[The so-called Darrach operation following fracture of the distal radius].
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Biomedical subjects
Publications and source records attributed to K Mann.
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We investigated the plasma disappearance of purified urinary human choriogonadotropin (hCG) and acidic variants of hCG (AV-hCG) that are excreted in the urine of patients with testicular cancer to determine if there are differences in their disappearance rates. All cancer patients had relatively increased fractions (10% to 46%) of AV-hCG in their serum when compared with hCG from pregnant control subjects (less than 4% present as AV-hCG). After initiation of therapy in 12 patients with nonseminomatous testicular tumors, the proportion of hCG present as acidic variants in serum rose despite lower serum total hCG concentrations. Samples of highly purified AV-hCG (pI, 3.3 to 4.0) obtained from three patients by concentration from urine and isoelectric focusing were evaluated for their disappearance from serum after injection into rats. All AV-hCG samples had decreased clearance rates when compared with that of highly purified hCG (CR123). These data indicate that acidic forms of hCG have a delayed clearance that contributes to the increased proportion of AV-hCG in the serum of patients with hCG-producing neoplasia after therapy.
The role of TSH in thyroid cell growth and the pathogenesis of goiter has become a matter of recent debate, since many investigators have failed to demonstrate a growth-promoting effect of TSH in human thyroid cells in culture. While those studies have focused on the action of TSH in human thyroid cells, the influence of assay conditions and cofactors has received scant attention. In the present study, we have therefore undertaken to elucidate the effects of insulin and insulin-like growth factor (IGF I) on 3H-thymidine uptake in human thyroid cells, particularly with respect to their relation to the actions of bTSH. We could demonstrate a considerable, dose-dependent stimulation of 3H-thymidine incorporation in the cells by bTSH that was dependent on the presence of insulin or IGF I; bTSH alone was ineffective in that respect. The concentrations of insulin and IGF I required to facilitate the TSH response were of a magnitude at which both peptides were totally ineffective by themselves. At concentrations of insulin or IGF I that produced a maximum stimulation of 3H-thymidine incorporation, the addition of bTSH did result in a slight decrease rather than a further increase of that stimulation. We conclude from these findings, first, that TSH appears to be a growth factor for human thyroid cells under the conditions described, and, second, the effects of TSH on thyroid cell proliferation are under the control of cofactors like insulin and IGF I.
The laminin-nidogen complex and purified nidogen both bind collagen IV but not other collagens, as shown by solid-state ligand-binding and inhibition assays. Laminin purified from the dissociated complex and a variety of laminin proteolytic fragments failed to bind collagen IV. Complexes formed in solution between nidogen or laminin-nidogen and collagen IV were visualized by rotary shadowing which identified one major binding site about 80 nm away from the C-terminus of the collagen triple helix. A second, weaker binding site may exist closer to its N-terminus. Binding sites of nidogen were assigned to its C-terminal globular domain which also possesses laminin-binding structures. A more diverse collagen-IV-binding pattern was observed for the laminin nidogen complex, whereby interactions may involve both nidogen and short-arm structures of laminin.
The epidermal growth factor (EGF) and alpha-tumor growth factor are mitogenic proteins which bind to the EGF-receptor and may play a role in carcinogenesis or tumor progression. Our study investigated whether colorectal carcinomas and adenomas express altered levels of EGF-receptors or overproduce EGF-like activity by comparing histologically normal mucosa to carcinomas resected from the same patients. EGF-receptors were characterized by radioligand binding studies. Carcinomas contained unchanged or decreased levels of EGF-receptors in 13/16 and moderately increased levels in 3/16 patients as compared to normal mucosa. Adenomas obtained from 2 patients with familial polyposis coli and from a third patient with a coincident carcinoma had similar numbers of EGF-receptors as normal mucosa. EGF-like growth factors, in contrast, were significantly elevated in carcinoma extracts as compared to extracts from normal mucosa of the same patients. Adenomas did not contain elevated levels of EGF-like activity. We conclude that increased expression of EGF-receptors is infrequent in colonic adenocarcinomas. Increased production of EGF-like growth factors may frequently occur but seems to be associated with tumor progression rather than with premalignant lesions as represented by adenomas.
