Morphomechanics of the humero-ulnar joint: II. Concave incongruity determines the distribution of load and subchondral mineralization

Background: A deeper joint socket (concave incongruity) is found at most angles of flexion of the humero-ulnar joint and maintained over a wide range of physiological loading. It is, however, unclear how far this incongruity affects the distribution of load and subchondral mineralization of this joint as compared with a congruous configuration. Methods: Two nonlinear, axisymmetrical finite element models with two cartilage layers were constructed, one congruous and one incongruous, with a joint space of realistic magnitude. The distribution of subchondral mineralization was determined by computed tomography osteoabsorptiometry in the same six specimens that were investigated in the first part of the study, and compared with the biomechanical data obtained there and the predictions of the models. Results: In the congruous case, the center of the socket is highly loaded, whereas the periphery does not experience mechanical stimulation. A central bone density maximum is predicted. With concave incongruity the position of the contact areas shifts from the joint margin towards the center as the load increases, and the peak stresses are considerably lower. A bicentric ventro-dorsal distribution pattern of subchondral mineralization is predicted, and this is actually found in the six specimens. Conclusions: Concave incongruity is shown to determine load transmission and subchondral mineralization of the humero-ulnar joint. It is suggested that this shape leads to a more even distribution of stress, provides intermittent stimulation of the cartilaginous tissue, and has beneficial effects on the metabolism, nutrition, and lubrication of the articular cartilage during cyclic loading. © 1995 Wiley-Liss, Inc.     

HIGH-GRADE SURFACE OSTEOSARCOMA OF THE LEFT ILIUM A Case Report and Review of the Literature

A rare case of high-grade surface osteosarcoma of the left ilum is reported. Trephine biopsy performed on a 31-year-old woman suffering from a huge tumor of the left buttock revealed high-grade osteosarcoma, and hemipel-vectomy was undertaken. The surgical specimen showed that the tumor was present on the surface of the left ilium. Ten months after the operation, the patient died of brain metastasis. From these results, we considered this case to be one of high-grade surface osteosarcoma. ACTA PATHOL JPN 38: 235 -240, 1988.     

Determination of specific oxygen uptake rates in human hematopoietic cultures and implications for bioreactor design

Oxygen plays an important role in the cultivation of primary cellsex vivo. In this study, we used hermetically sealed tissue culture well inserts equipped with oxygen electrodes to measure the oxygen utilization of cultured human bone marrow mononuclear cells (BM MNCs). The oxygen uptake rate (OUR) of BM MNCs was determined during a 14-day culture in which both adherent and nonadherent cells were present. Early in the culture, the cells exhibited very low OURs. The specific OURs (uptake rate per cell) were at approximately 0.005 μmol/10⁶ cells/hr shortly after the initiation of culture. The OUR then increased as the cultures developed. After about 8 to 10 days of cultivation the specific OURs had increased to 0.038±0.006 and 0.025±0.005 μmol/10⁶ cells/hr for adherent and nonadherent cells, respectively, after which no further increase was observed. Based on these oxygen uptake rate data, a mathematical model of oxygen diffusion was formulated and use to investigate issues associated with hematopoietic bioreactor design, including initial cell density, medium depth, reactor configuration, and oxygen partial pressure.In situ OUR measurements confirmed predicted oxygen limitations based on the mathematical model and the experimentally determined OURs. High-density hematopoietic cultures present design challenges in terms of sufficient and uniform delivery of oxygen to an active hematopoietic culture. These challenges can be met by using parallelplate bioreactors with thin liquid layers.     

Cytological examination and cellular composition of bone marrow in healthy, adult, cynomolgus monkeys (Macaca fascicularis)

The purpose of this study was to evaluate the cellular composition of the bone marrow of cynomolgus monkeys (Macaca fascicularis). Femoral bone marrow smears from 23 healthy, adult animals (11 males and 12 females) were examined. For each animal, three femoral bone marrow smears were prepared immediately after euthanasia and stained with May-Grünwald-Giemsa. On two of the three smears available, and for each of these smears, a 500-cell differential count was performed and the myeloid: erythroid (M:E) ratio established. The M:E ratio for males varied from 0.67∶1.00 to 1.85∶1.00 with a mean of 1.03∶1.00 and for females from 0.67∶1.00 to 1.63∶1.00 with a mean of 1.02∶1.00. The mean percentage of granulocytic, lymphocytic, plasmacytic and erythroid series was 47.60, 5.44, 1.45 and 46.05% for males and 47.28, 5.12, 1.49 and 46.28% for females. No significant differences were noted between males and females. All cell lines were well represented and showed normal maturation in both sexes. Megakaryocytes were adequate in number and morphology in all animals. Cynomolgus monkeys showed a bone marrow composition similar to rhesus monkeys (Macaca mulatta). Cytological examination of bone marrow was found to be a simple and rapid procedure, well suited to the toxicological research environment. It provided excellent information on cell distribution, morphology and maturation of the haematopoietic system.     

