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PubMed1990

Developmental regulation of expression of the lactate dehydrogenase (LDH) multigene family during mouse spermatogenesis.

Expression of the Lactate Dehydrogenase (LDH) genes during various stages of spermatogenesis was studied by using a combination of Northern blot analyses and in situ hybridization techniques. These studies have indicated that developmentally programmed expression of all three functional LDH genes occurs during differentiation of germ cells. The LDH/C (ldh-3) gene was expressed exclusively during meiosis and spermiogenesis, beginning in leptotene/zygotene spermatocytes and continuing through to the elongated spermatids. LDH/C (ldh-3) gene expression was accompanied by transient expression of the LDH/A (ldh-1) gene in pachytene spermatocytes and round spermatids. The LDH/B (ldh-2) gene was expressed mainly in Sertoli and spermatogonial cells. By using somatic cell hybrids, the LDH/C (ldh-3) gene has been mapped to mouse chromosome 7, establishing that it is syntenic with the LDH/A (ldh-1) gene locus. Experimental observations made in this study provide new insight into the order and sequence of events involved in the regulation of gene expression of the LDH gene family during spermatogenesis.

Animals↗
PubMed1986

Skeletal muscle lactate dehydrogenase isozyme alterations in men and women marathon runners.

Total lactate dehydrogenase (LD) and LD isozyme activities in gastrocnemius muscle from trained men and women runners were measured in response to the chronic stress of training for a marathon race (42.2 km). Following 9 wk of training, total LD activity in skeletal muscle from men and women runners significantly (P less than 0.02) decreased 2.26 and 2.25 U/mg protein, respectively. However, men's total LD activities were significantly (P less than 0.001) less than the women's both before and after training. Significant (P less than 0.05) increases in LD1 activities in skeletal muscle in men and women runners were also observed after training. No significant correlations were detected between percent fiber type composition in men or women vs. the changes in total LD activity, changes in LD1 activity, maximal O2 consumption or training distance averaged per week after the training period. The biochemical adaptations in skeletal muscle that occurred in the LD isozyme composition in both men and women runners make the runners skeletal muscle appear similar to heart muscle in LD1 and LD2 activities.

Electrophoresis↗
PubMedDate not supplied

The lactate dehydrogenase isoenzyme pattern in the overacting inferior oblique muscle.

The lactate dehydrogenase (LDH) isoenzyme pattern in normal eye muscles of fetuses, children, and adults in overacting inferior oblique muscles of children was studied and compared. No significant differences were found between LDH isoenzyme activity in the horizontal and vertical recti. Isoenzyme fractions, by percentage, were distributed in these muscles in the order of III greater than IV greater than II greater than V greater than I. A significant difference, however, was noted between the LDH isoenzyme patterns of the inferior oblique muscle in normal adults and children. The percentages were in the orders of III greater than II greater than IV greater than V greater than I, and III greater than IV greater than II greater than V greater than I, respectively. The isoenzyme pattern in the overacting inferior oblique muscles of children was in the order of III greather than II greater than IV greater than V greater than I, identical to that of the adult control group. In addition, the overacting inferior oblique muscle of the children contained more H than M subunit than did the rectus muscle or the normal inferior oblique muscle of children by comparison.

Adult↗
PubMed1983

Lactate dehydrogenase levels in cellular extracts of human malignant lymphomas.

Serum lactate dehydrogenase (LDH) levels have been claimed as an independent prognostic factor in non-Hodgkin's lymphomas (NHL). In the present study, the intracellular and serum LDH levels in Hodgkin's (HD) and NHL were investigated. We found that among NHL, the histologic types of high-grade malignancy (lymphoblastic, immunoblastic and centroblastic), according to the Kiel classification, have a significantly higher intracellular (p less than 0.01) and serum (p less than 0.05) content of this enzyme than those of low-grade malignancy. This finding could explain in part the relation between high serum LDH levels and poor prognosis. It is also possible that the stage of the disease at the moment of the serum determination could be related to the serum LDH level, because a large tumor burden is likely to release more enzyme than a smaller one. However, we could not test this hypothesis because in our series there was ony one NHL patient with stage I or II. Serum LDH level could be a predictor of prognosis in NHL because of its relationship with more malignant histological types, and possibly with more advanced diseases.

Biopsy↗
PubMed1975

Lactate dehydrogenase in preimplantation rabbit embryos.

