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Biomedical subjects

A Keller

Publications and source records attributed to A Keller.

At least 181 records · Page 10Linked to original sources
PubMed1991

Prediction of hepatitis C virus infectivity in seropositive Australian blood donors by supplemental immunoassays and detection of viral RNA.

The prevalence of anti-hepatitis C virus (HCV) enzyme immunoassay (EIA)-positive in 167,511 Australian volunteer blood donors from Adelaide, Melbourne, Perth, and Sydney was 0.78%. One thousand two-hundred and eighteen EIA-positive serum samples were assessed by supplemental tests including a blocking EIA and two peptide EIAs corresponding to major epitopes of the HCV C-100-3 antigen. Seven hundred and eighteen samples (59%) were negative by supplemental testing; no evidence of reactivity with other HCV gene products or HCV RNA detected by cDNA polymerase chain reaction was found in selected samples from this group. In contrast, of 43 samples randomly selected from 400 samples (32.8%) positive by supplemental testing, 88% were reactive with HCV 33-C or core antigens and 52% contained HCV RNA, suggesting contact with HCV and infectivity of most donors in this group. Most samples equivocal by supplemental testing reacted only with C-100 and not with other HCV antigens when tested by dot immunoblot assay. Only 21% had detectable HCV RNA. The battery of assays used in this study indicated that approximately 32% of HCV EIA repeatably reactive serum samples were serologically related to HCV, corresponding to a 0.25% prevalence of potentially infectious donors.

Adult↗
PubMed1991

Human immunodeficiency virus antibodies in sera of Australian blood donors: 1985-1990.

OBJECTIVE: To describe the results of human immunodeficiency virus type 1 (HIV-1) antibody testing of blood donations in Australia. DESIGN: Blood transfusion services tabulated the number of HIV-1 antibody tests carried out on blood donations and the number of donations found to be positive, from 1985 to 1990. SETTING: All blood transfusion services in Australia. PARTICIPANTS: All donors of blood in Australia from 1 May 1985 to 31 December 1990. OUTCOME MEASURES: The proportion of blood donations found to have HIV-1 antibody, according to State or Territory, year of donation and, when available, age, sex and donation status (repeat or first-time) of the donor. RESULTS: To the end of December 1990, 5,367,970 donations had been tested for HIV-1 antibody, and 46 were found to have the antibody, giving an overall prevalence rate of 0.86 per 100,000 donations. The highest rate was recorded in New South Wales, followed by Western Australia, and four of eight Australian States and Territories reported no donors with HIV-1 antibody. There has been no clear trend with time, but the rate is about 20% higher for 1989-1990 than for 1985-1986. Of donors found to have HIV-1 antibody, 67% were male and 33% female, and 41% reported no known or potential exposure to HIV-1 other than heterosexual contact. Among blood donors in two major Australian cities, the overall prevalence of HIV antibody was higher in those who were male, younger, and first-time donors. There has been a recent increase in the number of blood donors with HIV-1 antibody who were women reporting heterosexual contact as their only potential exposure. CONCLUSION: The rate of HIV-1 antibody in Australian blood donations remains very low and shows no clear temporal trend, but specific donor characteristics define higher rates of antibody prevalence.

Adult↗
PubMed1991

The pulmonary surfactant protein C (SP-C) precursor is a type II transmembrane protein.

Human pulmonary-surfactant-associated protein C (SP-C) is an extremely hydrophobic peptide comprising 34-35 amino acids. It is involved in the reduction of surface tension at the air/liquid in the lung. In order to understand the mechanism by which this molecule is generated from its 197-amino-acid-residues-long precursor and secreted into the alveolar space, we analysed the biosynthesis and processing of this precursor in an 'in vitro' system. Our results show that the SP-C precursor is a 21 kDa integral membrane protein. It is anchored in the membrane by a hydrophobic domain that comprises the 20-amino-acid-residues-long hydrophobic core of the mature SP-C peptide. The N-terminus remains in the cytoplasm, which leads to a type II transmembrane orientation of the precursor. Membrane integration occurs in a signal-peptidase-independent manner. The hydrophobic domain acts as both signal sequence and membrane-anchoring domain. We suggest that correct membrane insertion of the SP-C precursor, which is strictly dependent on the hydrophobic-amino-acid sequence represented by the hydrophobic core of the mature SP-C, is itself a prerequisite for further processing and intracellular transport of the mature SP-C.