Functional asymmetry of the brain and bone marrow in hemopoiesis in (CBAxC57Bl/6)F(1) mice

The role of functional asymmetry of the brain and bone marrow in the formation of exogenous 8-day splenic CFU was studied in (CBA×C57Bl/6)F1 mice. The intensity of hemopoiesis depended on the motor asymmetry of donors and recipients of bone marrow cells and differed for bone marrow transplantations from the right and left femoral bones.     

Neutrophil mobilization and clearance in the bone marrow

The bone marrow is the site of neutrophil production, a process that is regulated by the cytokine granulocyte colony‐stimulating factor (G‐CSF). Mature neutrophils are continually released into the circulation, with an estimated 10 11 neutrophils exiting the bone marrow daily under basal conditions. These leucocytes have a short half‐life in the blood of ～6·5 hr, and are subsequently destroyed in the spleen, liver and indeed the bone marrow itself. Additionally, mature neutrophils are retained in the bone marrow by the stromal cell‐derived factor (SDF‐1α)/chemokine (C‐X‐C motif) receptor 4 (CXCR4) chemokine axis and form the bone marrow reserve. Following infection or inflammatory insult, neutrophil release from the bone marrow reserve is substantially elevated and this process is mediated by the co‐ordinated actions of cytokines and chemokines. In this review we discuss the factors and molecular mechanisms regulating the neutrophil mobilization and consider the mechanisms and functional significance of neutrophil clearance via the bone marrow.     

Expression of Functional Molecules in Non-Hodgkin's Lymphoma

It is well known that non Hodgkin's lymphoma (NHL) cells express various antigens which are normally involved in a variety of functions. In addition, NHL is diverse in its proliferative capacity. To investigate the relation between these factors and the clinical picture, 45 cases of NHL were studied by immunohistochemistry using snap-frozen materials obtained before therapy. Reactivities with 27 monoclonal antibodies were examined and the results were correlated with clinical findings. The expression of surface μ and CAM-1 in B-NHLs and CD25 in T-NHLs were significantly associated with bone marrow involvement. B-NHLs without expression of CD21(B2) and T-NHLs with CD25 were seen more frequently in cases with a LDH value of over 500 units/ml. The positivity rate of Ki-67 on B-NHLs was correlated with serum LDH value, NHL histologic classification, and overall survival. These data indicate that immunophenotyping and determination of the proliferative capacity of NHL are of value not only for confirmation of the histopathologic classification of the tumor but also for assessment of clinical behavior.     

Alloresponses to HLA-DP Detected in the Primary MLR: Correlation with a Single Amino Acid Difference

