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B H Smith

Publications and source records attributed to B H Smith.

At least 91 records · Page 5Linked to original sources
PubMed1987

Regulation of the pentose phosphate pathway in human astrocytes and gliomas.

Several aspects of the regulation of the pentose phosphate pathway were examined in cultured normal human cortical astrocytes and gliomas of pathological grades I-IV. The generation of radiolabeled CO2 from [1-14C]glucose by the oxidative arm of the pentose phosphate pathway is a saturable process and has a maximum flux rate of 8-9 nmol/hr/mg cell protein. The flux can be blocked by the glycolytic inhibitor iodoacetamide but is unaffected by agents which inhibit oxidative phosphorylation. The magnitude of the pentose phosphate flux is directly related to the glioma grade. Grade IV gliomas (glioblastoma) show a pentose phosphate flux rate of approximately 4% of the total glucose flux. The flux rate can be increased by pharmacological agents which decrease the NADPH/NADP+ ratio. Both the activity and the regulation of glioma glucose-6-phosphate dehydrogenase (G6PDH) are altered in high-grade gliomas. While the affinity constants for cofactors in whole homogenates were not significantly different in glioma or normal astrocyte homogenates, normal astrocytes have a lower Km for glucose-6-phosphate and a G6PDH activity which is 10-fold greater than that of gliomas. NADPH is a powerful regulator of G6PDH activity in the normal astrocytes and in gliomas. At a NADPH/NADP+ ratio of 7:1 the normal astrocyte G6PDH is entirely inhibited, while the glioma enzyme is only 70% inhibited even at a ratio of 20:1. Increased metabolic flux through the oxidative arm of the pentose phosphate pathway is apparently due to an altered form of G6PDH.

Astrocytes↗
PubMed1987

Products of cells cultured from gliomas. VI. Immunofluorescent, morphometric, and ultrastructural characterization of two different cell types growing from explants of human gliomas.

Explants derived from human gliomas have been characterized with respect to their cellular outgrowth pattern after 1-22 weeks in culture. A mat of cells which were fibronectin (FN)-positive and glial fibrillary acidic protein (GFAP)-negative (hereafter designated FN+ cells) with a polygonal, flat morphology covered the growth substrate in a swirling pattern for a mean diameter of 9.2 mm around FN+ explants. FN+ cells showed ruffled plasmalemma, dilated rough endoplasmic reticulin (RDR), and extracellular filamentous strands. Rare desmosomes were compatible with at most minor leptomeningeal components or differentiation. FN+ cells predominated in six of seven cultures at passage 2, and their features were the same from various high-grade gliomas and gliosarcoma. Around other explants, elongated or stellate cells which were GFAP+ and FN- grew in a netlike pattern with little cell-to-cell contact. These GFAP+ cells surrounded explants at a mean diameter of 2 mm, substantially less than FN+ cells (P less than 0.005), and they grew more slowly than FN+ cells around explants. GFAP+ cells had an area/perimeter ratio which was less than that of FN+ cells. GFAP+ cells contained abundant intracellular filaments, rare desmosomes, and narrow RER cisternae. In mixed explants, GFAP+ cells often grew on top of FN+ cells. Individual cells which stained for both GFAP and FN were evident only from one glioma (8% doubly positive). Cells negative for both proteins resembled FN+ cells morphologically. Frozen sections of original glioma tissue showed FN+ vessel walls and GFAP+ parenchyma. Results are evidence for very early overgrowth of a preexistent FN+ cell type distinct from the GFAP+ parenchymal cell. The features of this distinct cell type are mesenchymal and resemble the proliferating vascular elements of gliomas in situ. The tendency for GFAP+ cells to grow on top of these FN+ cells suggests a feeder layer interaction. More knowledge of the origins and interactions of these two cell types may increase our understanding of the mechanism of antigenic changes in gliomas and may provide clues to improved therapeutic approaches.

Antigens, Neoplasm↗
PubMed1986

Development and evolution of the helicoidal plane of dental occlusion.

