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Biomedical subjects

M Holmes

Publications and source records attributed to M Holmes.

At least 91 records · Page 5Linked to original sources
PubMed1989

Informal versus formal supports for impaired elderly people: determinants of choice on Israeli kibbutzim.

Among 269 functionally impaired elderly people residing on 53 Israeli kibbutzim, those cared for principally by informal caregivers were compared with those cared for principally by formal caregivers. The major findings were that the variables differentiating between primary reliance on formal versus informal care are similar to those that have been found in other studies, and that the availability of formal resources was not accompanied by withdrawal of informal supports.

Aged↗
PubMed1989

Factors relating to institutional risk among elderly members of Israeli kibbutzim.

Characteristics of 269 functionally impaired elderly persons and their primary caregivers were examined in relation to long-term care planning. Contrary to expectation, there were no differences in rates of institutional risk between those elderly residents of Israeli kibbutzim cared for primarily by formal caregivers and cared for by informal caregivers. Lack of informal caregivers emerged as an important risk factor for institutional risk, even in the service-rich environment of kibbutzim.

Aged↗
PubMed1989

Characterization of the intracellular mechanism causing the alpha-1-antitrypsin Nullgranite falls deficiency state.

The alpha-1-antitrypsin (alpha 1AT) Null alleles are those for which no alpha 1AT can be detected in the serum attributable to the gene. The intracellular consequences of the various substitution, deletion, and insertion mutations causing the Null state can be categorized into two groups: those associated with detectable alpha 1AT mRNA transcripts and those with no detectable alpha 1AT mRNA transcripts. To classify the intracellular mechanism associated with the Nullgranite falls allele (Tyr160 TAC, C deletion, 5' frameshift----Stop160 TAG), a Nullgranite falls homozygote was evaluated. Genotypic diagnosis of the Nullgranite falls homozygous state was determined using the polymerase chain reaction and Nullgranite falls specific primers. Total cellular RNA extracted from alveolar macrophages of the index case was compared to that from a normal M1 homozygote for the presence of alpha 1AT mRNA transcripts using Northern blot analysis and hybridization to either a 32P-labeled full length alpha 1AT cDNA probe or (as a control) a 32P-labeled gamma-actin cDNA probe. Although the macrophages of both the Nullgranite falls homozygote and the normal showed gamma-actin mRNA transcripts in comparable amounts, Nullgranite falls macrophages contained no detectable alpha 1AT mRNA transcripts whereas the normal had the expected 1.8 kb alpha 1AT mRNA transcripts. Thus, the Nullgranite falls allele can be classified along with Nullbellingham as a Null allele associated with no detectable alpha 1AT mRNA. These observations highlight the marked heterogeneity in the molecular processes causing the Null state, despite an identical phenotype at the clinical level.

Adult↗
PubMed1988

Axonal domains within shared touch domes in the rat: a comparison of their fate during conditions favoring collateral sprouting and following axonal regeneration.

Low-threshold mechanosensory nerves in the adult rat differ both from their counterparts in lower vertebrates and from high-threshold nociceptive nerves in mammals in that they appear not to undergo collateral sprouting into adjacent denervated skin, although they will clearly regenerate into it after they are damaged. We have now studied the growth capabilities of the low-threshold nerves supplying touch domes, the visible mechanosensory structures scattered throughout the hairy skin. Touch domes in the rat are often multiply innervated. A serendipitous observation on such domes allowed us to investigate the possibility that a functional collateral sprouting of their nerves can indeed occur, but only to a spatially very restricted extent, e.g., within the confines of a partially denervated dome. We used a "prodder" with a tip diameter of 16 micron to examine the mechanosensory profile across single domes that were preselected as being supplied by only two axons, one running in each of two adjacent dorsal cutaneous nerves (DCNs). Simultaneous recordings were made of the afferent discharges evoked in these nerves when the prodder was applied at about 17 or more locations on a selected dome; the spatial resolution was better than 55 micron. We found that within such a shared dome, one axon can supply a discrete territory (its "domain"), which may or may not overlap with the corresponding domain of the other axon. In a preliminary electron microscopic study, we found no evidence for a sharing of single Merkel cells, which are the specialized sensory cells in touch domes, even in the regions of a shared dome where two domains overlapped; each innervated Merkel cell appeared to be contacted by a single nerve ending, implying that in a shared dome each axon probably supplies an exclusive subpopulation of the Merkel cells. We tested for functional collateral sprouting by eliminating one nerve to a shared dome, and at a selected time thereafter mapping the domain of the remaining axon to see whether it had enlarged. The result was the same whether the two domains initially had a region of overlap or not; no expansion of the surviving domain occurred over postoperative periods up to 4 months (an expansion of the domain by 55 micron would have been detected). Thus functional collateral sprouting had failed to occur.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Virus-liver cell interactions in duck hepatitis B virus infection. A study of virus dissemination within the liver.

