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Biomedical subjects

E Roberts

Publications and source records attributed to E Roberts.

At least 199 records · Page 11Linked to original sources
PubMed1983

Resistance to hepatotoxins acquired by hepatocytes during liver regeneration.

The appearance of resistance to a number of hepatotoxins in primary cultures of hepatocytes prepared at various time intervals up to 2 weeks after partial hepatectomy is the major focus in this study. Resistance to the cytocidal effect of aflatoxin B1, 2-acetylaminofluorene, N-hydroxy-2-acetylaminofluorene, methotrexate, or methyl methanesulfonate shows a progressive increase until 48 hr and then returns to the resting level of susceptibility by 2 weeks. The genesis of mutagens from 2-acetylaminofluorene and aflatoxin B1 by S-9 liver fractions shows a decrease from and return to control values after partial hepatectomy that parallels the resistance. The levels of total cellular cytochromes P-450 also decrease following partial hepatectomy and remain from 28 to 36% less than those of controls for at least 1 week. The glutathione and total soluble sulfhydryl ("glutathione") content increase following partial hepatectomy, and the pattern is consistent with a partial role for glutathione in the resistance phenomenon as it relates to 2-acetylaminofluorene. The possible relationship between resistance to the cytocidal effects in vitro and the resistance to inhibition of cell proliferation in vivo during liver carcinogenesis is discussed.

2-Acetylaminofluorene↗
PubMed1983

Test bias and the culturally different early adolescent.

Test bias has been defined as a phenomenon in which the effects of a given test result in negative outcomes for a given person because that person is identified with a certain group (Sedlacek, 1976). As this paper is specifically concerned with test bias and the culturally different, the latter should be defined as individuals "from lower socioeconomic groups who may also be members of a minority group" (Brown, no date). On IQ tests, blacks generally score one standard deviation below whites, and low-income Hispanics also score below average (Laosa, 1976). Test bias can be manifested in all or any of the following: 1) content bias, 2) atmosphere bias, and/or 3) use bias (Sedlacek, 1976). A discussion of each follows.

Adolescent↗
PubMed1982

A new synaptosomal biosynthetic pathway of proline from ornithine and its negative feedback inhibition by proline.

The biosynthesis of L-proline (Pro) was studied in sonicates of mouse brain synaptosomes (P2). Incubation with L-[14C]glutamic acid (Glu) resulted in formation of [14C]gamma-aminobutyric acid (GABA) and L-[14C]aspartic acid (Asp), but not [14C]Pro. On the other hand, L-ornithine (Orn) was found to be an effective precursor of Pro. Incubation of [3H]Orn with the sonicated mouse brain P2 fraction not only resulted in the extensive formation of [3H]Pro, but also yielded [3H]Glu and [3H]GABA. Almost 50% of [3H]Orn consumed was converted into [3H]Pro. In vitro addition of Pro (0.1-1 mM) inhibited the formation of [3H]Pro from [3H]Orn to the extent of 40-75%, while increasing the accumulations of [3H]Glu and [3H]GABA without affecting the consumption of [3H]Orn. These results clearly demonstrate that a potential site exists for negative feedback inhibition in Pro biosynthesis from Orn in the mammalian central nervous system.

Animals↗
PubMed1982

The cytoarchitecture of GABAergic neurons in rat spinal cord.

Glutamic acid decarboxylase (GAD), the enzyme that synthesizes the transmitter gamma-aminobutyric acid (GABA), has previously been localized within synaptic terminals in rat spinal cord by immunocytochemistry. In the present study, GAD was localized within the somata and dendrites of GABA neurons following colchicine injections into rat lumbar spinal cord. All regions of the spinal gray matter contained GAD-positive somata except the motoneuron pools (lamina IX). GAD-positive somata also were observed in the ependymal layer and in the dorsolateral funiculus. Small GAD-positive somata, averaging 9 X 13 micrometer in size, were located in laminae I-III, and the size of GAD-positive somata increased for cells located in progressively more ventral laminae, reaching a maximum in lamina VII where somal size averaged 12 X 19 micrometer. Lamina I contained two classes of GAD-positive cell bodies; lenticular shaped, intermediate size neurons that were reminiscent of stalked cells, and a smaller cell type that was elongated in the sagittal plane. GAD-positive somata in laminae II and III had the size and position of islet cells. In laminae IV-VI, GAD-positive somal profiles averaged 12 X 17 micrometer in size. Lamina IV neurons were concentrated along laminar edges, while those in laminae V and VI were distributed more homogeneously. In lamina VIII, GAD-positive cell bodies appeared in groups of 3 or 4 and were smaller than those in lamina VII. Lamina X contained GAD-positive somal profiles averaging 12 X 16 micrometer in size. In the ependymal layer, there were two types of cerebrospinal fluid (CSF)-contacting neurons that contained GAD; one spherical and the other elongated. Both types sent extensions into the central canal where these processes expanded into 4-5 micrometer-wide end bulbs. CSF-contacting cells with sizes and shapes similar to the GAD-positive ones were seen to receive synapses in electron micrographs. The widespread distribution of GABA neurons in spinal cord was suggestive of diverse functions for these cells, encompassing conventional synaptic roles and, perhaps, an involvement in hormonally modulated communication via GABAergic, CSF-contacting neurons.

