Ulrich Vetter

Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures (Bruck syndrome)

We describe a male patient with osteogenesis imperfecta (OI) who was born with contractures of the knee, elbow and ankle joints. During the first 4 years he suffered from recurrent fractures. He has white sclerae, mild dentinogenesis imperfecta, multiple wormian bones, severe scoliosis and short stature. Morphological analysis of cortical bone revealed typical characteristics of OI including varying width of the osteoid, swollen mitochondria and a dilated endoplasmic reticulum of the osteoblasts. Collagen fibrils of the osteoid had a varying diameter, a feature not found in typical OI patients. Analysis of compact bone showed that the size of apatite crystals and the extractability of collagen with pepsin were markedly elevated compared to controls and other OI type III and IV patients. Lysyl hydroxylation of collagen from the organic bone matrix and the electrophoretic mobility of collagen α1(I)- and α2(I)-chains were normal. Our results provide evidence that this patient belongs to a subtype of OI. The biochemical studies indicate that the underlying defect involves defective fibril-formation of collagen type I leading to an altered mineralization of bone.

Patterns of growth in human septal cartilage: a review of new approaches

Recent results of the growth activities of the septal cartilage in children, adolescents, and adults are reviewed. Cartilaginous biopsies were obtained during septoplasty . Matrix synthesis was measured by in vitro incorporation of labeled sulphate; DNA synthesis was measured by in vitro incorporation of labeled thymidine. The cell density of the septal cartilage was determined by cell counting, and chondrocytes were grown in culture in an assay to determine the number of chondrocytes capable of proliferation. With data from these 4 types of experiments 5 different areas could be distinguished in human septal cartilage: (1) anterior free end, (2) suprapremaxillary area, (3) central area, (4) posterior area, and (5) caudal prolongation. Metabolic activities, degree of cell replication, and proliferative capacity are highest in childhood in all areas; they decline with age, but remain surprisingly high in the central area and in the anterior free end, even in adults. These results help to explain some clinical observations and may help the rhinosurgeon in his decision to resect the septal cartilage, especially in children.

Human leukemic cells: Receptor binding and biological effects of insulin and insulin-like growth factors

Receptor binding and biological effects of insulin and insulin-like growth factors I and II (IGF I/II) were assessed in three human malignant cell lines: a Burkitt-type ALL-cell line, a ANLL-cell line and a Hodgkins disease-cell line. Insulin receptor binding could be demonstrated in Burkitt-type ALL cells and ANLL cells, whereas no insulin receptor binding was detectable in Hodgkin cells. IGF I and IGF II binding could be demonstrated in all leukemic cells. Insulin stimulated glycogen synthesis in the insulin receptor bearing cell lines. DNA synthesis was stimulated by insulin, IGF I and II. IGF I was more active in stimulating DNA synthesis than IGF II.

The Marfan syndrome —analysis of growth and cardiovascular manifestation

Forty-eight children and adolescents (mean age 10.5 years, range 1.25–18 years) with clinical evidence of Marfan syndrome were studies. Height and weight percentiles were established. Cardiac dimensions and morphology were studied by M-mode and 2D-echocardiography. At diagnosis left atrial and left ventricular end-diastolic diameter and left ventricular posterior wall thickness were within normal limits except in a few adolescent patients. Interventricular septum was thickened in about 20% and aortic diameter increased in 56% of the patients. An additional 13% of patients developed aortic dilation during the study period. At diagnosis regression analysis revealed a significant (P<0.05) correlation of the aortic diameter, septal thickness and the posterior left ventricular wall thickness and body surface area. Follow up studies of 19 patients allowed documentation of the development of aortic root dilation.

Gamma-globulin therapy in 6 newly diagnosed diabetic children.

