Evidence based medicine. Quality cannot always be quantified.
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Clinical Medicine↗
Biomedical subjects
B H Smith
Publications and source records attributed to B H Smith.
Ovarian hyperstimulation: actual and theoretical risks.
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Capillary Permeability↗
Conditional withholding of proboscis extension in honeybees (Apis mellifera) during discriminative punishment.
Proboscis extension conditioning of honeybee workers was used to test the ability of bees to respond to appetitive and aversive stimuli while restrained in a harness that allows subjects to move their antennae and mouthparts (Kuwabara, 1957; Menzel, Erber, & Masuhr, 1974). Subjects were conditioned to discriminate between two odors, one associated with sucrose feeding and the other associated with a 10 V AC shock if they responded to the sucrose unconditioned stimulus (US) in the context of that odor. Most Ss readily learned to respond to the odor followed by sucrose feeding and not to the odor associated with sucrose stimulation plus shock. Furthermore, in the context of the odor associated with shock, significantly more subjects withheld or delayed proboscis extension on stimulation with the sucrose US than they did in the context of the odor associated with feeding. Thus, restrained honeybees can readily learn to avoid shock according to an odor context by withholding proboscis extension to a normally powerful releaser. Analysis of individual learning curves revealed that subjects differed markedly in performance on this task. Some learn the discrimination quickly, whereas others show different kinds of response patterns.
Animals↗
Selective cytoplasmic and membrane changes induced by cisplatinum.
Cisplatinum (cis-dichlorodiammineplatinum II (NSC-119875], proven to be of therapeutic value in a variety of solid tumors, is thought to have DNA as its major target. Prior in vitro studies have suggested that it also induced cell membrane and cytoplasmic changes. To better understand glial tumor cell sensitivity to cisplatinum and to design more effective adjuvant therapy, three cisplatinum sensitive human glioma-derived cell lines, SNB-1, SNB-3, SNB-4, were examined by transmission electron microscopy for cisplatinum induced changes. Tumor cells were exposed to 25, 50, and 100 micrograms/ml cisplatinum in medium for varying time periods (4-72 hours). Four changes were consistent: cell rounding and reduced nuclear-cytoplasmic ratio, nuclear chromatin clumping, vesiculation and swelling of the golgi apparatus, and dilatation of the smooth endoplasmic reticulum. These morphologic changes are distinct for cisplatinum and unlike those induced by BCNU (plasma membrane blebbing) and AZQ (mitochondrial swelling and destruction) previously seen in our laboratory. The cellular events described here suggest that cytoplasmic, as well as nuclear, changes (occurring within the same time intervals) may both be relevant to the antitumor effects of cisplatinum.
Cell Line↗
Successful treatment of TMJ ankylosis?
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Ankylosis↗
DNA cross-linking responses of human malignant glioma cell strains to chloroethylnitrosoureas, cisplatin, and diaziquone.
Cell strains derived by culture of malignant glioma (astrocytoma grade III-IV) surgical specimens were tested for the production of DNA interstrand cross-links (ISC) and DNA-protein cross-links following treatment in vitro with 1-(2-chloroethyl)-1-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine), 1-(2-chloroethyl)-3-(2,6-dioxo-1-piperidyl)-1-nitrosourea (PCNU), cis-dichlorodiammineplatinum(II) (cisplatin), and 3,6-diaziridinyl-2,5-bis(carboethoxyamino)-1,4-benzoquinone (diaziquone). ISC and DNA-protein crosslinks were measured by means of the DNA alkaline elution technique. Large differences among the cell strains were observed in DNA cross-linking responses to individual agents. The DNA responses to the chloroethylnitrosoureas, cisplatin, and diaziquone were largely independent of each other, except for a weak correlation between ISC responses to chloroethylnitrosoureas were distributed bimodally, in accord with a phenotypic distinction between Mer+ and Mer- cells. ISC responses to cisplatin and diaziquone showed significant variation among cell strains, but the distributions were not bimodal. The results demonstrate the existence of diverse DNA cross-linking response patterns among cell strains from different tumors of a given histological type.
Aziridines↗
Polymorphisms in eruption sequence of permanent teeth in American children.
