Biomedical subjects
Publications and source records attributed to I Goldberg.
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.
Despite the limited data that are available concerning FF physicochemical properties, the following conclusions can be drawn. (1) FF temperature is lower than ovarian stroma and body temperatures. The physiological significance of this gradient is unknown. (2) Follicular size increases exponentially prior to ovulation. The relationship between FF volume and successful IVF outcome is well established. (3) A highly significant association exists between fertilization (but not embryo cleavage) and FF spectrophotometric absorbance at delta optic density of 455 nm. (4) FF behaves as a non-Newtonian fluid--its viscosity changes at different shear rates. Neither FF viscosity nor its refractive index was found to correlate with the presence of oocytes, their maturation grade, or their fertilizing capacity. (5) FF osmolarity is similar to that of the plasma. There is no information linking variations in FF osmolarity to IVF outcome. (6) FF pH is acidic, probably due to acid mucopolysaccharides. It appears that the intact follicle is capable of buffering any carbon dioxide which diffuses through its wall at the time of intraperitoneal insufflation. The transvaginal aspiration technique eliminates any possible effect of exogenous gas on FF pH. (7) Regarding the intact follicle, it was shown that (a) there is a small potential difference across the follicle wall, and (b) intrafollicular pressure remains steady prior to ovulation. This information may shed some light on mechanisms underlying FF formation and ovulation. No experiments relating these properties to IVF outcome have been performed.
Vitamin E uptake by Caco-2 cells, a human intestinal cell line, was studied by incubating the cells with alpha-tocopherol/triglyceride emulsions with or without bile activated lipase or lipoprotein lipase. During a 1-h incubation, vitamin E was transferred to Caco-2 cells only in the presence of triglyceride hydrolysis by bile activated lipase and not by lipoprotein lipase. Incubation with either lipase resulted in hydrolysis of approximately 20% of the medium [3H]-triolein to free fatty acids and a 3-5-fold increase in cellular radioactivity. In the absence of lipases but the presence of taurocholate, addition of oleic acid in an amount equal to the molar concentration of triglyceride (5.7 mM) to triglyceride emulsions containing either alpha-tocopherol or cholesteryl ester resulted in an increase in cellular [3H]-triglyceride and alpha-tocopherol or cholesteryl ester. We suggest that the absorption of hydrophobic molecules such as vitamin E may occur in the presence of bile and amphipathic lipids via the uptake of micellar neutral lipids by the intestine.
A simple plate-assay has been developed to screen microorganisms for L-malic acid production. Acid producing organisms were identified, after microbial colony growth on media containing glucose or fumaric acid as sole carbons sources, by formation of a dark halo of formazan. The halo was observed when the plate was covered with a soft agar overlay containing NAD(+)-malate dehydrogenase, NAD+, phenazine methosulfate (PMS) and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The assay developed is simple, specific for L-malic acid and therefore can be used to identify L-malic acid producing filamentous fungi using glucose as carbon source (e.g. Aspergillus strains). The assay is also applicable for screening bacteria with high fumarase activity, able to convert fumaric acid to L-malic acid.
The localization of pyruvate carboxylase (cytosolic or mitochondrial) was studied in nine different Aspergillus species (14 strains). In some species (A. aculeatus, A. flavus, A. foetidus, A. nidulans, A. ochraceus, and A. sojae), the pyruvate carboxylase activity could be detected only in the cytosolic fraction of the cells. Pyruvate carboxylase has been found only in the mitochondrial fraction of two strains of Aspergillus wentii. In Aspergillus oryzae and in five strains of Aspergillus niger, pyruvate carboxylase activity was detected both in the mitochondrial fraction and in the cytosol. There was no quantitative or qualitative correlation between the activities of pyruvate carboxylase in the mitochondrial and cytosolic fractions of the cells and the ability of the various Aspergillus strains to accumulate different organic acids.
