Histochemical contributions to the binding mechanism of complement (CR1, CR2) receptors.

Complement receptors (CR1, CR2, CR3), and their ligands (C3b, C3d, iC3b) are essentially involved in germinal center development and in binding, trapping, and retaining immunocomplexes. Methods studying complement receptor (CR1/CR2)-ligand (C3b/C3d) interactions mostly involve coating of sheep erythrocytes (E), sheep erythrocyte-antisheep erythrocyte antibody (EA complexes) and whole human (h) or mouse (m) sera as a source of complement, EACh/m complexes, as reagents. The observation of Dukor et al. (1970), that EACm complexes in native cryostat sections bind selectively and very strongly to the B lymphocyte regions of lymphoid organs allowed the topo-histochemical analysis of receptor (CR1/CR2)-ligand (C3b/C3d) interactions in such an immunologically important area as the germinal centers. The main finding of this study is, that periodic acid pretreatment of unfixed cryostat tonsil sections-oxidizing vicinal glycol groups of polysaccharide chains into dialdehydes-completely abolished the binding of all EAC/EC complexes to germinal center area. It may suggest the involvement of receptor carbohydrate in C3 receptor/ligand binding. In addition to, the subsequent sodium borohydride reduction-converting aldehydes (produced by periodic acid oxidation) into primary alcohols-restored selectively the binding of all applied EAC/EC complexes to follicular centers. These in vitro topo-histochemical studies give a strong hint for the participation of-OH groups of sugar residues in CR1/CR2 ligand (C3b/C3d) binding.

A study of the prevalence and associations of subchondral bone marrow lesions in the knees of healthy, middle-aged women.

OBJECTIVE: Bone marrow lesions (BMLs) have been shown to be associated with pain and progression of knee osteoarthritis (OA) in those with disease. The natural history of BMLs in a healthy population and their role in the pathogenesis of OA are unknown. The aim of this study was to determine the risk factors for BMLs in healthy subjects and the association of BMLs with knee structure. METHODS: One hundred and seventy-six healthy, adult women with no history of knee injury, or clinical knee OA had magnetic resonance imaging performed on their dominant knee to assess BMLs, tibiofemoral cartilage defects, tibial cartilage volume and bone area. RESULTS: Thirteen percent of subjects had knee BMLs. The prevalence was higher in the medial tibiofemoral compartment. There was a significant positive association between BMLs and cartilage defects after adjusting for the potential risk factors: age, height, weight and cartilage volume [odds ratio (OR) 1.78 (95% confidence interval [CI] 1.12, 2.82), P=0.01]. BML was positively associated with tibial plateau bone area in the lateral compartment [OR 1.67 (95% CI 1.02, 2.71), P=0.04]. There was no significant association between BMLs and cartilage volume. Independent risk factors for BMLs after adjustment were increasing height [OR 1.18 (95% CI 1.02, 1.36), P=0.02 for lateral compartment] and weight [OR 1.04 (95% CI 1.01, 1.08), P=0.005 for total knee]. CONCLUSION: These data support that BMLs are present in a similar distribution to tibiofemoral knee OA. Their presence is associated with risk factors (height and weight) for knee OA, and the early structural changes of knee OA in subjects without knee pain and thus no clinical disease. Longitudinal studies will clarify whether BMLs relate to the pathogenesis of clinical knee OA.

[Multiple lymphomatous polyposis--rare case of gastrointestinal hemorrhage]. / Multiplex lymphomatosus polyposis--gastrointestinalis vérzés ritka esete.

The authors report a case of a 57 years old male patient, who was admitted to gastroenterology department with upper gastrointestinal haemorrhage. The urgent upper gastrointestinal endoscopy revealed an ulcerated polypoid tumor in the region of angulus of the stomach, and multiple polypoid lesions in the bulbar part of the duodenum. Upon this endoscopic appearance colonoscopy was performed, which revealed a polyposis syndrome in the colorectum. Computer tomography detected mesenterial, retroperitoneal and mediastinal lymph node involvement as well. In this case the primary or secondary origin of the gastrointestinal lymphoma was not verifiable. According to literature data this histological type of the gastrointestinal lymphoma has poor response to chemotherapy, the prognosis is unfavourable. In this particular case the administered chemotherapy resulted in total remission at the lymphoma patient clinically staging III Ae. In the proper follow-up examinations of the patient upper and lower endoscopy, histology samples, laboratory parameters, computer tomography, and physical examination in every 3 months are the methods.

