Serum lactate dehydrogenase (S-LDH) and S-LDH isoenzymes in patients with testicular germ cell tumors

The activities of serum lactate dehydrogenase (S-LDH) and S-LDH isoenzymes were determined in 252 patients with a history of testicular germ cell tumors (TGCT). Fifteen of 37 patients with TGCT lesions and seven of 215 without had raised levels of S-LDH (above 8.0 mukat/l (480 U/l)). Of the patients with TGCT lesions, four had only raised S-LDH-1 levels, one only raised S-LDH-2 (and normal S-LDH), two only raised S-LDH-3 (one with normal S-LDH), and 10 had five combinations of raised levels of S-LDH isoenzymes with a predominance of S-LDH-1. S-LDH and S-LDH-1 correlated significantly with the total tumor volume in the patients with TGCT lesions, especially pronounced in those with lesions from seminoma. Of 34 patients with TGCT metastases, 13 with raised S-LDH levels lived significantly shorter lengths of time than 21 with normal S-LDH. Similarly, 11 with raised S-LDH-1 (above 3.0 mukat/l (180 U/l) lived significantly shorter times than 23 with normal S-LDH-1. S-LDH is a valuable tumor marker in patients with TGCT, especially in those with seminoma. Routine determination of S-LDH isoenzymes in addition to S-LDH in patients with TGCT is not recommended. In patients with a history of TGCT and an unexplained elevation of S-LDH levels, a raised S-LDH-1 level indicates the presence of TGCT lesions.     

Additional lactate dehydrogenase (LDH) isoenzymes in normal testis and spermatozoa of adult man

Summary Adult human testicular tissue contains up to six previously undescribed lactate dehydrogenase (LDH) isoenzymes in addition to the five LDH isoenzymes normally found and the sixth found in spermatogenic cells and spermatozoa, LDH-X. Additional LDH isoenzymes were also found in spermatozoa but not in seminal fluid or in serum. After electrophoresis one additional LDH isoenzyme of testicular tissue was localized between LDH-1 and LDH-2, two between LDH-2 and LDH-3, two between LDH-3 and LDH-4, and two between LDH-4 and LDH-5. These localizations indicate that the additional LDH isoenzymes are tetramers combining the A and B subunits of the five normal LDH isoenzymes and the C subunit of LDH-X. The additional LDH isoenzymes may be important in the metabolism of spermatogenic germ cells and spermatozoa.     

Changes in the lactate dehydrogenase isoenzyme spectrum during T-lymphocyte differentiation

The pattern of lactate dehydrogenase isoenzyme spectrum changes on different stages of T-lymphocyte differentiation was studied An enriched population of stem cells has LDH-5, 4 and 3 isoenzymes, and much less LDH-2 activity. The isoenzyme pattern of thymic cell precursors consists of LDH-5, 4, 3 and 2. All the five LDH isoenzymes were found in cortical thymocytes. Medullary thymocytes reveal LDH-5, 4 and 3 isoenzymes. T-lymphocytes of peripheral lymphoid organs contain mainly LDH-5 and in a lesser degree LDH-4 activity.     

Clinical impact of down-regulated plasma miR-92a levels in non-Hodgkin's lymphoma

Background

We undertook a study to evaluate the clinical relevance of miR-92a in plasma obtained from non-Hodgkin''s lymphoma (NHL) patients, because the miR-17-92 polycistronic miRNA cluster plays a crucial role in lymphomagenesis and affects neo-angiogenesis.

Methodology/Principal Findings

Plasma miR-92a values in NHL were extremely low (<5%), compared with healthy subjects (P<.0001), irrespective of lymphoma sub-type. The very low plasma level of miR-92a increased in the complete response (CR) phase but did not reach the normal range, and the plasma level was lower again in the relapse phase. Patients in CR or CR unconfirmed with a plasma miR-92a level of less than the cut-off level showed a significantly high relapse rate compared with patients with normalized plasma miR-92a level.

Conclusions/Significance

The current results therefore indicate that the plasma miR-92a value could be a novel biomarker not only for diagnosis but also for monitoring lymphoma patients after chemotherapy.     