The helicoidal plane of dental occlusion is a composite feature involving axial inclination of teeth and effects of dental attrition. Recent studies disagree on its distribution and significance in hominoid primates. The distribution, development, and functional basis of the helicoidal plane are investigated here, based on quantitative analysis of dental morphology and attrition in 667 human and 60 chimpanzee dentitions. Helicoidal planes are nearly universal in the human and chimpanzee dentitions studied. Increasing axial inclination of molars from M1 to M3 is primarily responsible for the helicoidal plane, although attrition acts to increase its expression. In hominoids, increased molar axial tilt appears to be associated with facial shortening and dental reduction. Population and species comparisons suggest a functional relationship with cranial structure. Progressive axial tilt of molars producing a helicoidal plane is found consistently in mammals with cheek teeth positioned partly under the cranium, as in hominids, pongids, some cebids, macropodids, ursids, and sciurids. Facial shortening is an important trend in hominid evolution and axial inclination of molars might be expected to show progressive change from Australopithecus afarensis to recent Homo sapiens.

Animals↗
PubMed1986

Ultrastructural features of the lymphocyte-stimulated halos produced by human glioma-derived cells in vitro.

Many glioma-derived cell lines have the capability of escaping cell-mediated immune attack. One mechanism of escape is the secretion of a hyaluronidase-sensitive mucopolysaccharide coat by these cells. This coat prevents contact and tumor cell killing by specific cytolytic allogeneic lymphocytes. The production of the coat by the tumor cells is stimulated by a macromolecular factor released by peripheral blood mononuclear (PBMC) cells in culture. We have examined the morphologic and ultrastructural features of this extracellular matrix. Three coat-producing lines were studied. Under phase contrast light microscopy, the coat is a clear pericellular 'halo'. To stain this zone, ruthenium red and Alcian Blue 8 G stains, which bind to acid mucopolysaccharides (to a large extent, hyaluronic acid), were used. The two stains produced similar results. With light microscopy, a weblike pattern of stain was evident throughout the halo region. With transmission electron microscopy, staining was found along the plasma membrane of the glioma cells and their microvilli, stretching in long, branching filaments from these surfaces and, in some instances, from one microvillus to the next. Since mucopolysaccharide matrices have a large aqueous component, it was necessary to determine whether dehydration alters the stain pattern. Therefore, undehydrated ruthenium red stained specimens from each culture were embedded in Quetal 651 (Ted Pella, Inc., Tustin, CA), a water soluble plastic. No morphologic differences were noted between the hydrated and dehydrated specimens. This study indicates that numerous long microvilli and a secreted mucopolysaccharide matrix are important structural elements of the lymphocyte-stimulated tumor cell halo in vitro. The mechanism by which the PBMC factor stimulates coat formation and the importance of the coat in in vivo tumor defenses remain to be elucidated.

Brain Neoplasms↗
PubMed1986

Glucose metabolism in human gliomas: correspondence of in situ and in vitro metabolic rates and altered energy metabolism.

The rates of disappearance of glucose from the medium of 13 human glioma-derived cell lines and one cultured of normal human cortical astrocytes were determined by fluorometric techniques. High-grade glioma-derived cultures showed a range of glucose consumption between 1 and 5 nmol/min/mg protein. Normal astrocyte cultures and cultures derived from grades I-III gliomas had a glucose consumption rate of 2-3 nmol/min/mg protein. Seven high-grade glioma lines were derived from surgical samples taken from patients who had been scanned by 18F-2-deoxy-d-glucose positron computed tomography. The rate of glucose consumption in these high-grade glioma-derived lines was close to the maximum local cerebral metabolic rate for glucose (LCMRglc) measured in situ in the tumors from which the cultures were derived. In cultured glioma-derived lines, approximately one-half of the glucose consumed was recovered as lactate and pyruvate, suggesting a reliance of glioma cells on aerobic glycolysis. ATP and phosphocreatine (PCr) levels were variable in the glioma-derived lines, and ATP was lower in the glioma-derived lines than in the normal astrocytes. Levels and regulation of glycogen differed significantly among the various glioma-derived cell lines. Glycogen content did not diminish as glucose was consumed, suggesting that glycogen utilization is not tightly regulated by the glucose metabolic rate. These results suggest that human glioma-derived cell cultures (1) adequately reflect the metabolic capacity of gliomas in situ and (2) are significantly altered in several aspects of their glycolytic metabolism.

Adenosine Triphosphate↗
PubMed1986

Secular trends in face size.

Comparison of lateral and postero-anterior radiographs of parents and their adult children shows a differential secular trend in facial depths, heights, and breadths. Children tend to have deeper, longer, and narrower faces than their same-sex parents.

