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Biomedical subjects

J DeGroot

Publications and source records attributed to J DeGroot.

At least 19 recordsLinked to original sources
PubMed2001

Accumulation of advanced glycation end products decreases collagen turnover by bovine chondrocytes.

The integrity of the collagen network is essential for articular cartilage to fulfill its function in load support and distribution. Damage to the collagen network is one of the first characteristics of osteoarthritis. Since extensive collagen damage is considered irreversible, it is crucial that chondrocytes maintain a functional collagen network. We investigated the effects of advanced glycation end products (AGEs) on the turnover of collagen by articular cartilage chondrocytes. Increased AGE levels (by culturing in the presence of ribose) resulted in decreased collagen synthesis (P < 0.05) and decreased MMP-mediated collagen degradation (P < 0.02). The latter could be attributed to increased resistance of the collagen network to MMPs (P < 0.05) as well as the decreased production of MMPs by chondrocytes (P < 0.02). Turnover of a protein is determined by its synthesis and degradation rates and therefore these data indicate that collagen turnover is decreased at enhanced AGE levels. Since AGE levels in human cartilage increase approximately 50 fold between age 20 and 80, cartilage collagen turnover likely decreases with increasing age. Impaired collagen turnover adversely affects the capacity of chondrocytes to remodel and/or repair its extracellular matrix. Consequently, age-related accumulation of AGE (via decreased collagen turnover) may contribute to the development of cartilage damage in osteoarthritis.

Animals↗
PubMed2000

Effect of collagen turnover on the accumulation of advanced glycation end products.

Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidine. To test the hypothesis that this higher AGE accumulation is primarily the result of the slow turnover of cartilage collagen, AGE levels in cartilage and skin collagen were compared with the degree of racemization of aspartic acid (% d-Asp, a measure of the residence time of a protein). AGE (N(epsilon)-(carboxymethyl)lysine, N(epsilon)-(carboxyethyl)lysine, and pentosidine) and % d-Asp concentrations increased linearly with age in both cartilage and skin collagen (p < 0.0001). The rate of increase in AGEs was greater in cartilage collagen than in skin collagen (p < 0.0001). % d-Asp was also higher in cartilage collagen than in skin collagen (p < 0.0001), indicating that cartilage collagen has a longer residence time in the tissue, and thus a slower turnover, than skin collagen. In both types of collagen, AGE concentrations increased linearly with % d-Asp (p < 0.0005). Interestingly, the slopes of the curves of AGEs versus % d-Asp, i.e. the rates of accumulation of AGEs corrected for turnover, were identical for cartilage and skin collagen. The present study thus provides the first experimental evidence that protein turnover is a major determinant in AGE accumulation in different collagen types. From the age-related increases in % d-Asp the half-life of cartilage collagen was calculated to be 117 years and that of skin collagen 15 years, thereby providing the first reasonable estimates of the half-lives of these collagens.

Adolescent↗
PubMed2000

Age-related accumulation of Maillard reaction products in human articular cartilage collagen.

Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, pentosidine levels themselves represent <1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute substantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs pentosidine, N(epsilon)-(carboxymethyl)lysine, and N(epsilon)-(carboxyethyl)lysine increase with age in cartilage collagen (all P<0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P<0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. As a functional measure of glycation the digestibility of articular collagen by bacterial collagenase was investigated; digestibility decreased linearly with age, proportional to the extent of glycation. Furthermore, the arginine content and the sum of the hydroxylysine and lysine content of cartilage collagen decrease significantly with age (P<0.0001 and P<0. 01 respectively), possibly due to modification by the Maillard reaction. The observed relationship between glycation and amino acid modification has not been reported previously in vivo. Our present results indicate that extensive accumulation of a variety of Maillard reaction products occurs in cartilage collagen with age. Altogether our results support the hypothesis that glycation contributes to stiffer and more brittle cartilage with advancing age.

Adolescent↗
PubMed1999

Age-related decrease in proteoglycan synthesis of human articular chondrocytes: the role of nonenzymatic glycation.