Thirty-five 1-day-old Pekin-Aylesbury ducks were inoculated intravenously or intraperitoneally with duck hepatitis B virus, and the time-course of infection was examined by Southern-blot, dot-blot, and in situ hybridization and by immunohistochemistry. Randomly scattered single infected hepatocytes were first seen on days 1 and 2 after inoculation and by day 3 occurred as single cells, pairs, and groups of 5-10 adjoining cells. From day 4 after inoculation all hepatocytes were positive for duck hepatitis B surface antigen and deoxyribonucleic acid. Duck hepatitis B virus deoxyribonucleic acid levels in liver extracts and serum increased logarithmically from days 2 to 3 to a plateau by days 4 to 5 after inoculation. Infected and control birds showed no significant differences during the first 7 days in terms of liver histology, hepatocyte morphology, or mitotic activity. It was concluded that (a) virus gains access to randomly distributed hepatocytes without first replicating in other cell types, and then begins disseminating to adjacent cells following anatomic boundaries; (b) markers of infection in liver and serum show reproducible kinetics, thus making this in vivo system amenable to further quantitative study; and (c) hepatocytes in this system are highly permissive to virus replication without the development of significant cytopathology.

Animals↗
PubMed1988

Chronic muco-cutaneous candidiasis and oral neoplasia.

Two patients with chronic muco-cutaneous candidiasis who subsequently developed oral neoplasia are presented. In both cases the tumours appeared in the fourth decade of life. The natural history of these tumours was not unique but varied from the norm. In one patient there was an obvious propensity for metastasis; in the other, three separate tumours evolved. An argument could be made to link the unusual features evident in these two cases with the state of altered immunity known to occur in chronic muco-cutaneous candidiasis, although the suggestion is speculative.

Adult↗
PubMed1987

Cerebral glucose metabolism in the Lennox-Gastaut syndrome.

We used positron emission tomography with fluorine 18-labeled 2-deoxyglucose to study cerebral glucose metabolism in 10 patients with Lennox-Gastaut syndrome who had normal neuroradiological studies. The scans showed decreased metabolic rates relative both to those in the caudate nucleus and to normal control values in 3 patients whose seizures began before the age of 1, as well as in a patient with hyperprolinemia. No patient had a region of persistent focal hypometabolism. Metabolic rates increased in parallel with increased electroencephalographic discharges in 1 patient; 3 patients had lower metabolic rates when the electroencephalogram showed epileptiform discharges and while the patients were taking barbiturates.

Adolescent↗
PubMed1987

Duck hepatitis B virus DNA in liver, spleen, and pancreas: analysis by in situ and Southern blot hybridization.

Tissues from a 10-week-old Pekin duck, experimentally infected at 1 day of age with duck hepatitis B virus (DHBV), were examined for the presence of replicative levels of DHBV DNA by in situ and Southern blot hybridization. Hepatocytes, pancreatic lymphoid follicle, exocrine, and endocrine cells, and splenic mononuclear cells all contained DHBV DNA localized predominantly to the cytoplasm of infected cells. Duck hepatitis B surface antigen distribution in the same tissues correlated well with the presence of DHBV DNA in many of these cells. In hepatocytes and pancreatic islet cells, 60% of DHBV DNA was present as single-stranded DNA, indicating the likelihood of ongoing virus replication in these cell types and providing further evidence that hepadnavirus DNA replication occurs largely within the cell cytoplasm. In contrast, DHBV in mononuclear cells within splenic germinal centers was wholly double-stranded, suggesting that limited, if any, DHBV DNA replication was occurring in this cell type. These data provide further information about the pathogenesis and cell-specific sites of DHBV infection.

