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Biomedical subjects

K McDermott

Publications and source records attributed to K McDermott.

At least 19 recordsLinked to original sources
PubMed2005

Two-year evaluation of restorations of a packable composite placed in UK general dental practices.

OBJECTIVE: The aim of this study was to assess the clinical performance at two years of 100 Solitaire 2 restorations placed in five United Kingdom dental practices by members of a practice-based research group. METHOD AND MATERIALS: Restorations were assessed after two years by a trained evaluator and the dental practitioner who had placed the material, for anatomic form, marginal adaptation, surface roughness, gingival condition and the presence or absence of secondary caries. In addition, the patients completed a questionnaire requesting details of the comfort and performance of the Solitaire 2 restoration(s). RESULTS: A total of 88 (58 Class II and 30 Class I) restorations of Solitaire 2 placed in 49 patients (mean age 43 years) were assessed. Twelve restorations could not be evaluated because of patient unavailability for the dates of the examinations. Two Class II restorations (2%) had failed by the time of the two-year evaluation and the remaining 86 restorations were found to be intact with no secondary caries. A high percentage of optimal scores were recorded for anatomic form and surface roughness. The colour match of two restorations (2%) was recorded as an obvious mismatch, but otherwise no unacceptable scores were recorded. CONCLUSIONS: After two years of clinical service a high proportion (96%) of the Solitaire 2 restorations that were available for re-examination, placed in general dental practice settings, were found to be performing satisfactorily.

Adhesives↗
PubMed2001

Identification of MUC1 proteolytic cleavage sites in vivo.

Mucins are high molecular weight glycoproteins that provide a protective layer on epithelial surfaces and are involved in cell-cell interactions, signaling, and metastasis. The identification of several membrane-tethered mucins, including MUC1, MUC3, MUC4, and MUC12, has incited interest in the processing of these mucins and the mechanisms that govern their release from the cell surface. MUC1 consists of an extracellular subunit and a membrane-associated subunit. The two moieties are produced from a single precursor polypeptide by an early proteolytic cleavage event but remain associated throughout intracellular processing and transport to the cell surface. We identified the MUC1 proteolytic cleavage site and showed it to be identical in pancreas and colon cell lines and not to be influenced by the presence of heavily glycosylated tandem repeats. The MUC1 cleavage site shows homology with sequences in other cell-surface-associated proteins and may represent a common mechanism for processing of these molecules.

Amino Acid Sequence↗
PubMed2001

Early development of rat ventral root transitional zone: an immunohistochemical and morphometric study.

Bundles of ventral motoneuron axons cross the white matter of the spinal cord, emerge through the cord surface at the CNS-PNS transitional zone (TZ) and continue in the PNS as ventral rootlets. This study identifies immunohistochemical and morphometric changes which characterise the key events in early TZ formation in the rat. E18 is a landmark stage, since it is then that the major events of TZ differentiation are initiated. In the glial processes associated with the TZ, vimentin expression decreases, while that of GFAP increases. In the proximal rootlets the transient expression of CNS markers such as GFAP and of neural adhesion molecules such as HNK-1/N-CAM begin to decrease. Their resulting differential expression clearly defines the CNS-PNS interface. These changes coincide with the arrival of glial nuclei at the TZ. Cell clusters which appear on proximal ventral rootlet surfaces shortly after their emergence from the cord, have by E18 formed an extensive matrix of processes which segregates the axon bundle. This comprises the earliest of two well-defined barriers across the axon bundle. An important function may be to prevent Schwann cell invasion of the cord. Cluster cells display some immunohistochemical features in common with Schwann cells. The second barrier becomes fully established only at P2 and forms the definitive CNS-PNS interface. It consists of processes arising from astrocytes surrounding the TZ. Changes in the nuclear density of the cell types correspond closely to their segregating activity. The immunohistochemical and ultrastructural changes complement one another to deepen and enhance understanding of TZ development.

Animals↗
PubMed2001

In vivo glycosylation of mucin tandem repeats.

The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease.

Amino Acid Sequence↗
PubMed1999

Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice.

Brain-derived neurotrophic factor (BDNF) promotes long-term potentiation (LTP) at hippocampal CA1 synapses by a presynaptic enhancement of synaptic transmission during high-frequency stimulation (HFS). Here we have investigated the mechanisms of BDNF action using two lines of BDNF knockout mice. Among other presynaptic impairments, the mutant mice exhibited more pronounced synaptic fatigue at CA1 synapses during high-frequency stimulation, compared with wild-type animals. Quantitative analysis of CA1 synapses revealed a significant reduction in the number of vesicles docked at presynaptic active zones in the mutant mice. Synaptosomes prepared from the mutant hippocampus exhibited a marked decrease in the levels of synaptophysin as well as synaptobrevin [vesicle-associated membrane protein (VAMP-2)], a protein known to be involved in vesicle docking and fusion. Treatment of the mutant slices with BDNF reversed the electrophysiological and biochemical deficits in the hippocampal synapses. Taken together, these results suggest a novel role for BDNF in the mobilization and/or docking of synaptic vesicles to presynaptic active zones.