OBJECTIVE: To examine the effect of nonenzymatic glycation of cartilage extracellular matrix on the synthetic activity of chondrocytes. METHODS: The proteoglycan-synthesis rate (35SO4(2-) incorporation) and levels of advanced nonenzymatic glycation (determined by high-performance liquid chromatography measurement of pentosidine) were evaluated in human articular cartilage from 129 donors, varying in age from 25 to 88 years, and in cartilage with enhanced levels of advanced glycation end-products (AGEs) resulting from incubation with ribose. RESULTS: Cartilage showed a strong age-related increase in pentosidine levels (r = 0.97, P < 0.0005) and, concomitantly, a decrease in proteoglycan synthesis (r = -0.98, P < 0.0002). This decrease in proteoglycan synthesis correlated with the increase in pentosidine (r = -0.95, P < 0.02). Moreover, the elevation of pentosidine levels in the in vitro-ribosylated cartilage was proportional with the decrease in proteoglycan synthesis (r = -0.95, P < 0.005). CONCLUSION: In both aged and in vitro AGE-enriched cartilage, the rate of proteoglycan synthesis was negatively correlated with the degree of glycation. This suggests that the age-related increase in cartilage AGE levels may be responsible, at least in part, for the age-related decline in the synthetic capacity of cartilage.

Adult↗
PubMed1998

Doxycycline inhibits collagen synthesis by differentiated articular chondrocytes.

Doxycycline (DOX) profoundly inhibited collagen synthesis by differentiated articular chondrocytes. At 25 microM, the rate of collagen synthesis was suppressed by more than 50% without affecting cell proliferation (DNA levels) and general protein synthesis (35S-Met and 35S-Cys incorporation). Steady-state mRNA levels of type II collagen were also reduced, indicating that DOX may have an effect at the transcriptional level of type II collagen. The IC50 value of DOX to downregulate collagen synthesis (17 microM) is close to DOX levels attained in vivo (< 10 microM), and it is more than ten-fold lower than the IC50 values to inhibit the activity of most matrix metalloproteinases (MMPs). As such, these findings support the hypothesis that the reduced severity of OA observed in the dog anterior cruciate ligament model resulting from prophylactic treatment with DOX may involve mechanisms other than MMP inhibition alone. Our findings suggest that prevention of changes in the chondrocyte phenotype may be involved in the beneficial effect of doxycycline in experimental osteoarthritis, for differentiated chondrocytes in early stages of osteoarthritis exhibit elevated collagen synthesis.

Animals↗
PubMed1990

Children at risk: I. Risk factors and child symptomatology.

The authors compared 134 6- to 12-year-old children from a military psychiatric clinic with a control sample to determine the salience of various risk factors in predicting levels of child psychopathology. Parents provided demographic information and completed standardized questionnaires on themselves and their children, while children completed two self-report symptom inventories. Results indicated that all hypothesized risk factors mediated effects on child psychopathology, but the effects of various risk factors differed as a function of the rater and type of psychopathological construct being measured. Generally, parental psychopathology and life stress mediated the greatest effects on overall child symptoms levels. Furthermore, the clinical and community samples differed in the presence and extent of risk factors. Results indicate the need for caution in studies of child psychopathology using only clinical samples and may suggest the importance of therapies based on environmental manipulations for a substantial proportion of patients seeking child psychiatric assistance.

Child↗
PubMed1986

Magnetic resonance imaging of the midbrain in Parkinson's disease.

We have analyzed magnetic resonance images of the midbrain in patients with Parkinson's disease, and have found that there is a narrowing of the signal from the pars compacta of the substantia nigra relative to controls. The nature of the histological changes that may be responsible for this effect is discussed. Magnetic resonance imaging has the potential of becoming a useful diagnostic tool in the management of parkinsonism.

Aged↗
PubMed1984

Magnetic resonance imaging of the nasopharynx.

Thirty subjects with normal nasopharyngeal anatomy and 12 patients with a variety of abnormalities were examined with computed tomography (CT) and magnetic resonance imaging (MR), using a prototype 0.35-T superconducting system. A spin-echo technique, a repetition time (TR) of 2.0 sec., and echo times (TE) of 28 and 56 msec. were optimal for depiction of both normal and abnormal anatomy. MR was superior to CT for display of both superficial and deep nasopharyngeal soft tissues in all 30 normal subjects and 10 of the 12 abnormal patients, clearly differentiating mucosal and lymphoid tissue (adenoids, lingual and palatine tonsils) from the surrounding musculature. MR was also superior to CT in distinguishing tumor from soft tissues and more sensitive to carotid sheath adenopathy, permitting a more detailed evaluation of retropharyngeal and deep cervical nodal metastases in 2 cases. Bones, calcification, and subtle abnormalities at the base of the skull were shown better by CT. The specificity of MR and its ability to differentiate nodal metastases from reactive lymphadenopathy require further evaluation.