Animals↗
PubMed1987

Evidence that endogenous beta nerve growth factor is responsible for the collateral sprouting, but not the regeneration, of nociceptive axons in adult rats.

A key role has not yet been identified for beta nerve growth factor (NGF) in the growth responses that continue to be expressed in the sensory neurons of adult animals. We have now examined the effects of daily administration to adult rats (and in a few experiments, mice) of antiserum to NGF on (i) the collateral sprouting of undamaged nociceptive nerves that occurs into denervated adjacent skin and (ii) the regeneration of cutaneous sensory axons that occurs after they are damaged. The results were unexpected. All collateral sprouting was prevented and that already in progress was halted; sprouting resumed when treatment was discontinued. In contrast, the reestablishment, and even enlargement, of cutaneous nerve fields by regenerating axons was unaffected by anti-NGF treatment, even after dorsal rhizotomy was done to eliminate any central trophic support. In denervated skin, regenerating and collaterally sprouting axons utilized the same cellular pathways to establish functionally identical fields, thus displaying apparently identical growth behaviors, yet anti-NGF treatment clearly distinguished between them. We suggest that endogenous NGF is responsible for the collateral sprouting of nociceptive axons, probably reflecting an ongoing function of NGF in the regulation of their fields. This demonstration in the adult sensory system of a defined role for NGF in nerve growth could apply to nerve growth factors generally in the adult nervous system. The regeneration, however, of nociceptive axons (and nonnociceptive one) is not dependent on NGF.

Animals↗
PubMed1987

Activation of mouse epidermal tumor ornithine decarboxylase by GTP: evidence for different catalytic forms of the enzyme.

In crude extracts of epidermal papillomas induced by an initiation-promotion protocol, ornithine decarboxylase (OrnDCase) activity was increased by the addition of GTP to the enzyme assay. No effect of GTP on the phorbol ester-induced enzyme isolated from normal epidermis was observed. Kinetic analyses indicated that the major effect of the nucleotide on the tumor-derived enzyme was to lower the apparent Km for L-ornithine. When papilloma OrnDCase was partially purified by gel-filtration chromatography, two forms of the enzyme were resolved, only one of which was found in an epidermal extract from phorbol 12-myristate 13-acetate-treated mice. The enzymatic properties of the two forms of papilloma enzyme were compared. The higher molecular weight form (peak I) was activated by GTP, while the lower molecular weight form (peak II) was not. As expected from the kinetic analyses of the crude papilloma extracts, the apparent Km of peak I enzyme for L-ornithine was very high (1.25 mM) but was much lower in the presence of GTP (0.02 mM). The two forms of papilloma OrnDCase differed in their sensitivities to heat inactivation and the ability of GTP to protect against heat inactivation. The K1/2 for activation of peak I OrnDCase by GTP was 0.1 microM. The activation process was irreversible and did not require Mg2+. When several nucleotides were tested for their ability to activate peak I OrnDCase, only GTP, dGTP, and the nonhydrolyzable derivative GTP[gamma-S] were effective, while GDP, GMP, ATP, and CTP were relatively ineffective. Our results demonstrated the existence of two forms of OrnDCase in epidermal tumor extracts, of which one can be activated by GTP and one cannot. The significance of these findings for the regulation of this enzyme in normal and tumor cells is discussed.

Animals↗
PubMed1986

Comparison and critical evaluation of six published extraction and clean-up procedures for aflatoxin M1 in liquid milk.

A practical evaluation has been carried out of six previously published extraction and clean-up methods for aflatoxin M1 in liquid milk. The procedures evaluated incorporated the most widely used stages of clean-up including solvent extraction and silica gel chromatographic clean-up, selective solvent extraction of the extracted residue, the use of deproteination prior to hydrophilic column liquid-liquid partition or solvent extraction and the use of pre-packed reversed-phase cartridges for the direct extraction of aflatoxin M1 from the milk. Analysis times for each method, recoveries and relative costs are reported together with fluorescence high-performance liquid chromatography chromatograms, obtained under identical conditions to compare the relative cleanliness of the final extracts produced by each method. A pre-packed reversed phase cartridge method was shown to be the most satisfactory in terms of speed, cost and cleanliness of the final residue.

