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Biomedical subjects

W W Grody

Publications and source records attributed to W W Grody.

88 records · Page 5Linked to original sources

Reversible dissociation of chick oviduct progesterone receptor subunits.

We report here the reversible dissociation of chick oviduct progesterone receptor subunits by pyridoxal 5'-phosphate. This agent has been reported to inhibit binding of steroid hormone receptors to DNA and nuclei (Cake et al., 1978). We have found that pyridoxal 5'-phosphate inhibits binding of chick oviduct progesterone receptors to DNA-cellulose, and also dissociates 6-8S cytosolic receptor aggregates to 4S monomers. Both of these effects are shown to be reversible if pyridoxal phosphate is removed, allowing in vitro reconstitution of receptor aggregates. Fidelity of reconstitution has been assessed by testing the reconstituted aggregate for binding to DNA-cellulose, phosphocellulose, and by studies using sedimentation velocity measurements. By these three criteria, the reconstituted product is indistinguishable from the native cytosol complex from which the monomers were derived. The reconstitution reaction shows an absolute requirement for the presence of both receptor monomers A and B. Titration experiments show a molar ratio of 1:1 for A and B in the reconstituted aggregates. These reconstitution studies confirm our hypothesis (originally based upon dissociation experiments) that native receptor aggregates are composed of the A and B proteins as subunits.

Animals↗

Pathologic evaluation of thymic hyperplasia in myasthenia gravis and Lambert-Eaton myasthenic syndrome.

Eleven thymectomy specimens from patients with myasthenia gravis or Lambert-Eaton myasthenic syndrome were thoroughly sectioned. The results were compared with the routine surgical pathology reports that were based on a median of four sections. Routine sampling was found to be inadequate because the thymectomy specimens were inhomogeneous--some random sections contained germinal centers while others did not. Thus, on more thorough examination, about half of the specimens should have been diagnosed as showing "follicular hyperplasia" rather than "no diagnostic change" or "involution." This helps explain the conflicting results of previous studies, based when stated on a mean of three sections, in which favorable response to thymectomy in patients with myasthenia gravis was either not correlated with the thymus histologic state or correlated variously with few or numerous germinal centers. Thus, nondiagnostic histologic findings based on only one or two thymus sections should be suspect, and if in doubt a larger number of sections should be examined for accurate pathologic diagnosis.

Adolescent↗

Thymus involution in the acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) is a severe disorder of unknown etiology and pathogenesis, predominantly affecting homosexual males and other high-risk groups and characterized by profound alterations in T-lymphocyte function. The authors have examined thymus tissue from 14 patients who died of AIDS and compared the results with findings in five control groups: healthy age-matched controls, elderly individuals, patients with chronic or debilitating illnesses other than AIDS, infants with conditions causing "stress atrophy," and patients with myasthenia gravis. The AIDS group included 11 homosexual males, 1 Haitian, 1 homosexual who was also a drug abuser, and a 10-month-old infant believed to have contracted AIDS following blood transfusion. All the AIDS cases showed marked thymus involution with severe depletion of both lymphocytes and epithelial elements. The latter component consisted primarily of thin cords and nests of primitive-appearing epithelial cells that could be defined by positive immunohistochemical staining for keratin. Many cases showed a variable plasma cell infiltration, and the majority exhibited distinct vascular changes in the form of hyalinization and/or onion-skin patterns, primarily in the adventitia. Most striking of all was the marked paucity of Hassall's corpuscles; four patients had none at all, while in the other ten patients all the Hassall's corpuscles were calcified. These changes were far more extensive than those seen in any of the control groups, which retained most of their complement of Hassall's corpuscles even in the face of marked overall involution. The physiologic function of Hassall's corpuscles is not known, but recent immunohistochemical studies have implicated them in the synthesis of "facteur thymique serique" (FTS, thymulin) and other thymic hormones known to play a role in regulating T-helper and suppressor cell activity. It is conceivable that the extensive destruction of Hassall's corpuscles observed in AIDS may be a crucial element in the pathogenesis of this syndrome.

Acquired Immunodeficiency Syndrome↗

Ependymoma-like tumor of the mesovarium.

We report a case of primary extramedullary ependymoma, arising from the mesovarium in a 47-year-old woman and discovered incidentally during routine hysterectomy for uterine leiomyomas. The tumor exhibited the light microscopic, immunohistochemical, and ultrastructural features of a typical ependymoma, including a prominent pseudorosette pattern, positive staining for glial fibrillary acidic protein, and electron microscopic visualization of microvilli, intermediate filaments, basement membranes, and long cytoplasmic processes. While the occurrence of subcutaneous ependymomas in the sacrococcygeal region and metastatic central nervous system tumors at various sites are familiar, we believe this case to be a rare example of a primary ependymoma arising in a different and unusual extramedullary location.

Ependymoma↗

Gastrointestinal lymphomas. Immunohistochemical studies on the cell of origin.

The classification of primary malignant lymphomas of the gastrointestinal tract by their cell of origin has been a subject of great controversy in recent years, with the proportion of histologic subtypes varying substantially in different published series. Much of this controversy was initially due to the widely recognized inherent difficulty of classifying lymphomas based on routine histologic sections alone. However, the advent of immunohistochemical techniques has also yielded disparate results. Particularly contentious has been the notion of true histiocytic lymphomas, which some investigators have claimed to be relatively frequent in the gastrointestinal tract, whereas others doubt whether they exist at all. We present here a classification of 25 gastrointestinal lymphomas seen in the surgical pathology services of UCLA Hospital and Stanford University Medical Center. Unlike all previously reported series, we have utilized frozen tissue sections for the performance of immunohistochemical studies, which we and others have found to be far more reliable than the use of formalin-fixed, paraffin-embedded tissues, particularly in detecting monoclonal surface staining of immunoglobulin light- and heavy-chain markers. We find that this technique lessens the likelihood of overinterpreting the stains for histiocyte markers (alpha 1-antitrypsin and lysozyme), which are often difficult to read owing to strong positive staining of benign reactive histiocytes within the tumor. Utilizing these techniques, we have been able to classify definitely 21 of our 25 lymphomas (84%) as of B-cell origin, whereas none appeared to be histiocytic. We conclude that true histiocytic lymphomas of the gastrointestinal tract must be very rare, and we recommend the routine use of frozen tissue sections for more accurate classification of these interesting lesions.

Adult↗

Issues in implementing prenatal screening for cystic fibrosis: results of a working conference.

PURPOSE: To summarize a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. METHODS: Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. RESULTS: Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost-effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. CONCLUSIONS: Once adequate facilities for patient and provider education, testing, counseling, quality control, and monitoring are in place, individual programs can begin prenatal screening for cystic fibrosis.

Clinical Trials as Topic↗

Informativeness of VNTR genetic markers for detecting chimerism after bone marrow transplantation.

We tested the feasibility and practicability of using VNTR-type DNA genetic markers to identify chimerism in the bone marrow of patients following bone marrow transplantation. We selected eight probes which were highly polymorphic when hybridized to DNA digested with MspI. In over 50 donor-recipient combinations, autoradiograms of Southern blots yielded patterns which allowed donor DNA to be distinguished from recipient DNA after an average of two or three serial hybridizations. The strong hybridization signal of VNTR probes also made it possible to detect as little as 1 per cent DNA in DNA mixing experiments.

Blotting, Southern↗