Animals↗
PubMed1991

Minimal stimulus parameters and the effects of hyperpolarization on the induction of long-term potentiation in the cat motor cortex.

The aim of the research program of which the present work is a part is to understand the neural mechanisms involved in motor learning and memory. One of the mechanisms postulated to be involved in this process is the induction of long-term potentiation (LTP) in the motor cortex. LTP can be induced in motor cortical neurons by tetanic stimulation of their afferents from the somatosensory cortex. In the present study, the effects of different stimulating parameters on the induction of LTP were examined, using in-vivo, intracellular recordings from anesthetized cats. The expression of LTP was documented by measuring the amplitude and rise-time of excitatory postsynaptic potentials (EPSPs) before and after tetanic stimulation. The minimal tetanic stimulation capable of systematically inducing LTP was found to consist of a train of stimuli at 50 Hz, 5 s. Shorter trains of stimulation produced only a short-lasting, transient potentiation. In different cells, identical stimulation parameters resulted in different degrees of potentiation of synaptic responses. Following all the stimulation trains examined, EPSP amplitudes were transiently depressed before reaching potentiated levels. The duration of this depression was directly correlated with the duration and the frequency of the tetanic stimulation. In all the cells in which LTP was induced, the variability in the amplitudes of potentiated EPSP was significantly greater than that of control EPSP amplitudes. Hyperpolarization of the postsynaptic cell, during the delivery of the tetanic stimulation, inhibited the induction of LTP. These phenomena are discussed in relation to the postulated mechanisms of LTP induction in the cortex.

Afferent Pathways↗
PubMed1991

Neuronal mechanisms of motor learning in mammals.

Neural mechanisms subserving the acquisition of new motor skills are discussed in this article. Motor learning is defined, in this context, as the acquisition of novel motor skills. It is proposed that complex motor skills are acquired through a process of segmental motor learning, in which movement segments are formed, and retrieved for the execution of the learned skill. Individual movement segments are created by modulating neural activity in loop circuits that link the motor cortex and the periphery. This neural modulation occurs through synaptic plasticity in the motor cortex. Increase of synaptic efficacy in existing neural circuits, in the form of long-term potentiation (LTP), is proposed to be involved in earlier stages of motor learning. It is suggested that the retention of motor skills involves formation of new synapses.

Animals↗
PubMed1991

Characterization of the transcriptional trans activator of human foamy retrovirus.

The human foamy viruses, or spumaviruses, a distinct subfamily of complex human retroviruses, remain poorly understood both in terms of their pathogenic potential and in terms of the regulatory mechanisms that govern their replication. Here, we demonstrate that the human spumaretrovirus shares with other complex human retroviruses the property of encoding a transcriptional trans activator of the homologous viral long terminal repeat. This regulatory protein is encoded by the viral Bel-1 open reading frame and is localized to the nucleus of expressing cells. The Bel-1 trans activator is shown to function effectively in cell lines derived from human, simian, murine, and avian sources. The viral target sequence for Bel-1 has been mapped 5' to the start of viral transcription and is therefore likely to be recognized as a DNA sequence. Our results further suggest that the mechanism of action of the Bel-1 protein may be distinct from those reported for the transcriptional trans activators encoded by members of the other human retroviral subfamilies.

Cell Line↗
PubMed1991

Long-term potentiation of thalamic input to the motor cortex induced by coactivation of thalamocortical and corticocortical afferents.

1. Intracellular recordings were obtained from neurons in the motor cortex (MCx), in which excitatory postsynaptic potentials (EPSPs) were evoked by microstimulation of the somatosensory cortex (SCx) and the ventrolateral nucleus (VL) of the thalamus. The effects of combined tetanic stimulation of SCx and VL on the amplitudes of these EPSPs were studied. 2. Amplitudes of both corticocortical (CC) and thalamocortical (TC) EPSPs were potentiated after combined tetanic stimulation. This potentiation occurred exclusively in neurons that were located in the superficial layers (II/III) and that received direct input from both the SCx and VL, with both inputs synapsing in close proximity to each other. In all cases, the potentiation lasted until the electrode went out of the cell (21 +/- 25 min, mean +/- SD) the longest being 90 min. We therefore refer to this potentiation as long-term potentiation (LTP). 3. Tetanic stimulation of the thalamus only did not produce LTP in neurons receiving direct input from the VL. 4. LTP was not induced in either CC or TC EPSPs in neurons located in layer V and/or in neurons receiving long-latency CC EPSPs. 5. It is concluded that TC input from the VL to the MCx is potentiated only when coactivated with the CC input from the SCx.

