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Biomedical subjects

B Johnstone

Publications and source records attributed to B Johnstone.

At least 37 records · Page 2Linked to original sources
PubMed1999

Retrovirally transduced bone marrow stromal cells isolated from a mouse model of human osteogenesis imperfecta (oim) persist in bone and retain the ability to form cartilage and bone after extended passaging.

Bone marrow stromal cells isolated from a model of osteogenesis imperfecta (oim) mice, were transduced with a retrovirus (BAG) carrying the LacZ and neor genes after passage 21. The transduced cells retained the ability to express alkaline phosphatase activity in vitro when treated with recombinant human bone morphogenetic protein two (rhBMP-2), formed cartilage in vitro in aggregate cultures and formed bone in ceramic cubes after 6 weeks of implantation in nude mice. X-gal staining of ceramic cubes seeded with the transduced cells demonstrated the presence of LacZ-positive cells on the edges of bone and also in the lacunae of the newly formed bone 6 weeks after implantation. After infusion into femurs of oim mice, the transduced cells were detected in the marrow cavity and on the edges of the trabecular bone of the injected and contralateral femurs by X-gal staining and PCR analysis at 4, 10, 20, 30 and 40 days after injection. The LacZ gene was also detected in the lung and liver of the recipient mice at 4 and 10 days after injection but not at later time-periods. The present findings suggest that long-term cultured bone marrow stromal cells from osteogenesis imperfecta (OI) animals have the potential to traffic through the circulatory system, home to bone, form bone and continue to express exogenous genes. These findings open the possibility of using these cells as vehicles to deliver normal genes to bone as an alternative approach for the treatment of some forms of OI and certain other bone acquired and genetic diseases.

Alkaline Phosphatase↗
PubMed1999

Variability of neuropsychological deficits associated with carbon monoxide poisoning: four case reports.

Carbon monoxide (CO) poisoning is associated with variable neuropsychological deficits, depending on levels of CO exposure and individual differences. Studies to date have reported variable findings, as their subjects have been exposed to different levels of CO from different poisoning sources. Four unique case studies are presented, all of whom experienced the same level of CO poisoning (17-29%) in the same accident. Two of the individuals were brothers with an identical genetic disorder (i.e. syndactylism) and the other two were brother/sister. The results indicated: (1) variable neuropsychological deficits despite similar levels of CO poisoning; (2) consistent estimated decline in intelligence; (3) similar memory decline for the two brothers, but not for the brother and sister; and (4) consistent late-onset emotional-behavioural difficulties. The results also suggested that the neuropsychological and emotional-behavioural deficits had an impact on the individual's ability to work.

Adolescent↗
PubMed1999

Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge.

The aim of this study was to investigate the potential of a composite matrix, containing esterified hyaluronic acid and gelatin, to facilitate the osteochondral differentiation of culture-expanded, bone marrow-derived mesenchymal progenitor cells. The cell loading characteristics and the effects of the matrix on cell differentiation were examined in vitro and in vivo. Empty and cell-loaded composites were cultivated for up to 28 days in a chemically defined medium with or without transforming growth factor-beta1 (TGF-beta1). A type II collagen-rich extracellular matrix was produced by cells loaded in the matrix and cultured in the presence of TGF-beta1. Empty and cell-loaded matrices were also implanted subcutaneously in immunodeficient mice. Three types of implant were used: empty (group I), cell-loaded matrices (Group II), and cell-loaded matrices cultured for 14 days in vitro in defined medium with TGF-beta1 (group III). No osteochondral differentiation was found in implanted empty matrices; however, the matrix supported osteochondrogenic cell differentiation in the cell-loaded implants. Preculture in vitro in a chondrogenic medium increased the percentage of osteochondral tissue found in the constructs after 3 weeks. These results indicate the potential use of this composite matrix for delivery of bone marrow-derived mesenchymal progenitor cells for the repair of chondral and osseous defects. The results also indicate that this composite matrix is useful for in vitro tissue engineering.

Animals↗
PubMed1999

Neuropsychological impairments, vocational outcomes, and financial costs for individuals with traumatic brain injury receiving state vocational rehabilitation services.