Animals↗
PubMed1982

Purification of choline acetyltransferase from Drosophila melanogaster.

Choline acetyltransferase (EC 2.3.1.6) from Drosophila melanogaster (Canton S, wild type) was purified 12,500-fold to a final specific activity of 500 mumol min-1 mg protein-1. The purification used homogenized fly heads and consisted of polyethylene glycol precipitation, DEAE-Bio-Gel A chromatography, Octyl-Sepharose chromatography, and affinity chromatography using solid phase Green A-agarose. The molecular weight of the native enzyme, as determined by molecular exclusion chromatography, was approximately 67,000 daltons. The final enzyme preparation showed two major protein bands at 67,000 and 54,000 daltons on polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS). After molecular exclusion chromatography, both SDS gel bands were present in the single symmetrical peak that contained the enzyme activity. Two-dimensional tryptic peptide maps prepared from the individual SDS gel bands indicated that they have very similar primary structures. Both SDS gel bands were precipitated by two different monoclonal antibodies derived against Drosophila choline acetyltransferase activity. The structural and immunological relatedness of the two SDS gel bands indicates that the enzyme is essentially homogeneous and that, in the native state, it may consist of more than one polypeptide chain.

Amino Acid Sequence↗
PubMed1982

Liver disease in Felty's syndrome.

Eighteen patients with Felty's syndrome were examined prospectively for the presence of hepatic abnormalities. Twelve patients had abnormal liver histologic features: five with nodular regenerative hyperplasia and seven with portal fibrosis or abnormal lobular architecture. Only seven of the 12 had abnormal liver chemistry results. Four of the 12 had portal hypertension, and three bled from esophageal varices compared with one of six with normal histologic features. When patients with normal and abnormal liver histologic findings were compared, there was no difference in clinical, serologic, or extra-articular manifestations between the two groups, although there was a tendency for the patients with abnormal findings to have a higher incidence of vasculopathy. All patients with Felty's syndrome should be screened for hepatic abnormalities and portal hypertension as they have an increased likelihood of bleeding from esophageal varices.

Adult↗
PubMed1982

A new synaptosomal biosynthetic pathway of glutamate and GABA from ornithine and its negative feedback inhibition by GABA.

In sonicates of mouse brain synaptosomes, we demonstrated that gamma-aminobutyric acid (GABA) can be formed when L-ornithine (Orn) through L-glutamic acid (Glu), but not through putrescine (Put). Incubation of these sonicates with [3H]ORN yielded not only [3H]Glu and [3H]L-proline (Pro) but also produced [3H]GABA from the [3H]Glu. Formation of each of these three major amino acids from [3H]Orn was strongly inhibited by the addition of GABA (1-5 mM). The likely enzymatic site of this negative feedback inhibition by GABA appeared to be ornithine delta-aminotransferase (OAT). A radiometric procedure was employed to study the effects of the three amino acids cited above and of others found in the free form in brain on the activity of a 30-fold-purified OAT from rat brain. Enzyme activity was measured in the presence of low concentrations of Orn, such as might occur in vivo. OAT was inhibited by GABA to a considerably greater extent than by Glu, L-glutamine, or Put; no inhibition was found with Pro, glycine, aspartarte, taurine, or beta-alanine. The inhibition of GABA was competitive with Orn. These results clearly show that one of the molecular mechanisms underlying the negative feedback inhibition of synaptosomal GABA biosynthesis from Orn is a competitive inhibition by GABA of the brain OAT activity that is responsible for the formation of L-glutamic-gamma-semialdehyde in equilibrium with L-delta 1-pyrroline-5-carboxylic acid from Orn. Thus, the results suggest that GABA may play an important role in restricting the metabolic flow from Orn to Glu and thence to GABA. It is confirmed that L-canaline (delta-aminooxy-L-alpha-aminobutyric acid) is a potent and specific inhibitor of brain OAT whereas much weaker inhibition was observed with two other carbonyl-trapping agents, aminooxyacetic acid and hydrazine.