Animals↗
PubMed1990

Identification of neurons producing long-term potentiation in the cat motor cortex: intracellular recordings and labeling.

Intracellular, in vivo recordings were used to identify and subsequently to label neurons in the cat motor cortex in which long-term potentiation (LTP) was induced. Thirty-nine motor cortical neurons that produced excitatory postsynaptic potentials (EPSPs) in response to microstimulation in areas 1-2 (SI) or in area 5a (SIII) were studied. Amplitudes of EPSPs produced in response to test stimulation (1 Hz) were recorded before and after tetanic stimulation (200 Hz, 20 seconds). In 25/39 cells (64%), EPSP amplitudes were significantly increased following the tetanic stimulation (65 +/- 51% average increase), and remained at the potentiated level as long as stable recordings could be maintained (20 +/- 18 minutes, maximum = 90 minutes). LTP was induced exclusively in cells that produced monosynaptic EPSPs in response to area 1-2 or area 5a stimulation. Of the 39 analyzed cells, 13 were labeled by intracellular injections of 5% biocytin. Neurons in which LTP was induced included both pyramidal and nonpyramidal cells and were located exclusively in layers II or III of the motor cortex; cells in deeper cortical layers were not potentiated. These findings indicate that various corticocortical inputs can increase the efficacy of synaptic transmission in a subset of motor cortical neurons. We propose that this plasticity in synaptic transmission constitutes one of the bases of motor learning and memory.

Animals↗
PubMed1990

Immunohistochemical localisation of nerve growth factor in a subpopulation of chick spinal ganglion neurons.

We have previously isolated and sequenced the chicken nerve growth factor (NGF) gene and now, from the deduced amino acid sequence, selected and produced peptides suitable for use as antigens. Anti-sera raised against these peptides inhibit the biological activity of a partially purified preparation of native chicken NGF and, when used in immunocytochemical studies, allow the visualisation of sensory neurons accumulating endogenous NGF. Immunoreactive cells form a distinct population of small neurons which may correspond to the well-described neurons generated in the dorsomedial area of spinal ganglia. We conclude that two subpopulations of neurons exist within dorsal root ganglia, whose requirements for, and use of, NGF may be quite distinct.

Amino Acid Sequence↗
PubMed1990

Formation of new synapses in the cat motor cortex following lesions of the deep cerebellar nuclei.

The effects of unilateral lesions of the deep cerebellar nuclei on the corticocortical (CC) projection from the somatosensory to the motor cortex were studied in adult cats, utilizing electrophysiological and electron microscopical methods. Axon terminals in the motor cortex belonging to CC afferents were labeled by degeneration induced by lesions of the somatosensory cortex; neurons in the motor cortex were labeled by the Golgi/EM method. In each cat, data from the motor cortex (MCx) contralateral (experimental) and ipsilateral (control) to the cerebellar lesion were compared. Cerebellar lesions produced marked motor deficits, which receded gradually and disappeared after 30 to 40 days. Subsequent lesions of the somatosensory cortex (area 2) contralateral to the cerebellar lesions resulted in the reappearance of the cerebellar symptoms. The number of CC synapses per unit area in experimental MCx was significantly higher than in control MCx. The increase in the number of CC synapses was apparent throughout layers II-V of the MCx, but was most prominent in layers II/III. The increase in the number of CC synapses in experimental MCx was due mainly to an increase of axon terminals synapsing with dendritic spines belonging to pyramidal neurons. In comparison, the numbers and spatial distribution of CC synapses with aspinous, nonpyramidal neurons from both experimental and control MCx were similar. Field potentials in the experimental MCx, evoked by stimulation of area 2, were altered following cerebellar lesions. In experimental MCx, the polarity of the early component of the field potentials reversed at cortical depths corresponding to layers II-III, whereas this reversal was not observed in control MCx. These findings suggest that lesions of the cerebellar nuclei induced sprouting of axon terminals in the MCx to establish a new function. The results provide the first anatomical evidence for the generation of new synapses in the adult CNS which is not induced by elimination of existing synapses.

Animals↗
PubMed1990

Emergency resection and primary anastomosis for sigmoid volvulus in an African population.