[Adult Hirschsprung's disease with mental retardation and microcephaly]. / Felnóttkori Hirschsprung-betegség elófordulása mentalis retardatio, microcephalia mellett.

Hirschsprung's disease occurs rarely and sporadically in adult, involving males. In cases, which are manifested perinatally, the so called Hirschsprung-associated congenital anomalies (mainly central nervous system, urogenital and cardiovascular) may present (2-21%), which have not observed in adult. Mental retardation and Hirschsprung's disease more frequently are associated with Down syndrome (5-10%). The discoveries of molecular genetics in the last 4-5-years through the examination of transgenic ("knockout") mice, proved the basic role the mutation of 4 genes: the RET (receptor tyrosin kinase), a proto-oncogene, coding its ligand, the glial cell-line derived neutrophic factor (GDNF), the gene of the endothelin-B receptor (ENDRB) and the gene one of its ligand, the endothelin-3 (EDN3), in the pathogenesis of Hirschsprung's disease. In our case, the short segment Hirschsprung's disease caused respiratory and cardiac failure, which was recognized by autopsy. Besides, the severe mental retardation, the role of the long term use of antipsychotic medicines comes up in the prolongation and masking of the symptoms. The accompanied mental retardation and microcephalia in early childhood are known, which are associated anomalies with Hirschsprung's disease. In cases of Hirschsprung diseases at adults, no other associated congenital anomalies has been published. The mental retardation in Down-syndrome, in association with Hirschsprung's disease (and presumable in our case, too) is supposed to be the consequence of the mutation in the gene of GDNF. In this case, we observed, that the so called short segment H-d was accompanied at a 33 years old men patient with mental retardation (who was originated from a gypsy ethnic minority), because of it the connection of the nurses and the patient was disturbed and the main symptom of the H-d (chronic obstipation) remained hidden. The mechanic ileus was going on behind the scenes, and in addition to the cardiac failure caused the death of the patient. Practical conclusion of the case is that, Hirschsprung's disease should be suspected in all adult patients, who had severe obstipation persisting since childhood, especially in males.

Watermelon-stomach as a cause of chronic iron deficiency anemia in a patient with systemic sclerosis.

Watermelon-stomach is a rare cause of gastrointestinal bleeding. There has been an increasing number of reports on the association of this lesion with diseases of the scleroderma group, causing chronic, sometimes severe gastrointestinal blood loss. The present report presents the case of a 75-year-old female with limited cutaneous systemic sclerosis and watermelon-stomach, which was the cause of her long-standing sideropenic anemia.

Immunohistochemistry of complement response on human renal cell carcinoma biopsies.

The goal of the study was to characterize the complement humoral and cellular antitumor responses on primary renal cell carcinoma biopsies. As an original observation, complement activation was found on 11/22 cases. Classical complement pathway activation was characterized by tumor C1q complement protein and IgG deposition (5/22 cases). Alternative or nonimmune complement pathway activation was seen as tissue deposition of C3 (6/22 cases). The membrane attack complex was present in cases with alternative complement pathway activation at the sites of tumor necrosis. Renal cell carcinomas with complement activation overexpressed at least one of the complement regulatory factors (membrane cofactor protein, decay accelerating factor, membrane attack complex inhibitor) and major histocompatibility complex class II molecules. Tumor infiltrating lymphocytes were present in most of the renal cell carcinomas with complement activation (8/11). However, the number of tumor-infiltrating lymphocytes was correlated with the intensity of major histo-compatibility complex-II expression in 18/22 cases. Detection of complement activation and immune cell infiltrates on renal cell carcinoma primary biopsies may serve as a new predictive factor for immunotherapy.