This study provides basic descriptive data on the frequency of pairwise eruption sequences ascertained in cross-sectional examination of 6,000 black and white American children in the Ten State Nutritional Survey of 1968-1970. All sex and race groups share a distinct pattern of sequence polymorphisms in terms of location, number, and level. Teeth in eruption phase I (M1, I1, I2) rarely reverse in sequence with those in phase II (C, P1, P2, and M2). Five sequences have variants that appear at greater than or equal to 20% in all groups, with M1I1 vs. I1M1 approaching maximum polymorphic values of 50%/50%. The traditional notation for eruption sequences can be modified to reflect these important variants, giving the sequence M1 I1 I2 [P1 C P2] M2 for the maxilla and [M1 I1] I2 [C P1] [P2 M2] for the mandible. The location of major polymorphisms is explicable by close timing of teeth within phase I and, separately, teeth within phase II eruption. However, strong integration of development of physically adjacent teeth apparently acts to reduce substantially the number of sequence reversals. The Ten State Survey data provide a sound descriptive basis for two populations, yet precise comparative data are available for few other human groups or primate species.
Adolescent↗
Immunocytochemical localization of factor VIII-related antigen in tumors of the human central nervous system.
Using both immunohisto- and immunocytochemical techniques with periodate-lysine-paraformaldehyde (PLP) fixation, we have studied the distribution of Factor VIII-related antigen (FVIIIR:Ag) in 12 cases of tumors of the human central nervous system (CNS) and one sample of non-tumor brain tissue. FVIIIR:Ag was found both extracellularly and intracellularly. It was localized in the vascular lumen, between endothelial cells, and in the endothelial cell basement membrane. In the endothelial cell cytoplasm, FVIIIR:Ag was found in the endoplasmic reticulum, perinuclear space, and in intracytoplasmic vacuoles and vesicles. Characteristic of malignant tumors (six out of seven) was a strongly-positive dilated endoplasmic reticulum. This may reflect increased FVIIIR:Ag synthesis in the endothelial cells of malignant tumors. Only one of five benign tumors showed such staining. Six of 12 tumors and the non-tumor brain showed perinuclear FVIIIR:Ag. Both ad- and abluminal vesicles in the tumor endothelial cells contained FVIIIR:Ag suggesting that endocytosis, transcellular transport, and/or endocytosis, as well as FVIIIR:Ag synthesis occurs. The non-tumor brain showed normal capillary structure and very little FVIIIR:Ag immunoreactivity. The relationship of these FVIIIR:Ag abnormalities to the hypercoagulable state seen in some malignant brain tumor patients remains to be clarified.
Antigens↗
Enzymes of glucose metabolism in cultured human gliomas: neoplasia is accompanied by altered hexokinase, phosphofructokinase, and glucose-6-phosphate dehydrogenase levels.
The enzymes of glycolysis and selected enzymes of the pentose phosphate pathways were measured by fluorometric methods in extracts prepared from cultures of normal cortical human astrocytes and from cultures derived from low-grade (II) or high-grade (IV) gliomas. The hexokinase and phosphofructokinase levels of the low-grade glioma-derived line were not significantly different from those of the normal astrocyte cultures. However, the activities of hexokinase and phosphofructokinase were consistently and significantly increased in the high-grade glioma-derived lines. The activity of glucose-6-phosphate dehydrogenase was significantly decreased in all glioma-derived lines and by more than 90% in the high-grade-derived lines. Other enzymes of the glycolytic pathway were not significantly different from those of normal astrocytes, or they showed a variation inconsistently related to the neoplastic state. Glucose flux is not apparently regulated to a significant degree of hexokinase in glioma-derived lines, since the measured Vmax values are in substantial excess over the measured flux rates. Reversible binding of hexokinase to the particulate fraction was observed in both the normal astrocytes cultures and the high-grade glioma-derived lines. A twofold displacement of particulate hexokinase by ATP, ADP, 1-O-methylglucose, sorbitol-6-phosphate, and dibutyryl cyclic AMP was observed in the high-grade glioma-derived lines. The degree of displacement by various agents and the basal ratio of free/bound was not significantly different between the transformers and the nontransformants. The hexokinase from both the gliomas and the normal astrocytes was noncompetitively inhibited by the glucose analogue 2-deoxy-d-glucose. Phosphofructokinase activity is close to the observed glucose flux rates in both the normal astrocyte and the glioma-derived cultures. The phosphofructokinase activity of normal astrocytes is activated twofold or more by ADP, AMP, fructose-2,6-diphosphate, and Pi. However, these same ligands activate phosphofructokinase by less than twofold in a typical high-grade glioma-derived line. ATP, dibutyryl cyclic AMP, and citrate inhibit glioma and normal astrocytic phosphofructokinase, but the magnitude of the inhibition is much less than in the glioma-derived lines.
Astrocytes↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
[Immunocytochemical localization of factor VIII-related antigen and tubular bodies (Weibel-Palade bodies) in blood vessels of human gliomas].
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Antigens↗