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Biomedical subjects

M G Smith

Publications and source records attributed to M G Smith.

At least 19 recordsLinked to original sources
PubMed2001

Lacrimal fossa block: an audit of a minimally invasive regional anaesthetic technique for endoscopic dacryocystorhinostomy (DCR).

The lacrimal fossa block (LFB), a new development to provide regional anaesthesia for endoscopic dacryocystorhinostomy, is reported. Cadaveric study showed that the block needle, inserted as described, made direct contact with the periosteum of the frontal process of the maxilla within the lacrimal fossa. This technique enables both relevant divisions of the trigeminal nerve to be anaesthetized through a single entry site and, as this injection is confined to the anterior part of the orbit, ocular complications are minimized. An audit of 66 patients has shown that this technique, combined with standard intranasal local anaesthesia, provides good intraoperative analgesia, causes minimal diplopia and has a high level of patient acceptability.

Adult↗
PubMed2001

Implementation of the STOP protocol for Stroke Prevention in Sickle Cell Anemia by using duplex power Doppler imaging.

PURPOSE: To compare the results of the nonduplex ultrasonography (US) Stroke Prevention Trial in Sickle Cell Anemia (STOP) with those of transcranial duplex power Doppler US by using the STOP protocol and to correlate abnormal transcranial Doppler findings with magnetic resonance (MR) imaging and MR angiographic findings. MATERIALS AND METHODS: One hundred twenty-five asymptomatic patients aged 2-16 years with sickle cell anemia or sickle cell-beta thalassemia were examined by using transcranial duplex power Doppler US with a 2.5-MHz transducer and classified according to STOP criteria. The results were compared with those obtained in the nonduplex STOP study. Eight of 10 patients with abnormal results, as well as one who had normal results and a subsequent stroke, were examined with MR imaging and MR angiography. RESULTS: Ten (8.0%) patients were judged to have abnormal findings by using the duplex Doppler US and STOP criteria compared with 9.4% of patients in the nonduplex US STOP study. Of the eight patients with abnormal transcranial Doppler US results who underwent MR imaging and MR angiography, six had abnormal MR imaging findings and all eight had abnormal MR angiographic findings. CONCLUSION: The STOP protocol can be reproduced by using duplex power Doppler US. Abnormal results with the STOP criteria strongly suggest vascular abnormality.

Adolescent↗
PubMed2001

The life cycle of actin patches in mating yeast.

Actin patches are core components of the yeast actin cytoskeleton that undergo redistribution during establishment of cell polarity. Using 4D imaging, we observe the life cycle of actin patches in living yeast for the first time. We observe assembly of actin patches at sites of polarized growth, and disassembly of actin patches concomitant with movement away from those sites. The total lifetime of an actin patch is 10.9+/-4.2 seconds. These findings indicate that actin patches are labile structures, and that the localization of actin patches during establishment of cell polarity occurs by assembly of these structures at sites of polarized cell surface growth. These findings were confirmed and extended by analysis of myosin I proteins and their receptor, verprolin, proteins implicated in actin assembly in yeast. Deletion of type I myosins or their receptor has no effect on the velocity of actin patch movement. However, these mutants show a 65% reduction in number of patch movements and a three-fold increase in patch lifetime. Finally, the actin patch resident proteins Abp1p, fimbrin, and Arp2p show normal association with actin patches in myosin I and verprolin mutants. However, cofilin accumulates in abnormal 'bars' of G-actin in myo3Delta,myo5Delta and vrp1Delta strains, and Las17p/Bee1p is not associated with actin patches in vrp1Delta strains. These findings imply a multi-step process for actin patch assembly. Early events in this process, including assembly of Abp1p, fimbrin and Arp2p with F-actin, can occur throughout the cell and do not require myosin I proteins or their receptor. Later events in this process are myosin I-dependent, and are required for assembly of actin patches at sites of polarized cell surface growth.

Actins↗
PubMed2000

An outbreak of Yersinia enterocolitica O:8 infections associated with pasteurized milk.

In October 1995, an outbreak of Yersinia enterocolitica O:8 infections occurred in the Upper Valley of Vermont and New Hampshire. Ten patients were identified, median age 9 years (range, 6 months-44 years). Three patients were hospitalized; 1 underwent an appendectomy. Consumption of bottled pasteurized milk from a local dairy was associated with illness (matched odds ratio undefined; lower 95% confidence interval, 1.9). No deficiencies in pasteurization procedures or equipment were detected. Y. enterocolitica O:8 was isolated from 1 raw-milk sample and from a fecal sample from 1 dairy pig. The route of contamination was not determined; this outbreak likely resulted from postpasteurization contamination of milk. Dairy pigs were the most likely source of contamination. Milk bottles were likely contaminated by rinsing with untreated well water prior to filling or by other environmental routes. Educating dairy owners about Y. enterocolitica and postpasteurization contamination is necessary to prevent further outbreaks.

