol per mg protein per min. Furthermore, different isozymes of red blood cell galactose-1-phosphate uridyltransferase were separated on DEAE-cellulose columns. In the case of a normal genotype, most of the enzyme activity is eluted at the earlier fractions with the low molar phosphate buffer, whereas the Duarte variant appeared at later fractions with higher molar phosphate buffer.

Chromatography, DEAE-Cellulose↗