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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 325 records · Page 18Linked to original sources

Radiation and chemotherapy of parameningeal rhabdomyosarcoma involving the orbit.

Eighteen patients with parameningeal rhabdomyosarcoma (RMS) involving the orbit were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between July 1971 and October 1983. Fifteen patients were children with a mean age of 6 years and three patients were adults with a mean age of 21 years. In four patients, the primary tumor originated in the orbit, while the remaining 14 had other parameningeal primary sites. The tumors were in a very progressive local stage, with destruction of facial bones in most patients. Six patients were treated with the T2 chemotherapy protocol and 12 received the T6 protocol. The radiation treatment plan for all patients was designed to deliver between 4500 and 7200 rad delivered to the primary tumor over 4 to 16 weeks. Eleven of the 18 patients (61%) are alive and well with a median follow-up time of six years. Two patients died of therapeutic complications and five died of tumor spread with central nervous system involvement. Ocular complications included acute and chronic conjunctival, corneal, lens, and retinal changes, which were less severe than those reported in previous series.

Cataract↗

Predictors of food preferences in adult humans.

Predictors of preferences for a wide variety of foods were examined in 303 male and female human subjects ranging from 14-68 years of age. The subjects completed questionnaires which requested information on the subject's sex, age, thinness, sensation seeking and ethnic background, as well as on the subjects' food preferences. Largely consistent with previous studies, female subjects reported higher preferences for low-calorie foods, candy and wine, and lower preferences for meat, beer, spicy foods and milk. Younger subjects reported higher preferences for sweet foods and lower preferences for foods such as chili pepper that are considered acquired tastes. Thinner subjects tended to rate both sweet foods and meat lower than did other subjects. Preferences for spicy foods or foods likely to cause illness were positively correlated with sensation seeking while preferences for sweet or bland foods or foods unlikely to cause illness were negatively correlated with sensation seeking. Subjects for whom the primary cuisine on which they were raised was Oriental cuisine preferred alcoholic beverages and non-Oriental foods less than did other subjects. A factor analysis of the food preferences yielded ten factors including those for meat and potatoes, alcohol, spices and junk food. Data on predictors of food preferences can assist research on the determinants of food preferences, however much of the variance in food preferences remains to be explained.

Adolescent↗

DNA content and prognosis of non-Hodgkin's lymphoma.

Ninety cases of non-Hodgkin's lymphoma diagnosed prior to the use of modern therapeutic regimens (1963-67) and 88 cases treated with such chemotherapy (1980-85) were studied using conventional morphology and flow cytometry. DNA aneuploidy as determined by flow cytometry was more common among high grade (38%) than low grade (19%) tumours (P less than 0.01). Measurements of proliferative index (S + G2 phase cells) revealed significantly increased values for high grade as compared with low grade lymphomas (P less than 0.001). In the first group of cases (1963-67) the relationship between histological grade and survival just failed to reach statistical significance over the long term (20 yr) (P = 0.1) but proved significant over 3 yr (P = 0.012). Differences in ploidy and proliferative index status were not associated with survival. In the second patient group (1980-85) attainment of complete remission following chemotherapy was associated with the presence of DNA aneuploidy in high grade tumours (P less than 0.05). The limited follow up of this group precluded assessment of survival in relation to ploidy.

Adolescent↗

Opsonization with antimyelin antibody increases the uptake and intracellular metabolism of myelin in inflammatory macrophages.

In most demyelinating diseases, macrophages are believed to be active agents of myelin destruction. In experimental encephalomyelitis, these cells appear to strip off and ingest the myelin lamellae, and myelin debris has been observed within the cell body. We show here in vitro conditions in which rat peritoneal macrophages phagocytose and metabolize CNS myelin lipids. Purified rat myelin, prelabeled in vivo with [14C]acetate, was incubated with preimmune serum or rabbit antiserum to rat CNS myelin and added to macrophage monolayers. Myelin opsonized with antimyelin antibodies was more readily phagocytosed and metabolized by cultured macrophages than untreated myelin or that preincubated with preimmune serum. In the presence of macrophages, levels of myelin polar lipids and cholesterol decreased, whereas radioactive cholesterol ester and triglyceride accumulated. Up to five times as much radioactive cholesterol ester and about twice as much triglyceride accumulated in macrophage cultures containing antibody-treated myelin as in cultures fed preimmune serum-treated myelin or in those incubated with untreated myelin. Both the fatty acid and the cholesterol from cholesterol ester contained radioactive label; therefore, both were derived at least partly from the radioactive myelin lipid. Antiserum to myelin purified from peripheral nerve was almost as effective as that to CNS myelin in stimulating cholesterol metabolism, whereas antiserum to galactocerebroside was about 70% as active. Antiserum to basic protein had less effect, whereas antiserum to the myelin-associated glycoprotein and proteolipid protein was inactive. Of the polar lipids, ethanolamine phosphatide was most degraded in both the antiserum- and preimmune serum-treated myelin, with the diacyl form and plasmalogen form degraded about equally. These experiments indicate that myelin-specific antibodies in inflammatory CNS lesions may participate in and stimulate macrophage-mediated demyelination.