Unfertilized eggs and early embryos up to the 2-day (16-cell) cleavage stage of development in the rabbit contain predominantly the most cathodal lactate dehydrogenase isoenzyme made up of A-type subunits. Following early cleavage there is a progressing increase in total LDH activity in the embryo as development proceeds through 4- and 6-day blastocyst stages. This is accompanied by an increase in the amount of B-type subunits and a concomitant shift in the lactate dehydrogenase isoenzyme electrophoretic pattern toward the anodal isoenzyme types.

Animals↗
PubMed1987

Electrophoresis and the isomune-LD and LD-1 immuno methods compared for measurement of lactate dehydrogenase isoenzyme-1.

We evaluated three different methods for measuring lactate dehydrogenase (EC 1.1.1.27) isoenzyme LD-1 activity--agarose gel electrophoresis and two immunoassays, Isomune-LD (Roche) and LD-1 Immuno (Seragen)--in patients' samples for which measurement of creatine kinase-MB was ordered. Regression analyses of the comparisons gave the following results: LD-1 (%) from Isomune-LD (y) vs electrophoresis (x) (n = 51), y = 1.05x + 1.99, r = 0.92; LD-1 (%) from LD-1 Immuno (y) vs electrophoresis (n = 27), y = 1.05x + 3.94, r = 0.88; LD-1 (%) from LD-1 Immuno (y) vs Isomune-LD (x) (n = 41), y = 1.06x + 0.48, r = 0.95. Comparison by Student's paired t-test yielded significant differences between the mean values by electrophoresis and both Isomune-LD (P less than 0.005) and LD-1 Immuno (P less than 0.001), but no significant difference between the two immunoassays (P greater than 0.2). Analyzing these results by the overlap index, we conclude that electrophoresis shows the best clinical correlation followed, in order, by the Isomune-LD and the LD-1 Immuno methods. Both immunoassays are simpler and more rapid than electrophoresis, but in our hands the Isomune-LD method demonstrated greater precision and better correlation with electrophoretic values.

Electrophoresis↗
PubMed2002

[Seminal lactate dehydrogenase C4 (LDH-C4) isozyme activity in infertile men].

Lactate dehydrogenase C4 (LDH-C4) is the specific isozyme of LDH produced by germ cells. We measured LDH-C4 activity in seminal plasma from infertile men with oligozoospermia or azoospermia using gel electrophoresis. Total LDH activity in seminal plasma from infertile patients (n = 99) was 2,487 +/- 1,384 IU/l (mean +/- SD). LDH-C4 isozyme activity was detected in 63 out of 75 seminal plasma samples from infertile patients with a mean of 383 +/- 356 IU/l (13.8 +/- 8.6% of total LDH). Sperm count was positively correlated with LDH-C4 (r = 0.298; P < 0.05), but not with any other LDH isozymes or with total LDH. Seminal LDH-C4 was significantly lower in patients with varicoceles (253 +/- 223 IU/l) than without varicoceles (474 +/- 262 IU/l). Six azoospermia patients were treated with hCG and hMG. Three out of four patients whose seminal plasma revealed LDH-C4 activity responded to the treatment, whereas none of the other two patients without seminal LDH-C4 activity did. These results indicate the clinical usefulness of seminal LDH-C4 as a potential marker for seminal epithelium activity in the diagnosis and treatment of male infertility.

Humans↗
PubMedDate not supplied

Usefulness of various lactate dehydrogenase isoenzyme 1 profiles after myocardial infarction.

Isoenzyme profiles of lactate dehydrogenase (percent LD-1 of total LD, LD-1/LD-2 ratio, and absolute LD-1) have all been studied as late markers for myocardial infarction. It is known, however, that elevations of LD-5 frequently occur in this period as a result of liver congestion. Elevations of LD-5 may also occur as a result of complicating conditions. Such elevations could result in a reduced percent LD-1 of total LD, giving rise to false negatives. Receiver operating characteristic (ROC) curves were constructed for LD-1, LD-1/LD-2 and percent LD-1 of total LD from 285 specimens (124 patients) with suspected myocardial infarction. There was little difference in overall diagnostic power among the three assays. Using cutoffs determined from the ROC curves, 6 patients (18 specimens) were evaluated who appeared to be in the late period or who exhibited complicating conditions which could increase LD-5. In 14/18 specimens, increases in LD-5 resulted in false negatives by percent LD-1 of total LD. Only 5/18 specimens were false negatives by LD-1 or LD-1/LD-2. It is concluded that the percent LD-1 of total LD was affected by an increase in LD-5, and caution is recommended when using it.

Creatine Kinase↗
PubMed1986

Lactate dehydrogenase isoenzymes in serum during unstable angina.