Cloning of the Saccharomyces cerevisiae FUM1 gene downstream of the strong GAL10 promoter resulted in inducible overexpression of fumarase in the yeast. The overproducing strain exhibited efficient bioconversion of fumaric acid to L-malic acid with an apparent conversion value of 88% and a conversion rate of 80.4 mmol of fumaric acid/h per g of cell wet weight, both of which are much higher than parameters known for industrial bacterial strains. The only product of the conversion reaction was L-malic acid, which was essentially free of the unwanted by-product succinic acid. The GAL10 promoter situated upstream of a promoterless FUM1 gene led to production and correct distribution of the two fumarase isoenzyme activities between cytosolic and mitochondrial subcellular fractions. The amino-terminal sequence of fumarase contains the mitochondrial signal sequence since (i) 92 of 463 amino acid residues from the amino terminus of fumarase are sufficient to localize fumarase-lacZ fusions to mitochondria and (ii) fumarase and fumarase-lacZ fusions lacking the amino-terminal sequence are localized exclusively in the cytosol. The possibility that both mitochondrial and cytosolic fumarases are derived from the same initial translation product is discussed.
Scatter factor (SF) is a cytokine that causes cohesive epithelial colonies to 'scatter' into isolated cells and stimulates epithelial cell migration. To investigate SF's mechanism(s), we screened agents that modulate various intracellular processes for effects on scattering of Madin-Darby canine kidney (MDCK) cells. Selected agents were studied in quantitative migration assays using microcarrier beads. Agents that activate the adenylate cyclase (AC) pathway caused mild to moderate inhibition of scattering and migration, while modulators of Ca2+/calmodulin pathways had little effect on scattering. In contrast, phorbol esters (PMA, PDD) and protein kinase C (PKC) inhibitors (staurosporine, H-7, 7,8-dihydroxychlorpromazine) markedly enhanced and accelerated scattering; PMA and staurosporine also stimulated migration. Diacylglycerol analogues (e.g. diC8), naphthalenesulfonamide PKC activators (SC-9, SC-10) and inactive phorbol esters (e.g. 4a-PDD) did not potentiate scattering, while PKC depletion by 48 h pre-incubation with PMA markedly stimulated scattering. Thus, PMA-enhanced scattering may be related to down-modulation of PKC. Scattering was blocked by inhibitors of protein and RNA but not DNA synthesis; SF- and agent-stimulated migration were ablated by cycloheximide. Scattering and migration were inhibited by an anti-microfilament (cytochalasin B) but not anti-microtubule (e.g. colcemid) agents. These findings suggest that SF-induced epithelial mobility may be mediated, in part, by protein synthesis, alterations in protein phosphorylation (?inhibition of PKC), and actin filament reorganization. They indicate directions for further studies.
We reviewed 28 patients with brachial plexus lesions caused by shoulder dislocation. Contrary to most other reports, we found that the neurological lesions involved the infraclavicular and the supraclavicular brachial plexus. With supraclavicular lesions the involvement was always of the suprascapular nerve, and this always recovered spontaneously. Isolated axillary nerve lesions had the poorest prognosis for spontaneous recovery. We explored all lesions that showed no recovery after three to five months and performed either grafting or neurolysis. We discuss the combinations of nerve lesions, their recovery, the surgical indications, and the operations. We also suggest a new classification for these injuries which is more clinically relevant than the anatomical classification of Leffert and Seddon (1965).
A dose of 48 Gy of X-irradiation given over two to five weeks after grafting caused no significant delay in the rate of healing and only a small and statistically non-significant decrease in the torsional strength of the graft-bone junction of either vascularised or non-vascularised bone grafts of the tibiae of rabbits. Healing was faster and the union between the graft and adjacent bone developed torsional strength significantly more rapidly with vascularised than with non-vascularised grafts. These findings suggest that postoperative radiotherapy is unlikely to have a significantly deleterious effect on the healing of bone grafts used to repair defects produced by excision of malignant bone tumours.