Animals↗
PubMed1999

Phosphorylation of the kinase suppressor of ras by associated kinases.

The kinase suppressor of Ras (KSR) is a loss-of-function allele that suppresses the rough eye phenotype of activated Ras in Drosophila and the multivulval phenotype of activated Ras in Caenorhabditis elegans. The physiological role of mammalian KSR is not known. We examined the mechanisms regulating the phosphorylation of this putative kinase in mammalian cells. Wild-type mouse KSR and a mutated KSR protein predicted to create a kinase-dead protein are phosphorylated identically in intact cells and in the immune complex. Phosphopeptide sequencing identified 10 in vivo phosphorylation sites in KSR, all of which reside in the 539 noncatalytic amino terminal amino acids. Expression of the amino terminal portion of KSR alone demonstrated that it was phosphorylated in the intact cell and in an immune complex in a manner indistinguishable from that of intact KSR. These data demonstrate that the kinase domain of KSR is irrelevant to its phosphorylation state and suggest that the phosphorylation of KSR and its association with a distinct set of kinases may affect intracellular signaling.

Amino Acid Sequence↗
PubMed1999

Women's knowledge about menopause, hormone replacement therapy (HRT), and interactions with healthcare providers: an exploratory study.

This community mail-based survey received responses from 665 women to questions in three areas: (1) sources of information about menopause, (2) knowledge of health risks associated with menopause, and (3) knowledge about hormone replacement therapy (HRT). Women received information from many sources, including healthcare providers, friends, and mothers, but the number one source of information about menopause was women's magazines (76%). Over half of women surveyed said they had left healthcare appointments with unanswered questions about menopause and HRT. Although women seemed to have a basic understanding of the symptoms of menopause, their knowledge of the long-term health risks affected by menopause was poor. For example, women were much more likely (60%) to know that osteoporosis risk increased with menopause than to know that heart disease risk increased (30%) despite the much higher prevalence and severity of heart disease as a health problem of menopausal women. Many women thought that menopause itself (independent of aging) increased the risk of breast cancer. This finding may help explain the low percentage of women who take HRT for menopause despite proven health benefits. It is clear that better education about menopause needs to be accomplished regarding the long-term risk associated with menopause and the pros and cons of HRT. Strategies for improving education and interactions with healthcare providers are suggested.

Aged↗
PubMed1998

Regulatory perspective on characterization and testing of orthopedic bone cements.

This paper provides a general regulatory background of acrylic bone cements, chemical composition information on several commercially available bone cements, physical and chemical methods of analyses, mechanical test methods, and risks and failure mechanisms of acrylic bone cements. Suggestions and recommendations presented in Tables 2 and 3 are not mandatory requirements but reflect data and methodologies which the FDA's Orthopedic Devices Branch (ORDB) believes to be acceptable to evaluate most pre-clinical data. FDA may require information in addition to that contained in this paper. In some instances, a sponsor may be able to sufficiently justify the omission of some tests. Although this paper describes certain administrative requirements, it does not take the place of the requirements contained in Title 21 of the Code of Federal Regulations (21 CFR) Parts 801, 807, 812, and 814 or those found in the statute.

Animals↗
PubMed1998

The ventral motoneurone axon bundle in the CNS--a cordone system?

In the developing CNS neighbouring structures are commonly separated by transient barriers termed cordones, some of which coincide with glial elements. Where ventral motoneuron axons cross the spinal white matter as intramedullary bundles to reach the CNS-PNS transitional zone they are surrounded from early development by a glial sleeve resembling a cordone. This becomes better developed with age and, like some cordones, persists into adult life. This could provide a radial conduit which might underlie the capacity of central segments of mature ventral motoneurone axons to regenerate. It may also provide a pathway for glial migration from the central cord to more superficial levels, including the transitional zone, where they help form the CNS-PNS barrier. Axons in the intramedullary bundle and in the surrounding ventral white column mature at different rates. Glial sleeve cells of the intramedullary bundles are apposed to both. Morphometric analysis of the axon-glial relationships of the two populations indicates that glial development proceeds at a different rate in relation to each axon class and that this is influenced by the degree of axonal maturation, which may in turn be related to target contact. Furthermore, early axon glial relationships differ between the two populations. For ventral motoneurone axons these take place in two stages: firstly, glial segregation of axons (resembling that in the PNS) and secondly, oligodendrocytic contact and ensheathment, which leads on to myelination. Axon-glial relationships in the ventral white column begin with the second of these events, as is more typical of early CNS myelination in general.

