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Biomedical subjects

P N Hoffman

Publications and source records attributed to P N Hoffman.

At least 19 recordsLinked to original sources
PubMed2000

Hospital infection control in an era of HIV infection and multi-drug resistant tuberculosis.

Tuberculosis infection control in hospitals has received renewed interest after decades of low prominence following the occurrence of multiply drug-resistant strains in populations of patients with immune systems affected by HIV. This paper examines the history of tuberculosis infection control in hospitals and how recent outbreaks have influenced contemporary measures. The principal infection control measure must always be early recognition and isolation of patients in HIV-care situations who may be dispersing Mycobacterium tuberculosis, in both ward and outpatient areas. If there is either a high degree of suspicion or proven TB, patients should be housed in negative pressure isolation rooms whilst undergoing treatment and investigation. Procedures which may generate infectious aerosols should be carried out in similarly ventilated rooms. The quality assurance in such infection control is through the administrative systems put in place, staff training and the engineering controls of isolation room ventilation.

AIDS-Related Opportunistic Infections↗
PubMed1998

Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice.

Superoxide dismutase 1 (SOD1), a ubiquitously expressed enzyme, detoxifies superoxide radicals and participates in copper homeostasis. Mutations in this enzyme have been linked to a subset of autosomal dominant cases of familial amyotrophic lateral sclerosis (FALS), a disorder characterized by selective degeneration of motor neurons. Transgenic mice expressing FALS mutant human (Hu) SOD1 at high levels develop a motor neuron disease, indicating that mutant Hu SOD1 gains properties that are particularly toxic to motor neurons. In this report, we demonstrate that transgenic mice expressing Hu SOD1 with the G37R FALS mutation, but not mice expressing wild-type enzyme, develop focal increases in immunoreactivity in the proximal axons of spinal motor neurons. This SOD1 immunoreactivity and immunoreactivity to hypophosphorylated neurofilament H epitopes are found adjacent to small vacuoles in axons. Using metabolic radiolabeling methods, we show that mutant G37R HuSOD1 as well as endogenous mouse SOD1 are transported anterograde in slow component b in motor and sensory axons of the sciatic nerve. Together, these findings suggest that anterogradely transported mutant SOD1 may act locally to damage motor axons.

Animals↗
PubMed1996

Changes in the isotype composition of beta-tubulin delivered to regenerating sensory axons by slow axonal transport.

beta-Tubulin is encoded by a family of genes that produces at least five distinct polypeptide isotypes in neurons. Two of these isotypes (i.e., classes II and III) preferentially accumulate in axons, and the expression of one of them (i.e., class II) correlates closely with axonal outgrowth during development and regeneration. In dorsal root ganglion (DRG) neurons, expression of the class II isotype declines to relatively low levels during early postnatal development, and increases dramatically in mature neurons during axon regeneration (i.e., to a level comparable to that in developing neurons). In contrast, expression of the class III isotype, which rises slightly during postnatal development, increases much less than the class II isotype during regeneration. We now document that these changes in gene expression are associated with an increase in the relative amount of class II as compared to class III beta-tubulin delivered to regenerating sensory axons of rat sciatic nerve by slow axonal transport. In this study, the tubulin transported in sensory axons was labeled by injecting [35S]methionine into the L5 DRG either 7 or 14 days after crushing the sciatic nerve; pulse-labeled class II and class III beta-tubulin were identified using immunoprecipitation. This change in the isotype composition of beta-tubulin transported in regenerating axons may influence outgrowth by altering the assembly and dynamic properties of axonal microtubules.

Animals↗
PubMed1996

The axonal transport of beta III-tubulin is altered in both branches of sensory axons after injury of the rat sciatic nerve.

We have analyzed the axonal transport of beta III-tubulin in the central (dorsal root) and peripheral (sciatic nerve) branches of sensory axons after injury of the sciatic nerve. Our finding that the relative amount of beta III-tubulin transported in slow component b (SCb) is increased in both axonal branches does not support the generally accepted hypothesis that the transport of cytoskeletal proteins is altered in the peripheral, but not the central branch after injury of the sciatic nerve.

Animals↗
PubMed1996

Motor neuron disease and model systems: aetiologies, mechanisms and therapies.