Role of lymphotoxin and the type I TNF receptor in the formation of germinal centers.

In mice deficient in either lymphotoxin-alpha (LT-alpha) or the type I tumor necrosis factor (TNF) receptor, but not the type II TNF receptor, germinal centers failed to develop in peripheral lymphoid organs. Germinal center formation was restored in LT-alpha-deficient mice by transplantation of normal bone marrow, indicating that the LT-alpha-expressing cells required to establish this lymphoid structure are derived from bone marrow.

Absence of lymph nodes in lymphotoxin-alpha(LT alpha)-deficient mice is due to abnormal organ development, not defective lymphocyte migration.

Mice homozygous for a targeted null mutation of lymphotoxin-alpha (LT alpha) are born without lymph nodes (LN) or Peyer's patches (PP) and with altered splenic architecture. To investigate the mechanism of failed LN organogenesis, we transferred bone marrow (BM) from Thy 1.2 LT alpha-deficient or Thy 1.2 wild type mice to lethally irradiated 8-12-week-old Thy 1.1 wild type recipients. Six to 10 weeks later, reconstitution of LN and spleen with Thy 1.2 cells was similar whether the BM was derived from LT alpha-deficient or wild type donors. In contrast, reconstitution of irradiated LT alpha-deficient mice with wild type BM did not induce the development of detectable LN, although reconstitution of the spleen occurred appropriately. The expression and regulation of the lymphocyte adhesion molecule L-selectin from the LT alpha-deficient mice appeared normal. These data indicate that LT alpha-dependent interactions must occur during development in order for LN genesis to take place; however, lymphocyte expression of LT alpha is not required for these cells to home to existing LN structures.

[Adjuvant BCG immunotherapy in the management of superficial bladder tumors]. / BCG immunterápia a felületes hólyagtumorok adjuváns kezelésében.

The net benefit of BCG immunotherapeutic prophylactic effect on recurrence of superficial bladder tumours was investigated. The BCG treatment group consisted of 121 stage Ta, T1 patients, while the control group, 49 patients, was treated only with transurethral resection. During 3-year follow-up recurrence rate in the control group was 55.1%, while in the BCG group in the two-and-a-half-year follow-up it was 23.9%. The yearly repeated 6-week cycles resulted in decrease of recurrence rate to 11.8%. The recurrence indexes were 2.2 and 0.6 in the control group and in the repeated treatment group respectively. A progression rate of 18.8% was recorded in the control group and 4.1% in the treatment group. Finally both clinical and investigative results were summarised and the necessity of repeated immunotherapeutic BCG courses were emphasized.

The distribution of ABO(H) isoantigens in urinary bladder tumours.

The distribution of blood group isoantigens (ABH) was studied with the specific red cell adherence test (SRCA); the red blood cells were visualized by the benzidine-peroxidase reaction. The H antigen was detected with Ulex europaeus agglutinin I lectin by direct immunoperoxidase technique. One hundred and seven bladder tumours were tested. It was found that blood group isoantigens diminished with immaturity (grade) and tumour invasiveness (T stadium). Patients with ABH blood group isoantigen deletion should be considered to be belong to a particularly high-risk group. The preservation of blood group antigens in grade II-III carcinomas may be useful in the choice of treatment (conservative or radical). In six cases in the area of squamous metaplasia of invasive carcinomas a strong false SRCA reaction was noticed detecting presumably the blood group determinants of the epidermal growth factor receptors.

Long-term BCG immune therapy of superficial bladder tumours.

Long-term local BCG treatment of superficial bladder tumours is described and the 5-year results are reviewed. Complications of major significance in the course of immune therapy did not occur, loss due to death was not recorded. PPD skin test failed to furnish extra information regarding the biologic behaviour of the tumour. Annual repeats of the therapy promise better results than one single 6-week course.

Enzyme negative blastic transformation of chronic myeloproliferative disorders: immunophenotyping of the blastic cell population.

