[Surgical management of brachial plexus birth injuries].
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Biomedical subjects
Publications and source records attributed to I Goldberg.
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Actin monomers with bound ATP, ADP, or fluorescent analogues of these nucleotides exchange the nucleotide on a second time scale, whereas filaments assembled from each of these species exchange their nucleotide with the solution at least 1,000 times slower than monomers. Filaments assembled from either ATP-actin or ADP-actin are indistinguishable by electron microscopy after negative staining. The dynamic elasticity and viscosity of filaments assembled from ATP-actin or ADP-actin or mixtures of these two species are the same over a wide range of frequencies. These observations do not support a recent suggestion (Janmey, P. A., Hvidt, S., Oster, G. F., Lamb, J., Stossel, T. P., and Hartwig, J. H. (1990) Nature 347, 95-99) that ATP hydrolysis within actin filaments stiffens the polymer and alters both their structure and affinity for nucleotides. The difference in observations between these two studies may be related to time-dependent changes in ADP-actin prepared in slightly different ways.
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Scatter factor (SF) is a protein produced by fibroblasts, smooth muscle cells, and human placenta which scatter cohesive epithelial cell colonies and increases cellular motility. SF bound to concanavalin A and other lectins with high affinity. SF could also be stained with a glycoprotein specific stain. Incubation of producer cells (N-ras-transformed 3T3), with tunicamycin homolog A1 did not have any significant effect on the secretory activity of SF. The treatment of SF with N- and O-glycanases as well as endoglycosidase H had no effect on its activity. However, treatment of target (Madin Darby canine kidney) cells with tunicamycin A1, abolished the scattering response. These studies suggest that scatter factor is a glycoprotein, but glycosylation is not required for its secretion or activity by the producer cells; however, glycosylation of proteins in the target cells is required for SF action.
A dnaA 'null' strain could not support replication of intact plasmid R6K or derivatives containing combinations of its three replication origins (alpha, gamma, beta). DnaA binds in vitro to sites in two functionally distinct segments of the central gamma origin. The 277-bp core segment is common to all three origins and contains DnaA box 2, which cannot be deleted without preventing replication. Immediately to the left of the core lies the 106-bp origin enhancer, which contains DnaA box 1. When the origin enhancer is deleted, the core alone can still initiate replication if levels of wt pi protein are decreased or if copy-up pi mutant proteins are provided in trans. DnaA does not effect expression of R6K replication initiator protein pi, although several DnaA boxes were identified in the coding segment of the pir gene, which encodes pi. Together these data suggest that a single DnaA box, 2, is sufficient for initiation from the gamma origin and might be sufficient for initiation from the gamma origin and might be sufficient and required for the activity of the alpha and beta origins as well. Implications of the DnaA protein binding to two domains of the gamma origin and the role of the 106-bp origin enhancer in replication are discussed.
We investigated the effects of human placental scatter factor (hSF), mouse scatter factor (mSF) and recombinant human hepatocyte growth factor (HGF) on motility and morphology of individual Madin-Darby canine kidney cells using a computerized cell tracking system. All three factors increased the velocity of individual cells and the ratio of moving to stationary cells. Similarly, all three factors caused changes in morphologic features of cells, leading to increased area, flatness, and polarity. Increases in area and flatness but not polarity were slightly greater with HGF than with hSF or mSF. These results suggest that SFs and HGF have similar effects on motility and morphology of isolated epithelial cells.
We have combined in vivo and in vitro approaches to investigate the function of CENP-B, a major protein of human centromeric heterochromatin. Expression of epitope-tagged deletion derivatives of CENP-B in HeLa cells revealed that a single domain less than 158 residues from the amino terminus of the protein is sufficient to localize CENP-B to centromeres. Centromere localization was abolished if as few as 28 amino acids were removed from the amino terminus of CENP-B. The centromere localization signal of CENP-B can function in an autonomous fashion, relocating a fused bacterial enzyme to centromeres. The centromere localization domain of CENP-B specifically binds in vitro to a subset of alpha-satellite DNA monomers. These results suggest that the primary mechanism for localization of CENP-B to centromeres involves the recognition of a DNA sequence found at centromeres. Analysis of the distribution of this sequence in alpha-satellite DNA suggests that CENP-B binding may have profound effects on chromatin structure at centromeres.
A 24-year-old woman in her 20th week of pregnancy sustained a severely displaced acetabular fracture. Skeletal traction failed to achieve reduction. Open reduction and internal fixation were performed through an extended iliofemoral approach without affecting the pregnancy. At full term, she had a normal delivery. Four years after the injury, the patient had a pain-free hip with full range of motion and a healthy child. The potential benefit or danger of surgery to the patient and her pregnancy was thoroughly considered.