Lactate dehydrogenase isoenzymes in diabetic patients

Lactate dehydrogenase (LDH) isoenzyme profiles in human platelets and the sera of patients with type I and II diabetes mellitus and vascular complications, as well as normal subjects were measured utilizing a recently established, modified micromethod. LDH-3 was the predominating species in platelets (37.5 +/- 3.0%), with LDH-2, 1, 4 and 5 following in decreasing order of concentration. The LDH-3/LDH-4 ratio in platelets varied from 6.2 to 1.38. Type I and type II diabetic patients with vascular complications showed a significantly higher ratio for LDH-3/LDH-4 (3.99 +/- 1.20 for DM I, 2.16 +/- 0.25 for DM II patients) than the mean ratio for normal subjects (1.14 +/- 0.08). This platelet-specific LDH isoenzyme pattern may be the result of frequent in vivo platelet-vessel wall interactions in the diabetic patients whose platelets are known to be hyperaggregable in in vitro test systems. Since non-diabetic patients patients with vascular complications also displayed a similarly elevated LDH-3/LDH-4 ratio, a wider classification is preferable, although the measurement of the LDH isoenzyme pattern will be helpful in assessing diabetic vascular complications.     

Energy enzymes of the flight muscle of the house sparrow, Passer domesticus--III. Comparative physical properties of heart and flight muscle lactate dehydrogenase

Purification of heart (LDH-4) and flight muscle (LDH-2 and LDH-3) lactate dehydrogenase isoenzymes from the house sparrow, Passer domesticus, has been accomplished. Although these isoenzymes electrophoretically migrate reversed to most other vertebrate LDH isoenzymes, comparison of the amino acid compositions of LDH-4 and LDH-2-LDH-3 fails to reveal the basis for their reversed electrophoretic migration. Amino acid compositions did reveal mol. wts between 141,000-142,000 as well as vp of 0.744 ml/g (LDH-4) and 0.745 ml/g (LDH-2-LDH-3). SDS-gel electrophoresis yielded single bands for each preparation with mol. wts of 35,000 suggesting that LDH in this species exists as a tetramer. LDH-4 has a lower Km for both pyruvate (0.005 mM) and NADH (0.002 mM) than does LDH-2-LDH-3 (0.062 mM for pyruvate, 0.013 mM for NADH).     

Selective inactivation of lactate dehydrogenase of rat tissues by sodium deoxycholate.

Soluble lactate dehydrogenase (EC 1.1.1.27) extracted from brain, skeletal and cardiac muscle and liver of rats, and purified isoenzymes LDH-1 and LDH-5, were incubated with sodium deoxycholate. Deoxycholate almost totally inactivated isoenzyme LDH-5 (A4), whereas it left isoenzyme LDH-1 (B4) unaffected. Tissue lactate dehydrogenase was inactivated to different degrees depending on the origin of the enzyme. Electrophoretic isoenzyme studies of tissue lactate dehydrogenase showed the loss of activity to be quantitatively related to the overall percentage of subunit A distributed among the homotetramer LDH-5 and the heterotetramers LDH-2, LDH-3 and LDH-4. It was concluded that subunit A of lactate dehydrogenase interacts selectively with deoxycholate, irrespective of its association with subunit B. Distinct changes in electrophoretic mobilities of deoxycholate-treated isoenzymes strongly indicated an indiscriminate binding of deoxycholate by all LDH isoenzymes, probably through hydrophobic interactions. The results suggest that the inactivation of the enzyme is non-competitive, but the basis of the selectivity of deoxycholate towards subunit A is not known at present.     

Lactate dehydrogenase isoenzymes in the larvae of Barathra brassicae and Galleria mellonella during microsporidan infection

Changes in the activities of lactate dehydrogenase isoenzymes in the gut and fat body of Galleria mellonella and Barathra brassicae larvac infected by the microsporidans Nosema plodiae and Pleistophora schubergi were studied by means of dise electrophoresis. In the normal last instar G. mellonella gut and fat body three isoenzymes, LDH-1, LDH-2-3, and LDH-4, and in B. brassicae two isoenzymes, LDH-1 and LDH-2-3, were present. In the fat body of both the animals infected by N. plodiae, the isoenzyme LDH-2-3 increased in activity substantially by the fifth day of infection. The gut LDH isoenzymes were not affected by the microsporidan. The same LDH-2-3 effect could be provoked by some enzymes toxic for G. mellonella larvae such as phospholipase-C and protease preparations.     