Radioiodine therapy (RITh) is an effective mode of treatment of different types of hyperthyroidism (immunogenic, IH; nonimmunogenic, NIH). The aim of this study was to evaluate the risk of thyroid storm after RITh. For this purpose a systematic determination of thyroid hormones (TT3, TT4) 5 and if possible 12 days after RITh was performed in 416 patients with borderline or overt hyperthyroidism. Additional antithyroid medication after RITh was necessary in 20 patients. Among the remaining 396 patients 48% had been pretreated with antithyroid drugs because of more severe clinical symptoms. This medication was canceled 10 to 5 days before RITh in all cases. After RITh the mean TT3 and TT4 levels of the subgroups, with and without antithyroid premedication, decreased nearly in parallel course. The whole group of 396 patients presented a significant decrease in TT3 levels with a mean from 1.9 to 1.4 ng/ml. In 18 cases (5%) an increase in TT3 level (greater than or equal to 0.5 ng/ml) was detected without requiring antithyroid therapy. No case of thyroid storm was observed in the entire patient group. TT3 decrease appeared to be more pronounced in patients with higher pretreatment levels. TT4 showed a significant decrease only in case of elevated levels. Post-therapeutic hormone levels were not dependent on the etiology of hyperthyroidism (IH, NIH). The decrease of TT3 levels in the IH group was more pronounced after application of 150 Gy compared with 60 Gy. The additional medication with propranolol (greater than or equal to 60 mg/day) enforced the TT3 decrease. Accompanying glucocorticoid medication had no influence on the hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)
The whole amino acid sequence of nidogen was deduced from cDNA clones isolated from expression libraries and confirmed to approximately 50% by Edman degradation of peptides. The protein consists of some 1217 amino acid residues and a 28-residue signal peptide. The data support a previously proposed dumb-bell model of nidogen by demonstrating a large N-terminal globular domain (641 residues), five EGF-like repeats constituting the rod-like domain (248 residues) and a smaller C-terminal globule (328 residues). Two more EGF-like repeats interrupt the N-terminal and terminate the C-terminal sequences. Weak sequence homologies (25%) were detected between some regions of nidogen, the LDL receptor, thyroglobulin and the EGF precursor. Nidogen contains two consensus sequences for tyrosine sulfation and for asparagine beta-hydroxylation, two N-linked carbohydrate acceptor sites and, within one of the EGF-like repeats an Arg-Gly-Asp sequence. The latter was shown to be functional in cell attachment to nidogen. Binding sites for laminin and collagen IV are present on the C-terminal globule but not yet precisely localized.
Amino acid sequences of human collagen alpha 1(VI) and alpha 2(VI) chains were completed by cDNA sequencing and Edman degradation demonstrating that the mature polypeptides contain 1009 and 998 amino acid residues respectively. In addition, they contain small signal peptide sequences. Both chains show 31% identity in the N-terminal (approximately 235 residues) and C-terminal (approximately 430 residues) globular domains which are connected by a triple helical segment (335-336 residues). Internal alignment of the globular sequences indicates a repetitive 200-residue structure (15-23% identity) occurring three times (N1, C1, C2) in each chain. These repeating subdomains are connected to each other and to the triple helix by short (15-30 residues) cysteine-rich segments. The globular domains possess several N-glycosylation sites but no cell-binding RGD sequences, which are exclusively found in the triple helical segment. Sequencing of alpha 2(VI) cDNA clones revealed two variant chains with a distinct C2 subdomain and 3' non-coding region. The repetitive segments C1, C2 and, to a lesser extent, N1 show significant identity (15-18%) to the collagen-binding A domains of von Willebrand factor (vWF) and they are also similar to some integrin receptors, complement components and a cartilage matrix protein. Since the globular domains of collagen VI come into close contact with triple helical segments during the formation of tissue microfibrils it suggests that the globular domains bind to collagenous structures in a manner similar to the binding of vWF to collagen I.
Twelve of sixteen different cell types including fibroblasts and tumor cells were able to attach and spread on substrates of pepsin-solubilized or intact collagen VI, and on its triple helical domain. Attachment and spreading were independent of soluble mediator proteins (fibronectin, laminin) and collagen VI was distinct from collagens I, IV and V in the cells with which it interacted. Many of the same cells bound and spread on substrates prepared from unfolded alpha 2(VI) and alpha 3(VI) chains but not on the alpha 1(VI) chain. The interactions with the chains were inhibited by low concentrations (10-100 microM) of synthetic RGDS and RGDT but not RGES peptides while the binding of cells to pepsin-solubilized collagen VI was more than 20-fold less sensitive to these peptides. The data indicate that cells have the ability to bind to collagen VI in a specific manner suggesting a similar function for collagen VI in situ.
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Nidogen, a multifunctional glycoprotein, is an integral part of all basement membranes. In this study, human nidogen cDNAs were isolated and characterized from human placental and skin fibroblast cDNA libraries by hybridization with a mouse nidogen cDNA probe. Six overlapping clones covering 4.9 kb were characterized. The composite cDNA contained a 3,741-nucleotide open reading frame which coded for a 1,247-amino-acid peptide that included a hydrophobic signal sequence. The deduced amino acid sequence contains seven epidermal growth factor-like cysteine-rich repeats, one possible tyrosine O-sulfation site, and a possible N-glycosylation site. The tripeptide sequence -Arg-Gly-Asp- (RGD), a potential cell attachment site, was also present. Human and mouse nidogen sequences were 84% homologous at the nucleotide level and 85% homologous at the deduced amino acid level. Southern blotting of human leukocyte DNA from 23 individuals indicated that nidogen probably is a single-copy gene and shows multiple restriction fragment length polymorphisms when cleaved with Eco RI, Pvu II, Taq I, and Msp I. In particular, digestions with Pvu II revealed polymorphism in four discrete DNA fragments, which could be discriminated by hybridizations with nidogen subclones. One of the polymorphisms revealed an allelic frequency of 0.52/0.48. Thus, human nidogen gene displays RFLPs which provide analytical tools to establish genetic linkage between the nidogen gene and a clinical phenotype.
