Lymphocyte dysfunction in autoimmune oophoritis. Resumption of menses with corticosteroids

In a 32-year-old woman with secondary amenorrhea and biopsy-proven oophoritis, the circulating T lymphocytes were examined utilizing monoclonal antibody L243 to the nonpolymorphic region of the Ia antigen. The percentage of peripheral T cells expressing the Ia "immune-associated' antigen was 5.6 percent (normal 3 percent or less). With corticosteroid therapy, the percentage decreased to 2 percent and menses resumed after secondary amenorrhea of two years' duration. Following cessation of steroid administration, the percentage of Ia-positive T cells rose to 7.0 percent and secondary amenorrhea redeveloped in the patient. After corticosteroid therapy was reinstituted, menses resumed and the percentage of Ia-positive T cells fell to normal. This report represents additional new evidence of immune dysfunction in patients with "autoimmune" oophoritis.     

Granulocytic sarcoma with an indolent course and destructive skeletal disease. Tumor characterization with immunologic markers, electron microscopy, cytochemistry, and cytogenetic studies

A 6-year-old girl with a granulocytic sarcoma (GS) of the left maxillary sinus that followed a uniquely indolent clinical course (3.5 years) and was associated with highly destructive skeletal disease is described. The tumor cells demonstrated an unusual hematogenous "homing" preference for bone and soft tissue sites. Tumor cell characterization with immunologic markers, electron microscopy, cytochemistry, and cytogenetic studies revealed that the tumor cells expressed OKM1 and MMA (Leu-M1), but not HLA-DR, B-, or T-cell markers. The cells were nonspecific esterase- and myeloperoxidase-positive, had ultrastructural features of promyelocytes, and were clonal. The laboratory characterization of the tumor cells in this clinically unusual case of GS illustrates the utility of monoclonal antibodies, applied in conjunction with cytochemistry and ultrastructural analysis, in establishing the specific diagnosis, cell lineage, and maturational stage of this tumor.     

Aerobic Capacity after Contracting lnfectious Mononucleosis

Infectious mononucleosis can be disabling to athletes of all ages. Traditionally, long periods of limited physical activity are prescribed. During this time period a significant level of detraining can occur. Sixteen cadets from USMA who were identified as having mononucleosis had their aerobic capacity determined immediately after becoming afebrile. Nine of these cadets then entered a 2-week exercise program while the others remained inactive. After this time period all cadets were allowed to exercise at their own discretion. After an additional 2-week period (4 weeks after becoming afebrile), aerobic capacity was again determined. There were no differences within the groups when comparing VO2 max, METS, or run time to exhaustion on the two aerobic tests. One individual served as a case study with aerobic tests every week for 4 weeks and then 6 months after becoming afebrile. Again, no differences were observed in any variables measured. Thus, prolonged bed rest does not seem to be indicated for the individual recovering from mononucleosis. Noncontact activities can be initiated as soon as the fever disappears. J Orthop Sports Phys Ther 1986;8(4):199-202.     

Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow

Bone marrow houses a multifunctional stromal cell population expressing C-X-C motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like subset of CXCL12⁺ stromal cells (“Adipo-CAR” cells) is localized to sinusoidal surfaces and particularly enriched for hematopoiesis-supporting cytokines. However, detailed characteristics of these CXCL12⁺ pre-adipocyte-like stromal cells and how they contribute to marrow adipogenesis remain largely unknown. Here we highlight CXCL12-dependent physical coupling with hematopoietic cells as a potential mechanism regulating the adipogenic potential of CXCL12⁺ stromal cells. Single-cell computational analyses of RNA velocity and cell signaling reveal that Adipo-CAR cells exuberantly communicate with hematopoietic cells through CXCL12-CXCR4 ligand-receptor interactions but do not interconvert with Osteo-CAR cells. Consistent with this computational prediction, a substantial fraction of Cxcl12-creER⁺ pre-adipocyte-like cells intertwines with hematopoietic cells in vivo and in single-cell preparation in a protease-sensitive manner. Deletion of CXCL12 in these cells using Col2a1-cre leads to a reduction of stromal-hematopoietic coupling and extensive marrow adipogenesis in adult bone marrow, which appears to involve direct conversion of CXCL12⁺ cells to lipid-laden marrow adipocytes without altering mesenchymal progenitor cell fates. Therefore, these findings suggest that CXCL12⁺ pre-adipocyte-like marrow stromal cells prevent their premature differentiation by maintaining physical coupling with hematopoietic cells in a CXCL12-dependent manner, highlighting a possible cell-non-autonomous mechanism that regulates marrow adipogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Prism adaptation and brain damage

Brain damaged (BD), psychiatric (P), and normal (N) groups were compared on adaptability to prism-displaced vision. Although no difference among the groups was found on compensatory pre-post shifts of felt limb position (“proprioceptive shift”), the BD group manifested significantly less shift in target-pointing accuracy (“negative aftereffect”) than either of the other two groups. The latter result suggests that brain damaged individuals are, in general, unable to acquire the “cognitive” component of adaptation which results from consistently accurate target-pointing performance during the prism-exposure period. Frontal and non-frontal BD Ss adapted equally on proprioceptive shift, while the non-frontals evidenced significantly less negative aftereffect. It was suggested that this result and the fact that frontals adapted equally (on all measures) with the N group had implications for Teuber's “corollary discharge” hypothesis.     

