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Studies were carried out to characterize the effects of cyclosporines and FK506 on the formation and survival of osteoclasts deriving from mouse bone marrow cultures. Cyclosporin A (CsA), cyclosporin B (CsB), cyclosporin H (CsH), and FK506 all inhibited receptor activator of NFkappaB ligand (RANKL)-stimulated tartrate-resistant acid phosphatase (TRAP) activity and generation of TRAP+ multinucleated cells in the cultures. CsA and CsG were approximately equipotent, CsH was approximately one order of magnitude less potent than the other cyclosporines, and FK506 was approximately two orders of magnitude more potent than CsA and CsG. All of the inhibitors demonstrated greater potency and efficacy on decreasing the number of TRAP+ multinucleated cells than on decreasing total TRAP activity. Further evidence that late stages were more sensitive to inhibition was obtained in experiments in which CsA was present for different segments of the RANKL-stimulated culture period. CsA was as efficacious when added for the final 2 days of a 4-day culture as when added for the entire culture period, whereas it was less effective if added for only the first 2 days of the culture. When CsA or FK506 were added for 1 day to cultures in which osteoclasts had already formed, the numbers of TRAP+ osteoclasts decreased. Treatment with CsA or FK506 produced nuclear fragmentation and disruption of the multinucleated osteoclasts and an increase in caspase-3 activity. The apoptosis inhibitor z-VAD partially prevented the inhibitory effects of CsA and FK506 on the survival of TRAP+ multinucleated cells in the cultures and also preserved the normal osteoclast morphology. The data indicate that an important component of the inhibitory effects of CsA and FK506 on marrow-derived osteoclasts is the induction of apoptosis.

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Activin A, a member of the TGF-b superfamily, is abundant in bone matrix, but little is known about its physiological role in bone metabolism. The present study was undertaken to determine whether topical activin A can increase the bone mass of isografted bone. The tibiae were bilaterally dissected from a donor C3H/HeJ mouse and transplanted subcutaneously in the dorsal region of a recipient mouse. One isografted tibia was topically infused for either 1, 2, 3, or 4 weeks with activin A, using an osmotic minipump at a dose of 0.02, 0.2, or 2 ng/hr. The other tibia was infused with 0.9% NaCl (control). The following results were obtained: (1) Topical activin A (2 ng/hr) stimulated periosteal bone formation after 2 or 3 weeks. The bone area in a standardized transverse section averaged 1.3 fold that in the control. (2) Numerous cuboidal or conical osteoblasts appeared on the surface of newly formed bone after the infusion of activin A for 2 or 3 weeks. Autoradiographic studies using 3H-proline revealed that the surface area of newly formed bone labelled with autoradiographic silver grains was greater in activin A-treated bone than in the control, suggesting an increased synthesis and secretion of collagen by osteoblasts. (3) Topical activin A increased the number of osteoclasts after 2 to 4 weeks. Furthermore, enhanced or increased bone resorption was observed in the projected anterior site of activin A-treated bone after 4 weeks. These results suggest that topical activin A increases the bone mass of isografted bone by increasing bone turnover.

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Pain drawings were obtained from three groups of patients: 51 with lumbar disc herniation; 55 with lumbar stenosis, and 42 with benign low back pain. On grid assessment, patients with disc herniation and stenosis who complained of radiating pain or intermittent claudication had a significantly larger number of grids for the extremities than those with benign low back pain. In studies of the relation between the characteristics of the pain drawing and the outcome of treatment, most patients with 19 grids or less, or a score of 3 points or less, had a satisfactory outcome. Those with more grids or a higher score tended to be unsatisfactory. Pain drawing permits differentiation of the three patterns of pain and is useful for predicting the outcome of treatment.

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The antiviral extract from Rhodopseudomonas capsulata was purified and the predominant active component was defined as cis-vaccenic acid (Cl-8:1 delta 11) by gas-liquid chromatography and gas chromatography-mass spectrometry analyses. Antiviral activities of unsaturated fatty acids and related alcohols against T5 phage were also tested. Among them, linoelaidic acid, oleic acid, and petroselenyl alcohol inactivated 98%, 53%, 67% of T5 phage at the concentration of 50 micrograms/ml, respectively.