OBJECTIVE: To determine the relationship among neuropsychological variables, vocational outcomes, and vocational costs for Missouri Division of Vocational Rehabilitation (MO-DVR) clients with traumatic brain injury (TBI). DESIGN: Clients referred for neuropsychological evaluations were followed until DVR case closure. Subjects were grouped according to the following DVR status at case closure: Successfully Employed, Services Interrupted, and No Services Provided. Spearman correlations with Bonferroni corrections were calculated to determine relationships among variables, and Kruskal-Wallis nonparametric one-way analyses of variance (ANOVAs) were conducted to evaluate differences in DVR group status in terms of neuropsychological variables and DVR costs. SETTING: All evaluations were completed through a Midwestern university neuropsychology laboratory. PATIENTS: 110 consecutively referred DVR clients with nonacute TBI referred for neuropsychological evaluation. MAIN OUTCOME MEASURES: Absolute level (ie, raw/standard scores) of neuropsychological functioning and relative degree of decline in: intelligence (WAIS-R), memory (WMS-R General and Delayed Memory Indices), attention (WMS-R Attention Index), speed of processing (Trails A), and cognitive flexibility (Trails B); DVR costs at closure. RESULTS: 1) Surprisingly, the Successfully Employed group had significantly greater neuropsychological impairments; 2) Greater decline in delayed memory was associated with higher DVR costs (r = -0.30, P <.05); and 3) More indices of relative decline were significantly correlated with vocational outcomes (5/6) than were indices of absolute functioning (3/6). CONCLUSIONS: DVR is effective in providing services to individuals with the most significant neuropsychological deficits; it is important to consider both absolute level of functioning and relative decline in functioning when evaluating TBI.

Adolescent↗
PubMed1999

Autologous mesenchymal progenitor cells in articular cartilage repair.

The lack of repair of articular cartilage where the damage does not penetrate the subchondral bone indicates the importance of marrow components in the repair of the articular cartilage. In adult animals, there is an inability of articular cartilage chondrocytes to heal chondral defects, but if the damage extends beyond the subchondral bone, a repair process ensues in which mesenchymal progenitor cells migrate into the injured site and undergo chondrogenic differentiation. However, analysis of animal models and human biopsy samples indicates that fibrocartilage, rather than true articular cartilage is the predominant tissue synthesized. To improve this outcome, the use of cell based implants of culture expanded progenitor cells from various sources has been proposed and attempted. This paper describes some of the age related differences in the natural repair of osteochondral defects, the in vitro characterization of the chondrogenic potential of certain mesenchymal cell types, and some of the characteristics required of cell and matrix constructs that may be used for repair or regeneration of articular cartilage.

Animals↗
PubMed1999

A quadripotential mesenchymal progenitor cell isolated from the marrow of an adult mouse.

Adult marrow contains mesenchymal progenitor cells (MPCs) that have multiple differentiation potentials. A conditionally immortalized MPC clone, BMC9, has been identified that exhibits four mesenchymal cell phenotypes: chondrocyte, adipocyte, stromal (support osteoclast formation), and osteoblast. The BMC9 clone, control brain fibroblasts and another marrow-derived clone, BMC10, were isolated from a transgenic mouse (H-2Kb-tsA58) containing a gene for conditional immortality. To test for chondrogenic potential, cells were cultured in defined medium containing 10 ng/ml transforming growth factor beta and 10-7 M dexamethasone in 15-ml polypropylene tubes ("aggregate cultures"). Adipogenic potential was quantitated by flow cytometry of Nile Red-stained cells cultured for 1 and 2 weeks in medium containing isobutyl methylxanthine, indomethacin, insulin, and dexamethasone. Support of osteoclast formation was measured by quantitating multinucleated tartrate-resistant acid phosphatase-positive cells in spleen cell cocultures of test clones (immortomouse clones and positive control ST2 cells) cultured in the presence of 10-7 M vitamin D3 and 150 mM ascorbate-2-phosphate. In vivo osteogenic potential was assayed by histologic examination of bone formation in subcutaneous implants, into athymic mouse hosts, of a composite of cells combined with porous calcium phosphate ceramics. The bone marrow-derived clone BMC9 has the potential to express each of the four mesenchymal characteristics tested, while brain fibroblasts, tested under identical conditions, did not exhibit any of these four mesenchymal characteristics. BMC10 cells exhibited osteogenic and chondrogenic phenotypes, but showed only minimal expression of adipocytic or osteoclast-supportive phenotypes. Clone BMC9 is, minimally, a quadripotential MPC isolated from the marrow of an adult mouse that can differentiate into cartilage and adipose, support osteoclast formation, and form bone. The BMC9 clone is an example of an adult-derived multipotential progenitor cell that is situated early in the mesenchymal lineage.