Animals↗

Immunological nonidentity of 19K protein and TP0 in peripheral nervous system myelin.

Peripheral nervous system myelin contains as the major structural protein a glycoprotein known as P0. Another glycoprotein present in smaller amounts, known as the 19K or X protein, has been previously identified as derived from P0 and identical with the main tryptic degradation product of P0 (TP0). Although both P0 and 19K protein incorporated fucose in vitro and stained on polyacrylamide gels with the periodic acid-Schiff stain for carbohydrate, only the P0 blotted to nitrocellulose paper showed immunoreactivity to an antibody to P0, whereas the 19K protein did not. Furthermore, when P0 was hydrolyzed with trypsin or elastase, the main degradation products reacted with P0 on immunoblots, whereas the 19K protein showed no immunoreactivity. From these studies and those of others, it may be concluded that the 19K protein shows some similarities to TP0, but probably has a different structure. P0 and 19K protein do not appear to be related as shown by lack of cross-immunoreactivity.

Amino Acids↗

Growth factors suppress and phorbol esters potentiate the action of dibutyryl adenosine 3',5'-monophosphate to stimulate aromatase activity of human adipose stromal cells.

In previous studies, we observed that the stimulatory effect of (Bu)2cAMP on aromatase activity of human adipose stromal cells was markedly attenuated when fetal calf serum was present in the culture medium. To determine whether growth factors may be the inhibitors of (Bu)2cAMP-stimulated aromatase activity in serum, the effects of growth factors and phorbol esters on aromatase activity of human adipose stromal cells in monolayer culture were investigated. Epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) were all without effect on aromatase activity when added by themselves, but markedly inhibited aromatase activity stimulated by (Bu)2cAMP. On the other hand, nerve growth factor, multiplication-stimulating activity, relaxin, and insulin had no effect on aromatase activity, either by themselves or in the presence of (Bu)2cAMP. Thus, EGF, PDGF, and FGF can mimic the inhibitory action of fetal calf serum on (Bu)2cAMP-stimulated aromatase activity of these cells. By contrast, none of these substances was capable of mimicking the effect of serum to facilitate the stimulatory action of dexamethasone on aromatase activity of these cells. The phorbol esters phorbol-12-myristate-13-acetate, phorbol-12,13-didecanoate, and phorbol-12,13-diacetate were also capable of facilitating the action of (Bu)2cAMP to stimulate aromatase activity, but had little or no action on dexamethasone-stimulated aromatase activity or when added by themselves. It is concluded that aromatase is under multifactorial regulation in human adipose stromal cells. The activity is induced by glucocorticoids and by agents that stimulate cAMP-dependent protein kinase; the latter effect is potentiated by factors that stimulate protein kinase C, but is suppressed by growth factors such as EGF, FGF, and PDGF, whose actions are believed to be mediated by receptor-linked tyrosine kinase activity.

Adipose Tissue↗

Neoplastic angioendotheliomatosis. A variant of malignant lymphoma immunohistochemical and ultrastructural observations of three cases.

Neoplastic angioendotheliomatosis (NAE) is a rare, fatal disease characterized by widespread intravascular proliferations of malignant cells of putative endothelial origin. Clinically, dermatologic and bizarre neurological manifestations predominate, but review of the reported cases of NAE reveals ophthalmic involvement to be frequent. To our knowledge, no reports of NAE have appeared in the ophthalmic literature. We describe three cases of NAE with the ocular manifestations of visual loss, cells in the vitreous, retinal artery occlusion, retinal vascular and pigment epithelial alterations, nystagmus, and cortical blindness. Autopsies (including eyes and central nervous system) revealed pancorporal involvement by intravascular anaplastic cells in each patient. In two patients massive extravascular involvement was also present. The tumor cells lacked ultrastructural features of endothelial cells and failed to stain for factor-VIII-related antigen. Common leukocyte antigen, a maker for hematopoietic cells, particularly lymphocytes, was detected on tumor cells in all cases, indicating that NAE is probably an extranodal lymphoma. The dramatic response of the central nervous system lesions to radiotherapy in one case supports this contention. It is suggested that this disorder be treated as a malignant lymphoma.

Aged↗

Evaluation by quantitative acid elution and radioimmunoassay of multiple classes of immunoglobulins and serum albumin associated with platelets in idiopathic thrombocytopenic purpura.