Adult↗
PubMed1985

Plasma fibronectin in patients with brain tumors.

Fibronectin, a large molecular weight glycoprotein normally found on the surface of many cells, was measured in the plasma of 15 normal volunteers and 75 patients with various kinds of brain tumors or other kinds of neurological disorders. The mean plasma fibronectin in the control group was 253 micrograms/ml. Statistically significant elevations in fibronectin levels were found in patients with progressive high grade astrocytomas (mean = 413 micrograms/ml). The majority of patients with high grade astrocytomas in remission had normal levels of fibronectin (mean = 273 micrograms/ml). Elevations were noted in patients with low grade astrocytomas, meningiomas, and benign nonneoplastic neurological disorders. Plasma fibronectin may be useful diagnostically and therapeutically in identifying and managing some patients with high grade gliomas. However, of greater importance is the observation that fibronectin elevation is the result of a tumor-host interaction.

Astrocytoma↗
PubMed1985

Regulation of hexokinase in cultured gliomas.

Positron emission computed tomographic (PECT) scanning studies have demonstrated that high grade gliomas exhibit increased 2-[18F]fluoro-2-deoxyglucose (18FDG) uptake compared to cerebral white matter and low grade gliomas. Hexokinase catalyzes the phosphorylation of glucose, as well as 18FDG and 2-deoxyglucose (2DG), thereby "trapping" these slowly metabolized analogues intracellularly. We hypothesize that a similar hexokinase-mediated uptake of glucose and glucose analogues occurs in vitro. Hexokinase activity was assayed in homogenates of tissue-cultured lines derived from high (IV) and low (II) grade gliomas and in fibroblasts derived from skin. With glucose as substrate, the maximal activity (Vmax) in the Grade IV lines was 200% of the activity found in the Grade II line, fibroblasts, and astrocytes; however, the Michaelis substrate affinity constant (Km) bore no relationship to tumor grade. With 2DG as substrate, the Vmax of all cell lines decreased, but the Grade IV lines still tended to have greater activity than the others. The Km values for 2DG were 5 times higher than those for glucose. Hexokinase is found in two subcellular compartments: an active form reversibly bound to mitochondria and a less active, cytosolic form. Up to 20% of the total hexokinase was found in the cytosol in all lines tested. High energy phosphate compounds (ATP, ADP, CTP, and others) displaced mitochondria-bound hexokinase, which increased the cytosolic form by 2-fold in the glioma lines, but fibroblast hexokinase distribution was unaffected. Our results suggest that: (a) high grade gliomas have increased hexokinase activity, which may explain the grade-related differences in 18FDG uptake observed by PECT scanning, and (b) human glioma hexokinases may be regulated by reversible subcellular compartmentation.

Cell Line↗
PubMed1985

Quantification of dysmorphogenesis: pattern variability index, sigma z.

The pattern variability index (sigma z) is the standard deviation of Z-scored radiogrammetric measurements of an individual expressed relative to norms for age and gender. As applied to standardized measurements of the head and face, a sigma z value of 1.2 approximates the 95th percentile of the normal range of children, adolescents, and adults. Individuals with congenital malformation syndromes tend to exceed 1.2 in the pattern variability index and may achieve values of 1.8-2.0 and above. sigma z thus provides objective indications of dysmorphogenesis and quantification of the degree of departure from the normal appearance.

Adolescent↗
PubMed1985

[Tubular bodies (Weibel-Palade) in the endothelial cell of glioblastoma].

Authors have studied the ultrastructure of endothelial cells in the microvessels of malignant and benign gliomas and in particular, the numbers of tubular bodies (Weibel-Palade) in endothelial cells of glioma microvessels in related with blood vessel proliferation. Glioblastoma 6, astrocytoma grade II 1, oligodendroglioma 1 and 2 samples of non-tumor brain tissue were analyzed quantitatively using light and electron microscope with Karnovski fixative. All tissues were obtained from the center, the intermediate and the margin in each tumor tissue and just outside of the tumor at operation. 389 microvessels were examined in the total gliomas electronmicroscopically. Tubular body was first described by Weibel and Palade in the vascular endothelial cells of various organs in both man and animals. This is now considered to be an organelle specific to the endothelial cell, but its function is still unknown. Tubular body observed in the endothelial cells of the gliomas vessels consisted of a membrane-limited round, oval or elongated shaped intra cytoplasmic body (about 0.1-0.2 micron) which contained tubules of 150-200 A outer diameter. Tubular bodies were classified in the two types. One of them (mature type) was relatively electron dense to be more compact, the other (immature type) had relatively pale matrix. In the immature type they are located in close proximity to the Golgi complex or endoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

Astrocytoma↗
PubMed1985

Stromal and nuclear markers for rapid identification of pituitary adenomas at biopsy.