An autoimmune process may be involved in the pathogenesis of type I diabetes mellitus (1). Consequently, numerous therapeutic attempts for an early immunointervention have been carried out (2). Based on the favourable results with the gamma-globulin therapy in idiopathic thrombocytopenia (3), 6 newly diagnosed diabetic type I patients were treated with high doses of gamma-globulin to possibly prolong partial remission as defined by bikerblom (4). The pertinent clinical data at diagnosis and the results at follow-up are shown in Table 1. All patients were treated with human insulin (Lilly, FRG or Novo, Denmark). Within the first week of therapy the children received 0.4 glkg body weight Sandoglobulin@ (kindly provided by Sandoz, Nurnberg, FRG) on 5 consecutive days and the same dose once per week for up to 6 months. After discharge self-control was obtained with 3 daily urinary glucose tests and frequent blood glucose determinations (Diabur 5 OOO, Haemoglucotest 20-800, Boehringer, Mannheim, FRG). At intervals of 2-3 months C-peptide release was determined after an i.v.-glucose-arginene test or after a standard breakfast.

Growth of the human septal cartilage: Cell density and colony formation of septal chondrocytes†

Human chondrocytes from 24 patients (5 to 52 years) with septal deviation were isolated in different areas of the septal cartilage. Cell density was counted, and the chondrocytes were grown in an assay system for determining the number of chondrocytes capable of proliferating.

Growth activity in human septal cartilage: age-dependent incorporation of labeled sulfate in different anatomic locations.

Growth activity in different areas of human septal cartilage was measured by the in vitro incorporation of 35S-labeled NaSO4 into chondroitin sulfate. Septal cartilage without perichondrium was obtained during rhinoplasty from 36 patients aged 6 to 35 years. It could be shown that the anterior free end of the septum displays high growth activity in all age groups. The supra-premaxillary area displayed its highest growth activity during prepuberty, showing thereafter a continuous decline during puberty and adulthood. A similar age-dependent pattern in growth activity was found in the caudal prolongation of the septal cartilage. No age-dependent variations could be detected in the posterior area of the septal cartilage.

Postnatal Growth of the Human Septal Cartilage: Preliminary Report

Growth activities in different areas of the human septal cartilage were determined by the extent of DNA synthesis and matrix synthesis in 20 patients aged 6 to 40 years. DNA synthesis measured by in vitro incorporation of 3H-labelled thymidine was markedly elevated in the anterior free end and the central area of the septum in all age groups. Matrix synthesis measured by in vitro incorporation of labelled sulphate into proteoglycans showed a comparable age-independent activity in the anterior free end, whereas in the suprapremaxillary area, matrix synthesis displayed its greatest activity during childhood, showing thereafter a continuous decline during puberty and adulthood. A similar age-dependent pattern in this area, though at a much lower level, could also be demonstrated for the extent in DNA synthesis.

Expression of p53 in human leukemic cell lines

The cell-encoded p53 antigen seems to be tightly associated with various human malignancies. We have analyzed biochemical properties of p53 in two different cell lines derived from patients with ALL or ANLL. p53 was found in elevated levels in both leukemic cell lines compared to unstimulated or stimulated normal lymphocytes. High levels of p53 in these cell lines are due to an extended stability of p53 protein rather than to different rates of synthesis. p53 from both cell lines formed low- and high-molecular weight oligomers which revealed that p53 exists in a heterogenous population in these tumor cells. The presence of immunologically different subsets of p53 was demonstrated by sequential immunoprecipitation experiments with different p53 specific monoclonal antibodies. Our results showed structural and immunological variabilities of p53 in cell lines derived from human tumors and may thus provide an insight into the role p53 may play in human malignancies.

Human nasal septal cartilage: Local distribution of different enzyme activities in healthy adults and acromegalic patients

Septal cartilage was obtained during septoplasty from healthy adults or during transnasal hypophysectomy from acromegalic patients. Small strips of cartilage were excised from five different areas of the septum: the anterior free end, the suprapremaxillary area, the central area, the posterior area, and the caudal prolongation of the septum. Five different enzymatic pathways were analyzed in these areas.