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The pathomechanism of atlantoaxial rotatory fixation (AARF) was studied using roentgenography and computerized tomography in affected children as well as cadaver studies of upper cervical spine anatomy. The increased incidence of AARF in children may be related to certain anatomical differences between children and adults. The dens-facet angle of the axis was steeper in children than in adults. Meniscus-like synovial folds were found in the C0/1 and C1/2 facet joints of the spines of children but not in those of adults.

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During the past 4 years, 15 fractures in 10 patients were encountered among 48 hospitalized patients with myopathies. The dominant sites were the femur (supracondylar) and humerus (subcapital). By assessing the total body potassium volume, bone mineral content, serum calcium, inorganic phosphorus, 25-OH vitamin D3, parathyroid hormone, and calcitonin, it is concluded that the proclivity to fracture in myopathic patients is caused by bone atrophy due to a lack of muscle tension related to decrease in muscle volume.

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Pathologic subtrochanteric fracture in a femur rarefied by fibrous dysplasia of bone was successfully treated with condylocephalic nailing and bone grafting. This procedure is recommended not only for traumatic fractures but also for pathologic fractures secondary to bone tumor.

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The fate of the articular cartilage of the hip joint with intracapsular neck fracture was studied by histological, histochemical and autoradiographic techniques and by using a polarized microscope and a scanning electron microscope. Cartilage specimens from 93 femoral heads and 7 acetabula were obtained from fractured hips 2 days to 4 1/3 years postfracture and from control hips with various disorders. The cartilage degeneration appeared 2 weeks after fracture and advanced steadily with time. The matrix was covered, invaded and ultimately replaced by the fibrous tissue. Chondrocyte viability, though it was lost from the surface, was recognized in the deep matrix even in the oldest fracture examined. It is concluded that the humoral factor directly caused by the injury as well as the biomechanical impairment, i.e. a loss of physical stress, may play an essential role in the pathogenesis of the degeneration. The possibility of regeneration was discussed.

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Sixty-one peripheral nerve repairs in 48 patients sutured by the funicular suture technique were followed up for a minimum of 2 years after operation, the average follow-up period being 48 months. Useful recovery was obtained in 100 per cent of cases with radial and musculocutaneous nerve repairs. Seventy-five per cent of cases with median, 82 per cent with ulnar and 88 per cent with digital nerve lesions attained "useful" grade recovery. In the lower extremity, the motor recovery was excellent, whereas the sensory recovery was poor. In two out of three cases where cable grafting was performed between important funiculi the result obtained was excellent. To obtain satisfactory neurological recovery, the funicular suture, technique using the surgical microscope is the method of choice for primary and secondary nerve suture and cable grafting.

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Autoradiographic studies using thymidine-3H reveal the mitosis of chondrocytes in degenerated joints, i.e. joints having secondary osteoarthritis or aseptic necrosis of the femoral head. The findings obtained provide additional support for the recent investigations regarding chondrocyte mitosis in primary osteoarthritic cartilage. Histologic and histochemical examinations suggest that a loss of glycosaminoglycans in the matrix is evidence for conversion of chondrocyte activity to mitosis which occurs, however, within the limit of "the point of irreversibility", analogous to the observations from the biochemical point of view. Biomechanical and nutritional factors are also discussed in relation to the results obtained from cartilages of the femoral heads in cases of femoral neck fracture and aseptic necrosis of the femoral head.

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The specimens from 19 femoral heads with various abnormalities are observed with scanning electron microscopy, comparing with light microscopic findings. Villi and plica appearance implies the fibrillated surface of degenerated cartilage with fibrous tissue proliferation. Beside these findings, craters with their associated undulations of concentric circles or guitar-shaped figures are visualized in the areas histologically showing the exposed cartilage of the deep zone. The undulations are correspondent to the fine clefts of the shredding surface. From the observations reported here, the existence of the lamellar system around the chondrocyte lacuna is proposed in the deep matrix of the articular cartilage.

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