Values for total lactate dehydrogenase (LD, EC 1.1.1.27) activity in serum, LD isoenzymes 1 and 2, and the LD 1:2 ratio in 25 patients with unstable angina were compared with the same variables in 25 patients whose angina was stable 24, 48, and 72 h after admission. Mean total LD activity and mean LD-2 activity were found to be within the normal range, both in the unstable angina and stable angina groups of patients. In the unstable angina group the mean LD-1 was significantly higher (p less than 0.01) than in the stable angina group at each time studied. The mean LD 1:2 ratio was also significantly different (p less than 0.001) between the two groups of patients. In the unstable angina group of patients the ratio was increased (0.85, SD 0.09), as in patients with acute myocardial infarction, whereas in the stable angina group of patients the ratio was normal (0.60, SD 0.06). We conclude that a high LD 1:2 ratio, even in the presence of normal total LD activity, may indicate myocardial damage in some patients with unstable angina and could therefore help in the clinical and functional evaluation of patients with unstable angina.

Adult↗
PubMed1977

The thin-layer isoelectric focusing of lactate dehydrogenase isoenzymes in rabbit lens parts and in intraocular tissues.

Lactate dehydrogenase (LDH) isoenzymes of rabbit lens and other intraocular tissues are separated by thin-layer isoelectric focusing and localized as discrete groups of multiple bands with defined isoelectric points after staining by the tetrazolium method. In the rabbit lens parts, the predominant isoenzymes are LDH-4 and LDH-5. The bands show microheterogeneity, are composed of 2-4 subcomponents, and the pattern shows a distribution of the liver type. The activity of the LDH-4 decreases and that of LDH-5 increases in an order given by the equator, anterior and posterior cortex, and nucleus. LDH-3 remains almost constant in all lens parts. LDH-4 is composed of two subcomponents, one of which, the most cathodic with higher isoelectric point, is almost absent in the lens nucleus. Of the LDH localized in the rabbit intraocular tissues, only the retina shows a pattern of five isoenzymes also of the liver type. In all intraocular tissues LDH-3, -4, and -5 are very prominent, show also microheterogeneity of their isoenzyme bands, and are each composed of 4-6 subcomponents. LDH-1 and -2 show only one isofocused component. Species specificity is shown of the LDH isoenzymes in the rabbit, mouse, dog, and calf lens.

Animals↗
PubMed2002

The role of poly(ethyleneimine) in stabilization against metal-catalyzed oxidation of proteins: a case study with lactate dehydrogenase.

The protection provided by poly(ethyleneimine) (PEI) to muscle lactate dehydrogenase (LDH) in metal-catalyzed oxidation (MCO) systems (CuSO(4) or FeCl(2) combined with H(2)O(2)) was studied, and comparisons were made with the chelators EDTA and desferal, respectively. The analytical chelating capacity of PEI was estimated to be around 1 mol Cu(2+)/10 mol ethyleneimine for all molecular weights of the polymer. The effect of [PEI monomer]/[metal ion] molar ratio on the oxidatively induced aggregation of LDH exhibited a similar trend as that of the other chelators; aggregation was enhanced at lower ratios and subsequently decreased until it was undetectable with increasing ratio. In contrast, the LDH activity showed a monotonic increase with increasing concentrations of the chelator. Total protection to the enzyme by PEI was provided at concentrations lower than that needed for full chelation of the copper ions, i.e. at [PEI monomer]/[Cu(2+)] ratio above 9 in case of PEI 2000, and above 7 for PEI 25000 and 2.6 x 10(6), respectively. The polymer also provided protection against oxidation in an iron-based MCO system. Hydroxyl radical formation during the MCO reaction was inhibited in the presence of PEI. The polymer of higher molecular weights also exhibited a stronger free radical scavenging effect.

Animals↗
PubMed1985

Lactate dehydrogenase levels in aqueous humor and serum in retinoblastoma.

The lactate dehydrogenase (LDH) levels were measured in the aqueous humor and serum of 16 patients (20 eyes) with retinoblastoma. The enzyme activity in the aqueous humor and serum did not show any correlation with each other. Age of presentation, age of enucleation, sex and disease duration had no correlation with the enzyme level either in the serum or aqueous humor. The stages of retinoblastoma were classified in Stages I to V: eyes with Stages I to III were included in Group 1, and those with Stages IV and V were in Group 2. The differences in LDH levels in the aqueous humor and in the aqueous to serum LDH ratio were highly significant (P less than 0.001) by Wilcoxon's nonparametric test between Groups 1 and 2. A considerable rise in the aqueous humor LDH level was observed without any alterations in the serum levels in Group 2 as compared to Group 1; hence the aqueous/serum ratio was increased in the former group. The LDH level in the aqueous humor and the aqueous/serum ratio can be a diagnostic tool in retinoblastoma of Stages IV and V. Though the lower aqueous levels of LDH do not rule out the presence of the disease, the higher levels are definitely helpful for diagnosis of retinoblastoma.

