Incidence of bone formation by whole bone marrow cell suspensions and by its stromal cell cultures injected into kidney parenchyma of Balb/c mice.

The evaluation of incidence of bone formation by whole syngeneic bone marrow cell suspension and by bone marrow stromal cell cultured in vitro injection into kidney parenchyma was done. Bone tissue was found in 26 kidneys out of 100 injected with whole bone marrow cells suspension. Cultured stromal bone marrow cells grafted into kidney parenchyma produced ossicles in only 4 out of 101 injected kidneys. Such low incidence of bone forming ability of the marrow stromal cell cultures grafted into kidney indicate their useless for study on bone histogenesis in the kidney by murine marrow stromal cell cultures.

Non-adherent bone marrow cells are a rich source of cells forming bone in vivo.

Syngeneic, allogeneic and xenogeneic (rat) freshly isolated bone marow cells + stromal cell cultures maintained in vitro for 10-30 days, as well as non-adherent cells removed from these cultures on 3rd-4th day were injected into the kidney parenchyma of mice, immunosuppressed with hydrocortisone. In syngeneic grafts the immunosuppression was omitted. In all transplant systems bone tissue was formed inside the kidney with 20% to 32% variation. Bone produced by allogeneic and xenogeneic cells is subject to rejection when immunosuppression ceases, as the bone formed is of donor origin. The "floating" cells, regardless of the transplant system, normally discarded during media replacement, turned out to be efficient bone producers. This notion is of practical implication when bone marrow cells are used for bone healing.

Local hypertrophic/hyperplastic changes of keratinizing squamous epithelium of pinna induced by concanavalin A and other immunomodulators in mice.

Intradermal administration of concanavalin A, a potent T-cell mitogen, into an ear lap resulted in activation of chondrogenesis and stimulation of epidermis proliferation. This proliferation is sometimes invasive in character (pearls and epidermal nests form in the underlying connective tissue) but never turns into true cancerous lesions. This reaction can be delayed, but not prevented, by the prostaglandin inhibitor indomethacin. Stimulation of epidermis proliferation was also caused by administration of other immunomodulators, such as carrageenan type IV, Moloney sarcoma development, and rarely in the course of GvHr, but to much lesser degree than with concanavalin A. It is suggested that the same growth factors, which are mediators of local chondrocyte stimulation, are also mediators of keratinocyte activation.

The histophysiology of fracture healing.

The authors present, in somewhat simplified form, a synthetic collection of information pertaining to fracture healing form the histological perspective. The mechanisms of fracture healing are described in reference to the histological construction of bone, phases in the healing process, the reactions taking place at the fracture site, and the mechanisms for regulating these processes with growth and discrimination factors.

Fluvastatin increases heterotopically induced ossicles in mice.

1. The aim of the present study was to evaluate the influence of fluvastatin (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor) on heterotopic ossification (HO) induced by HeLa cells. 2. C57Bl/6 mice were injected with 3 x 10(6) HeLa cells into right thigh muscles. Mice in the experimental group received fluvastatin 1.2 mg/kg per day for 17 consecutive days, while mice in the control group received placebo. Intact mice served as an additional control. Seventeen days post-HeLa cell grafting, blood samples were collected to measure total serum cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol and alkaline phosphatase (AP). 3. In all animals injected with HeLa cells, the mass of mineral deposited in the induced ossicle was established after hydrolysis of soft tissues surrounding the induced ossicles. In fluvastatin-treated mice, the mass of mineral deposited in heterotopically induced ossicles was significantly increased, when compared to mice receiving placebo. This was followed by a significant decrease of TG concentration; whereas the levels of serum AP were not significantly affected. 4. These results indicate that administration of statins may affect heterotopic ossification. This may also have clinical implication, because patients predisposed to HO and receiving statins during hypocholesterolemic treatment, may be at even greater risk of HO.

Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23.

Hereditary nonchromaffin paragangliomas (PGL; glomus tumors; MIM 168000) are mostly benign, slow-growing tumors of the head and neck region, inherited from carrier fathers in an autosomal dominant fashion subject to genomic imprinting. Genetic linkage analysis in two large, unrelated Dutch families assigned PGL loci to two regions of chromosome 11, at 11q23 (PGL1) and 11q13.1 (PGL2). We ascertained a total of 11 North American PGL families and confirmed maternal imprinting (inactivation). In three of six families, linkage analysis provided evidence of linkage to the PGL1 locus at 11q23. Recombinants narrowed the critical region to an approximately 4.5-Mb interval flanked by markers D11S1647 and D11S622. Partial allelic loss of strictly maternal origin was detected in 5 of 19 tumors. The greatest degree of imbalance was detected at 11q23, distal to D11S1327 and proximal to CD3D. Age at onset of symptoms was significantly different between fathers and children (Wilcoxon rank-sum test, P < .002). Affected children had an earlier age at onset of symptoms in 39 of 57 father-child pairs (chi2 = 7.74, P < .006). However, a more conservative comparison of the number of pairs in which a child had > or = 5 years earlier age at onset (n = 33) vis-a-vis that of complementary pairs (n = 24) revealed no significant difference (chi2 = 1.42, P > .2). Whether these data represent genetic anticipation or ascertainment bias can be addressed only by analysis of a larger number of father-child pairs.