3-Mercaptopropionic Acid↗
PubMed1982

Characterization of glutamic acid decarboxylase activity in cerebral blood vessels.

Glutamic acid decarboxylase activity associated with cerebral blood vessels appears to be part of a specific cerebrovascular system involving gamma-aminobutyric acid. This activity was characterized kinetically and pharmacologically and compared with that in brain and several nonneuronal tissues. Formation of gamma-aminobutyric acid from [14C]glutamate was measured in a soluble extract of pia-arachnoid blood vessels isolated from bovine brain. The vascular activity was like brain glutamate decarboxylase in that it required pyridoxal phosphate, was completely inhibited by aminooxyacetic acid, and had a similar affinity for glutamate. Cerebrovascular decarboxylase activity differed, however, from brain decarboxylase in that it was less sensitive to sulfhydryl reagents, was stimulated by 3-mercaptopropionic and cysteic acids, and was competitively inhibited by cysteine sulfinic acid. The glutamate decarboxylase activity of the cerebral vessels was similar to that in renal cortex and mesenteric blood vessels in its responses to sulfhydryl reagents and 3-mercaptopropionic acid. These findings are consistent with previous suggestions of a nonneuronal form of the enzyme and offer the possibility that synthesis of gamma-aminobutyric acid in cerebral blood vessels can be manipulated independently from that in neuronal tissue.

Animals↗
PubMed1982

gamma-Aminobutyric acid system in cardiovascular and cerebrovascular function.

gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate CNS. Recent experiments have begun to delineate the roles of GABA neurons in control of both central sympathetic and parasympathetic outflows to the heart and vasculature. It is suggested that incoordination in these regions resulting from inadequate function of GABA neurons could lead to cardiac arrhythmias and large fluctuations in blood pressure that would predispose to cardiac and vascular damage. A role for GABA in cerebrovascular function is supported by the observation that specific GABA receptors and GABA-related enzymes are associated with cerebral blood vessels. It is suggested that a non-neural, indigenous GABA system in cerebral blood vessels is involved in the control of cerebrovascular tone. GABA probably plays an important role in the complex processes involved in normal regulation of cerebral circulation and its dysfunction.

4-Aminobutyrate Transaminase↗
PubMed1981

Dose-conductance relationships for GABA agonists and the effect of uptake inhibitors in crayfish stretch receptor neurons.

The interaction of GABA (gamma-aminobutyric acid) and structurally-related compounds with postsynaptic GABA receptors was studied quantitatively by measuring receptor-mediated increases in membrane input conductance in isolated crayfish stretch receptor neurons (SRN). The following compounds, in order of decreasing potency, were effective agonists: muscimol greater than GABA greater than isoguvacine greater than (-)gamma-amino-beta-hydroxybutyric acid greater than beta-gu anidinopropionic acid greater than 3-aminopropanesulfonic acid greater than (+)gamma-amino-beta-hydroxybutyric acid greater than isonipecotic acid greater than THIP. A highly significant correlation was found between the log potencies for GABA agonists that were obtained in the SRN and those obtained in our laboratory using mammalian GABA receptor binding assays. Hill plot analyses of the log concentration-conductance data from the SRN indicated a Hill slope (nH) of approximately 2 for all agonists except GABA and guanidinopropionic acid (nH greater than 2), two compounds known to be actively accumulated by cellular GABA uptake processes. Nipecotic acid, guvacine, and L-alpha, beta-diaminopropionic acid, blockers of GABA uptake processes, had essentially no effect by themselves on the SRN membrane input conductance at concentrations up to 5 mM, however, they potentiated the effects of sub-maximal concentrations of GABA and decreased the steepness of the log concentration-conductance curve, and consequently nH, for GABA. The effects of muscimol, however, were not affected. When the influence of uptake processes was considered, it appeared that all agonists tested acted by the same cooperative mechanism which required at least two molecules of agonist to activate a receptor-ionophore unit.

Animals↗
PubMed1981

Specific cerebrovascular localization of glutamate decarboxylase activity.

Glutamate decarboxylase (GAD) activity and GABA levels, determined with a [3H]muscimol radioreceptor assay, were found to be significantly higher in cerebral blood vessels from the piaarachnoid membrane as compared to extracranial vessels (aorta, mesenteric and femoral arteries, and vena cava). A cerebrovascular localization for GABA and GAD is consistent with earlier studies suggesting that an indigenous GABA system is involved in cerebral vascular function.

Animals↗
PubMed1981

GABAergic amacrine cells in rat retina: immunocytochemical identification and synaptic connectivity.

