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Biomedical subjects

K R Jones

Publications and source records attributed to K R Jones.

At least 37 records · Page 2Linked to original sources

Efficient bicistronic expression of cre in mammalian cells.

Cre recombinase-mediated DNA recombination is proving to be a powerful technique for the generation of mosaic mutant mice. To develop this technology further, we have altered the cre gene to enhance its expression in mammalian cells and have tested its efficiency of expression in a bicistronic message. Using a transient transfection assay, we found that the extension of a eukaryotic translation initiation consensus sequence, the insertion of two N-terminal amino acids, and the mutation of a cryptic splice acceptor site did not detectably alter Cre recombinase activity. The addition of either of two introns resulted in an approximately 2-fold increase in recombination frequency. We then tested the relative efficacy of Cre-mediated recombination in several bicistronic messages having the encephalomyocarditis virus internal ribosome entry site (IRES). Recombination frequencies were only reduced 2-fold relative to a comparable monocistronic cre gene. The latter results indicate that it will be possible to generate transgenic mouse strains having tissue-specific expression of the Cre recombinase through integration of an IRES-cre gene without disabling the targeted gene.

Animals↗

Health status improvement after surgical correction of primary hyperparathyroidism in patients with high and low preoperative calcium levels.

BACKGROUND: We conducted a prospective cohort study to determine whether there are differences in functional health status between patients with low (< 10.9 mg/dL) and high (> or = 10.9 mg/dL) serum calcium levels before surgical correction of primary hyperparathyroidism (HPT) and to compare changes in health status after correction of primary HPT. METHODS: The SF-36 Health Survey, which provides demographic and condition-specific information, was used to obtain information on patients with primary HPT seen in a university hospital endocrine surgery clinic over a 4-year period before operation and again 2 months and 6 months after operation. RESULTS: A total of 155 patients were studied; 86 had calcium levels < 10.9 mg/dL (normal < 10.5 mg/dL) and 69 had serum calcium levels > or = 10.9 mg/dL (range 10.9 to 13.4 mg/dL). One hundred four patients completed 6-month reports, 55 with low calcium levels and 49 with high calcium levels. Both high and low calcium groups showed marked and virtually identical impairment of functional health status. Both groups showed marked improvement in health status at 2 months and additional improvement at 6 months, returning to normal or near normal in 6 of 8 SF-36 domains. CONCLUSIONS: Patients with primary hyperparathyroidism have significant functional health status impairment independent of the level of serum calcium. Dramatic improvement is seen after surgical correction. Referral for surgical treatment of primary HPT should not be delayed until serum calcium is elevated, as recommended in the 1990 National Institutes of Health consensus statement.

Calcium↗

Patterned expression of BDNF and NT-3 in the retina and anterior segment of the developing mammalian eye.

PURPOSE: The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are hypothesized to play an important role in vertebrate eye development because of their patterned expression in the developing and adult neuroretina, their regulated response to retinal and optic nerve injury, and the effects of altered neurotrophin signaling on retinal development. To further characterize the role of these neurotrophins in mammalian eye development and maintenance, the pattern of expression of BDNF and NT-3 was analyzed in the developing and mature mouse eye. METHODS: Using mouse strains in which the reporter gene lacZ, encoding the enzyme beta-galactosidase, was targeted to either the BDNF or NT-3 locus, the expression of BDNF and NT-3 in the eyes of mice heterozygous for these mutations was analyzed by enzyme histochemistry during embryogenesis, postnatal development, and adulthood. RESULTS: BDNF and NT-3 expression were first observed in the inner and outer segments of the developing optic cup at embryonic days 10.5 to 11.5. As the retina matured, BDNF expression was restricted to retinal ganglion cells and a subset of cells in the inner nuclear layer (INL), whereas NT-3 expression was confined to a small subset of cells in the INL and ganglion cell layer. Both neurotrophins were expressed within the developing retinal pigment epithelium. In the anterior segment, BDNF and NT-3 were expressed at high levels in the developing and mature ciliary epithelium. In the lens and cornea, however, these neurotrophins displayed distinct patterns of expression during development and adulthood. BDNF expression was found in the lens epithelium, immature trabecular meshwork, corneal endothelium, and corneal epithelium, whereas NT-3 expression was confined to the corneal epithelium. CONCLUSIONS: BDNF and NT-3 exhibit different, yet overlapping, patterns of expression during the development and differentiation of the mouse eye. In addition to the neuroretina, the spatiotemporal expression of BDNF and NT-3 may play an important role in the development and maintenance of the lens, ciliary body, trabecular meshwork, and cornea.