The one-way mixed lymphocyte reaction (MLR-1) response was measured in both directions in 50 HLA-A, B, DR and DQ identical pairs and the role of DP studied in MLR stimulation. DR, DQ and DP typing was performed at the allele level by the polymerase chain reaction-sequence specific oligotyping (PCR-SSO) technique. The group consisted of 19 potential bone marrow transplant recipients and 34 matched unrelated donors. When more than one matched donor was available for a patient, donor/donor MLR-1 was also studied. DP identity was observed in 3 out of 50 pairs (6%), however due to homozygosity no incompatibility was present in the stimulating cells in 21 out of 100 cases (21%). There was a significant difference in the range of relative responses (RR) between zero DPB1 mismatches and one (p = 0.002) and two (p = 0.02) DPB1 mismatches: 52.4% of cases in the zero DPB1 mismatch group had RR < 1.0% compared with 31.6% and 27.3% in the one and two DPB1 mismatches. Stimulation by DPB1*0201 and 0301 gave the highest RR (12.9 ± 22.5 and 17.5 ± 17.0, respectively) while stimulation with DPB1*0401 and 0402 resulted in low levels of T cell response (1.3 ± 8.2 and 0.6 ± 11.5, respectively). When the responses were restricted to DPB1*0401 homozygotes to standardise for responder type similar results were obtained (DPB1*0201 v DPB1*0402 p = 0.008). The protein products of the DPB1*0201 and 0402 alleles differ by a single amino acid at position 69 (DPB1*0402—Lysine, DPB1*0201—glutamic acid). A further analysis was performed therefore scoring responders and stimulators as glutamic acid positive (E+) or negative (E−). There was a highly significant increase in the response to E+ stimulators compared with E− stimulators (p = 0.004). There was also a significant difference in the distribution of relative responses between the E+ stimulator group and the subgroups of E− responders/E− stimulators (p = 0.012) and E+ responders/E− stimulators (p = 0.009). However the amino acid difference at position 69 does not explain all responses due to DP in the MLR-1 as evidenced by the strong responses observed in cases where DPB1*0301 (lysine pos.) was the only difference on the stimulator cells. The results indicate that not all DP incompatibilities elicit a measurable T cell MLR response, but where a response does occur residue 69 in the first domain of DP appears to be pivotal. These results may have implications with respect to GVHD in bone marrow transplantation.     

Haemangiosarcoma of bone

Summary Haemangiosarcoma of bone is a very rare primary tumour with a variable history and differing radiographic and histological appearances. In some cases the lesion has similar features to the so-called adamantinoma of long bones in which the histogenesis is also unknown.Such a lesion is described which ocurred in the shaft of the right humerus of a 31-year-old man. Radiographically a centrally located area of osteolysis was seen without marginal sclerosis, but with erosion of the bony cortex. A biopsy was performed 16 months after the first radiographic examination and showed malignant tumour tissue which was difficult to classify histomorphologically. Several different neoplasms such as Ewing's sarcoma, myeloma, liposarcoma, malignant fibrous histiocytoma or a bone metastasis were suggested. Finally, a haemangiosarcoma or so-called adamantinoma of long bones was considered. The tumour was completely removed by en-bloc resection.Careful histomorphological investigation of the tumour tissue by means of light microscopy, cytology and electronmicroscopy showed a vascular pattern characteristic of a haemangiosarcoma. Using cytophotometric DNA measurements of the tumour cells, the lesion could be classified as being of lowgrade malignancy. This is confirmed since there has now been a 4-year follow up with no local recurrence or metastasis.There are many similarities between a well-differentiated haemangiosarcoma and an adamantinoma of long bones. The differential diagnosis and the histogenesis of the latter lesion is discussed. It is emphasized that the so-called adamantinoma of a long bone probably has a vascular origin.

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Résumé L'hémangiosarcome est une tumeur osseuse primaire très rare, dont l'evolution est variable et dont les aspects radiologiques et histologiques sont divers. Dans quelques cas, la lésion ressemble à ce que l'on appelle «adamantinome des os longs», dont l'histogénèse est également inconnue.On présente ici un cas d'une telle tumeur, siégeant au niveau de la diaphyse humérale droite, chez un homme de 31 ans. Radiologiquement, il existait une zone centrale d'ostéolyse sans sclérose marginale mais avec érosion de la corticale. Une biopsie effectuée 16 mois après le premier examen radiologique a montré un tissu tumoral malin, difficile à classer histomorphologiquement.Plusieurs diagnostic ont été envisagée: sarcome d'Ewing, myélome, liposarcome, histiocystome fibreux malin, ou métastase osseuse. Finalement on a retenu le diagnostic soit d'hémangiosarcome, soit d'adamantinome. La tumeur a été complètement enlevée par résection en bloc.Des investigations histomorphologiques poussées du tissu tumoral par microscopie optique, cytologie et microscopie électronique ont mis en évidence les aspects vasculaires caractéristiques d'un hémangiosarcome. En utilisant les mesures cyto-photométriques d'ADN des cellules tumorales, la lésion a pu être classée comme ayant un degré de malignité peu élevé. Ceci a été confirmé par l'évolution, puisqu'avec 4 ans de recul il n'y a ni récidive locale ni métastase.Il y a beaucoup de similitudes entre un hémangiosarcome bien différencié et un adamantinome des os longs. Le diagnostic différentiel et l'histogénèse de cette dernière lésion sont discutes. L'origine vasculaire probable de l'adamentinome est soulignée.