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Biomedical subjects

H E Jones

Publications and source records attributed to H E Jones.

At least 91 records · Page 5Linked to original sources

Lipid composition of subcellular membranes from larvae and prepupae of Drosophila melanogaster.

Subcellular membranes were analyzed for their lipid composition and protein content at two developmental points representing the third instar wandering larvae and prepupal stages of Drosophila. At both stages, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were the major constituents with phosphatidylinositol (PI), phosphatidylserine (PS), diphosphatidylglycerol (DPG) and phosphatidic acid (PA) being relatively minor components. In total homogenates and in the nuclear-enriched fraction there was no significant difference in the phospholipid composition of the wandering larvae and prepupae. In mitochondria only a significant increase in the minor component PS was observed in the prepupae. In lysosomal membranes on the other hand, the relative abundance of the major components PE and PC increased in the prepupae although the molar ratios of the two lipids remained almost constant. The fatty acid composition of the phospholipids remained virtually unchanged in all of the fractions examined, including the lysosomes, and there was no evidence of lipid peroxidation. With regard to cellular degeneration and the involvement of lysosomes, we conclude that mechanisms other than gross modification of the lipid and/or lipid/protein ratio of their membranes are involved in the liberation of the acid phosphatase contents.

Animals↗

The action of the putative neurotransmitters N-acetylaspartylglutamate and L-homocysteate in cat dorsal lateral geniculate nucleus.

1. We have examined the actions and pharmacology of two putative optic nerve transmitters, N-acetylaspartylglutamate (NAAG) and L-homocysteic acid (L-HCA), in the feline dorsal lateral geniculate nucleus (dLGN). We compared the responses obtained to iontophoretic application of these substances with those elicited by visual stimulation and application of specific N-methyl-D-aspartate (NMDA) and non-NMDA receptor agonists. The relative effects of the selective NMDA antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and the selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were tested on these responses. 2. There was a pronounced contrast between the influence of iontophoretically applied NAAG and L-HCA on dLGN cells. Iontophoretic application of NAAG [ejection current range 75-200 nA (mean 125 nA)] evoked either no effect (17/37), or very weak and sluggish excitatory (16/37) or inhibitory (4/37) effects. Conversely, L-HCA application [current range 25-136 nA (mean 67 nA)] elicited brisk and powerful excitatory responses (32/32) that were comparable with those produced by visual stimulation and iontophoresis of NMDA, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). 3. Responses to L-HCA were selectively antagonized by application of the NMDA receptor antagonist CPP but were generally much less affected by the non-NMDA receptor antagonist CNQX. The weak and inconsistent responses to NAAG were not compatible with an evaluation of antagonist effects. 4. CPP application at dose levels selective for NMDA with respect to kainate and AMPA did not exert equal effects on L-HCA and NMDA. Whereas the mean responses to L-HCA were reduced to 32% of control for Y cells and 21% for X cells, those to NMDA were 11 and 11%, respectively. However, the level of reduction of the visual response for X and Y cells was very similar to that of L-HCA, visual responses being reduced to 35 and 22% of control for Y and X cells. 5. CNQX application reduced the visual response level of Y cells to 64% of control and that of X cells to 65%. The mean level for the L-HCA response of Y cells was 106% of control; the mean for X cells, 79%, was substantially below control. The responses to kainate and AMPA were reduced to a much greater extent. 6. The data suggest that it is unlikely that NAAG is the optic nerve transmitter.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗

The length-response properties of cells in the feline dorsal lateral geniculate nucleus.