Adipocytes↗
PubMed1998

In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells.

A culture system that facilitates the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal progenitor cells has been developed. Cells obtained in bone marrow aspirates were first isolated by monolayer culture and then transferred into tubes and allowed to form three-dimensional aggregates in a chemically defined medium. The inclusion of 10(-7) M dexamethasone in the medium induced chondrogenic differentiation of cells within the aggregate as evidenced by the appearance of toluidine blue metachromasia and the immunohistochemical detection of type II collagen as early as 7 days after beginning three-dimensional culture. After 21 days, the matrix of the entire aggregate contained type II collagen. By 14 days of culture, there was also evidence for type X collagen present in the matrix and the cells morphologically resembled hypertrophic chondrocytes. However, chondrogenic differentiation was achieved in only approximately 25% of the marrow cell preparations used. In contrast, with the addition of transforming growth factor-beta 1 (TGF-beta 1), chondrogenesis was induced in all marrow cell preparations, with or without the presence of 10(-7) M dexamethasone. The induction of chondrogenesis was accompanied by an increase in the alkaline phosphatase activity of the aggregated cells. The results of RT-PCR experiments indicated that both type IIA and IIB collagen mRNAs were detected by 7 days postaggregation as was mRNA for type X collagen. Conversely, the expression of the type I collagen mRNA was detected in the preaggregate cells but was no longer detectable at 7 days after aggregation. These results provide histological, immunohistochemical, and molecular evidence for the in vitro chondrogenic differentiation of adult mammalian progenitor cells derived from bone marrow.

Alkaline Phosphatase↗
PubMed1998

The effects of normal ageing on neuropsychological functioning following traumatic brain injury.

Increasing age is associated with greater absolute neuropsychological impairment (e.g. slower processing speed, diminished memory), although it is unclear if older individuals with traumatic brain injury (TBI) show greater relative impairment than younger individuals with TBI. The current study evaluated the effects of normal ageing on TBI by using age-based normative data to calculate indices of relative decline from pre-morbid levels (expressed as z-deficit scores) for different age groups (20-39 years, 40-59 years, 60+ years). The sample included 279 individuals with TBI between the ages of 20 and 65 who were assessed in a department of rehabilitation neuropsychology laboratory over a 4-year period. Spearman correlations and ANOVAs did not show age-related differences in relative memory, attention or speed of processing abilities, although results did indicate that increasing age is associated with relatively less impairment in intelligence. The results suggest that the greater neuropsychological impairment noted in older individuals with TBI is most likely related to normal ageing. The importance of considering both absolute and relative degrees of impairment is discussed.

Achievement↗
PubMed1998

The role of osteochondral progenitor cells in fracture repair.

The repair of a fracture necessarily entails synthesis of osseous tissue requiring the transformation of undifferentiated osteochondral progenitor cells to mature osteoblasts and chondrocytes. Owen and Friedenstein proposed that there are stem cells for all mesenchymal tissues, resident in bone marrow throughout life, that have a lineage comparable to that described for hematopoiesis. Subsequent with this initial study, marrow derived and periosteal derived progenitor cells have been shown to produce bone and cartilage in numerous in vivo and in vitro studies. The differentiation process appears to depend heavily on the influences of numerous cytokines, especially the transforming growth factor beta superfamily. Initial cartilage formation from progenitor cells is important in any secondary fracture repair. In the in vitro study of chondrogenesis, the marrow derived progenitor cells were shown to differentiate into their terminal phenotype, the hypertrophic chondrocyte, as indicated by the detection of Type X collagen messenger ribonucleic acid and protein. A concomitant elevation in the alkaline phosphatase level suggests that these cells are ready to mineralize. Despite the importance of these cells in fracture repair, the characterization of these cells and the mechanism of their differentiation have only begun to be explored.