Scatter factor (SF) was first identified as a fibroblast-derived protein which disperses (i.e., "scatters") cohesive colonies of epithelium. SF-like proteins were found in human smooth muscle cell conditioned medium, amniotic fluid, and placental tissue. SFs markedly stimulate migration of epithelial, carcinoma, and vascular endothelial cell types at picomolar concentrations. Hepatocyte growth factors (HGFs) were originally described as platelet- and serum-derived proteins which stimulate hepatocyte DNA synthesis. Partial amino acid sequence data for mouse and human SFs indicate significant homology with HGFs. We used biological, biochemical, and immunological assays to evaluate and compare the activities, properties, and mechanisms of action of mouse SF, human SF (fibroblast or placenta derived), and recombinant human HGF (hrHGF). We report the following findings: (a) mouse SF exhibits species-related differences in biological activities relative to the human factors; (b) human SF and hrHGF show significant overlap in biological activities (i.e., hrHGF stimulates motility of multiple normal and carcinoma cell types, whereas human SF stimulates DNA synthesis in several normal cell types); (c) the three factors contain common antigenic determinants; and (d) all three proteins stimulate rapid phosphorylation of tyrosine residues on the c-met protooncogene protein product (the putative receptor for HGF) and on another protein with Mr 110,000. A few biological and immunological differences between human SFs and hrHGF were observed. These may reflect minor variations in amino acid sequence or posttranslational modification related to the sources of the factors. Taken as a whole, our findings suggest that by structural, functional, immunological, and mechanistic criteria, human SF and human HGF are essentially identical.
The bacterium Klebsiella pneumoniae synthesizes three different types of catalase: a catalase-peroxidase, a typical catalase and an atypical catalase, designated KpCP, KpT and KpA, respectively (Goldberg, I. and Hochman, A. (1989) Arch. Biochem. Biophys. 268, 124-128). KpCP, but not the other two enzymes, in addition to the catalatic activity, catalyzes peroxidatic activities with artificial electron donors, as well as with NADH and NADPH. Both KpCP and KpT are tetramers, with heme IX as a prosthetic group, and they show a typical high-spin absorption spectrum which is converted to low-spin when a cyanide complex is formed. The addition of dithionite to KpCP causes a shift in the absorption maxima typical of ferrous heme IX. KpCP has a pH optimum of 6.3 for the catalatic activity and 5.2-5.7 for the peroxidatic activity, and relatively low 'Km' values: 6.5 mM and 0.65 H2O2 for the catalatic and peroxidatic activities, respectively. The activity of the catalase-peroxidase is inhibited by azide and cyanide, but not by 3-amino-1,2,4-triazole. KpT has wide pH optimum: 5-10.5 and a 'Km' of 50 mM H2O2, it is inhibited by incubation with 3-amino-1,2,4-triazole and by the acidic forms of cyanide and azide. A significant distinction between the typical catalase and the catalase-peroxidase is the stability of their proteins: KpT is more stable than KpCP to H2O2, temperature, pH and urea.
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We recorded pattern electroretinograms, scotopic threshold responses, oscillatory potentials and ganzfeld flash electroretinograms in patients with glaucoma or other optic nerve diseases and in cats with inner retinal damage caused by intravitreal injections of kainic acid. In both studies, the scotopic b-wave and the scotopic threshold responses were normal but the oscillatory potentials and pattern electroretinograms were not. The photopic b-wave was also often reduced in patients with scotopic oscillatory potential reduction, and the reduction was proportionate to the oscillatory potential change. Oscillatory potentials were as frequently reduced as pattern electroretinograms in both patient groups, and in the few cases where only one response was reduced, there was no bias toward either measure. In cats, the effects of intravitreal injection of various doses of kainic acid on the retina were evaluated electrophysiologically, and structural damage was assessed histologically. After 25 nmol of kainic acid, the pattern electroretinograms and oscillatory potentials were reduced but neither the b-waves nor the scotopic threshold responses, were affected. Histologic studies of retinas after this dose showed swollen dendrites that were restricted to the outer part (off-sublamina) of the inner plexiform layer. Serial semithin sections indicated that most, if not all, of the swelling was confined to dendrites of large ganglion cells. Our results indicate that the size and sensitivity of the oscillatory potential response may have a role in the diagnosis and management of early glaucoma and optic nerve disease, and that the photopic electroretinogram may give similar information.
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A rare case of hepatocellular carcinoma in a 31-year-old woman is reported. The diagnosis was made at 16 weeks of pregnancy when very high levels of alpha-feto-protein were found upon routine examination. The pregnancy was terminated and cytostatic therapy was given. The patient died one year later.
2 cases of damage to peripheral nerves following bicycle riding are described in males aged 13 and 35 years, respectively. In 1 there was injury to the ulnar nerve at the level of the wrist, with hypesthesia of the 2 ulnar digits and paresis of intrinsic muscles. In the other case there was involvement of the pudendal nerves with numbness of the buttocks and genitalia, and with difficulty in achieving erection. After cycling was stopped for a few weeks the symptoms disappeared spontaneously, with full recovery. Once symptoms subside completely cycling can be resumed, although with certain precautions.
Vision lost to glaucoma is as irrecoverable as it is asymptomatic. Early detection by attending medical practitioners is vital if treatment is to halt the disease before such disabling visual loss occurs. This article discusses simple measures to use in the early diagnosis of this potentially disabling condition.
Scatter factor (SF) is a protein produced by cultured fibroblasts which causes epithelia to "scatter" into isolated cells. We found significant scatter activity in vivo in second trimester (but not term) human amniotic fluid and in human placenta. Placental SF was purified 500,000-fold and identified as a protein with Mr 78 kd. Factor scattered Madin-Darby canine kidney and human squamous carcinoma cells at 15 pM. Amino acid sequences from tryptic peptides did not match any known protein. Human placental fibroblasts produced high titers of scatter activity. SF may be involved in development and may enhance carcinoma invasion.