The phenotypes of many neurological diseases, including motor neuron disease (amyotrophic lateral sclerosis; ALS) and Alzheimer's disease (AD), are determined by the vulnerabilities of populations of nerve cells and the character/ evolution of cellular abnormalities. Because different cell types respond selectively to individual trophic factors, these factors may be useful in ameliorating pathology in cells that express their cognate receptors. To test therapies for ALS and AD, investigators require model systems. Although there are a variety of models of ALS, two models are particularly attractive: transgenic mice that express human superoxide dismutase 1 (SOD-1) mutations linked to familial ALS develop paralysis associated with a gain of adverse property of the mutant SOD; and axotomy of facial axons in neonatal rats, a manipulation that causes retrograde cell degeneration, which can be ameliorated by several trophic factors.

Animals↗
PubMed1996

Neurofilament subunit NF-H modulates axonal diameter by selectively slowing neurofilament transport.

To examine the mechanism through which neurofilaments regulate the caliber of myelinated axons and to test how aberrant accumulations of neurofilaments cause motor neuron disease, mice have been constructed that express wild-type mouse NF-H up to 4.5 times the normal level. Small increases in NF-H expression lead to increased total neurofilament content and larger myelinated axons, whereas larger increases in NF-H decrease total neurofilament content and strongly inhibit radial growth. Increasing NF-H expression selectively slow neurofilament transport into and along axons, resulting in severe perikaryal accumulation of neurofilaments and proximal axonal swellings in motor neurons. Unlike the situation in transgenic mice expressing modest levels of human NF-H (Cote, F., J.F. Collard, and J.P. Julien. 1993. Cell. 73:35-46), even 4.5 times the normal level of wild-type mouse NF-H does not result in any overt phenotype or enhanced motor neuron degeneration or loss. Rather, motor neurons are extraordinarily tolerant of wild-type murine NF-H, whereas wild-type human NF-H, which differs from the mouse homolog at > 160 residue positions, mediates motor neuron disease in mice by acting as an aberrant, mutant subunit.

Animals↗
PubMed1996

Home-use nebulizers: a potential primary source of Burkholderia cepacia and other colistin-resistant, gram-negative bacteria in patients with cystic fibrosis.

Inhalation of aerosols contaminated with gram-negative bacteria generated from home-use nebulizers used by cystic fibrosis (CF) patients may be a primary route for bacterial colonization of the lung. Burkholderia cepacia was isolated from 3 of [corrected] 35 home-use nebulizers, and Stenotrophomonas maltophilia was isolated from 4 of 35 home-use nebulizers. Sputum cultures for two patients whose nebulizers were contaminated with B. cepacia did not yield the organism. However, DNA macrorestriction analysis by pulsed-field gel electrophoresis confirmed that one of two strains of B. cepacia recovered from the nebulizer of a third patient was also present in the sputum of that patient. Although Pseudomonas aeruginosa was isolated from 34 patients, none of the nebulizers were positive for the organism. Sixty-nine percent of nebulizers were contaminated, and up to 16 different environmental colistin-resistant, gram-negative species were identified. The heaviest contamination was found beneath the chamber atomizer. A questionnaire survey showed that the majority of patients (28 of 34) were receiving nebulized colistin and/or gentamicin. Patients who followed recommended instructions for good nebulizer hygienic practice and paid particular attention to drying had minimal or no contamination of their nebulizers.

Adult↗
PubMed1995

The infection hazards of human cadavers.

Cadavers may pose infection hazards to people who handle them. None of the organisms that caused mass death in the past--for example, plague, cholera, typhoid, tuberculosis, anthrax, smallpox--is likely to survive long in buried human remains. Items such as mould spores or lead dust are much greater risks to those involved in exhumations. Infectious conditions and pathogens in the recently deceased that present particular risks include tuberculosis, group A streptococcal infection, gastrointestinal organisms, the agents that cause transmissible spongiform encephalopathies (such as Creutzfeldt-Jakob disease), hepatitis B and C viruses, HIV, and possibly meningitis and septicaemia (especially meningococcal). The use of appropriate protective clothing and the observance of Control of Substances Hazardous to Health regulations, will protect all who handle cadavers against infectious hazards.

Autopsy↗
PubMed1994

Identification of outbreak-associated and other strains of Clostridium difficile by numerical analysis of SDS-PAGE protein patterns.

Seventy-three cultures of Clostridium difficile isolated both during, and in the period immediately following, an outbreak of infection in a group of three hospitals, were characterized by one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole-cell proteins. Each protein pattern was characterized by the presence of one or two dense bands which were highly reproducible. The protein patterns were used as the basis for a numerical analysis which divided the strains into five phenons (electrophoretic or EP types). The majority, 60 of the 73 cultures, belonged to a single phenon which included strains from both patients and the environment. We conclude that high-resolution SDS-PAGE of proteins provides an effective method for typing C. difficile and therefore for tracing the possible spread of epidemic strains in hospitals and other institutions, thereby allowing a better understanding of the epidemiology of the organism.