Aqueous Humor↗
PubMed1981

Selective inactivation of lactate dehydrogenase isoenzymes with ionic surfactants.

Ionic surfactants selectively inactivate porcine lactate dehydrogenase (LDH) isoenzymes in 30 mM phosphate buffer, pH 7.4. The cationic surfactants hexadecylpyridinium bromide and hexadecyltrimethylammonium bromide rapidly inactivate LDH isoenzymes containing the B subunit; inactivation of LDH-A4 is slower and also retarded by the cofactor reduced nicotinamide adenine dinucleotide. The anionic surfactants sodium decyl sulfate and sodium dodecyl sulfate rapidly inactivate LDH isoenzymes containing the A subunit; inactivation of LDH-B4 is much slower and retarded by the cofactor. The selectivity of the inactivation process correlates with electrostatic interactions: positively charged surfactants preferentially inactivate isoenzymes containing a subunit of net negative charge, and negatively charged surfactants preferentially inactivate isoenzymes containing a subunit of net positive charge. Inactivation takes place near the critical micelle concentration for the cationic surfactants. Inactivation with anionic surfactants occurs above the critical micelle concentration. The cationic surfactants show little discrimination among LDH-B4 and the hybrid isoenzymes, AB3, A2B2, and A3B, inactivating all at approximately the same surfactant concentration. The anionic surfactants, however, show a more graded inactivation-concentration profile with discrete differences in threshold surfactant concentrations required for complete inactivation of the four A subunit containing isoenzymes. At a particular surfactant concentration, loss in activity can be correlated with the percent A- or B-subunit composition of the isoenzyme.

Animals↗
PubMed2002

[Effect of Consupren, Carvedilol and BL-443 on the composition of lactate dehydrogenase in tissues of rats with cyclosporin nephropathy].

L-Lactate dehydrogenase pattern in tissues was determined by polyacrylamide gel electrophoresis adjusted to be more sensitive to LD1 and LD2. Three groups of rats (Wistar) were treated for 18 days with single oral daily doses of 45 mg consuprene/kg body weight to induce cyclosporine nephropathy. Two treated groups were further medicated either with carvedilol or BL-443 in single daily doses of 10 mg/kg b.w., unmedicated rats were given single i.p. daily doses of 1 ml saline. No significant difference in the LD(1-4) isoenzyme pattern in the liver between intact rats, rats with cyclosporine nephropathy, and rats with cyclosporine nephropathy medicated with carvedilol or BL-443 was found by F-test and t-test (p < 0.05). However, a significant difference in the LD(1-4) isoenzyme pattern in the myocardium between rats with cyclosporine nephropathy and intact rats was found. The present study reports the preliminary results of the effects of consupren on the LD(1-4) pattern in the muscle, spleen, and lung, as well as the effects of carvedilol and BL-443 in the tissues under the conditions of experimental cyclosporine nephropathy. The tissues with an increased risk of affection can be identified by evaluation of LD patterns that may become an additional tool to microscopic examination of the sample.

Adrenergic Antagonists↗
PubMed2006

Inactivation of lactate dehydrogenase by several chemicals: implications for in vitro toxicology studies.

Lactate dehydrogenase (LDH) release is frequently used as an end-point for cytotoxicity studies. We have been unable to measure LDH release during studies using para-aminophenol (PAP) in LLC-PK(1) cells. When LLC-PK(1) cells were incubated with either PAP (0-10 mM) or menadione (0-1000 microM), viability was markedly reduced when assessed by alamar Blue or total LDH activity but not by release of LDH into the incubation medium. In addition, we incubated cells with PAP or menadione and compared LDH activity using two different assays. Both assays confirmed our observation of decreased LDH activity in cell lysates without corresponding increases in LDH activity in incubation media. Using purified LDH and 10 mM PAP, we found that PAP produced loss of LDH activity that was inversely proportional to the amount of LDH initially added. In additional experiments, we incubated 0.5 units of LDH for 1 h with varying concentrations of PAP, menadione, hydrogen peroxide (H(2)O(2)) or cisplatin. All four chemicals produced concentration-dependent decreases in LDH activity. In previous experiments, inclusion of antioxidants such as reduced glutathione (GSH) and ascorbate protected cells from PAP toxicity. GSH (1 mM) preserved LDH activity in the presence of toxicants while ascorbate (1 mM) only prevented LDH loss induced by PAP. These studies suggest that LDH that is released into the incubation medium is susceptible to degradation when reactive chemicals are present.