Aflatoxin M1↗
PubMed1986

Ornithine decarboxylase from mouse epidermis and epidermal papillomas: differences in enzymatic properties and structure.

The properties of ornithine decarboxylase (OrnDCase) from mouse epidermis and benign epidermal tumors (papillomas) induced by the initiation-promotion protocol were compared. When crude extracts from each tissue were incubated at 55 degrees C, epidermal OrnDCase was rapidly inactivated, but the papilloma OrnDCase was more heat stable. Each of five individual papilloma extracts contained OrnDCase activity that was considerably more resistant to heat inactivation than was epidermal OrnDCase. Mixing of a papilloma and epidermal extract produced an intermediate heat-inactivation profile, suggesting that the differences in OrnDCase heat stability are not due to non-OrnDCase components of the extracts. Kinetic analyses indicated that the papilloma OrnDCase has an altered affinity for its substrate, L-ornithine, compared to epidermal OrnDCase. The apparent Km for L-ornithine for the epidermal enzyme was 0.07 mM while the Km values for the individual papilloma OrnDCases clustered around two higher values, 0.3 mM and 1.0 mM. The papilloma OrnDCases, but not epidermal OrnDCase, were activated by GTP and to a lesser extent by CTP. Immunoblot analysis showed the existence of multiple forms of OrnDCase in both epidermis and papilloma that differed in isoelectric point but not subunit molecular weight. None of the species of OrnDCase present in the epidermal extract coincided with the species present in papilloma. These results suggest that one consequence of neoplastic transformation in this in vivo system is the presence of an OrnDCase protein in benign tumors that differs structurally and functionally from the OrnDCase present in normal epidermis. The possible mechanisms responsible for these results and their significance for neoplastic development in this tissue are discussed.

Animals↗
PubMed1986

Are Merkel cell-neurite reciprocal synapses involved in the initiation of tactile responses in salamander skin?

In salamander skin the Merkel cell-neurite complexes located near the base of the epidermis are the morphological correlates of the rapidly adapting touch receptors (Parducz, Leslie, Cooper, Turner & Diamond, 1977). The present electron microscopic studies revealed that these complexes contain reciprocal synapses polarized in the direction Merkel cell to neurite, and in the opposite direction, neurite to Merkel cell. The possible involvement of chemical transmission in the initiation of the mechanosensory response, was studied in vitro with the aid of a stable skin-nerve preparation in which single mechanoreceptors were activated under controlled conditions. Mechanosensitivity was measured with a calibrated prodder (tip diameter 10-30 micron) applied to random or selected points on the surface of the skin while the afferent impulse was recorded in the attached nerve twig. In some experiments the (tungsten) prodder was also used as a surface electrode, allowing the same mechanosensory axon to be excited mechanically (i.e. physiologically), and/or electrically. When applied at a single 'touch spot', suitably timed subthreshold mechanical and subthreshold electrical stimuli could summate to produce a single action potential. The temperature coefficient (Q10) between 5 and 15 degrees C for the latency of the afferent spike was small, in the range 1.3-2, whether it was evoked by mechanical or electrical stimulation. The latency following the mechanical stimulus, which included the transduction step, was longer than that following the electrical stimulus by 0.5-2.5 ms, and this additional delay was also relatively insensitive to temperature. In several cases removal of the epidermis with its Merkel cells (and presumably the most distal portions of the afferent nerve terminations) did not render the remaining skin totally insensitive to mechanical stimulation; however, the remaining receptive elements, though still rapidly adapting, generally had increased mechanosensory thresholds. The mechanosensitivity of the skin was unaffected by bath application of several aminergic (e.g. noradrenaline, 5-hydroxytryptamine, octopamine) and purinergic (e.g. ATP, quinacrine) compounds at concentrations in the range 0.2-2 mM. Removal of extracellular Ca2+ combined with elevation of extracellular Mg2+ (10-40 mM) had relatively little effect on the mechanosensitivity over periods of up to 1 h. In contrast, application of Co2+ (2-10 mM) produced a decrease or blockade of the mechanosensitivity that was not associated with any obvious alterations in the ultrastructure of the Merkel cell-neurite complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