Immunoglobulins (Igs) and serum albumin were eluted from normal platelets and platelets from patients with idiopathic thrombocytopenic purpura (ITP) with a quantitative acid elution procedure followed by solid-phase radioimmunoassay (SPRIA). Acid elution was shown to release a reproducible fraction of platelet-associated Igs, and the amounts released per platelet were independent of the platelet concentration over a wide range of concentrations. This procedure is suitable for sensitive, reproducible, and specific quantitation of large numbers of samples. Washed platelets from 13 normal donors contained the following components (expressed in femtograms per platelet, mean +/- 2 SEM): IgG, 1.40 +/- 0.26; IgA, 0.72 +/- 0.36; IgM 0.078 +/- 0.036; albumin 7.7 +/- 1.5. Immunoglobulins and albumin eluted from the platelets of ten ITP patients (two in remission), expressed as femtograms per platelet, mean (range), were: IgG 104 (0.3 to 750); IgA 90 (0.9 to 715); IgM 162 (1.2 to 1,300); and albumin 34 (6.8 to 199). All platelet-associated Igs from thrombocytopenic ITP patients were found to be elevated twofold to 2,300-fold with one Ig class occasionally elevated 50-fold to 100-fold higher than the others. A similar group of ten thrombocytopenic ITP patients was found to have twofold to 26-fold elevations of platelet-associated albumin. This demonstration of increases in multiple classes of Igs as well as serum albumin associated with platelets from ITP patients suggests that some nonimmune process may be contributing to the phenomenon of increased platelet-associated proteins in ITP.

Blood Platelets↗

Inhibition of phosphatidylinositol phosphodiesterase activity in skeletal muscle by metal ions and drugs which block neuromuscular transmission.

The calcium-dependent phosphatidylinositol phosphodiesterase activity of skeletal muscle cytosol was determined. The enzyme was inhibited by Zn2+, Cu2+ and Pb2+ ions but Mg2+ and Mn2+ were without effect. The antimalarial drugs chloroquine and the quinine and the aminoglycoside antibiotics gentamicin and neomycin all of which, like Zn2+, have been shown to block neuromuscular transmission, also inhibited the enzyme.

Aminoglycosides↗

Presence of immunoreactive alpha-melanotropin and beta-endorphin in spinal motoneurones of the dystrophic mouse.

Two derivatives of the stem hormone opiomelanocortin, alpha-melanotropin (alpha-MSH) and beta-endorphin, were detected immunocytochemically in the cell bodies and in the peripheral axon terminals of spinal motoneurones in immature but not in adult healthy mice. Immunoreactivity was demonstrated in motoneurones in both immature and adult mice with inherited muscular dystrophy. These results provide evidence for a motoneurone abnormality in murine dystrophy. The observations are discussed in the light of trophic influences over neuromuscular transmission which have been attributed to this family of neuropeptides.

Animals↗

Magnetic resonance imaging in the evaluation of leukocoria.

Leukocoria is an important clinical sign in ophthalmology. Conditions producing this white pupillary reflex must be differentiated from retinoblastoma to insure appropriate and timely treatment. Auxiliary diagnostic testing has been helpful in securing a clinical diagnosis. A new diagnostic modality, magnetic resonance imaging, provides similar morphologic information with the additional potential for biochemical characterization. A series consisting of 14 patients presenting with leukocoria as a result of retinoblastoma and simulating conditions was examined. The magnetic resonance imaging findings are discussed.

Child↗

Computed tomography of the nonrhegmatogenous retinal detachment in the pediatric patient.

Nonrhegmatogenous retinal detachments occur in the pediatric population secondary to other ocular disorders. The most important cause to identify is retinoblastoma. Computed tomography has proven to be the most reliable ancillary diagnostic test in this pediatric population. A series of eighty patients, presenting with nonrhegmatogenous retinal detachments, was examined. The role of computed tomography and characteristic clinical findings are discussed.

Child↗

Ocular findings in incontinentia pigmenti.

Incontinentia pigmenti is an uncommon disorder affecting females, and is associated with ocular, dental, skeletal, and central nervous system abnormalities. Ocular abnormalities are found in 35% of cases. The authors present an eight-month-old girl with neonatal history of skin bullae, who was noted to have esotropia, leukocoria, and a fixed pupil. Histologic examination of the enucleated globe reveals total retinal detachment with retinal neovascularization into the collapsed vitreous, reactive retinal gliosis, and scattered giant nodular proliferations of retinal pigment epithelium. It is suggested that the underlying defect is at the level of the retinal pigment epithelium and that the neurosensory retinal changes are secondary.

Child Development↗