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The authors have investigated hypothalamic-pituitary function in 8 patients (aged 9-27 years) with surgically and histologically proven suprasellar germinomas. Diabetes insipidus was found in 7 patients. All the patients had hypogonadism and hypocortisolism as judged by dynamic endocrine testing. Hypothyroidism was found in 6. Moreover, growth hormone secretion, as assessed by insulin-induced hypoglycemia, was defective in all patients. Comparison of results of insulin-induced hypoglycemia testing and stimulation tests by CRH and GHRH suggested that all patients had a primary suprahypophyseal lesion rather than a primary pituitary defect. The authors conclude that suprasellar germinomas, although uncommon, should be included in the differential diagnosis of juvenile suprasellar tumours and in cases suggestive of idiopathic diabetes insipidus, even if neuroradiological investigation fails to demonstrate a discrete tumour.
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The liver enzymes GGT, GOT and GPT, as well as MCV, of 40 alcoholics were examined. They had presented at the psychiatric department of the University for withdrawal therapy. All of them had consumed alcohol up to the time of admission. The laboratory values were obtained on admission, then at weekly intervals for a period of 5 weeks, under total alcohol abstinence. GGT (85 per cent) and MCV (95 per cent) demonstrated a high sensitivity relating to alcohol abuse. While the raised GGT values reduced gradually, the MCV values remained consistently high even after strict withholding of alcohol. The sensitivity of MCV was not impaired by the previous substitutions of vitamin B complex. At the beginning GOT and GPT were elevated in only about half the number of cases and quickly became normal. Because of the more rapid lowering of the GOT activities, compared to the GPT activities, the De Ritis quotient sank to below 1 even after only one week. To demonstrate the clinical chemical evidence of the appraisement more clearly, the MCV as well as liver enzymes, must be taken into account. In general there was a decline in the diagnostic value of the laboratory results, the longer the period of alcohol abstinence lasted. Therefore, it is recommended not to set a long term time limit for examination, to favour the motivated total abstinence periods.
Thermometry of the forehead and cheeks was done in 35 longtime trainees of Autogenic Training (AT). Results revealed a significant increase in forehead skin temperature rather than the hypothesized decrease. Cheek temperature rose significantly more than forehead temperature. This difference between cheek and forehead temperatures could explain the subjective impression of coolness of the forehead during the sixth standard exercise of Autogenic Training.
Immediate initiation of controlled active movement is recommended as optional method to handle fresh injuries to collateral knee joint ligaments. This conclusion was drawn from retrospective (1968-1978) and prospective (1979-1987) studies into 581 cases. The three-fixed-point splint (Mann, 1971) is considered to be an ideal device to cope with simple and complex valgus and varus instabilities at the quantitative stages of monad and duad A. Treatment is possible without surgery. Joint motion is restricted to 0/20/80 for six weeks. No-delay high-accuracy diagnosis is essential.
The complete amino acid sequence of the triple-helical domain of human collagen VI was deduced from sequences of appropriate cDNA clones and confirmed to about 50% by Edman degradation of tryptic peptides. This domain consists of three different peptide segments containing some 335-336 amino acid residues originating from central portions of the alpha 1 (VI), alpha 2(VI), and alpha 3(VI) chains, respectively. Sequence identity in the X/Y positions of the Gly-X-Y repeats is rather low (10-15%) between the chains. Peculiar features of these sequences include 3 cysteine residues about 50 (alpha 3(VI)) and 89 (alpha 1(VI), alpha 2(VI)) residues away from the N-terminus and several Gly-X-Y interruptions clustered in the C-terminal two-thirds of the triple helix. These structures are presumably required for cross-linking collagen VI oligomers and for super-coiling of triple helices in the dimers. Other features include 11 Arg-Gly-Asp sequences, some of which are likely to be used as cell-binding sites, and four Asn-X-Thr sequences, allowing N-linked glycosylation along the triple helix. Junctional areas close to the helix contain short, cysteine-rich segments which may seal the triple-helical domain through disulfide bond formation, endowing it with high stability. These features, together with a low sequence homology to fiber-forming and basement-membrane collagens, document the unique character of collagen VI, whose triple helix is specifically adjusted for forming microfibrils in tissues.