We tested fluorescent and light microscopic markers to improve recognition of pituitary adenomas at biopsy. The optimal reagent was 100 mg/L of fluoresceinated Ricinus communis agglutinin 120 (RCA 120) lectin plus 3 mg/L of propidium iodide. The refrigerated solution was immediately available for use on routine frozen sections. The sections were stained for one minute and viewed immediately after they were rinsed with saline and coverslips applied. Fluorescein-labeled RCA 120, which binds galactose, localized vascular stroma. Propidium iodide, which binds nucleic acids, stained nuclei. Stromal configuration, nuclear morphology, and cell to stroma ratio were illuminated and used to distinguish adenoma from adenohypophysis. We also describe a method utilizing peroxidase-conjugated RCA 120 that demonstrates the same features by light microscopy. Fluoresceinated RCA 120-stained vessels and stroma of routinely processed material more reliably than hematoxylin-eosin or labeled antibody to fibronectin and faster than peroxidase-conjugated RCA 120 or the rapid method for reticulin.

Adenoma↗
PubMed1984

The beta-adrenergic receptor system in human glioma-derived cell lines: the mode of phosphodiesterase induction and the macromolecules phosphorylated by cyclic AMP-dependent protein kinase.

beta-Adrenergic receptors and the activities of adenylate cyclase, phosphodiesterase and protein kinase were examined in two human glioma cell lines, U 251 and LM, as well as in rat C6 glioma. [3H]Dihydroalprenolol binding to beta-adrenergic receptors was specific, saturable and of high affinity in each cell line. The dissociation constant (Kd) and maximal binding (Bmax) extrapolated from Scatchard curves were Kd = 17.4 +/- 3.2 nM and Bmax = 1110 +/- 197 fmol/mg protein for the U-251 cells; Kd = 14.4 +/- 2.2 nM and Bmax = 655 +/- 105 fmol/mg protein for the LM cells; and Kd = 5.6 +/- 1.1 nM and Bmax = 454 +/- 80 fmol/mg protein for the C6 glioma cells. L-Isoproterenol stimulated cyclic AMP formation in all 3 cell lines. beta-Adrenergic agonists also increased calcium-dependent and calcium non-dependent phosphodiesterase activity in these tumor cells. Cytosolic protein kinase in the 3 cell lines phosphorylated exogenous histone as a substrate. The phosphorylation was enhanced by cyclic AMP. Cytosolic protein kinase also phosphorylated endogenous cytosolic macromolecules. The phosphorylated proteins had molecular weights of 30,000, 51,000 and 90,000 in the two human glioma cell lines. The present results indicate that human glioma cell lines have functional beta-adrenergic receptors linked to adenylate cyclase. These beta-receptors can also regulate phosphodiesterase activity and cyclic AMP in human glioma cells can activate protein kinase and induce the phosphorylation of specific proteins.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Depressed cerebellar glucose metabolism in supratentorial tumors.

Fifty-four patients with supratentorial tumor and one with brainstem tumor were examined with positron emission tomography (PET) using [18F]fluoro-deoxyglucose (FDG). Twenty-one of these cases had satisfactory studies of the cerebellum. Of these, 12 showed significant metabolic asymmetry between the two cerebellar hemispheres, with the rate of glucose utilization in the hemisphere contralateral to the cerebral tumor being 8-34% lower than on the ipsilateral side, as compared with a right-left asymmetry of only--1.6% +/- 2.1% standard deviation for a group of 5 normal subjects. In these 12 cases the tumor involved the sensorimotor cortex and/or the thalamus with varying degrees of hemiparesis being present. For the remaining 9 patients with no significant cerebellar metabolic asymmetry, the tumor involved regions other than the sensorimotor cortex, and unilateral motor dysfunction was not a prominent clinical feature. The correlation between cerebellar metabolic suppression and unilateral motor dysfunction observed in our cases appears to be due to impairment or interruption of the cortico-thalamo-ponto-olivo-cerebellar circuitry by either the tumor itself or by edema. These results illustrate the ability of FDG-PET scans to detect metabolic changes, not apparent on CT scans, in areas of the brain remote from the primary lesion.

