Stjepan Gamulin

Sex steroid receptors in intracranial tumors.

Estrogen (ER), progestin (PGR), and androgen (AR) receptors were assayed in cytosols prepared from 38 various intracranial tumors. The receptors were in the following proportions (number of receptor‐positive/number of tumors examined): meningiomas were positive for PGR (4/6) and AR (2/5); glioblastomas were also positive for PGR (3/21) and AR (7/21); astrocytomas were positive only for PGR (4/5); and oligodendrogliomas only for AR. In two hamartomas AR was present, while in one chordoma both PGR and AR were present. In this latter tumor ER were not assayed due to insufficient material. The receptors were present in concentrations between 10 and 20 fmol/mg protein. Exceptions were two meningiomas and a chordoma with a high concentration of PGR and AR. Our results support the notion that a proportion of intracranial tumors contains sex steroid receptors, and some of these tumors might be hormonally dependent.

Inhibition of Mitogen and Specific Antigen-Induced Human Lymphocyte Proliferation by Cadmium

Cadmium chloride (CdCl2) added to human lymphocyte culture inhibits the proliferative response induced by phytohaemagglutinin (PHA), pokeweed mitogen and allogenic lymphocytes in mixed lymphocyte reaction. Minimally effective concentrations of CdCl2 were 3.3, 1.6 and 1.6 microM, respectively. The inhibition was greatest when CdCl2 was added at initiation of cultures and declined if the addition of CdCl2 was postponed. The presence of CdCl2, regardless of the presence of PHA during the first 24 h of incubation suppressed the proliferative response to subsequent stimulation with PHA, indicating that cadmium affects an early step of blastogenic transformation.

Cyclic adenosine 5′-monophosphate in synovial fluid of rheumatoid arthritis and osteoarthritis patients

The relationship between synovial fluid (SF) cAMP level and IL-18 and PGE2 SF levels in rheumatoid arthritis (RA) and osteoarthritis (OA) patients, and between SF cAMP level and disease as well as inflammatory activity in RA were investigated in 17 RA and 19 OA patients. Erythrocyte sedimentation rate (ESR), serum (S) C-reactive protein (CRP) level and SF IL-18 level were higher in RA than in OA patients. SF PGE2 level was similar in both groups. SF cAMP level was higher in OA than in RA patients. In RA patients, SF cAMP level showed negative correlation with Disease Activity Score including a 28-joint count and S CRP, ESR and SF IL-18 level. The results suggest that cAMP promotes anti-inflammatory response in RA and OA patients, which is higher in the latter. Promotion of anti-inflammatory response by cAMP elevating agents might be useful in the treatment of RA.

Correlation of two methods for determination of cathepsin D in breast carcinoma (immunohistochemistry and ELISA in cytosol)

We have studied the correlation of two methods(immunohistology and ELISA in cytosol) of cathepsin D(CD) determination in breast carcinoma patients. Fifty sixspecimens of tumor tissue were collected consecutively, andCD expression in tumor tissue and tissue macrophageswas determined by standard immunohistochemistry using the aNCL-CDmanti-cathepsin D mouse monoclonal antibody (Novocastra Laboratories Ltd.,Newcastle, UK). Additionally, CD concentration was determined byELISA in cytosol of the same breast carcinomaspecimens. CD positivity was correlated with tumor size,histological grade of tumor, and the cytosol progesteroneand estrogen receptor concentrations. There was no statisticallysignificant correlation between examined parameters and either CDpositivity by immunohistochemistry or cytosol CD concentration. Thecorrelation between CD expression in tumor cells ofbreast carcinoma by immunohistochemistry and cytosol CD positivitywas not found either. However, there was asignificant association between abundance of CD positive stromalmacrophages and cytosol CD concentration in all histologicaltumor types (p < 0.05). CD positive macrophageswere abundant in most of cytosol CD positivespecimens.These results suggest that breast cancer cytosol CDconcentration is the cumulative result of CD contentin both carcinoma cells and stromal macrophages.