Adolescent↗
PubMed1981

The CT-topography of retrobulbar anesthesia. Anatomic-clinical correlation of complications and suggestion of a modified technique.

The anatomic relationship of an injection needle as traditionally placed in retrobulbar anesthesia to optic nerve, orbital vessels and eye muscles is demonstrated by computed tomography. The clinical complications of retrobulbar injections are reviewed and correlated to the orbital topography in different positions of gaze, as analyzed in anatomic sections and CT images. The results indicate that with the transitional technique of retrobulbar injection the most important orbital structures are in the immediate neighbourhood of the needle. A different injection technique is discussed.

Anesthesia, Local↗
PubMed1980

Images of the optic nerve: anatomic-CT correlation.

The course of the intraorbital part of the optic nerve, as demonstrated on anatomic sections in various planes, is correlated with the appearance of the nerve in computed tomographic (CT) images. Discrepancies between the anatomic and CT appearance are analyzed and discussed. Since the optic nerve has a sinuous course in both the horizontal and vertical planes, no thin axial or sagittal section can be entirely parallel to the nerve. Any section will transsect the optic nerve obliquely, leading to an apparent hypodensity or "thinning" of certain segments as shown on CT. The appearance of the course of the nerve on reformatted CT images depends on the plane of the original CT section. Computed tomograms that are obtained with the eye in primary position do not allow reliable judgments regarding the course and size of the optic nerve.

Humans↗
PubMed1979

Lymphocyte blastogenic response to human thyroglobulin in Graves' disease, Hashimoto's thyroiditis, and metastatic thyroid cancer.

In view of the past contradictory reports concerning in vitro lymphocyte transformation induced by human thyroglobulin (Tg) in thyroid diseases, the present study was undertaken to re-examine the response using improved methods in cell separation, culture, and cell harvesting. It has been found that the optimal dose level of Tg for maximal blastogenesis in culture differs from patient to patient. Consequently, it is inappropriate to use a single dose level of Tg for evaluation of the blastogenesis in study groups. By using serial Tg dose levels of 0.5 through 30 micrograms/ml in cultures, it was found that that incidence of positive responders in Graves' disease was 69.2%, in Hashimoto's thyroiditis 71.4%, and in healthy controls 9.1%. Metastatic thyroid cancer patients responded in a 50% incidence. All of the positive responders in the cancer group had elevated Tg levels, but no anti-Tg antibody in their sera.

Adenocarcinoma↗
PubMed1973

Evaluation of new urinary tract infection screening devices.

Several new methods for detection of bacteriuria were studied to evaluate their usefulness as screening procedures. A new filter paper device incorporating dehydrated media and tetrazolium was found to be reliable when compared with the standard pour plate method in the laboratory and with the dip-slide method in a field test. It failed to detect yeasts and slowly growing streptococci. Antibiotics blocked the test when susceptible organisms were present. An agar-cup method was found to be quite reliable, but could be improved by use of differential media. The Griess test was confirmed in a small trial to be highly specific when used in conjunction with a first morning specimen, but of little value with random specimens. Phenzopyridine was found to give false positive reactions. The subnormal glucose test, although highly sensitive and specific, gave too many false positive tests to be useful other than as a screening method.

Agar↗
PubMedDate not supplied

Work and life: the end of the zero-sum game.

Most companies view work and personal life as competing priorities in a zero-sum game, in which a gain in one area means a loss in the other. From this traditional perspective, managers decide how their employees' work and personal lives should intersect and often view work-life programs as just so much social welfare. A new breed of managers, however, is trying a new tack, one in which managers and employees collaborate to achieve work and personal objectives to everyone's benefit. These managers are guided by three principles. The first is to clearly inform their employees about business priorities and to encourage them to be just as clear about personal priorities. The second is to recognize and support their employees as whole people, not only acknowledging but also celebrating their roles outside the office. The third is to continually experiment with the way work gets done, looking for approaches that enhance the organization's performance and allow employees to pursue personal goals. The managers who are acting on these principles have discovered that conflicts between work and personal priorities can actually be catalysts for identifying inefficiencies at the workplace. For example, one manager and his staff found a way to accommodate the increased workload at their 24-hour-a-day command center while granting the staff more concentrated time off. So far, these managers have usually been applying the principles without official sanction. But as the business impact of their approach becomes better appreciated, the authors predict, more and more companies will view these leaders as heralds of change.

Commerce↗