大豆黄酮对衰老小鼠脑组织SOD、LDH同工酶的影响

利用SOD和LDH同工酶电泳分析,研究大豆黄酮对衰老小鼠的抗氧化作用。结果显示大豆黄酮没有改变SOD和LDH同工酶谱的特征,但对因衰老引起的小鼠脑组织LDH和SOD同工酶活性、各组分的相对活性和比活力的变化有不同程度的改善作用,即LDH同工酶中LDH-2、LDH-3的活性明显下降,LDH-1的活性下降最为明显,而LDH-4的活性有所下降,但不显著,LDH-5的活性几乎没有变化,SOD同工酶的SOD-1和SOD-2的活性有不同程度的升高。这表明大豆黄酮是通过抑制LDH同工酶H亚基的合成来降低LDH的活性,而对M亚基的合成没有影响,并且能够促进SOD同工酶SOD-1和SOD-2的合成,不影响其遗传稳定性。     

ICE方案治疗复发难治性非霍奇金弥漫大B细胞淋巴瘤临床观察

目的:观察ICE方案(异环磷酰胺IFO,卡铂CBP,依托泊苷VP-16)治疗复发/难治性非霍奇金弥漫大B细胞淋巴瘤(Non-hodgkin's lymphoma,NHL)的疗效及安全性。方法:20例经系统化疗后复发或进展的非霍奇金弥漫大B细胞淋巴瘤(DLBCL)患者,采用ICE方案化疗至少2周期,IFO 5 g/m2,第2天,持续24小时静脉输注,CBP按AUC=5,max 800 mg,第2天,静脉输注,VP-16.100 mg/m2,第1-3天,静脉输注。结果:完全缓解(complete response,CR)5例,部分缓解(partial response,PR)8例,疾病稳定(stable disease,SD)4例,疾病进展(progress disease,PD)3例,总有效率(overall response rate,ORR,CR+PR)65%,化疗副作用主要为骨髓抑制(Ⅰ、Ⅱ度6例,Ⅲ、Ⅳ度14例),其他不良反应包括胃肠道反应、粘膜损伤、肝肾毒性及脱发等均可耐受。结论:ICE方案可用于非霍奇金弥漫大B细胞淋巴瘤的二线化疗方案。     

Diagnosis of follicular lymphoma by fine needle aspiration biopsy.

This study evaluated the diagnostic accuracy of fine needle aspiration biopsy (FNAB) of follicular lymphoma (FL). Fourteen aspirates of lymph nodes in which follow-up surgical biopsy revealed FL were studied. Two aspirates were deemed unsatisfactory because of a paucity of cells. The remaining 12 cases received the following diagnoses: 4 positive for malignant lymphoma, 4 highly suspicious for malignant lymphoma and 4 false negatives. FNAB of FL can show a monomorphic or polymorphic cell population. The aspirates with a positive or suspicious diagnosis showed monomorphic cell populations. False-negative diagnoses were attributable to misleading sampling or preparation methods in most cases. We conclude that FNAB of FL is less accurate than FNAB of non-Hodgkin's malignant lymphoma (NHL) in general, but the accuracy rate is similar to that of FNAB of all low-grade NHL. The value of current approaches to the diagnosis of suspected lymphoma by FNAB is emphasized.     

氟达拉滨联合化疗方案对复发性非霍奇金淋巴瘤的疗效研究

目的：探讨氟达拉滨为主联合化疗方案对复发性非霍奇金淋巴瘤的临床疗效。方法：用氟达拉滨为主的方案（FMD）化疗复发性非霍奇金淋巴瘤17例,以EPOCH方案化疗14例患者,比较两组疗效。结果：FMD方案化疗有效率为70．6％,高于EPOCH方案的50．0％,但是差异无统计学意义（P〉0．05）。FMD化疗方案在对低度恶性组疗效最佳,优于高度恶性组和中度恶性组（P〈0．05）;对不同临床分期（I、II、III、Ⅳ期）患者和不同免疫细胞分型患者,其有效率无统计学差异（P〉0．05）。在各种不良反应中,FMD组白细胞减少率、转氨酶升高率低于EPOCH组（P〈0．05）。结论：以氟达拉滨为主联合化疗方案对复发性非霍奇金淋巴瘤的临床疗效好,毒副反应轻,预后良好。     

FNAC of malignant lymphoma in an area with a high incidence of T-cell lymphoma. Correlation of accuracy of cytologic diagnosis with histologic subtype and immunophenotype