GABAergic neurons have been identified in light and electron microscopic preparations of rat retina by an immunocytochemical localization of the GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD). GAD-positive neuronal somata are found only in the inner and middle parts of the inner nuclear layer, and GAD-positive neuronal terminals are observed exclusively within the inner plexiform layer (IPL) and the outermost part of the ganglion cell layer. Dense aggregations of GAD-positive terminals alternate with less dense zones to form a lamination of the IPL. GAD-positive terminals contain pleomorphic synaptic vesicles and are the presynaptic elements of conventional synapses onto bipolar and amacrine cell processes, as well as onto the somata and dendrites of ganglion cells. In addition, GAD-positive terminals are postsynaptic to unstained bipolar terminals and are components of synaptic dyads where they occasionally appear to form reciprocal synapses with the bipolar terminals, and serial with unstained amacrine processes. Probable synaptic contacts between adjacent GAD-positive terminals also have been observed. Most of the synaptic input to GAD-positive terminals comes from bipolar cells, while the small remaining input mainly comes from other GAD-positive terminals. The synaptic output to GAD-positive terminals is greatest to bipolar cells, followed in decreasing order by GAD-negative amacrine cells, ganglion cells, and other GAD-positive cells. The total synaptic output of GAD-positive cells appears to be more than twice as great as the total input of these cells. The location of GAD-positive somata, the distribution of GAD-positive terminals, and the synaptic relationships formed by these terminals all indicate that amacrine cells are the only GABAergic neurons in rat retina. Our observations also indicate that not all amacrines are GABAergic and suggest that GABAergic neurons may be limited to a narrow field subclass of amacrine cell. The findings concerning the synaptic connections of GABAergic amacrines suggest that such cells are the first link in several divergent pathways from bipolar to ganglion cells and that they probably serve more than one function since they feed synaptic activity forward directly upon ganglion cells as well as back upon bipolar cells.

Animals↗
PubMed1981

Per rectal ultrasound in the investigation of prostatic disease.

Primary prostatic disease is usually assessed by digital palpation of the prostate. This method lacks objectivity and has been shown to be inaccurate, especially in the staging of primary prostatic cancer. This paper describes the investigation of 200 subjects using per rectal ultrasound. Of 70 patients with histological evidence of carcinoma of the prostate, 96% were correctly diagnosed ultrasonically and 87% correctly diagnosed by digital palpation. Of the 37 patients with ultrasonic evidence of a capsular breach, only 65% were diagnosed as such by digital palpation. A study of 10 cadaver specimens confirmed the accuracy of per rectal ultrasound as a technique for staging primary prostatic cancer . The ultrasonic appearances of the prostate, seminal vesicles and bladder base are described. Per rectal ultrasound is acceptable to patients, and its use is recommended in all cases where accurate assessment of primary prostatic cancer is required.

Adult↗
PubMed1981

A comparison between digital examination and per-rectal ultrasound in the evaluation of the prostate.

Three hundred and fifty-two patients have been examined by per-rectal ultrasound and histological confirmation of the diagnosis was obtained in 242 cases. Per-rectal ultrasound compared favourably with digital palpation both as a method of diagnosing prostatic cancer and also as a method of staging a primary tumour. Confirmation of the accuracy of this technique as a method of staging was gained by a study involving the use of cadaver material. Repeat examinations on patients with prostatic carcinoma have shown that per-rectal ultrasound is an ideal method for monitoring response of the primary tumor to treatment.

Humans↗
PubMed1981

Glutamic acid decarboxylase and gamma-aminobutyric acid in Huntington's disease fibroblasts and other cultured cells, determined by a [3H]muscimol radioreceptor assay.

A sensitive and reproducible [3H]muscimol radioreceptor assay was developed for measuring low levels of both glutamic acid decarboxylase activity and gamma-aminobutyric acid. By using this technique, endogenous gamma-aminobutyric acid and glutamic acid decarboxylase activity were detected in two rat neuroblastomas, B35 and B50, a human medulloblastoma cell line, TE671, and cultured human skin fibroblasts. Glutamic acid decarboxylase activities and gamma-aminobutyric acid levels were compared for human skin fibroblasts obtained from patients with Huntington's disease and their controls in a well-controlled, blind study. However, no significant difference was found to either measure between Huntington and control cells. Glutamic acid decarboxylase activity was relatively low in all cell types examined except for the TE671 cells, which had more than four times the activity found in the other cells. This human medulloblastoma cell line appears to be a good model for studying gamma-aminobutyric acid metabolism and the control of glutamic acid decarboxylase expression.

Carboxy-Lyases↗