Astrocytoma↗
PubMed1984

Patterns of molar wear in hunger-gatherers and agriculturalists.

Tooth wear records valuable information on diet and methods of food preparation in prehistoric populations or extinct species. In this study, samples of modern and prehistoric hunger-gatherers and agriculturalists are used to test the hypothesis that there are systematic differences in patterns of tooth wear related to major differences in subsistence and food preparation. Flatness of molar wear is compared for five groups in hunger-gatherers (N = 298) and five groups of early agriculturalists (N = 365). Hunger-gatherers are predicted to develop flatter molar wear due to the mastication of tough and fibrous foods, whereas agriculturalists should develop oblique molar wear due to an increase in the proportion of ground and prepared food in the diet. A method is presented for the quantitative measurement and analysis of flatness of molar wear. Comparisons of wear plane angle are made between teeth matched for the same stage of occlusal surface wear, thus standardizing all groups to the same rate of wear. Agriculturalists develop highly angled occlusal wear planes on the entire molar dentition. Their wear plane angles tend to exceed hunger-gatherers by about 10 degrees in advanced wear. Wear plane angles are similar within subsistence divisions despite regional differences in particular foods. This approach can be used to provide supporting evidence of change in human subsistence and to test dietary hypotheses in hominoid evolution.

Agriculture↗
PubMed1984

Issues in the in vivo measurement of glucose metabolism of human central nervous system tumors.

Over 150 cases of central nervous system tumors have been studied with positron emission tomography using fluorine-18-labeled fluorodeoxyglucose (18FDG) as a tracer. From this material 100 consecutive cases of cerebral glioma have been reviewed and analyzed. The results show a strong correlation of tumor grade with glycolytic rate, with visual "hot spots" present in all high-grade neoplasms and in only four low-grade tumors. The quantitative accuracy is limited by three basic factors. First, the measurement of tissue uptake, as compared with the parent technique, autoradiography, is more difficult because detection must be done outside the body. Effects such as scattered radiation and self-attenuation introduce errors unless properly corrected. A more serious problem when measuring small structures, such as a rim-shaped high-grade glioma, is the limited spatial resolution. The most advanced scanner, the Neuro-PET, has a resolution of 6 to 7 mm. Second, corrections are needed for backflow, including free tracer at the time of the scan that will return to the blood and "trapped" tracer that will backflow because of the presence of phosphatase. These corrections are calculated from the blood activity using nominal rate constants for 18FDG. Our study found no significant alteration in rate constants between normal and tumoral tissue. Finally, a lumped constant is needed to correct for kinetic differences between 18FDG and glucose. If there is a change in the mechanism of either membrane transport or the hexokinase reaction, the lumped constant may change. However, measurements of actual glucose utilization in tissue culture lines from six patients support the 18FDG results.

Animals↗
PubMed1984

A human ganglioglioma containing paired helical filaments.

Neurofibrillary tangles composed of paired helical filaments were found in a human ganglioglioma. This is the first reported occurrence of neurofibrillary tangles in a neoplasm. These tangles were visible light microscopically with hematoxylin-eosin and Bodian's stains. They were confirmed as neurofibrillary tangles with Congo red staining under polarized light and with thioflavine S fluorescence. Untrastructurally, the tangles were composed of 10-nm filaments twisted in a helix with 80 nm between constructions. Thus, neoplastic proliferation does not preclude production of paired helical filaments. Cells grew from explants of this tumor, but no paired helical filaments were found in the cells examined. Two other gangliogliomas and normal brain tissue studies by the same procedures did not show paired helical filaments. Gangliogliomas that contain neurofibrillary tangles provide an alternative source of abnormal filaments for analysis.

Adolescent↗
PubMed1984

Applications of pattern profile analysis to malformations of the head and face.

The craniofacial pattern profile approach to dysmorphogenesis syndromes affecting the head and face combines graphic and numerical measures of pattern variability and pattern comparison. Selected dimensions of the head and face are expressed as Z-scores (standard deviation units) relative to standards for age and sex. As with the metacarpophalangeal pattern profile, this method identifies highly deviant but undiagnosed patterned departures from normal and allows comparison with individuals or groups of individuals with known diagnoses.

Adolescent↗