1. In this report we have systematically examined the length-response properties of a large population of cells recorded in the cat dorsal lateral geniculate nucleus (dLGN). The responses of A laminae dLGN cells were assessed by the use of conventional single-unit extracellular recording techniques. The length preference of these cells was examined by plotting multihistogram length tuning curves to moving bars of light. Bar length was randomized in an interleaved fashion under computer control. The other stimulus parameters were standardized within the limits of those routinely used to assess the length preference of cortical cells. 2. The majority of cells (186/198), whose length-response properties are considered in detail in this report, exhibited strong centre-surround antagonism and a mean degree of length tuning equivalent to, or exceeding, that seen in most cortical hypercomplex cells (71 +/- 1.18%, S.E.M., n = 186). 3. The values for X cells (74 +/- 1.41%, S.E.M., n = 100) and Y cells (67 +/- 2.13%, S.E.M., n = 74) were very similar, as were those of the on-centre (71 +/- 1.51%, S.E.M., n = 123) and off-centre (71 +/- 1.85%, S.E.M., n = 63) subgroups. 4. A distinct subgroup of the Y cell population was identified. These comprised the remaining twelve out of the 198 cells examined and their response properties were sufficiently distinct to merit classification as a discrete subpopulation of cells which we have termed nlY cells. They were characterized by very poor levels of both centre-surround antagonism and length tuning, and were most frequently encountered close to laminar borders. Their response properties have been described in detail elsewhere. 5. We quantitatively compared the degree of length tuning seen with moving bars to the strength of centre-surround antagonism assessed with flashing spots. The degree of length tuning did not necessarily follow the level of centre-surround antagonism. 6. Examination of the effects of unilaterally extending bar length to one or other side of the receptive field did not reveal the type of asymmetry frequently seen in cortical hypercomplex cells. 7. The high degree of length tuning seen in this study underlines the potential importance of geniculate response properties to the generation of the length-response properties of cortical hypercomplex cells. The findings are discussed in relation to the synaptic mechanisms contributing to the generation of length tuning at subcortical and cortical levels.

Animals↗

A specific subgroup of non-length tuned relay cells in the feline dorsal lateral geniculate nucleus.

Length tuning was first described for the "hypercomplex cell category" in the visual cortex. However it has subsequently become apparent that cells in the dorsal lateral geniculate nucleus (dLGN) also exhibit a high degree of length tuning and that for the majority of the population this matches or exceeds that associated with cortical hypercomplex cells (Cleland et al. 1983; Jones and Sillito 1987). In this paper we describe a distinct subpopulation of dLGN Y cells that lack length tuning. These cells were also characterised by poor centre-surround antagonism, and tended to be located close to laminar borders. They appeared to constitute 25% of the Y cell population. Following recent evidence showing relay cells to be powerfully excited by acetylcholine, and inhibitory interneurones to be inhibited, we have examined the responses of these non-length tuned cells to iontophoretic application of acetylcholine. Their brisk excitatory responses suggest that these cells are in fact relay cells. Their presence raises the possibility of a discrete non-length tuned component to the geniculate input to the cortex, and has potentially important implications for the way in which synaptic processes contributing to the length tuning profiles of visual cortical cells are modelled.

Acetylcholine↗

Problems of resistant dermatophytes.

Recalcitrant fungal infections are defined as infections that are difficult or impossible to eradicate despite seemingly adequate treatment with appropriate oral or parenteral antibiotics. Relative or absolute microbial resistance is only one of the many causes of recalcitrance. Others include failure of the patient to comply with the prescribed treatment regimen, drug degradation in the liver, drug-drug interactions, reabsorption or washout of the drug from the stratum corneum, and failure of the drug to reach the stratum corneum. Excretion in the eccrine sweat is the principal pathway by which griseofulvin and ketoconazole, the two currently available oral antifungal agents, are delivered to the stratum corneum. Measures that promote delivery of these drugs to this site by enhancing sweating and minimizing drug run-off and absorption onto clothing may aid in optimizing the therapeutic response to these agents.

Antifungal Agents↗

The laryngeal mask airway in paediatric anaesthesia.

Forty-eight children, aged between 2 and 10 years, admitted as day cases for otological surgery were allocated at random into two groups. The first group was anaesthetised using a standard facemask, and the second with a laryngeal mask airway. The laryngeal airway produced a satisfactory airway in all children, and was inserted on the first attempt in 67% of patients. Hypoxia was significantly less frequent in the laryngeal airway group (p less than 0.05), and there were significantly fewer interruptions to surgery than in the facemask group (p less than 0.001). Patient safety, operating and anaesthetic conditions were all considered superior in the laryngeal airway group.

Ambulatory Surgical Procedures↗

Consensus of the role and positioning of the imidazoles in the treatment of dermatophytosis.