Animals↗

Features resembling Tourette's syndrome in developmental stutterers.

Developmental stuttering (DS) may be related to the extrapyramidal motor system and shares many clinical similarities with Tourette's syndrome (TS), which is widely believed to be associated with extrapyramidal dysfunction. Twenty-two stutterers were examined for neuropsychiatric features commonly seen in TS, including tics, obsessive-compulsive behaviors (OCB), and attention deficit disorders. Eleven stutterers displayed motor tics, and symptoms of OCB were observed at rates similar to those seen in persons with TS. Few stutterers demonstrated significant attentional deficits. Findings are consistent with models suggesting extrapyramidal involvement in DS and raise the possibility that DS and TS are pathogenetically related.

Adolescent↗

Differences in heartbeat awareness among males with higher and lower levels of systolic blood pressure.

Recent empirical findings related to the baroreceptor hypothesis indicate that elevated heart rate, pulse pressure, and blood pressure may dampen exteroception and interoception. We thus predicted that persons with elevated systolic blood pressure would be less able to accurately perceive their heartbeats and profit from feedback training. This study examined the plausibility of this hypothesis by exposing 57 male students (11 with elevated SBP levels and 46 with normotensive SBP levels) to the Whitehead heartbeat perception task with, and without, feedback training. Results indicated that participants with elevated SBP levels were more able to accurately perceive their heartbeats prior to, and after, feedback training. Participants with elevated SBP levels also showed a significant increase in heartbeat perception accuracy when they were provided with feedback training while participants with normotensive blood pressure levels did not show a significant response to feedback training. These findings are interpreted in terms of the ballistic perception model of cardiac awareness.

Adult↗

Do aluminium and/or glutamate induce Alzheimer PHF-like formation? An electron microscopic study.

Paired helical filaments (PHFs) constitute the majority of filaments in neurofibrillary tangles (NFTs), an Alzheimer's disease (AD) characteristic. PHFs consists of two filaments helically twisted around one another in a regular pattern. The effects of possible PHF-inducing candidates, namely aluminium and glutamate, were observed at the ultrastructural level in this investigation. Rat cerebral explants were exposed to aluminium, citric acid and glutamate singly or combined from 7-12 days in vitro (DIV), while control explants remained in basal medium. On 12 DIV, explants were processed for EM. Three-four EM explants were serially sectioned per condition. Ten 60 nm sections from five systematically sampled areas per explant were collected. One section was randomly chosen per sampled area and all neurons within it observed at 81,200x to record the presence of accumulations of curved filaments (CFs), straight filaments (SFs) or PHFs. Using stereological methods, absolute numbers and the percentage incidence of CFs and SFs were calculated. A significant increase in the frequency of neurons containing CF aggregations in aluminium explants compared to glutamate explants was found. There were no significant differences between conditions for neurons containing SF accumulations. Possible PHFs were observed in one aluminium/glutamate-treated explant. These results suggest that aluminium alone can cause significant formation of accumulations of C- or S-shaped CFs, some of which are double-stranded and twisted around one another regularly. However, structures that were possibly PHF-like were only observed in one aluminium-treated explant, thus making it premature to draw an association between aluminium and the induction of AD-like pathology.

Aluminum↗

Do aluminium and/or glutamate induce Alz-50 reactivity? A light microscopic immunohistochemical study.

