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Biomedical subjects

M A Meyers

Publications and source records attributed to M A Meyers.

At least 19 recordsLinked to original sources

Contrasting calcium dependencies of SAPK and ERK activations by glutamate in cultured striatal neurons.

Stress-activated protein kinase (SAPK) and extracellular signal-regulated kinase (ERK), both members of the mitogen-activated protein kinase (MAPK) family, may in some circumstances serve opposing functions with respect to cell survival. However, SAPK and ERK can also be coordinately activated in neurons in response to glutamate stimulation of NMDA receptors. To explore the mechanisms of these MAPK activations, we compared the ionic mechanisms mediating SAPK and ERK activations by glutamate. In primary cultures of striatal neurons, glutamatergic activation of ERK and one of its transcription factor targets, CREB, showed a calcium dependence typical of NMDA receptor-mediated responses. In contrast, extracellular calcium was not required for glutamatergic, NMDA receptor-mediated activation of SAPK and phosphorylation of its substrate, c-Jun. Increasing extracellular calcium enhanced ERK activation but reversed SAPK activation, further distinguishing the calcium dependencies of these two NMDA receptor-mediated effects. Finally, reducing extracellular sodium prevented the glutamatergic activation of SAPK but only partially blocked that of ERK. These contrasting ionic dependencies suggest a mechanism by which NMDA receptor activation may, under distinct conditions, differentially regulate neuronal MAPKs and their divergent functions.

Animals

Identification and characterization of a pro-tumor necrosis factor-alpha-processing enzyme from the ADAM family of zinc metalloproteases.

Tumor necrosis factor-alpha (TNF) is initially expressed as a 26-kDa membrane-bound precusor protein (pro-TNF) that is shed proteolytically from the cell surface, releasing soluble 17-kDa TNF. We have identified human ADAM 10 (HuAD10) from THP-1 membrane extracts as a metalloprotease that specifically clips a peptide substrate spanning the authentic cleavage site between Ala76 and Val77 in pro-TNF. To confirm that HuAD10 has TNF processing activity, we cloned, expressed, and purified an active, truncated form of HuAD10. Characterization of recombinant HuAD10 (rHuAD10) suggests that this enzyme has many of the properties (i.e. substrate specificity, metalloprotease activity, cellular location) expected for a physiologically relevant TNF-processing enzyme.

ADAM Proteins

Morison pouch.

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Anatomy

Human lung cell beta 2-adrenergic receptors desensitize in response to in vivo administered beta-agonist.

Few studies have addressed whether target tissue adrenergic receptors in humans undergo desensitization in response to agonist administration. To determine whether lung cell beta 2-adrenergic receptors (beta 2-AR) undergo such desensitization, we harvested bronchial epithelial cells and alveolar macrophages via bronchoscopy from eight normal subjects before and after inhalation of six doses of the beta-agonist metaproterenol given over 24 h. After metaproterenol inhalation, beta 2-AR expression as determined by 125I-labeled cyanopindolol binding decreased approximately 70% on bronchial epithelial cells, from 6.3 +/- 0.7 to 2.0 +/- 0.2 fmol/mg (P < 0.001) and to a similar extent on macrophages from 13.3 +/- 0.4 to 3.9 +/- 0.6 fmol/mg (P < 0.001). Agonist inhalation also resulted in impairment of beta 2-AR function in both cell types. With bronchial epithelial cells, maximal isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation decreased from 9.5 +/- 1.8 to 4.9 +/- 1.2 pmol/10(6) cells (P = 0.003), which amounts to a 48 +/- 6% desensitization. Isoproterenol-stimulated cAMP accumulation in alveolar macrophages decreased from 39.5 +/- 9.0 to 2.9 +/- 0.3 pmol/10(6) cells (P = 0.007), equivalent to 86 +/- 5% desensitization. The cAMP response to forskolin in both cell types was unaffected by metaproterenol inhalation. Thus administration of inhaled beta-agonists results in substantial downregulation and functional desensitization of lung cell beta 2-AR. This supports the concept of a dynamically regulated beta 2-AR in humans, the function of which can be attenuated in relevant target tissues by administration of standard doses of beta-agonist.

Administration, Inhalation

Glen W. Hartman Lecture. Science, creativity, and serendipity.