Enzyme negative blast cells from 27 patients with chronic myeloproliferative disorders (CMPDs) in blastic transformation were analysed with a panel of monoclonal antibodies (MoAbs). According to morphologic features of the bone marrow and laboratory data, the 27 cases were divided into 8 cases of myelofibrosis (MF), 3 cases of chronic megakaryocytic granulocytic myelosis (CMGM) and 16 cases of chronic myeloid leukaemia (CML). Of the 27 cases, 23 showed a positive reaction with myeloid MoAbs, but in 12 cases expressing myeloid markers, megakaryocytic, monocytic or lymphoid cell features were also detected. In 7 cases of MF, 1 case of CMGM and 1 case of CML a bilineage, myelo-megakaryocytoid immunophenotype of peripheral blast cells was seen. Of the 4 patients with CML expressing lymphoid markers, 2 showed early B-cell, 1 T-cell surface antigens, and 1 both myeloid and early B-cell features. In this group of cytochemically immature blastic transformation of CMPD, only 1 case was termed "undifferentiated" blastic transformation.

Binding of CD 35, CD 21 and CD 11B monoclonal antibodies and EAC complexes to lymphocytes. A comparative histochemical study.

Using cryostat sections of human tonsils after various pretreatments, the adherence of sheep erythrocyte--antisheep erythrocyte (EA) complexes coated with either fresh mouse complement (EACm) or fresh human complement (EACh) has been compared with the binding of monoclonal antibodies (MAbs) against C3b (CD 35), C3d (CD 21) and iC3b (CD 11b) receptors (clusters). After periodic acid oxidation the binding of MAbs to CD 35, CD 21 was well preserved, whereas EACm and EACh complex adherence and CD 11b binding were abolished. These findings seem to prove that the binding sites for EACm and EACh complexes, as well as those for CD 35, CD 21 clusters (antigenic structure of the C3b and C3d receptors) are different.

[Extra-gonadal germ-cell tumors]. / Az extragonadalis csírasejtes tumorokról.

Authors describe the clinico-pathological and immunohistochemical findings of two mediastinal (seminoma and yolk-sack) and a pineal mixed (seminoma and yolk-sack) tumours. In the mediastinal yolk-sack tumour the light microscopic picture of cellular components, alpha-fetoprotein (AFP), haemoglobin F (Hgb F), blood group antigen, carcinoembryonal antigen (CEA), post-digestion (neuraminidase) peanut antigen (neu-PNA) positivities suggest hepatic and intestinal differentiation. In some cells of mediastinal seminoma the glucose- and mannose-binding concanavalin-A (Con A) showed reaction. In the mixed tumour of the pineal region in addition to AFP positive cell cords some cell groups reacted with Leu-M1 (CD15) monoclonal antibodies raised against stage specific embryonic antigen 1 (SSEA1).

[Osteoplastic pneumopathy (disseminated bone formation in the lung)]. / Pneumophathia osteoplastica (disseminált csontképzödés tüdöben).

8 cases of pneumophathia osteoplastica (ppo) of branching type observed at patients having no vascular deformities and one case of a focal ppo at a patient with mitral stenosis are reported. Pathogenesis of the ppo of branching type in the majority of cases could not be clarified since the process appeared to be in the phase of definitive bone formation. Nevertheless in one of the cases in a septum of Y shape in addition to collagen fibres ending in bone tissue numerous elastic fibres have also been revealed. This fact, considering the presence of a normal bronchus in the area seems to evidence vascular origin of the lesion. The latter hypothesis could be verified by the bone-formation in the media of a vessel wall in another case. Further, in a case of primary chronic polyarthritis with ppo, bone-formation could be seen in the perivascular lung tissue with necrotizing pulmonal arteritis. Considering this finding the possibility of the primary role of necrotizing pulmonal arthritis in the pathogenesis of ppo have to be taken into account. Ppo should be classified as one of the alveolocapillary block syndromes. In some cases it may have clinico-pathological significance. It may lead to bronchietasis, emphyseme or cor pulmonale chronicum.