L. Jakab

Human fetuin/α2HS-glycoprotein level as a novel indicator of liver cell function and short-term mortality in patients with liver cirrhosis and liver cancer

Objective Human fetuin/α2HS-glycoprotein (AHSG) is synthesized by hepatocytes. We intended to determine whether liver dysfunction or acute phase reaction is dominant in the regulation of its serum concentrations and to see if decreased AHGS levels are associated with short-term mortality. Design We determined the serum AHSG levels in patients with acute alcoholic, acute A, B, and Epstein–Barr virus hepatitis, alcoholic cirrhosis, and hepatocellular cancer and correlated them to conventional laboratory parameters of inflammation and liver function. Patients were followed for 1 month. Methods Serum AHSG was determined by radial immunodiffusion. Results Compared to controls, significantly lower AHSG levels were found in patients with liver cirrhosis and hepatocellular cancer but not the acute viral hepatitides. Strong positive correlation with serum transferrin, albumin and prothrombin was found. Febrile episodes were not associated with significantly decreased AHSG levels. Concentrations below 300 μg/ml were associated with high mortality rate (52.0%; relative risk, 5.497; 95% confidence interval, 2.472–12.23;P < 0.0001). Of all laboratory parameters studied serum AHSG levels showed the greatest difference between deceased and survived patients with cirrhosis and cancer. Moreover, other acute phase reactants did not differ significantly. The multiple logistic regression analysis indicated that the decrease of serum AHSG is independent of all other variables that were found decreased in deceased patients. Conclusions Decreased serum AHSG concentration is due rather to hepatocellular dysfunction than the acute phase reaction and is an outstanding predictor of short-term mortality in patients with liver cirrhosis and liver cancer.

Concentration of Soluble Adhesion Molecules (sVCAM-1, sICAM-1 and sL-Selectin) in the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis and Systemic Lupus erythematosus with Central Nervous Involvement

Objectives: The aim of the present study was to investigate the role of soluble adhesion molecules in the pathogenesis of multiple sclerosis (MS) and systemic lupus erythematosus (SLE) with demyelinating syndrome. Methods: Paired cerebrospinal fluid (CSF) and serum samples were analysed by an ELISA method to determine the concentrations of sVCAM-1, sICAM-1 and sL-selectin. Intrathecal syntheses of the adhesion molecules were calculated. Results: Elevated serum and CSF concentrations of sVCAM-1 were present in all patient groups. Intrathecal synthesis of sVCAM-1 was present in the relapsing-remitting and secondary progressive forms of MS. Intrathecal synthesis of sICAM-1 was observed in all clinical forms of MS. MS patients with progressive forms of the disease and SLE patients were characterised by intrathecal synthesis of sL-selectin. Conclusions: The data presented suggest that (1) blood-brain barrier damage can be assumed both in systemic disease and organ-specific disease (sVCAM-1), (2) clinical forms of MS differ from each other in respect to concentrations of adhesion molecules and (3) similar immunological events in the central nervous system of SLE patients with demyelinating syndrome and progressive forms of MS can be assumed (sL-selectin).

Serum α2-HS glycoprotein concentration in patients with hematological malignancies: A follow-up study

SummaryWe observed significantly reduced serum α2-HS glycoprotein concentrations in patients with acute lymphocytic, acute nonlymphocytic, chronic granulocytic and chronic myelomonocytic leukemias, Hodgkins and non-Hodgkins lymphomas, myelofibrosis, and multiple myeloma, but not in patients with chronic lymphocytic leukemia and polycythemia vera, as compared with healthy controls. We followed the serum level of the protein for 18 months. Patients with infectious complications, those receiving cytostatic treatment, and those in the preterminal period had further reduced serum α2-HS glycoprotein levels. The reduction of serum α2-HS glycoprotein concentration was primarily due to decreased production caused by infiltration of the liver, a hepatotoxic effect of cytostatic treatment, and, to a lesser degree, to increased consumption. We found statistically significant negative correlations between serum α2-HS glycoprotein concentration and erythrocyte sedimentation rate, serum aspartate aminotransferase and alkaline phosphatase activities, and IgG and IgM concentrations. The determination of the α2-HS glycoprotein concentration is useful for the assessment and follow-up of the clinical status and therapy of patients with hematological malignancies and also has prognostic significance.

Soluble L-selectin levels in serum and cerebrospinal fluid in patients with multiple sclerosis and systemic lupus erythematosus

Soluble L‐selectin (sL‐selectin) concentrations were measured in paired samples of serum and cerebrospinal fluid by an ELISA method. Patients with several forms of multiple sclerosis (MS) and systemic lupus erythematosus with central nervous system involvement (SLE‐CNS) were investigated. Elevated CSF sL‐selectin concentrations were found in patients with SLE‐CNS (7.62±3.31 ng/ml) and with relapsing–remitting form of MS (6.99±4.72 ng/ml) compared to the control group (4.00±0.95 ng/ml). The data presented suggest some similarities between inflammatory/immunological events in the central nervous system in patients with SLE‐CNS and relapsing–remitting form of MS. Immunological heterogeneity in MS is suspected.