Kidney Ischaemia-Reperfusion Injury and Polyribosome Structure

Background: Inhibition of protein synthesis and polyribosome disaggregation are the early events in cell injury provoked by various pathogenic mechanisms, including energy depletion. Polyribosome disaggregation might be expected to occur during ischaemia-reperfusion injury due to ischaemic energy depletion, but also due to detrimental effects of reactive oxygen species on various macromolecules and cellular structures. Methods: Mouse kidney ischaemia-reperfusion injury was provoked by temporary clamping of the renal artery. The polyribosome sedimentation pattern was analyzed by sucrose density centrifugation of kidney postmitochondrial supernatant. Results and Conclusions: Ischaemia for 5 min in the mouse kidney provoked polyribosome disaggregation and an increase of monomer ribosome fraction which was augmented during 10–360 min of reperfusion. Recovery of polyribosome aggregates appeared between 6 and 24 h of reperfusion. Cycloheximide pretreatment prevented only polyribosome disaggregation caused by ischaemia and not that caused by reperfusion. This indicates different mechanisms of polyribosome disaggregation during ischaemia and reperfusion. It probably occurs in the former due to inhibition of initiation of translation, resulting in accumulation of unprogrammed monomer ribosomes, and in the latter due to the splitting of mRNA and breakdown of polyribosomes. Reperfusion did not increase ribonuclease activity in kidney cytosol, but increased the tissue concentration of malonaldehyde, indicating an augmentation in oxygen free radical generation. Possibly these may have caused a non-enzymatic breakdown of polyribosomes. However, pretreatment with allopurinol did not prevent polyribosome breakdown during ischaemia-reperfusion injury.

Effects of Cadmium on Polyribosome Sedimentation Pattern in Mouse Liver

Cadmium injected to mice provokes an acute disaggregation of hepatic polyribosomes. The effect appears within 15 min, it is maximal after 1 h and then gradually disappears. The reaggregation of polyribosomes takes place 6--12 h after injection. The disaggregation of polyribosomes is linear with log doses in a range of 7.25--20 mumol/kg CdCl2. Cycloheximide pretreatment prevents the disaggregation of polyribosomes in the livers of cadmium-treated mice.

Prognostic significance of cell cycle parameters in infiltrative ductal breast carcinoma

Flow‐cytometric DNA analysis was performed retrospectively from paraffin‐embedded blocks in 158 consecutive ductal infiltrative breast carcinoma patients grades I–III. Normal breast tissue was used as control. Tumor proliferative activity, cell ploidy, and DNA index (DI) were related to age of patients, histological grade of tumor, tumor size, axillary lymph node status, estrogen and progesterone receptor status, menopausal status, TNM clinical classification, and survival. There was a significant association between DNA aneuploidy and a high cellular proliferative activity, increased DI, poor differentiation of tumor, primary tumor size, number of positive lymph nodes, and postmenopausal state. Increased proportion of cells in S‐phase was associated with positive lymph node status and higher number of positive lymph nodes. The cell cycle parameters had no prognostic value either for overall survival of disease‐free survival of the patients. J. Clin. Lab. Anal. 12:131–136, 1998.

Effects of Cadmium on Mouse Liver Polyribosome Function

The distribution of ribosomes between their various functional states (native subunits, unprogrammed ribosomes, monoribosomes and polyribosomes) was analyzed in livers of cadmium-treated (CdCl2, 20 umol/kg, l h) and control mice. The ribosomes with double-labelled RNA were separated by sucrose density-gradient centrifugation in zonal rotor, and monomeric ribosome fraction was subsequently isolated and analyzed by selective dissociation of unprogrammed ribosomes. The analysis shows that the increase in monomeric ribosomes, occurring during polyribosome disaggregation in livers of cadmium-treated mice, entirely due to the increase of the unprogrammed ribosome fraction at the expense of polyribosomes. Protein synthetic activity of polyribosomes in vivo in livers of cadmium-treated and control mice were compared by double labelling of nascent and soluble polypeptides with [14C]-and [3H]-leucine. Incorporation of radioactivity was relatively higher in nascent polypeptides and lower in soluble polypeptides in cadmium-treated as compared with control mice. The results indicate that cadmium inhibits protein synthesis in livers of mice, affecting both the rate of initiation and the rate of elongation, but decreasing the former more than the latter.

Ambulatory arterial stiffness index and carotid intima-media thickness in hypertensive rheumatoid patients: a comparative cross-sectional study.

Rheumatoid arthritis is associated with accelerated atherosclerosis. However, little is known about preclinical atherosclerosis in hypertensive rheumatoid arthritis patients. In this cross‐sectional study we assessed the expression of preclinical atherosclerosis in hypertensive rheumatoid arthritis patients in comparison with matched hypertensive non‐rheumatoid arthritis patients.

Anti-TNFα Therapy and Control of Chronic Pain in Ankylosing Spondylitis

In this article, anti-TNFα therapy and control of chronic pain in ankylosing spondylitis are discussed.