The imidazoles have been appreciated for approximately fifteen years as a family of antifungals. Most derivatives, like the protype compounds, miconazole and clotrimazole, are effective only in a topical dose form. The topical imidazoles are generally thought to be superior to other topical antifungals. The first orally available imidazole, ketoconazole has ushered in a new era of potent, oral, broad-spectrum antifungal therapy. The imidazoles as a class are the treatment of choice for four dermatophyte infection syndromes. They are the preferred alternative therapy in another six syndromes. There is insufficient data to recommend one topical azole over the other. The topicals are inadequate for control of six clinical-anatomical infection syndromes. Griseofulvin remains the standard oral therapy in all situations except chronic, extensive dermatophytosis, where ketoconazole has proven to be more efficacious. The recognition of potential significant adverse effects, namely an idiopathic hepatitis and dose-dependent adrenal and testicular dysfunction have reduced ketoconazole's potential role in the dermatophytoses. Ketoconazole is a useful alternative to griseofulvin when oral therapy is required and the causative organism is insensitive to griseofulvin, or infection fails to respond to griseofulvin, or griseofulvin is contraindicated due to allergy, photosensitivity, porphyrinuria, intolerance, etc.

Administration, Oral↗

Cell-mediated immunity in the immunopathogenesis of dermatophytosis.

CMI to dermatophyte antigens, principally trichophytin, is central to both (1) pathogenesis of the typical "ringworm" lesion and (2) an acquired, relative resistance that affords partial immunity to the host. The exact form of effector "T" cell immunity and the cellular and molecular mechanism(s) which eliminate dermatophytes from the skin, are poorly understood, but may involve lymphokine and accelerated epidermal turnover. Recent studies in the "nude" rat suggest that this thymic deficient animal offers potential for study of chronic, extensive dermatophytosis. The pathogenesis of the indolent inflammation of chronic infection is unclear, but may involve fungal derived chemotactic factors and/or activation of the alternative complement pathway. Chronic, extensive dermatophytosis may be caused by several different organisms, including T. rubrum, T. mentagrophytes, T. tonsurans and T. concentricum. Despite the multiple, microbial etiologies, most patients with this distinctive syndrome share similar immunological characteristics, including deficient, antigen-specific CMI to trichophytin. Approximately half of the patients have either an immediate hypersensitivity to trichophytin or an elevated serum IgE level, and in addition, they exhibit other stigmata of atopy including a positive family history. It is intriguing to consider the possibility that genetic control of the immune response may render a certain IgE hyperresponsive subpopulation unable to mount sufficient host resistance to reject dermatophyte infection.

Animals↗

An animal model for altering the irritability threshold of normal skin.

Theory behind conditioned hyperirritability (autoeczematization) predicts the lowering of the irritation threshold in the presence of a pre-existing dermatitis. We have attempted to develop an animal model that parallels the syndrome seen in man. Groups of 10 guinea pigs were shaved and depilated; irritation thresholds to benzalkonium chloride and trichloroacetic acid were determined using 1 cm diameter open patches. Reactions were scored 24 h later on the basis of erythema and induration. Animals having as little as 1.56 cm2 of skin acutely inflamed with a known irritant had lowered irritation thresholds to the same irritant on normal skin at remote sites (p less than 0.01). Mild irritation of a much larger surface area produced the same effect (p less than 0.01). More extensive, severe dermatitis did not lower the irritation threshold further. Acute dermatitis induced by a contact allergen (DNCB) lowered the irritation threshold of normal skin to the same level as that obtained with irritants (p less than 0.01). Induction of chronic cutaneous ulcers 3-4 cm in diameter lowered the irritation threshold of normal skin to the same point defined by the acute studies (p less than 0.01). These results indicate that an acute irritant or contact dermatitis, as well as chronic skin ulceration, may alter the reactivity of unaffected normal skin to exhibit a heightened response to irritation. This model appears to differ from that seen in humans, in that a more extensive or chronic dermatitis did not further heighten the susceptibility to irritation.

Animals↗

Chronic dermatophyte infection: evaluation of the Ig class-specific antibody response reactive with polysaccharide and peptide antigens derived from Trichophyton mentagrophytes.

An enzyme-linked immunosorbent assay was used to detect serum antibodies within Ig classes IgG, IgM, IgA, and IgE against two partially purified Trichophyton mentagrophytes-derived antigens: polysaccharide (SAC) and peptide (PEP). Sera from 27 chronically infected adults, 16 normal noninfected adults, and 17 noninfected children were evaluated. All sera were reactive, indicating that circulating antibody reactive to PEP and SAC is a feature common to most people, regardless of age and the presence of active infection. The reactivity to SAC was much greater than to PEP. Inhibition assays revealed that components of PEP are found in SAC. Chronically infected adults showed slightly elevated IgG and IgA reactivity to both SAC and PEP compared with noninfected normal adults. This elevated reactivity correlated with the extent (% surface affected) of cutaneous infection. IgE antibody reactivity was detected only against SAC and was somewhat elevated in chronically infected adults. There was no association between antibody reactivity and immunoglobulin level or between the individual subject's level of antibody reactivity to PEP and SAC.