We report 30 patients who underwent operation for sigmoid volvulus during a two year period at the St. Francis Hospital, Tanzania. Five patients were managed initially by non-operative reduction. They all underwent elective resection of the sigmoid during the same hospitalisation with one operative death. Twenty-five patients underwent emergency laparotomy, 12 of them having gangrenous bowel. Resection was carried out in 21 patients, 18 of whom had a primary anastomosis without protective colostomy. In spite of the high incidence of gangrenous bowel (57%), there was only one operative death (5%) in the 18 patients. Initial management of sigmoid volvulus should consist of non-operative attempts at reduction provided that the bowel is viable. Elective resection should be performed during the same hospitalisation. Where non-operative therapy fails or bowel gangrene is present, emergency laparotomy has to be carried out. In the authors' experience resection of the sigmoid and primary anastomosis can be performed safely in this situation.

Adolescent↗
PubMed1990

The surgical implications of purpura fulminans.

Purpura fulminans is an uncommon catastrophic syndrome that occurs in children, typically one to four weeks after a seemingly benign infectious process. The child usually presents with a high fever, purpuric ecchymosis, hypotension, disseminated intravascular coagulation, and gangrene of the extremities. We have recently treated six children, whose mean age was 22 months; three were male and three were female. Five of the six had a change of mental status upon initial examination. Their mean temperature was 104 degrees F. All six children had purpuric involvement of their extremities; three had involvement of their hands, two had involvement of their faces, and two had involvement of their trunks. All had absent palpable pulses and sluggish capillary refill in the involved hands and feet. Two patients died shortly after admission as a result of severe end-stage sepsis. The platelet counts in these two patients, and the white blood cell counts were markedly depressed. The mean platelet count of the survivors was 370,000 and the mean white blood cell count was 25,000. Lumbar punctures were positive for bacterial meningitis in five patients and viral meningitis in one patient. All patients were treated with intravenous heparin. Of the four survivors, two lost significant tissue and required multiple plastic reconstructive procedures, and two improved on heparin alone with no tissue loss. In addition to systemic support and intravenous antibiotics, the mainstay of treatment is one of immediate heparinization and a continuous heparin drip. Heparin prevents subsequent small vessel thrombosis and limits tissue loss due to ongoing purpura. Conservative management of the purpuric lesions is the treatment of choice until final demarcation occurs.

Anti-Bacterial Agents↗
PubMed1990

Long-term potentiation in the cat somatosensory cortex.

Intracellular, in-vivo recordings were used to identify neurons in the cat somatosensory cortex in which long-term potentiation (LTP) was induced. Amplitudes of EPSPs produced by microstimulation in the motor cortex (area 4 gamma) were recorded before and after tetanic stimulation (200 Hz, 20 s). In 8/13 cells (62%), EPSP amplitudes increased significantly following the tetanic stimulation. LTP was induced exclusively in cells which produced monosynaptic EPSPs. Six of these cells were labeled by intracellular injections of biocytin. All the cells in which LTP was induced were pyramidal neurons, and were located exclusively in layers II or III of the somatosensory cortex; cells in deeper cortical layers were not potentiated. These data substantiate our previous findings demonstrating LTP in corticocortical pathways and suggest that these pathways play an important role in cortical synaptic plasticity.

Animals↗
PubMed1990

The saddle prosthesis for salvage of the destroyed acetabulum.

We report the 12 to 74 month results of our mark I saddle prosthesis after its use as a salvage device for gross loss of pelvic bone stock in 76 patients with failed hip arthroplasties. The implant transmits load between iliac bone and bare polish chrome-cobalt. Our clinical and radiological results indicate that a useful and stable articulation can be achieved in most cases, provided that continued deep infection can be avoided. The appearance of radiological sclerosis at the bearing site in successful cases seems to indicate that significant late migration will not occur. Based on our experience with the mark I prosthesis we have designed and developed a mark II model which has freedom of axial rotation of the saddle. Our early results in 40 cases show a significant improvement over the results which could have been predicted for the mark I device.

Acetabulum↗
PubMed1990

Long-lasting facilitation of pyramidal tract input to spinal interneurons.

The purpose of this study was to determine whether long-term changes in synaptic efficacy can be induced in the pyramidal tract (PT). Tetanic stimulation of the PT induced long-term facilitation of PT input to spinal cord neurons. In contrast, tetanic stimulation of the pyramidal tract did not alter the efficacy of synaptic inputs of PT cells' intracortical axon collaterals to other cortical neurons. These findings suggest that the PT participates in motor learning by modulating the excitability of spinal cord neurons. The results also indicate that induction of LTP in the PT is dependent on postsynaptic mechanisms.

Animals↗