Alzheimer's disease is thought to be characterized by conformational and phosphorylation changes in tau protein, leading to the formation of aggregations of paired helical filaments within neurons. Potential agents for inducing conformational changes in tau, namely aluminium and glutamate, were investigated in this study. Explant cultures of cortical neurons were established from embryonic day 17 rat fetuses. Cultures were exposed to aluminium, glutamate, aluminium/glutamate, aluminium/citric acid and citric acid (since aluminium is thought to enter cells via the transferrin receptor by complexing with citric acid) from 7-12 days in vitro. Control explants were exposed to basal medium only. On day 12, explants were paraffin-embedded. Four-six explants were serially sectioned per condition. For each explant, every 10th and adjacent 4 microm section were randomly selected and processed, with controls, for: (1) alcoholic morin histochemistry (to detect intracellular aluminium), (2) Perls' iron histochemistry (to control for the morin stain which also detects iron), (3) neurofilament immunohistochemistry (to estimate total neuronal number per explant) and (4) Alz-50 immunohistochemistry (to detect possible conformational changes in tau). The absolute number of stained/immunoreactive neurons was determined per explant. The percentage incidence was then determined per explant and averaged per condition. Explants in the aluminium conditions contained significant increases in the incidence of morin-positive aluminium containing neurons. There was also a significant increase in the incidence of Alz-50 positive neurons for the aluminium compared with control explants. These results suggest: (1) aluminium enters neurons and (2) aluminium alone induces possible conformational changes in tau as detected by the Alz-50 antibody, while aluminium combined with glutamate, or glutamate alone, do not.

Aluminum↗

Effects of implementing patient-centered care models on nurse and non-nurse managers.

Evaluation of new patient care delivery models often focuses on their impact on the role of the staff nurse and the introduction of a variety of assistive personnel. This article examines the effects of patient-centered care models on the roles of nurse and non-nurse managers. Interviews with 26 managers approximately 6 months after models have been implemented reveal a number of issues and challenges faced by the managers during and after implementation. The data provide a number of new insights not previously reported in the literature.

Allied Health Personnel↗

Allergic fungal sinusitis: CT findings.

PURPOSE: To determine the computed tomographic (CT) findings in patients with allergic fungal sinusitis. MATERIALS AND METHODS: The authors retrospectively reviewed CT scans and surgical and histopathologic reports in 45 patients (27 male, 18 female; age range, 8-68 years) with allergic fungal sinusitis from multiple institutions. The median age (25 years) and demographics of the patients were determined. Two head and neck radiologists together evaluated the CT scans for the presence of intrasinus high-attenuation areas, extent of sinus involvement, bone expansion and thinning, bone erosion, and extension of disease into the adjacent soft tissues. RESULTS: Allergic fungal sinusitis was more common in male patients and in patients aged 20-30 years. All patients had increased intrasinus attenuation at non-contrast material-enhanced CT. Multiple sinus involvement occurred in 43 patients. Bilateral involvement was more common than unilateral disease. Forty-four patients had complete opacification of at least one of the involved sinuses; 43 of these patients had expansion of an involved sinus, 42 had remodeling and thinning of the bony sinus walls, and 41 had erosion of the sinus wall. CONCLUSION: Allergic fungal sinusitis is a distinct clinical entity with nonspecific symptoms that may be initially suggested by the CT findings. These findings should alert the clinician to the possibility of allergic fungal sinusitis and prompt other diagnostic studies to establish the diagnosis and treatment plan.

Adolescent↗

Bartonella henselae antibody prevalence in free-ranging and captive wild felids from California.

In order to determine the importance of wild felids in the epidemiology of Bartonella spp. infection, 136 Nobuto strips or serum samples from free-ranging mountain lions (Felis concolor) and bobcats (Felis rufus) captured in California (USA) between 1985 and 1996 were tested for B. henselae antibodies (titer > or = 1:64) using an immunofluorescence test. Similarly, 124 serum samples from 114 captive wild cats representing 26 species or subspecies collected between 1991 and 1995 were retrieved from the serum banks of four California zoological parks. Fifty-three percent (33/62) of the bobcats, 35% (26/74) of the mountain lions, and 30% (34/114) of the captive wild felids (genera Acinonyx, Panthera and Felis) had B. henselae antibodies. In captive wild felids, prevalence varied widely among the species, but seropositivity was more likely to occur in the genus Felis than in the genus Acinonyx or Panthera. Prevalence was evenly distributed between sexes, except for free-ranging mountain lions. Antibody prevalence ranged from 25% in 0- to 2-yr-old captive felids to 35% in cats > or = 9-yr-old, but the highest antibody titers were observed in cats < 5-yr-old.

Age Factors↗