In this Roentgen centennial year, honoring the epochal discovery of the X-ray in 1895 [2], it is particularly appropriate to reflect on the circumstances of creativity that lead to important discoveries in science. In radiology as in general medicine and surgery, histories of the development of the discipline have generally presented a chronicle of sequential events without specific consideration of the underlying creative impulse [3-7]. I wish to consider features of creativity that may be relevant to us, that may enlighten us, and that may allow us to incorporate them individually into our view of the world and our appreciation of the grandeur of such contributions.

Creativity

Spread of disease via the subperitoneal space: the small bowel mesentery.

The designation of the subperitoneal space emphasizes the continuum of the potential space of extraperitoneal and intraperitoneal areolar tissue traversed by blood vessels, lymphatics, and nerves. Across its root, the subserous connective tissue of the small bowel mesentery is anatomically continuous with that deep to the posterior parietal peritoneum. There is thereby provided an avenue of spread from multiple sites to and from the small bowel mesentery and its relationships. These include perforated lesions of the bowel, pancreatitis, lymphoma, neuroblastoma, leiomyosarcoma of small bowel, and hemorrhage of retroperitoneal and pelvic origin.

Female

Bidirectional spread of disease via the subperitoneal space: the lower abdomen and left pelvis.

In early fetal life a persistent interconnection between the peritoneum and retroperitoneum of the abdomen and pelvis is formed--the subperitoneal space (SS). This paper serves to complete the description of the specific anatomical nuances of the SS as they relate to the bidirectional direct spread of disease in the left lower abdomen and pelvis. Described are the two avenues of communication (central and lateral pathways) within this portion of the SS. Selected cases illustrating the bidirectional spread of disease processes within this portion of the SS are reported.

Abdominal Neoplasms

Demographic, social and stress correlates of hypertension among the urban poor.

The relationship of demographic, social, and psychological variables to the diagnosis of hypertension in a population of urban, poor, predominantly black out-patients is reported. Subjects were 182 patients presenting for health care at Wayne State University Family Practice Clinic. Age, race, marital status, attendance at religious services, education, employment status, income, source of income and interpersonal stress were significantly related to a diagnosis of hypertension in this sample. Of those characteristics found to be significantly related to hypertension, discriminative analysis showed that age, race, education and frequency of church attendance were most important in predicting a diagnosis of hypertension among this out-patient sample of the urban poor. Implications for clinical care and for future research needs are considered.

Adolescent

Grey Turner's sign and Cullen's sign in acute pancreatitis.

Four patients with acute pancreatitis presenting with Grey Turner's sign or Cullen's sign have been studied by computed tomography (CT). These observations help confirm the precise anatomic pathways by which the extravasated pancreatic enzymes and their effects lead to these cutaneous discolorations. Grey Turner's sign is produced by spread from the anterior pararenal space to between the two leaves of the posterior renal fascia and subsequently to the lateral edge of the quadratus lumborum muscle. Communication may be established to the posterior pararenal space and to the structures of the flank wall. The lumbar triangle, a site of anatomic weakness on the flank wall, may serve as a structural predisposition. Cullen's sign can be seen to be secondary to the tracking of liberated pancreatic enzymes to the anterior abdominal wall from the inflamed gastrohepatic ligament and across the falciform ligament. Another more direct pathway may be extension from inflammatory changes of the small mesentery or greater omentum to the round ligament, and then to properitoneal fat deep to the umbilicus.

Abdomen

Imaging the direct bidirectional spread of disease between the abdomen and the female pelvis via the subperitoneal space.

This report expands the concept of the subperitoneal space (SS) as the potential conduit for direct spread of disease in the abdomen to include the female pelvis. The normal anatomy of the SS in the lower abdomen, the female pelvis, and its uninterrupted continuation between the abdomen and pelvis are demonstrated by several imaging modalities. Surgically proven cases of bidirectional spread of disease between the abdomen and female pelvis are reported. The unifying concept of the interrelationship formed by the SS provides an understanding of the basic concepts of the pathways of direct spread of disease and the pathogenesis of the clinical presentation of disease distant from its site of origin.

Abdomen

Representation of the black elderly in Detroit metropolitan nursing homes.