Adolescent↗

Orally administered ketoconazole: route of delivery to the human stratum corneum.

Delivery of ketoconazole to human stratum corneum was studied. Thirteen healthy volunteers, three patients with chronic fungal disease and one patient with palmar-plantar hyperhidrosis were given 400 mg of ketoconazole daily for various lengths of time. The ketoconazole content of palmar stratum corneum, eccrine sweat, sebum, and serum was measured by high-pressure liquid chromatography (sensitivity, 0.005 to 0.010 microgram/ml). Palmar stratum corneum obtained after 7 and 14 days of daily administration contained up to 14 micrograms of ketoconazole per g. Ketoconazole was not found in sebum after 7 or 14 days of daily ingestion of the antimycotic agent. Sebum from three patients with chronic fungal infection treated for greater than 9 months contained ketoconazole (means, 4.7 micrograms/g). Thermogenic whole body eccrine sweat contained a mean of 0.059 microgram/ml on day 7 and 0.084 microgram/ml on day 14 of daily administration. Ketoconazole appeared in thermogenic whole body eccrine sweat and palmar hyperhidrotic sweat within 1 h after a single oral dose. Partition studies of ketoconazole containing eccrine sweat demonstrated a 10-fold greater concentration in the sediment phase (desquamated keratinocytes) compared with the clear supernatant phase. In vitro studies with [3H]ketoconazole-supplemented supernatant sweat revealed preferential binding to stratum corneum, hair, and nails and its partitioning to lipid-rich sebum. We conclude that eccrine sweat rapidly transports ketoconazole across the blood-skin barrier, where it may bind or partition to keratinocytes and surface lipids.

Administration, Oral↗

Restoration of Trichophyton mentagrophytes growth in medium depleted of metals by chelation: importance of iron.

The present study examined the requirement of Trichophyton mentagrophytes ATCC-18748 for iron. Nutrient broth depleted of iron by the chelating cation exchange resin Chelex-100 did not support the growth of T. mentagrophytes beyond germ tube formation. The soluble chelate of iron, ferric ammonium citrate, restored the capacity of the chelated medium to support fungal growth in proportion to the amount of iron added. Ferric chloride, which rapidly becomes insoluble at neutral pH, was not effective in the medium. The soluble salts of cobalt, chromium, copper, manganese, nickel, and zinc individually did not replace the requirement for iron. A method for defining the iron requirement based upon utilization of iron from ferric ammonium citrate is described. These data indicate that the growth of T. mentagrophytes ATCC-18748 is iron-dependent, which is consistent with the hypothesis that serum transferrin inhibits dermatophyte growth by the mechanism of iron deprivation.

Chelating Agents↗

Serum concanavalin-A binding in rheumatoid arthritis.

A nephelometric assay of concanavalin-A binding of serum acute phase proteins (con-A binding) has been used in cross-sectional and sequential studies of disease activity in rheumatoid arthritis (RA). Con-A binding correlated well with blood viscosity, C-reactive protein, and other individual acute phase reactants in patients with active RA. Twenty-four patients were treated for 6 months with D-penicillamine and assessed clinically and seriologically. Clinical improvement was accompanied by significant falls in both C-reactive protein and con-A binding, although the serological changes did not always occur in parallel in individual patients. The advantages of this simple, cheap assay of acute phase proteins are discussed.

Adolescent↗

Pyrophosphate arthropathy: a clinical and radiological study of 105 cases.

105 consecutive patients who presented to a rheumatologist because of joint disease and who also had evidence of deposition of calcium pyrophosphate dihydrate (CPD) were studied clinically and radiologically. There were 76 women (mean age 73) and 29 men (mean age 62). Of only 18 patients below the age of 60 at presentation 12 were men. The majority of the younger male group suffered from acute attacks of synovitis, and had no clinical or radiological evidence of joint damage. In contrast the older female group had widespread destructive changes. Associated joint disease included generalised osteoarthritis (45), rheumatoid arthritis (8), joint hypermobility (13), previous knee surgery (8), and gout 92). Sixteen patients had received long-term steroid therapy. Severe destructive joint changes were seen in 16 patients. The radiological features in those with rheumatoid arthritis by ARA criteria were atypical. The relationship between CPD deposition and arthritis is discussed in the light of these findings.

Acute Disease↗