Alkaline Phosphatase↗
PubMed1998

The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells.

Mesenchymal progenitor cells provide a source of cells for the repair of musculoskeletal tissue. However, in vitro models are needed to study the mechanisms of differentiation of progenitor cells. This study demonstrated the successful induction of in vitro chondrogenesis with human bone-marrow-derived osteochondral progenitor cells in a reliable and reproducible culture system. Human bone marrow was removed and fractionated, and adherent cell cultures were established. The cells were then passaged into an aggregate culture system in a serum-free medium. Initially, the cell aggregates contained type-I collagen and neither type-II nor type-X collagen was detected. Type-II collagen was typically detected in the matrix by the fifth day, with the immunoreactivity localized in the region of metachromatic staining. By the fourteenth day, type-II and type-X collagen were detected throughout the cell aggregates, except for an outer region of flattened, perichondrial-like cells in a matrix rich in type-I collagen. Aggrecan and link protein were detected in extracts of the cell aggregates, providing evidence that large aggregating proteoglycans of the type found in cartilaginous tissues had been synthesized by the newly differentiating chondrocytic cells; the small proteoglycans, biglycan and decorin, were also detected in extracts. Immunohistochemical staining with antibodies specific for chondroitin 4-sulfate and keratan sulfate demonstrated a uniform distribution of proteoglycans throughout the extracellular matrix of the cell aggregates. When the bone-marrow-derived cell preparations were passaged in monolayer culture as many as twenty times, with cells allowed to grow to confluence at each passage, the chondrogenic potential of the cells was maintained after each passage.

Adult↗
PubMed1998

Utility of a seven-subtest version of the WAIS-R among an Alzheimer's disease sample.

Recent health care sector changes have created a need for shorter, more focused neuropsychological assessments. The WAIS-R provides useful information on patients' general cognitive abilities, but poses problems in that it is time-consuming and may contribute to fatigue, especially among geriatric patients with dementia. This study evaluated Ward's (1990) 7-subtest version of the WAIS-R among 32 patients with presumptive Alzheimer's disease. Among all patients, the abbreviated test underestimated full WAIS-R scores by an average of 2.0, 0.2, and 1.8 points for the Verbal Intelligence Quotient (VIQ), Performance Intelligent Quotient (PIQ), and Full-Scale Intelligence Quotient (FSIQ). This general finding held true regardless of whether scores were generated using the standard WAIS-R method (for patients age 75 and younger) or using age corrections (i.e., Mayo Older Americans' Normative Studies [MOANS]) for older patients. Most patients scored within the mean standard errors of measurement defined in the WAIS-R manual for VIQ, PIQ, and FSIQ. In general, the 7-subtest and full versions of the WAIS-R yielded similar findings among this closely screened sample, but further testing among a more typical sample of patients with multiple risk factors for dementing conditions is needed.

Journal Article↗
PubMed1997

Clinical utility of a seven subtest WAIS-R short form in the neuropsychological assessment of traumatic brain injury.

Comparison of IQ scores from the standard Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Ward (1990) seven-subtest short form (WAIS-R/7 SF) was performed on a sample of 459 patients with traumatic brain injury due to head trauma. The results indicate that this short form provides Verbal, Performance, and Full Scale IQ scores that vary little from the complete WAIS-R, at approximately one-half the typical administration time. The seven subtest short form predicted WAIS-R Full Scale IQ within 6 points in 95% of this clinical sample, with Verbal-Performance IQ discrepancies that were highly correlated (r(s) =.85, p <.0001). No differential gender effect in proration of IQs was found. Applications and pitfalls of abbreviated neuropsychological testing batteries are discussed, with utilization of the WAIS-R/7 SF offered as a means to reduce intelligence testing time while maintaining the ability to detect subtle information processing abnormalities with appropriate supplemental tasks.

Journal Article↗
PubMed1997

Preparing neuropsychologists for the future: The need for additional training guidelines.

