Psychomotor retardation, anorexia, weight loss, sleep disturbances, and loss of energy: psychopathological correlates of hyperhaptoglobinemia during major depression.

Recently, we have established that major depression is characterized by hyperhaptoglobinemia, which may be regarded as an index of an "acute" phase response in that illness. The present study investigates the psychopathological correlates of increased plasma concentrations of haptoglobin (Hp) in major depression. To this end, the authors studied the Hp levels in relation to depressive items of the Structured Clinical Interview for DSM-III (SCID) and the Hamilton Rating Scale for Depression (HRSD) in 90 depressed subjects. There was a significant positive relationship between the SCID symptoms anorexia/weight loss, sleep, and psychomotor disorders and Hp plasma concentrations. Hp plasma levels were significantly and positively correlated with overall severity of illness (HRSD). The HRSD symptom correlates of higher Hp levels were loss of interest, middle insomnia, and psychomotor retardation. Up to 31.4% of the variance in Hp plasma values could be explained by psychomotor disorders, anorexia, weight loss, middle insomnia, and less diurnal variation of mood. It is suggested that hyperhaptoglobinemia, as an index of an "acute" phase response in major depression, is related to the somatic dimension of depressive illness.

Molecular characterization of an extracellular acid-resistant lipase produced by Rhizopus javanicus.

An extracellular lipase (triacylglycerol acylhydrolase EC 3.1.1.3), produced by the fungus Rhizopus javanicus was purified to homogeneity using an expeditious two-step isolation method. The enzyme, with a molecular mass of 36 kDa and a specific activity of 9260 microequivalent of fatty acid released per minute and mg under standard conditions, consists of three isoforms with isoelectric points of 7.8, 7.7, and 7.1, respectively. The purified lipase was digested using chemical and enzymatical procedures: CNBr cleavage, partial acid hydrolysis, and proteolytic cleavage by means of trypsin. Amino-acid sequencing of the resulting peptides indicates that the three lipases from Rhizopus javanicus, Rhizopus niveus and Rhizopus delemar are produced as identical proenzymes but processed differently. These Rhizopus lipases show 54% identity with the lipase from Rhizomucor miehei. Using the structure of the Rhizomucor miehei lipase, the molecular model of Rhizopus javanicus lipase was constructed. Both enzymes are alpha/beta type proteins with a central 8-stranded mixed beta-pleated sheet and have a remarkably similar distribution of hydrophobic amino acids at their surface. The tryptophan in the center of the helical lid covering the active site of Rhizomucor miehei lipase is mutated into an alanine, indicating that it is not essential for the proper movement of the helical lid.

The presence of antibodies against extractable nuclear antigens in serum: a comparison of immunoblotting versus radial immunodiffusion.

A commercial immunoblotting kit has recently been introduced to determine auto-antibodies against extractable nuclear antigens. We compared this new test with radial immunodiffusion for its usefulness in the routine laboratory procedures of a general hospital. Antigen preparation in immunoblotting includes a protein denaturation step prior to electrophoretic separation of the different proteins. In this way antigenic determinants that depend heavily on the protein superstructure are lost. In theory, auto-antibodies against these epitopes may be missed. In our series of 100 samples that had tested positively for antinuclear antibodies, radial immunodiffusion was able to detect one SSA positive sample that was negative by immunoblotting. However, 47 samples positive in immunoblotting, 37 positive for UBP, seven for anti-SSA, are for anti-Jo-1, one for anti-RNP and one for anti-Sm were missed by radial immunodiffusion. Most of these samples had low antinuclear antibody titres (1/80 or 1/160).

Disturbances in acute phase plasma proteins during melancholia: additional evidence for the presence of an inflammatory process during that illness.

1. Leukocyte enumeration through flow cytometry has revealed that severe depression may be accompanied by a systemic immune activation, indicative of an inflammatory response. The latter condition allegedly involves an important modification of acute phase plasma protein (APP) equilibrium. 2. In order to elucidate whether the state of severe depression is represented by alterations in APPs, the authors measured: alpha 1 antitrypsin (alpha 1 AT), alpha 2 macroglobulin (alpha 2 M), haptoglobin (Hp), alpha 1 acid glycoprotein (alpha 1 S), transferrin (Tf), complement component 4 (C4) and C-reactive protein (CRP). Interleukin-1-beta (II-1 beta) and interleukin-6 (II-6) circulating levels were determined. 3. Hyperhaptoglobinemia and hypotransferrinemia are hallmarks for major depression and depression per se, respectively. The disorders in Hp and Tf circulating levels are highly sensitive to (83%) and specific for (100%) melancholia as opposed to the healthy state. 4. Disorders in both APPs are significantly related to the absolute number of blood monocytes. 5. The authors observed a trend towards lower alpha 2M and higher alpha 1S values in severely depressed subjects. Severity of depression was significantly related to Hp and alpha 1S (both positively) and to alpha 2M and Tf (both negatively) values. 6. No significant intercategory differences in C4 could be established, whilst only a few subjects exhibited measurable CRP, II-1 beta and II-6 circulating levels. 7. Our findings may support the hypothesis that depression is accompanied by an inflammatory response.