Age Factors↗
PubMed1997

Determination of deltoid fat pad thickness. Implications for needle length in adult immunization.

OBJECTIVE: To measure deltoid fat pad thickness and determine the optimal needle length for deltoid intramuscular immunization in healthy adults. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 220 healthy health care workers (126 women, 94 men) at the Mayo Medical Center, Rochester, Minn. MAIN OUTCOME MEASURES: Deltoid fat pad thickness determined by high-resolution ultrasound scanning, weight, height, and mid-deltoid arm circumference. RESULTS: We found a highly significant difference between women and men in deltoid fat pad thickness, with women having a thicker deltoid fat pad (11.7 vs 8.3 mm; P<.001). Women had a greater deltoid skin-fold thickness than men (34.7 vs 17.2 mm, P<.001) and an equal body mass index. According to the ultrasound findings, a standard 16-mm (5/8-in) needle would not have reached 5 mm into muscle in 17% (16/94) of men and 48.4% (61/126) of women in this study. CONCLUSIONS: Among healthy adults of the age range we studied, the following needle lengths appear to be appropriate for true deltoid intramuscular immunization: For men across the weight ranges we studied (59-118 kg), use of a 25-mm (1-in) needle would result in at least 5 mm of muscle penetration in all subjects. For women who weighed less than 60 kg, a 16-mm (5/8-in) needle would be sufficient to achieve muscle penetration of 5 mm. For women between 60 and 90 kg, a 25-mm (1-in) needle would be sufficient, and women greater than 90 kg would require a 38-mm (1.5-in) needle to ensure intramuscular administration.

Adult↗
PubMed1996

Work empowerment and organizational commitment.

As organizations struggle to deliver the same level and quality of services with fewer resources, administrators are challenged with redesigning workplaces to maximize nurses' commitment. This study used Kanter's Structural Theory of Organizational Behavior to examine the relationship between job-related empowerment perceptions of staff nurses and their commitment to the organization. Strategies for creating more empowered work environments are discussed.

Adult↗
PubMed1996

Male and female sexual and urinary function after total mesorectal excision with autonomic nerve preservation for carcinoma of the rectum.

BACKGROUND: We performed a study to assess sexual and urinary function after total mesorectal excision with autonomic nerve preservation for primary carcinoma of the rectum. STUDY DESIGN: We studied retrospectively postoperative sexual and urinary function in 136 (78 percent) of 175 eligible patients (82 males and 54 females) who responded to a standardized questionnaire. RESULTS: The ability to engage in intercourse was maintained by 86 percent of the patients younger than 60 years of age, and by 67 percent of patients 60 years and older. Eighty-seven percent of male patients maintained their ability to achieve orgasm. The type of surgery (abdominoperineal resection compared to low anterior resection), and age equal to or greater than 60 years were significantly associated with male sexual dysfunction. Of the female patients, 85 percent were able to experience arousal with vaginal lubrication and 91 percent could achieve orgasm. The majority of patients had few or no complaints related to urinary function. Serious urinary dysfunction such as neurogenic bladder was not encountered. CONCLUSIONS: Autonomic nerve preservation in association with total mesorectal excision reduces the operative morbidity rate and is successful in minimizing sexual and urinary dysfunction in the operative treatment of patients with carcinoma of the rectum.

Adult↗
PubMed1994

Divergent lineages for oligodendrocytes and astrocytes originating in the neonatal forebrain subventricular zone.

Although previous studies have revealed that the prenatal rat ventricular zone contains separate progenitor cells for neurons, astrocytes, and oligodendrocytes during the development of the cerebral cortex as early as the beginning of neurogenesis (Luskin et al., 1993; Grove et al., 1993), it is still unclear whether there are bipotential progenitor cells in the neonatal telencephalic subventricular zone which give rise to both astrocytes and oligodendrocytes during the peak of gliogenesis. To investigate this possibility, discrete groups of clonally related cells, generated by infecting progenitor cells of the neonatal subventricular zone with a retroviral lineage tracer, were analyzed ultrastructurally. An intracerebral injection of retrovirus encoding the reporter gene E. coli beta-galactosidase (lacZ) was made into the subventricular zone of newborn rats. Two weeks later their brains were perfused, sectioned, and histochemically reacted with X-Gal to identify at the light microscopic level clones of lacZ-positive cells. The sections were processed for electron microscopy to enable the identity of clonally related cells to be assessed at the ultrastructural level. All of the clones analyzed contained cells of the same phenotype and could be divided into four distinct types: immature cell clones situated in the subependymal zone surrounding the lateral ventricle, oligodendrocytes clones, and white or gray matter astrocyte clones. Not all of the cells in every clone displayed ultrastructural features of a mature cell. Rather, in some glial clones the lacZ-positive cells appeared to be at different stages of differentiation. However, we never encountered clones which contained both macroglial subtypes or clones containing neurons. Although the existence of bipotential progenitor cells cannot be completely dismissed, our results indicate the absence of progenitor cells in vivo in the neonatal subventricular zone which divide and generate astrocytes and oligodendrocytes.