Adolescent↗
PubMed1997

Predicting rodent carcinogenicity from mutagenic potency measured in the Ames Salmonella assay.

Many in vitro tests have been developed to identify chemicals that can damage cellular DNA or cause mutations, and secondarily to identify potential carcinogens. The test receiving by far the most use and attention has been the Salmonella (SAL) mutagenesis test developed by Ames and colleagues [(1973): Proc Natl Acad Sci USA 70:2281-2285; (1975): Mutat Res 31:347-364], because of its initial promise of high qualitative (YES/NO) predictivity for cancer in rodents and, by extension, in humans. In addition to the initial reports of high qualitative predictivity, there was also an early report by Meselson and Russell [in Hiatt HH et al (1977): "Origins of Human Cancer, Book C: Human Risk Assessment," pp 1473-1481] of a quantitative relationship between mutagenic potency measured in SAL and carcinogenic potency measured in rodents, for a small number of chemicals. However, other reports using larger numbers of chemicals have found only very weak correlations. The primary purpose of this study was to determine whether mutagenic potency, as measured in a number of different ways, could be used to improve predictivity of carcinogenicity, either qualitatively or quantitatively. To this end, eight measures of SAL mutagenic potency were used. This study firmly establishes that the predictive relationship between mutagenic potency in SAL and rodent carcinogenicity is, at best, weak. When predicting qualitative carcinogenicity, only qualitative mutagenicity is useful; none of the quantitative measures of potency considered improves the carcinogenicity prediction. In fact, when qualitative mutagenicity is forced out of the model, the quantitative measures are still not predictive of carcinogenicity. When predicting quantitative carcinogenicity, several possible methods were considered for summarizing potency over all experiments; however, in all cases, the relationship between mutagenic potency predictors and quantitative carcinogenicity is very weak.

Animals↗
PubMed1996

Mass human exposure to rabies in New Hampshire: exposures, treatment, and cost.

OBJECTIVES: This study assessed the rabies exposure and treatment that at least 665 persons in Concord, NH, received as a result of one proven rabid pet-store kitten in October 1994. METHODS: All treatment recipients were interviewed by person or phone. RESULTS: The median age of the treatment recipients was 14 years; 58% were female. The most common exposures were low risk (e.g., picking up, petting, nuzzling, or being scratched by a potentially rabid kitten). Local reactions to vaccine or immune globulin were reported by 76.5% of recipients, while 48.8% reported at least one systemic reaction. Cost for the biologicals was estimated at more than $1.1 million. CONCLUSIONS: Because of the inadequacy of pet store records, the inconsistent application of treatment guidelines, and other factors, many people received postexposure treatment as a result of contacts that were unlikely to transmit rabies. The rates of local and systemic adverse reactions experienced were consistent with previous reports.

Adolescent↗
PubMed1995

Organelle-cytoskeletal interactions: actin mutations inhibit meiosis-dependent mitochondrial rearrangement in the budding yeast Saccharomyces cerevisiae.

During early stages of meiosis I, yeast mitochondria fuse to form a single continuous thread. Thereafter, portions of the mitochondrial thread are equally distributed to daughter cells. Using time-lapse fluorescence microscopy and a membrane potential sensing dye, mitochondria are resolved as small particles at the cell periphery in pre-meiotic, living yeast. These organelles display low levels of movement. During meiosis I, we observed a threefold increase in mitochondrial motility. Mitochondrial movements were linear, occurred at a maximum velocity of 25 +/- 6.7 nm/s, and resulted in organelle collision and fusion to form elongated tubular structures. Mitochondria do not co-localize with microtubules. Destabilization of microtubules by nocodazole treatment has no significant effect on the rate and extent of thread formation. In contrast, yeast bearing temperature-sensitive mutations in the actin-encoding ACT1 gene (act1-3 and act1-133) exhibit abnormal mitochondrial aggregation, fragmentation, and enlargement as well as loss of mitochondrial motility. In act1-3 cells, mitochondrial defects and actin delocalization occur only at restrictive temperatures. The act1-133 mutation, which perturbs the myosin-binding site of actin without significantly affecting actin cytoskeletal structure in meiotic yeast, results in mitochondrial morphology and motility defects at restrictive and permissive temperatures. These studies support a role for the actin cytoskeleton in the control of mitochondrial position and movements in meiotic yeast.