OBJECTIVE: To analyze the usefulness of fine needle aspiration cytology on malignant lymphoma in an area with a high incidence of T-cell lymphoma and to correlate the accuracy of cytologic diagnosis with histologic subtype and immunophenotype. STUDY DESIGN: We retrospectively studied the usefulness of fine needle aspiration cytology in the diagnosis of 49 cases of nodal and extranodal non-Hodgkin's lymphoma (NHL) and seven cases of Hodgkin's disease in a total of 56 patients in whom subsequent excisional biopsy revealed lymphoid malignancy. Slides showing the results of cytologic investigation were reviewed together with the information on which histologic diagnosis was based. On the basis of pathologic variables, such as prognostic groups based on the Working Formulation, so-called grade, cell size based on the modified Rappaport classification, and--in cases of NHL--immunophenotype, the accuracy of original and reviewed cytologic diagnoses was compared. RESULTS: Of the 49 cases of NHL, 8 (16.3%) were inadequate for cytologic diagnosis, and malignant lymphoma was diagnosed or suspected in 36 (73.5%), excluding inadequate specimens; the diagnostic accuracy for NHL was 87.8%. In high grade cases, malignant lymphoma was more easily diagnosed or suspected than in those that were low or intermediate grade. The rate of inadequate cases was highest in the "mixed small and large cell" category, and cases that were "false negative" were either composed entirely of small cells or contained a small cell component. Cytologic diagnosis or suspicion of malignant lymphoma was easily obtained in the "large cell" category, followed by mixed small and large cell and "small cell." Aspirates from non-B-cell type were more frequently acellular than those of B-cell type; with regard to diagnostic accuracy, however, there was no noticeable difference between the two immunophenotypes. CONCLUSION: In many cases in the mixed small and large cell category or where the immunophenotype was non-B, the aspirate was inadequate, and no definitive diagnosis was possible. Many of our cases of T-cell lymphoma were mixed small and large cell, and in Korea, where the incidence of extranodal and T-cell lymphoma is high, the usefulness of FNAC for the initial diagnosis of malignant lymphoma is limited. For a definitive diagnosis, biopsy is required.     

Juvenile malignant lymphomas. 2 Non-Hodgkin lymphomas

Between 1970 and 1978 33 children with Non-Hodgkin-lymphomas at the age of 2-15 years were treated at the university children's hospital of Jena. 27 patients showed the first appearance of the disease, 6 patients had already been treated in other hospitals and were admitted with relapses. The biopsy material was classified or re-classified after the Kiel-classification. Beside the histological classification the surface markers of the malignant cells of NHL-patients were determined. 20 of 33 children were already in stage IV (Ann-Arbor-classification). Among our patients were 6 lymphoblastic NHL of Brukitt type, 10 of the convoluted cell type and 16 unclassified and one lymphoblastic lymphoma. The main localization of the NHL were mediastinum [15] and the gastrointestinal tract [10]. The therapy consisted of irradiation and chemotherapy (2 protocols) and, in case of an abdominal localization, in the attempt at a radical operation. Patients of stage I and stage II showed a complete remission rate of 50 per cent for 3 years; patients of stages III and IV of 20 per cent only. NHL of the convoluted cell type and of the Burkitt-type proved to have worse three-year-remission rates (16 per cent and 27 per cent) than unclassified lymphoblastic NHL (42 per cent).     

A clinicopathological study of non-Hodgkin's malignant lymphomas in terms of the Kiel classification.

A group of 25 patients with non-Hodgkin's lymphoma was investigated. Patients diagnosed earlier were reclassified according to the Kiel system. A correlation between age distribution and histological malignancy was found. The time between the onset of symptoms and diagnosis was 1 year on an average. The majority of the patients belonged to stage IV. The survival rate was higher in the low-grade malignancy group than in the high-grade group. When assessing the prognosis, the histological classification as well as the clinical staging ought to be considered. The bone marrow was the most frequent extranodal site of involvement in stage IV. Cytopenic changes were almost invariably accompanied by bone marrow infiltration. All the 7 cases analysed for lymphocyte surface markers proved to be B cell type. No significant difference was seen between the results of single agent and combined chemotherapy.     

Blood concentrations of tumor necrosis factor-alpha in malignant lymphomas and their decrease as a predictor of disease control in response to low-dose subcutaneous immunotherapy with interleukin-2

Tumor necrosis factor-alpha (TNF-alpha), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-alpha secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-alpha secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-alpha serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-alpha levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-alpha concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-alpha levels in seven evaluable lymphoma patients (NHL: 6; HD: 1)--who did not respond to conventional therapies--during subcutaneous low-dose IL-2 (3 MIU/day, 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-alpha concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-alpha secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-alpha levels in malignant lymphomas.     