Animals↗
PubMed1994

Clinical comparison of radiolocalization of two monoclonal antibodies (mAbs) against the TAG-72 antigen.

Ten patients with colorectal cancer metastases received 125I-B72.3 and 131I-CC49 prior to laparotomy (five patients received 1 mg, and five 20 mg of each mAb). Tumor:serum ratios of 131I-CC49 were better than those of 125I-B72.3 (P < 0.01 at 1 mg; P = 0.05 at 20 mg; P < 0.01 at both doses). All known lesions > or = 1 cm in diameter were visualized at the 20 mg dose. There was no difference in absolute tumor uptake of 125I-B72.3 or 131I-CC49. We conclude that mAb CC49 has better relative uptake in colorectal cancers than mAb B72.3.

Adrenal Gland Neoplasms↗
PubMed1993

Lesion-by-lesion comparison of computerized tomography and indium-111-labeled monoclonal antibody C110 radioimmunoscintigraphy in colorectal carcinoma: a multicenter trial.

C110 is an anti-carcinoembryonic antigen murine IgG1 monoclonal antibody. Indium-111-labeled C110 radioimmunoscintigraphy (RIS) in colorectal cancer was studied in 51 presurgical patients at four institutions. Planar and SPECT images were obtained at least twice between 48 and 96 hr after injection of 5 mCi/5 mg of 111In-C110. Fifty-one patients had 87 biopsy-proven lesions at surgery (57 hepatic, 30 extra-hepatic). Thirty-three patients (64.7%) had positive radionuclide scans, while 32 (62.8%) had positive CT scans (p = NS). While CT was better at overall lesion detection (62.1% versus 56%, p < 0.05), radionuclide scans were better than CT for extra-hepatic disease (60% versus 46.7%, p < 0.01). Hepatic metastases (52.6%) were visualized by Mab scans to selectively concentrate radioactivity. Uptake in draining lymph nodes was a significant limitation, making evaluation of these sites difficult. Indium-111-C110 shows selective uptake in metastatic colorectal cancer, including more than half of all hepatic lesions evaluated.

Adult↗
PubMed1991

Insulin secretion and action in patients with pancreatic cancer.

The authors investigated insulin secretory capacity and insulin action in 11 preoperative patients with pancreatic carcinoma and 15 age-matched and weight-matched healthy subjects (C). Five patients were classified as diabetic (D), two as impaired glucose tolerant (IGT), and four as nondiabetic (ND). Postabsorptive serum insulin levels (mean +/- SE, in uU/ml) in D (12 +/- 2), IGT (17 +/- 7), and ND (10 +/- 2) were comparable. After administration of 100 g of oral glucose, peak insulin achieved in D (60 +/- 11) was lower than in IGT (101 +/- 26) and ND (83 +/- 20), whereas peak insulin levels in IGT and ND were significantly (P less than 0.05) higher than in C (45 +/- 6). Comparable insulin response to nonglucose stimuli was documented in all subjects using the slow arginine infusion test with mean serum insulin of 27 +/- 4 in D, 28 +/- 6 in IGT, 34 +/- 10 in ND, and 32 +/- 5 in C. In six patients (P) and six controls, insulin action was assessed by the euglycemic hyperinsulinemic clamp technique, with glucose turnover rates estimated by [3-3H]glucose infusion. Steady-state plasma glucose concentrations were maintained at 92 +/- 3 (P) and 91 +/- 1 mg/dl (C). After insulin infusion at the rate of 1.0 mU/kg/min, comparable high physiologic insulin levels were observed in P (73 to 104 uU/ml) and in C (81 to 103 uU/ml). Postabsorptive rates of endogenous glucose appearance (Ra) were higher in P (2.86 to 3.02 mg/kg/min) than in C (1.50 to 2.80 mg/kg/min). At high physiologic insulin concentrations, negative Ra values were documented in all subjects, and complete suppression of Ra was assumed. Total body glucose use (M) was consistently lower in P (3.90 to 6.40 mg/kg/min) than in C (6.98 to 10.40 mg/kg/min), consistent with a state of insulin resistance. Patients with pancreatic cancer manifest insulin resistance by virtue of a decrease in total body glucose use (M) and decreased insulin response to glucose due to either inherent beta cell dysfunction or decreased islet cell mass. The latter is not identifiable by histologic morphology.

Adenocarcinoma↗