New guidelines for training in neuropsychology are needed for several reasons: increased diagnostic accuracy of neuroradiologic techniques: an increasing need for functional neuropsychological evaluations; emergence of other psychological specialties; and managed care/economic factors. Current INS-Division 40 guidelines emphasize neurological and diagnostic areas with minimal suggestions for training in rehabilitation and functional issues. The recent publication of training guidelines for Rehabilitation Psychology (APA Division 22) illustrates weaknesses in Division 40 training. It is proposed that neuropsychological training guidelines (formal guidelines and informal training experiences) incorporate another content area for training and demonstration of competency, defined as Functional Outcomes. Specific training is suggested in: (a) issues in disability; (b) ecological validity of tests; (c) vocational evaluation/training; (d) academic programs for students with disabilities; (e) independent living resources; (f) specific cognitive-behavioral interventions; (g) resources for individuals with disabilities; and (h) government assistance programs for individuals with disabilities.

Journal Article↗
PubMed1997

Determining neuropsychological impairment using estimates of premorbid intelligence: comparing methods based on level of education versus reading scores.

When inferring brain dysfunction, test scores are typically compared to normative data based on estimates of premorbid intelligence (e.g., by educational level or reading scores). However, these methods are likely to lead to differing results, with important diagnostic and forensic implications. The current study compared estimates of impairment (reported in z-scores) based on educational level versus reading scores in a population with traumatic brain injury. The study included 174 patients (M age = 27.3; M education = 12.3) evaluated as outpatients at a university hospital rehabilitation department. Wilcoxen ranked sign tests indicated that the two methods yielded estimates that were statistically different (p <.0001) for all variables. The education based method yielded greater estimates of impairment than the reading score method for WAIS-R FIQ. Grip Strength, and Finger Tapping, with a pattern of generally consistent impairment across cognitive/motor areas (z-score range = -0.59 to -.97). In contrast, the reading score based method yielded greater estimates of impairment in processing speed (Trails A) and flexibility (Trails B), with a wider range of impairment noted between cognitive and motor domains (z-score range = +0.21 to -2.95). Clinical implications are discussed.

Journal Article↗
PubMed1996

Experimental osteoarthritis in dogs: a comparison of the Pond-Nuki and medial arthrotomy methods.

Lesions induced by transecting the cranial cruciate ligament in two surgical models of osteoarthritis (OA) in mature, male, cross-bred dogs were compared by using an established grading system and alternatives. Previously, we relied on evaluations of lesions in articular cartilage on femurs alone. No statistically significant differences were found between grades for lesions in cartilage when either treated or control joints were compared by surgical method. Because the Pond-Nuki method yielded statistically significant differences between grades for lesions affecting treated and control femurs or tibias, and for some parameters indicative of synovitis, we preferred this method of surgery. Although by using the medial arthrotomy method of surgery, we were able to destabilize the joint in a more consistent manner, significant differences between treated and control joints were found for lesions on tibias, but not femurs, a frequent site for OA in humans. Suggestions are made for enhancing the surgical models and for a more holistic approach to evaluating joints morphologically.

Animals↗
PubMed1996

The longitudinal stability of the WRAT-R Reading subtest: is it an appropriate estimate of premorbid intelligence?

Reading tests are assumed to be accurate estimates of premorbid intelligence, based on the belief that reading remains relatively stable following cerebral injury/disease. However, this assumption has been primarily inferred only from studies comparing differences in reading/intelligence measures between neurologically impaired and normal groups. The current study, using within-subject comparisons, compared the longitudinal stability of reading (WRAT-R/3) and intelligence (WAIS-R FIQ) scores for 39 individuals with cognitive dysfunction referred for repeat neuropsychological evaluation. Wilcoxon signed-ranks tests indicated that reading scores: (1) did not statistically change for those demonstrating intellectual decline (> 0 point decline in FIQ), or for those who remained relatively stable (FIQ increase between 0 and 6 points) over retest, but (2) did significantly improve for those demonstrating intellectual improvement greater than 6 points. These results suggest that reading scores may be appropriately considered as "hold" tests for individuals who intellectually decline/remain stable over time, but not for those demonstrating significant intellectual improvement. Additionally, significant variability in reading score decline/improvement suggests that caution must be used when estimating premorbid intelligence based on WRAT-R/3 Reading scores.

Achievement↗