Family characteristics and behavior problems of suicidal and non-suicidal children and adolescents.

The present study examined familial and individual variables in youngsters at high risk for suicide and non-suicidal youngsters. One hundred inpatient children and adolescents completed a battery of questionnaires including, FACES II, Family Strengths, and Problem Behavior Scales, to assess family dysfunction and individual behavior problems. The results indicated that suicidal youngsters have lower pride in their families and perceived them as less adaptable than non-suicidal youngsters as indicated by scores on the Family Strengths and FACES II, respectively. Scores on the Problem Behavior Scales indicated that suicidal youngsters also exhibited self-inflicted behaviors, withdrawal from others, little interest in activities, poor concentration, and difficulties with sleeping. In addition, youths at risk for suicide were more likely to be diagnosed with a mood disorder, including major depressive disorder and dysthymia, as well as substance abuse and phobias. These findings suggest that suicidal youngsters' negative perceptions of their families and their maladaptive behaviors should be given special attention in designing appropriate interventions. In this way, treatment would likely be effective by providing appropriate coping skills and preventing future suicidal attempts in high risk youngsters.

Type X collagen isolated from the hypertrophic cartilage of embryonic chick tibiae contains both hydroxylysyl- and lysylpyridinoline cross-links.

Hypertrophic cartilage from the tibiotarsus of Day 20 chick embryonic tibiae was found to contain an unusually high concentration of lysylpyridinoline (LP), a nonreducible collagen cross-link normally found only in bone and dentin but not in cartilage. Since type X collagen is abundant in this cartilage, research was conducted to see if type X was the primary source of LP. The 45-kDa pepsin-resistant form of type X was purified by immunoaffinity chromatography. It contained a high concentration of the LP cross-link while type II contained primarily hydroxylysylpyridinoline (HP), the predominant cross-link in cartilage. This, to our knowledge is the first time that type X has been shown directly to form nonreducible cross-links and that a collagen other than type I has a high level of LP. Also, it is interesting that the HP and LP cross-links are found in a collagen that is degraded so rapidly. Possible explanations for these findings are discussed.

Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation.

OBJECTIVE: The effects of doxycycline were tested in an in vitro system in which the cartilages of embryonic avian tibias are completely degraded. METHODS: Tibias were cultured with 5, 20, or 40 microgram/ml doxycycline. Control tibias were cultured without doxycycline. Conditioned media and tissue sections were examined for enzyme activity and matrix loss. RESULTS: Cartilages were not resorbed in the presence of doxycycline, whereas control cartilages were completely degraded. Collagen degradation was reduced in association with treatment with doxycycline at all doses studied. Higher concentrations of doxycycline reduced collagenase and gelatinase activity and prevented proteoglycan loss, cell death, and deposition of type X collagen in the cartilage matrix; in addition, treatment with doxycycline at higher concentrations caused increases in the length of the hypertrophic region. CONCLUSION: The effects of doxycycline extend beyond inhibition of the proteolytic enzymes by stimulating cartilage growth and disrupting the terminal differentiation of chondrocytes.

Type X collagen degradation in long-term serum-free culture of the embryonic chick tibia following production of active collagenase and gelatinase.

Type X collagen has a very limited distribution during skeletal development in regions of hypertrophic cartilage destined for degradation. In solution assay, type X collagen is degraded to a 32-kDa cleavage product which is resistant to further degradation, suggesting this product may have a function in skeletal development. In this study, we have identified the 32-kDa cleavage product of type X collagen present in the conditioned media (CM) during incubation of isolated 12-day chick tibiae in the absence of serum. In this culture system, chondrocytes throughout the tibial cartilages hypertrophied and deposited type X collagen within their matrix. During culture, the cartilage matrix was degraded in two stages. First proteoglycan was lost followed by degradation of the collagenous components. Collagen degradation was accompanied by the release of active interstitial collagenase and gelatinase into the CM. Purified type X collagen incubated in this CM was cleaved to form a 32-kDa product which was resistant to further degradation. This cleavage product has the same electrophoretic mobility as the 32-kDa chain produced by purified human collagenase.

The influence of bone and marrow on cartilage hypertrophy and degradation during 30-day serum-free culture of the embryonic chick tibia.

In this study, an organ culture system is defined which demonstrates complete loss of cartilage matrix from embryonic chick tibiae. Efficient loss of the cartilage matrix occurs within 30 days of serum-free culture only when the intact tibiae containing bone, marrow, and cartilage tissue are cultured. During organ culture nonhypertrophic chondrocytes become hypertrophic and stain positively for type X collagen and alkaline phosphatase. The cartilage loses Safranin O staining, and finally all cartilage matrix disappears leaving the bony collar and marrow cells. If the tibial cartilage is separated from the bony collar and cultured alone in serum-free medium, the nonhypertrophic chondrocytes also hypertrophy; the matrix loses Safranin O staining; however, some components of the matrix including type X collagen still remain after 30 days. In the presence of serum, the chondrocytes will hypertrophy but cartilage degradation is not evident. The results of this study support the conclusions that 1) hypertrophy is inherently programmed in the chondrocyte and 2) while Safranin O staining of cartilage cultured alone is diminished in serum-free organ culture, the degradation of cartilage is complete only when bone and marrow are also present.

Late events in chondrocyte differentiation: hypertrophy, type X collagen synthesis and matrix calcification.

During endochondral bone formation chondrocytes pass through several stages of differentiation which are characterized by cell proliferation, matrix synthesis and cell hypertrophy. Type X collagen is synthesized in vivo after chondrocytes have become hypertrophic, but before abundant mineral accumulates in the cartilage extracellular matrix. The molecule is also present in the uncalcified membranes of the avian eggshell. Type X collagen synthesis increased with the concentration of calcium phosphate deposited in the cell layer of chondrocyte cultures. The addition of calcium chloride to chondrocyte cultures increased the synthesis of type X collagen in a dose-and time-dependent manner.