Adult↗
PubMed1994

Contamination of hospital linen by Bacillus cereus.

An investigation into two cases of post-operative Bacillus cereus meningitis revealed that hospital linen laundered by a batch continuous washing machine was heavily contaminated by B. cereus spores. The washing machine, detergents, other chemical additives and the water supply were eliminated as the source of contamination. It was found that the linen introduced into the washing machine had a high B. cereus spore content and that this was still present after the wash process. The spores were not killed by either the heat disinfection stage of the wash or the addition of chemical disinfectants and were not removed by the dilution in the process. The multiplication of B. cereus was thought to have occurred on used, damp linen stored in plastic bags, particularly when ambient temperatures were high. An increase in the water flow through the washing machine was the only measure associated with a decrease in B. cereus on laundered linen.

Bacillus cereus↗
PubMed1994

Assessment of microwave-based clinical waste decontamination unit.

A clinical waste decontamination unit that used microwave-generated heat was assessed for operator safety and efficacy. Tests with loads artificially contaminated with aerosol-forming particles showed that no particles were detected outside the machine provided the seals and covers were correctly seated. Thermometric measurement of a self-generated steam decontamination cycle was used to determine the parameters needed to ensure heat disinfection of the waste reception hopper, prior to entry for maintenance or repair. Bacterial and thermometric test pieces were passed through the machine within a full load of clinical waste. These test pieces, designed to represent a worst case situation, were enclosed in aluminium foil to shield them from direct microwave energy. None of the 100 bacterial test pieces yielded growth on culture and all 100 thermal test pieces achieved temperatures in excess of 99 degrees C during their passage through the decontamination unit. It was concluded that this method may be used to render safe the bulk of of ward-generated clinical waste.

Aerosols↗
PubMed1993

Altered gene expression after optic nerve transection: reduced neurofilament expression as a general response to axonal injury.

Previous studies have shown that axonal injury (axotomy) in neurons of the mammalian peripheral nervous system (PNS) results in a recapitulation of the developmental program for cytoskeletal gene expression; these changes include the increased expression of a developmentally regulated isotype of beta-tubulin (class II) and reduced neurofilament (NF) expression. In the present study we examined the abundance of mRNAs encoding the low-molecular-weight NF protein (NF-L) and class II beta-tubulin in RNA purified from the retinae of newborn rats, from the retinae of adult rats at 2, 7, and 14 days after intracranial transection of the ipsilateral optic nerve, and from contralateral control retinae. In order to facilitate comparison with representative PNS neurons, parallel analyses were carried out in axotomized dorsal root ganglion (DRG) sensory neurons. Since NF-L and class II beta-tubulin are neuron-specific proteins, axotomy-induced alterations in the levels of retinal mRNAs encoding these proteins largely reflect corresponding changes in expression by retinal ganglion cell neurons. Comparison of retinal RNA from newborn and adult (70-day-old) animals demonstrated a postnatal increase in NF-L and a decline in class II beta-tubulin mRNAs comparable to those previously described in DRG neurons. Reductions in NF-L mRNA levels were noted in retina at 2, 7, and 14 days after axotomy and in DRG neurons at 7 and 14 days after axotomy. The abundance of class II beta-tubulin mRNAs increased after axotomy in DRG neurons, but not in retina.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system.

Amyloid deposits are a characteristic feature of the senile plaques identified in the brains of aged primates, individuals with Down's syndrome, and cases of Alzheimer's disease. The beta-amyloid protein (A beta), the principal component of amyloid, is a 4 kDa peptide derived from larger amyloid precursor protein(s) (APP). Four mRNAs, generated by alternative splicing of pre-mRNA derived from a single gene, encode A beta-containing membrane glycoproteins termed APP-695, -714, -751, and -770; the latter two isoforms contain a domain homologous to Kunitz protease inhibitors (KPI). The present study uses in vitro and in vivo strategies to examine the expression of APP in neurons of the dorsal root ganglia and the nature of APP transported in sciatic nerves of rats. Using quantitative in situ hybridization and semiquantitative PCR analysis, we document that mRNAs encoding APP-695 are expressed preferentially over transcripts that encode KPI-containing isoforms in rat sensory ganglia. Furthermore, we provide compelling evidence that APP-695 is the predominant isoform synthesized in sensory neurons of the rat PNS and that full-length APP-695 and, to a lesser extent, APP-751/770 are rapidly transported anterogradely in axons.

Amino Acid Sequence↗
PubMed1992

Re-use of syringes.

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Disposable Equipment↗