This paper presents the results of an analysis of the distribution of black elderly patients in the long-term care systems of Detroit City, Wayne, and Oakland counties, Michigan. These areas were chosen because of their proximity to Wayne State University and because Detroit has a large black population. Wayne and Oakland counties are largely suburban areas. Black, long-term care utilization was compared with the black elderly representation of the base population in these three locations. The sex-specific distribution between whites and blacks in long-term care populations revealed that black men utilized the greatest amount of long-term care and were more dependent on Medicaid. One hundred twenty-one licensed nursing homes were contacted by telephone and a follow-up questionnaire was sent to the respondents during the five-month study périod.It has been observed nationally that the elderly black population is underrepresented in the long-term care system. The findings obtained in this study, however, are not in agreement with the national trend. In Detroit, the black elderly are represented in nursing homes in approximate proportion to their representation in the larger community.This analysis raises questions of need vs utilization of long-term care by the black elderly in urban areas. This is the first study of black elderly long-term care representation in a specific urban area in the United States.

Black or African American

The peritoneal ligaments and mesenteries: pathways of intraabdominal spread of disease.

The abdomen has been conveniently divided anatomically and clinically into specific intraperitoneal and extraperitoneal sites. A recognition of the pathways of spread and localizing features of infections, malignancies, and traumatic collections has immeasurably extended diagnostic imaging capabilities. Yet, while the abdomen may be visualized as subdivided into compartments, it must also be essentially appreciated that these compartments are an actual or potential interconnecting network. In the upper abdomen peritoneal reflections comprise 11 major ligaments and mesenteries. These are generally readily recognizable on computed tomographic scans by either their typical location and organ relationships or the landmarks provided by their major constituent vessels. These ligaments and mesenteries provide continuity of anatomic planes, which permits the spread of disease between intraperitoneal compartments, between extraperitoneal spaces, and between intraperitoneal and extraperitoneal localized sites.

Gastrointestinal Diseases

Kaposi's sarcoma of the intestinal tract: roentgen manifestations.

Five cases of generalized Kaposi's sarcoma are reported with roentgen evidence of involvement of the intestinal tract. In three instances, there was extensive involvement of the small bowel with multiple intramural nodules. The fourth patient demonstrated multiple polypoid lesions of the colon, and in the fifth a constricting lesion of the ileum was present. Two patients with small bowel involvement had significant malabsorption. This latter complication of diffuse Kaposi's sarcoma of the small bowel has not been previously reported. The diagnosis of the nature of the roentgen intestinal abnormality can usually be made, because intestinal involvement generally occurs late in the disease, when both extensive cutaneous nodules and edema of the extremities are apparent.

Aged

Calcified primary tumors of the gastrointestinal tract.

The dominant pattern and location of calcifications occurring within 23 primary gastrointestinal tumors have been analysed and correlated with the data from the literature. The provided guidelines for radiologic diagnosis of such calcified tumors include: (1) a retrocardiac mass containing amorphous calcifications is typical of leiomyoma of the esophagus; (2) calcific deposits similar to that in uterine fibroids may be the feature of gastric leiomyoma or intestinal leiomyosarcoma; (3) sand-like deposits within the wall of the stomach or colon are characteristic of a mucinous adenocarcinoma; (4) clusters of phleboliths in the gastrointestinal wall suggest a hemangioma particularly if recurrent intestinal bleeding and cutaneous hemangiomas are associated; (5) sunburst type of calcification in the pancreas indicates a cystadenoma or cystadenocarcinoma of that organ; and (6) aggregates of granular calcifications in the liver are diagnostic for metastatic adenocarcinoma of the colon but may rarely be seen in a primary malignancy of the liver.

Adenocarcinoma

Pathogenesis of diverticulitis complicating granulomatous colitis.

The involement of diverticula by granulomatous colitis may cause an increased incidence of diverticulitis. Of 21 patients with Crohn's disease and associated diverticulosis who underwent resection, sigmoid diverticulitis was pathologically confirmed in 10 (48%). The clinical recognition of the coexistence of the two diseases is often difficult. The radiological signs of peridiverticulitis complicating granulomatous colitis usually show clear evidence of the underlying pathological changes. They include localized diverticular performation, perhaps with multiple communications via a paracolonic sinus tract, mass pressure from the paracolicabscess, and occasionally some degree of communication with deep fissuring ulcers of Crohn's disease. Because diverticula breach the colonic wall, histological analysis confirm that their involvement by the transmural process of granulomatous colitis predisposes to peridiverticulitis and/or abscess formation.

Aged