The skeleton as a unique environment for breast cancer cells

Bone is a favored location for several cancer metastases especially breast, prostate and myeloma. This review evaluates various properties of the skeleton that contribute to its successful colonization by breast cancer cells. The first consideration is the unique aspects of the vasculature of metaphyseal bone, which may account for the initial lodging of breast cancer cells in specific regions of the skeleton. Metasphyseal bone, found at the ends of long bone, in ribs and in vertebrae, is comprised of trabecular bone interspersed with marrow and a rich vasculature. The chemotactic factors that arise from bone marrow and bone cells are discussed in terms of cancer cell migration out of the vasculature and entry of cancer cells into the marrow cavity. Once the breast cancer cells have migrated into the metaphysis, they interact both directly and indirectly with bone cells and other cells in the marrow. As tumor growth progresses, functional bone cells are lost, most likely through apoptosis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Craniopharyngiomas in children. Long-term effects of conservative surgical procedures combined with radiation therapy

Thirty-seven patients with craniopharyngioma were treated at Children's Hospital, Boston, between 1972 and 1981, the mean follow-up period now being 10.5 years. Twenty of these patients are old enough to have finished high school and have been queried about their college or job activity. None of the four patients who had undergone radical excision of their tumor and who had reached the age of finishing high school was able to work independently. Among the 16 patients who reached this age and who were treated by more conservative operations and irradiation or irradiation alone, job performance or college attendance varied considerably, indicating that psychosocial impairment occurred in this group, but suggesting that the risk was less. The rate of tumor recurrence or of failure to respond to treatment was 57% (four of a total of seven survivors) following radical surgery and 7% (two of 27 survivors) after conservative operations and irradiation. The overall mortality rate was 8%; the causes of the three deaths were: "hypothalamic crisis" 1 year after radical resection; progressive tumor growth despite two attempts at resection and irradiation; and a brain-stem glioma in the field of irradiation 8 years after treatment.     

Testing a policy for skull radiography (and admission) following mild head injury

There has been, and continues to be, conflicting advice regarding skull radiography following an apparently uncomplicated head injury. Policies on admission are often ill defined. In 1983, representatives of the Royal College of Radiologists met neurosurgeons at a seminar in Harrogate organized by the DHSS and laid down clear, but little publicized, joint recommendations: "The Harrogate Criteria". The survey described here evaluated an existing liberal policy for skull radiography (and a loose policy for admissions) against these recommendations, and it was concluded that the number of patients having skull radiography (74% of head injury attenders) was excessive. Measured against the "Harrogate Criteria", requests for 36% of the adult and 47% of children's skull radiographs did not fulfil these criteria. As a corollary, it was also concluded that loose admissions policies could usefully be altered to comply more closely with the Harrogate recommendations. This would not necessarily reduce the numbers admitted, but would provide casualty officers with a framework on which to base this crucial aspect of clinical decision making, where presently there is often very little structure at all. The authors suggest that all the options have not been fully explored, and that a simple but important alteration to the Harrogate guidelines would provide an even closer link between policy on skull radiography and patient admission. Specifically, most patients who are to be admitted do not need skull radiographs.     

Further studies on the antinociceptive effects ofΔ acid

The antinociceptive effects of (THC-7-oic) acid have been investigated further with particular regard to the influence of certain experimental parameters in the hot plate test. These included the degree of the thermal stimulus, the nature of the vehicle and a possible role for copper in the response. A temperature effect similar to that seen with nonsteroidalantiinflammatory drugs (NSAIDs) was observed, 55° produced observable antinociception, however, at a surface temperature of 58°C no drug effect was seen. Non-aqeous vehicles such as peanut oil increased the potency of THC-7-oic acid. Finally, the substitution of purified water for tap water reduced,the drug response which could be partially restored by adding copper to the purified drinking water. An increase in the inhibitory effect when copper was added was also seenin vitro in a cell culture model where the acid reduced prostaglandin synthesis induced by THC. Our findings suggest that THC-7-oic acid probably acts by mechanisms similar to the NSAIDs and that the above mentioned experimental conditions can greatly influence the outcome of studies with this agent.