Higher alpha 1-antitrypsin, haptoglobin, ceruloplasmin and lower retinol binding protein plasma levels during depression: further evidence for the existence of an inflammatory response during that illness.

Recently, a few reports have shown that severe depression may be associated with higher levels of positive acute phase proteins (APPs), such as haptoglobin (Hp), alpha 1-acid glycoprotein (alpha 1S) and lower levels of negative APPs (visceral proteins), such as albumin (Alb) and transferrin (Tf). In order to reassess whether depression is related to alterations in the expression of plasma APP concentrations, we measured in 84 normal controls and depressed inpatients positive APPs such as Hp, alpha 1-antitrypsin (alpha 1AT), hemopexin (Hpx), ceruloplasmin (Cp), complement component C3C and one visceral protein, i.e., retinol binding protein (RBP). We found increased plasma concentrations of Hp, alpha 1AT, and Cp in major depressed subjects as compared with healthy controls, with minor depressives exhibiting an intermediate position. RBP was significantly lower in minor and major depressives than in normal controls. The disorders in these proteins were rather sensitive (62%) for major depression, with a specificity equalling 96%. Our findings are compatible with the hypothesis that major depression may be accompanied by inflammatory changes with higher levels of positive APPs (i.e., alpha 1AT, Hp, Cp, alpha 1S) and lower levels of visceral proteins (i.e., RBP, Tf, Alb).

Flow-cytometric analysis of erythrocytic blood group A antigen density profile.

Blood group A antigen density on red blood cells (RBC) was studied using flow cytometry (FCM) and fluoresceinated polyclonal and monoclonal IgG anti-A antisera. Agglutination was a problem, which could only be solved by prefixation of the RBC with glutaraldehyde or formaldehyde. However, this treatment resulted in a significant reduction of the number of antigen sites as compared to the native (i.e. nonfixed) RBC. Two major new findings came out of this study: (1) A antigen density on native RBC seems to be higher than previously recognized, and (2) A antigen density distribution is probably non-Gaussian. The absolute number of A antigen sites was determined, using a human polyclonal IgG antiserum and commercially available absolute fluorescence standards. The site numbers on fixed RBC were comparable to those found by earlier radioimmunological studies (x 10(6)/RBC): A1, 1.07 +/- 0.28; A2, 0.21 +/- 0.09; A1B, 0.79 +/- 0.26 sites (mean +/- SD). The values found for native RBC were considerably higher (x 10(6)/RBC): A1, 2.86 +/- 0.95; A2, 0.47 +/- 0.29; A1B, 1.98 +/- 0.58 sites (mean +/- SD). With the 1 monoclonal and the 3 polyclonal antisera used in this study, and in contrast to Rh D, the erythrocytic A antigen density distribution of a given sample is highly asymmetrical. This non-Gaussian distribution profile does not seem to be affected by such factors as antibody heterogeneity, variability in antibody fluoresceination range, RBC density and reticulocyte content. This suggests that the asymmetrical A antigen distribution may be an intrinsic property of the RBC population.

Cimetidine induced pancytopenia. Effect on human CFU-MIX colony formation.

We describe a 26 year-old male with a pancytopenia possibly due to cimetidine. Using progenitor cell culture techniques we investigated the mechanism of this bone marrow toxicity. Our results show a cimetidine dose-dependent inhibition of normal human CFU-GM colony formation as described by Fitchen and Koeffler in 1980. No differences in growth inhibition were found between the patients' recovery marrow and the controls. Toxicity on normal human CFU-MIX colony formation was, however, far more pronounced. At concentrations as low as 5 micrograms/ml the numbers of CFU-MIX colonies were decreased by almost 20% and more than 30% in cultures of two normal bone marrow samples. A significant decrease in CFU-MIX colony size was measured even at therapeutic levels (0.5 micrograms/ml). No obvious decrease in CFU-GM colony size was noticed at low concentrations. Experiments with T-cell- and monocyte-depleted bone marrow samples gave similar results: a pronounced inhibition of the CFU-MIX colony formation at low concentrations of cimetidine whereas the CFU-GM formation was less affected. It is therefore very unlikely that Accessory cells play part in the cimetidine induced CFU-MIX inhibition. Our results suggest the existence of H2 histamine receptors on human CFU-MIX (= multipotent progenitor cell). Blocking these receptors prevents the multipotent progenitor cell from going into the DNA-synthesis phase of the cell cycle.