Aminophenols↗
PubMed1997

Serum lactate dehydrogenase and its isoenzyme pattern in ex-coalminers.

Serum lactate dehydrogenase (LDH) activity, a marker of cell damage, is increased in several pulmonary disorders, especially when fibrosis is involved. In rats exposed to silica, high levels of LDH activity were found. A rise of serum LDH3 has been associated with lung tissue injury. The aim of this study was to investigate the serum LDH isoenzyme pattern after coal-dust exposure and the possible relation to pulmonary function tests. Ex-coalminers (n = 201), with a history of coal-dust exposure more than 20 yr ago, were admitted to the authors' hospital for a medical check-up and were included in the study. The serum LDH activity was found to be elevated in 79.1% of the ex-coalminers (634 +/- 245 U I-1). Moreover, in 196 of the 201 cases (97.5%), a high LDH3 level (31 +/- 4%) was demonstrated. A moderate negative relation was found between the forced expiratory volume in 1 s (FEV1) and the LDH activity (r = -0.26; P < 0.001), as well as between FEV1 and LDH3 activity (r = -0.23; P < 0.001), even in the subgroup (n = 42) with a normal LDH. All other liver function tests were within normal limits. These results suggest that coal-dust, even many years after the actual exposure, causes an increase in the total serum LDH activity and changes in the LDH-isoenzyme pattern, mainly characterized by a high LDH3 activity.

Aged↗
PubMed1995

Reversible contraception in female baboons immunized with a synthetic epitope of sperm-specific lactate dehydrogenase.

In previous experiments, the sperm-specific isozyme of lactate dehydrogenase (LDH-C) had been purified from mouse testes and shown to suppress the fertility of female baboons by 70% compared to controls. Although these results demonstrated the feasibility of this approach for contraceptive vaccine development, it is not practical to purify enough of the protein from natural sources for human use. Therefore, a need exists to develop a contraceptive vaccine based on synthetic peptides. In the current study, baboon LDH-C cDNA was amplified by the reverse transcriptase-polymerase chain reaction technique. The amino acid sequences of human and baboon LDH-C were 99.3% identical, indicating that the human LDH-C would be an effective antigen in nonhuman primates. The immunodominant epitope of human LDH-C was identified, synthesized, and conjugated to diphtheria toxoid (DT). This construct was used to immunize 15 female baboons; 15 control animals were immunized with DT alone. The fertility of the experimental group was reduced by 75% as compared to the controls (p < 0.02). One year after the last immunization, the contraceptive effect was completely eliminated (no statistical difference between the groups). These results show that a synthetic peptide based on the sequence of human LDH-C is effective in preventing pregnancy in nonhuman primates. The effect is completely reversed 1 yr after the last immunization. The contraceptive effect is not related to serum antibody titers, and human LDH-C is only slightly more effective than mouse LDH-C in female baboons.

Adjuvants, Immunologic↗
PubMedDate not supplied

Serum lactate dehydrogenase isoenzyme pattern in non-Hodgkin's lymphomas.

Serum lactate dehydrogenase (S-LDH) and its isoenzyme pattern were assayed in 63 non-Hodgkin's lymphoma (NHL) patients, 37 at diagnosis, 15 at relapse and 11 in complete remission (CR). S-LDH in NHL patients with active disease was higher than in normal subjects and CR patients (p less than 0.001). Among the isoenzymes, LDH-2 and LDH-5 showed no remarked differences; LDH-1 was reduced and LDH-3 and LDH-4 raised in comparison to the normal group (p less than 0.001). S-LDH levels and isoenzymes 1 and 4 were influenced by the stage, the histological subgroup and by the presence of general symptoms. In fact, cases in stage IV, with "high-grade malignancy" and with general symptoms, had higher S-LDH levels and more evident LDH-1 and LDH-4 changes than the other stages, the other histopathological subgroups and the cases classified as "A". S-LDH was the same as in normal subjects in the "low-grade" and "intermediate-grade" malignancies as was LDH-1 in stage II and LDH-4 in stages II and III, in "low-grade" malignancy and in the A cases. In contrast, LDH-3 was always high, with no significant difference in relation to the variables considered. Thus, in NHL, LDH-3 seems to be a reliable marker of the presence of the disease in any case, whereas S-LDH is more related to the spread of the lymphoma.

Adolescent↗