Human lactic dehydrogenase as a marker for monitoring the growth of prostatic carcinoma in nude mice

Human lactate dehydrogenase (1,1,1,27-LDH) isoenzymes were determined in human prostatic carcinoma cell lines. The isoenzymes LDH-4/LDH-5 were identified and quantified in the serum of athymic mice bearing the human prostatic carcinoma cell lines PC-3, PC-3/M and DU 145 subcutaneously. The amounts of the slowly migrating isoenzymes released by the solid tumors correlated with increasing tumor volume and tumor weight. These correlations indicate that the human LDH-4/LDH-5 isoenzymes are useful parameters for monitoring the presence and growth of prostatic cancer in the athymic animal model.     

A prospective analysis of low-grade gastric malt lymphoma after Helicobacter pylori eradication

BACKGROUND: Primary gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is known to be successfully treated with anti-Helicobacter pylori (H. pylori) therapy alone. However, there are few reports on long-term results after eradication therapy. The aims of this study were to analyze the rate and the interval to reach complete remission (CR), and to assess the rate and the factors affecting recurrence of MALT lymphoma. MATERIALS AND METHODS: Between 1996 and 2003, a total of 90 H. pylori-infected patients with low-grade MALT lymphoma were included in this study. For initial staging, endoscopic ultrasonography, chest-abdomen-pelvis CT scans, and bone marrow examination were taken. All patients were made to take anti-H. pylori therapy for 14 days. Tumoral response was assessed by endoscopy every 3 months till CR and every 6 months after achieving CR. RESULTS: Among 90 treated patients, 85 (94.4%) reached CR. The median interval to CR was 3 months (range, 1-24). Seventy-nine (92.9%) patients were in CR at 12 months. Median follow-up period after CR was 45 months (range 15-109). Among 77 patients who were followed-up after CR, 8 (10.4%) patients were proved with recurrence of MALT lymphoma. Cumulative recurrence rate was 2.7, 11.5, and 12.2% at 1, 2, and 3 years. The presence of H. pylori was only a significant risk factor affecting recurrence. CONCLUSIONS: The status of H. pylori is the most important risk factor affecting recurrence. Therefore, adequate eradication regimen and accurate regular evaluation for H. pylori status are needed during follow up of primary gastric low-grade B-cell MALT lymphoma.     

Chronic gamma-irradiation results in increased cell killing and chromosomal aberration with specific breakpoints in fibroblast cell strains derived from non-Hodgkin's lymphoma patients.

Cultured skin fibroblast cells from 6 patients with non-Hodgkin's lymphoma (NHL) and 2 clinically normal subjects were compared for cell survival and chromosomal aberration after chronic gamma-irradiation. Fibroblasts from an ataxia telangiectasia (AT) homozygote and an AT heterozygote were used as positive controls. Following irradiation, fibroblasts from all 6 NHL patients showed an increase in both cell death and chromosomal aberration (breaks and rearrangements) compared to the normal subjects. The difference in the frequency of chromosomal aberration between the normals and the NHL patients remained virtually unchanged over a period of 24-72 h post irradiation incubation of the cells. Cell cycle analysis by flow cytometry carried out in 1 normal and 1 NHL fibroblast cell strain showed that more cells representing the NHL patient were in G2/M phase compared to the normal at various times of cytogenetic analysis. While the AT homozygote appeared to be the most radiosensitive, the AT heterozygote showed a slightly higher incidence of cell death and chromosomal aberration than the normals. The cellular and chromosomal radiosensitivity of fibroblast cell lines from the NHL patients differed slightly from that of the AT heterozygote but clearly occupied an intermediate position between the AT homozygote and the normal subjects. Cells from 3 of the NHL patients showed radiation-induced specific chromosomal breaks involving chromosomes 1, 2, 6, 8, 10 and 11 which correspond to known fragile sites. Such breakpoints associated with increased radiosensitivity may be indicative of predisposition to malignancy in the patients studied.     

L.D.H. and L.D.H. isoenzymes of the intra-uterine secretions of the cow during the estrous cycle

Uterine secretions were collected from 20 mature cows during estrus (day 0), metestrus (day 5), diestrus (day 10) and proestrus (day-1). Lactate dehydrogenase (LDH) and LDH isoenzymes activity were evaluated. No significant cyclic variations of LDH activity was found in the uterine secretions while the mean of the enzyme activity was higher during the estrogenic period of the cycle. The relative activity of LDH-1, LDH-2 and LDH-3 isoenzymes were higher during proestrus and estrus whereas LDH-5 activity was more important during metestrus. The LDH-3 seems to have the higher relative activity in uterine secretions of the cow.