A study of increased levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) in the cerebrospinal fluid of patients with multiple sclerosis and systemic lupus erythematosus.

The concentration of soluble vascular cell adhesion molecules (SVCAM‐1) of serum and cerebrospinal fluid (CSF) was measured in clinically selected multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients, using an ELISA assay. The mean SVCAM‐1 concentration in the serum of SLE patients was higher than normal. The mean CSF SVCAM‐1 concentration was increased in the MS as in the SLE group. On analysis, the data suggests that there are some similarities in the immunological effects of these two different diseases of the central nervous system. A longitudinal analysis of the CSF is requested.

Multicentric plasmocytic Castleman's disease with polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes syndrome and coexistent human herpes virus-6 infection -A possible relationship

Authors report a case of Castlemans disease (CD) with polyneuropathy, organomegaly, endocrinopathy, M protein, skin change (POEMS) syndrome. According to the present knowledge, these two rare conditions are often induced by Human Herpes Vírus- 8 (HHV-8) or by Human Immunodefeciency Virus, separately or in combination. In this case, however, HHV-6 viral DNA had been detected in the blood and lymph node samples by PCR. The authors conclude that the modulation of immune functions by HHV-6 might be responsible for the development of CD and POEMS syndrome in the referred case.

Binding of fibronectin to human lipoproteins

High molecular mass adhesive glycoprotein plasma fibronectin binds to isolated HDL and LDL lipoprotein fractions in a solid phase radioimmunoassay. Mean dissociation constants of interaction of fibronectin and immobilized HDL and LDL lipoproteins isolated from eight patients with type IIa and type IV hyperlipoproteinemia are 7.8 +/- 3.2 X 10(-7) mol/l and 6.8 +/- 2.6 X 10(-7) mol/l, respectively. Fibronectin can also bind to HDL and LDL isolated from six healthy subjects with mean dissociation constants of 2.07 +/- 0.45 X 10(-6) mol/l and 2.25 +/- 0.48 X 10(-6) mol/l, respectively. The binding is not dependent on the presence of divalent cations. Fibronectin-lipoprotein interaction is inhibited by soluble lipoproteins. There is no observable interaction between fibronectin and VLDL fraction. Binding of fibronectin to HDL and LDL lipoproteins can have an in vivo significance, since the interaction may play a role in the metabolism, deposition of lipoproteins into the vessel wall and in atherogenesis.

Fibronectin on the surface of human lymphocytes

Fibronectin was detected by immunofluorescence technique on the surface of one part of separated normal peripheral blood lymphocytes by using FITC-conjugated anti-human fibronectin antibodies. Approximately one-fifth of isolated B cells and 7% of O cells contained surface-bound fibronectin but T cells failed to stain. There were no detectable free receptors for fibronectin on the surface of lymphocytes of different subsets as it was studied with FITC-labelled purified fibronectin. The percent of B and O cells bearing surface bound fibronectin was markedly decreased in patients with acute and chronic lymphocytic leukemias.

Bone tissue: Rebuilding and inflammation

In this review the author summarizes the knowledge related to structural elements of bone tissue. The process of bone reorganisation and knowledge about the special feature of bone metabolism in human are also discussed. It is noted that due to the reorganisation, there is a complete renewal of bone tissue in every 10 years, and this renewal lasts throughout the life. However, there are life periods when osteoclast activity is low, e.g. in childhood and the second decade of life when the gain of bone mass may be as much as 40% of the final bone mass. Overactivity of osteoclasts occurs at age 60 years in men and somewhat earlier in women. Reorganization of bone tissue is an elementary requirement for the physiological functions (locomotion, hemopoiesis, immune functions). The RANK-RANKL-osteoprotegerin axis plays an important role in the regulation of bone metabolism. Bone mass is dependent on osteocytes; osteoblasts are building up while osteoclasts are reabsorbing bone tissue. In this process transcription factors, hormone-like substances and a large number of cytokines are involved. In addition, the inflammatory process within the bone tissue as well as the defending, reparative inflammation and specific immune response are of great importance in bone reorganisation. This is particularly valid for α2-macroglobulin and transforming growth factor, although the exact role in bone reorganization has not been fully explored. It can be concluded that the elements, which participate in bone reorganization and in defending inflammatory and specific immunological processes, are essentially identical. Therefore, the existence of an osteo-immunological complex system has emerged.

Connective tissue and inflammation

The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.