Actins↗
PubMed1995

Identifying anxiety disorders in adolescents hospitalized for alcohol abuse or dependence.

In structured clinical interviews of 43 adolescents hospitalized for alcohol abuse or dependence, 17 subjects met criteria for an anxiety disorder, with social phobia (N = 9) and posttraumatic stress disorder (N = 7) most common. Of these 17 subjects, only four were identified in hospital records as having an anxiety disorder. In a comparison of 30 hospitalized adolescents with a matched control group of 30 adolescents from the community, the hospitalized adolescents had a higher rate of anxiety disorders, psychoactive substance use disorders, disruptive behavior disorders, and mood disorders.

Adolescent↗
PubMed1994

GM1 ganglioside treatment partially reverses the nigrostriatal dopamine defect in the weaver mutant mouse.

The weaver mutation in the mouse is a developmental disorder characterized by cerebellar atrophy as well as decreased numbers of substantia nigra dopaminergic neurons and a striatal dopamine loss. Since the nigrostriatal dopamine loss occurs postnatally, the present study was performed to determine whether early intervention with GM1 ganglioside could alter the extent of this dopamine loss. Weaver mice that received injections of GM1 ganglioside (30 mg/kg) daily, beginning at 7-10 days of age, had significantly higher striatal dopamine levels and significantly more tyrosine hydroxylase-positive substantia nigra pars compacta neurons than weaver mice that received only daily saline injections. These results show that GM1 treatment can alter at least some aspects of this inherited developmental disorder. If the weaver defect is related to a deprivation of trophic support for certain midbrain dopaminergic neurons, the presence of GM1 may be able to enhance the survival of these neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Yeast mitochondria contain ATP-sensitive, reversible actin-binding activity.

Sedimentation assays were used to demonstrate and characterize binding of isolated yeast mitochondria to phalloidin-stabilized yeast F-actin. These actin-mitochondrial interactions are ATP sensitive, saturable, reversible, and do not depend upon mitochondrial membrane potential. Protease digestion of mitochondrial outer membrane proteins or saturation of myosin-binding sites on F-actin with the S1 subfragment of skeletal myosin block binding. These observations indicate that a protein (or proteins) on the mitochondrial surface mediates ATP-sensitive, reversible binding of mitochondria to the lateral surface of microfilaments. Actin copurifies with mitochondria during subcellular fractionation and is released from the organelle upon treatment with ATP. Thus, actin-mitochondrial interactions resembling those observed in vitro may also exist in intact yeast cells. Finally, a yeast mutant bearing a temperature-sensitive mutation in the actin-encoding ACT1 gene (act1-3) displays temperature-dependent defects in transfer of mitochondria from mother cells to newly developed buds during yeast cell mitosis.

Actins↗
PubMed1994

Panic in otolaryngology patients presenting with dizziness or hearing loss.

This study compared 50 patients presenting to an otolaryngology clinic with a complaint of dizziness and 50 patients presenting with hearing loss on questionnaire measures of panic, phobic avoidance, generalized anxiety, and depression. Clinical and laboratory evaluations of vestibular and audiological complaints were also completed. Twenty percent of the group with dizziness and none of the group with hearing loss reported symptoms that met DSM-III-R criteria for panic disorder. Patients with dizziness and peripheral vestibulopathy had more symptoms of phobic avoidance, generalized anxiety, and depression than patients with confirmed hearing loss.

Adult↗
PubMed1994

Some comments on potency measures in mutagenicity research.

In this article, the measurement of the potency of a chemical or mixture from its dose response in a particular assay is addressed. Attention is focused on data from the Ames Salmonella assay. Three measures of potency are explored and shown to be highly correlated. The presentation then discusses specific areas of research that might benefit from a study of potency.

Dose-Response Relationship, Drug↗
PubMed1994

Targeted integration of transfected and infected adeno-associated virus vectors containing the neomycin resistance gene.

Human adeno-associated virus (AAV) integrates specifically into a site (AAVS1) on chromosome 19q13.3-qter. We report that both transfected and infected AAV-vectors will target a foreign gene preferentially to AAVS1. Of 11 infected cell lines studied, nine (82%) showed integration of the neomycin resistance marker into AAVS1, which confirms the findings of previous investigations. We also show site-specific integration (nine out of 12 cell lines, 75%) following transfection of an AAV vector containing the neomycin gene. The ability of transfected AAV sequences to preferentially target and express selectable genes at a known site in the human genome extends the potential use of AAV as a vector in gene therapy.

Anti-Bacterial Agents↗