The goals of this article are to review the similarities and differences in the pathogenesis of acute gastric mucosal injury induced by alcohol, exemplified mostly by ethanol, and aspirin, as a representative of nonsteroidal anti-inflammatory drugs, and to deduce implications from pathogenetic studies for a better understanding of the concept of gastric cytoprotection. The main similarity between the hemorrhagic erosions caused by ethanol and aspirin is their localization in the acid-producing glandular stomach, the rate-limiting step in their pathogenesis being the extent of microvascular injury in the gastric mucosa. The major differences include the fast healing and low probability of transition into chronic gastritis after a single exposure to aspirin. On the other hand, perforated ulcer may develop, especially in the elderly, after chronic aspirin but not ethanol consumption. The main implications of pathogenetic investigations include the relative nature of gastroprotection: that is, initially, the superficial epithelial layer is not protected against concentrated luminal solutions, but it is rapidly replaced by migrating, adjacent, surviving cells if blood flow is maintained and the basement membrane is relatively intact. Vascular changes thus seem to be the rate-limiting step both in the pathogenesis and prevention of chemically induced acute gastric mucosal injury. The ultimate biochemical mechanisms of gastroprotection seem to include an effect on structural and enzymic proteins, and vascular mediators which influence vascular permeability and, indirectly, the extent of tissue injury.
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A family of totally synthetic genes coding for multiple tandem repeats of the amino acid sequence (Gly-Pro-Pro) has been prepared and inserted into the ClaI cloning site of the expression vector pJL6. A representative recombinant plasmid, pAC1, with an insert of about 340 bp was established in an Escherichia coli strain bearing a defective lambda prophage, to study expression of the CII-collagen analog fusion protein produced from pAC1 upon heat induction. Authentic fusion protein production was demonstrated by nucleotide sequencing, Northern-blot analysis, and in vivo synthesis. Conversion of a wild-type rpoH allele to the rpoH165 mutation was shown to suppress proteolysis of the unstable fusion protein.
A novel type of catalase, designated KpA, was purified from the bacterium Klebsiella pneumoniae. The enzyme is unique in that it is a dimer with subunit molecular weight of 80,000, it bears a chlorine-type heme as prosthetic group, and is active over a very wide range of H+ concentrations, with a plateau from pH 2.8 to 11.8. Yet, some properties of KpA are characteristic of typical catalases: it is stable when treated with with ethanol/chloroform, cannot be reduced by dithionite and it is inhibited by 3-amino-1,2,4-triazole and by the conjugate acid forms of azide and cyanide. The protein of KpA is outstandingly resistant to denaturing conditions: it retains full activity when incubated with 8 M urea, at 30 degrees C for 4 days, it is stable for 1 h at 70 degrees C and at pH values 3.1 and 11.5 and, when dialyzed against 50 mM H2O2, it still retains 42% of its activity after 80 min.
Crude extracts from aerobically grown bacterium Klebsiella pneumoniae contain three different types of catalases, designated KpT, KpCP, and KpA, whose activities in crude extracts are in the ratio 4.1:1:0.3. KpT resembles typical catalases: its molecular weight is 259,000, its activity is independent of pH in the range 5.5-10.5, it is stable at 52 degrees C but loses 80% of its activity when incubated at 60 degrees C for 45 min, and it has hydrophobic properties revealed by binding to phenyl-Sepharose and stability in ethanol-chloroform. KpCP is a catalase-peroxidase with a molecular weight of 278,000, has a sharp pH optimum at 6.3, and is inactivated by treatment at 52 degrees C for 45 min and by ethanol-chloroform. KpA has been reported to be a dimer with molecular weight of 160,000 which contains a chlorin-type heme, has a plateau of maximal activity between pH's 2.8 and 11.8, and is stable to treatment with ethanol-chloroform and to incubation at 70 degrees C. All three enzymes are inhibited by cyanide.