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Biomedical subjects

B H Smith

Publications and source records attributed to B H Smith.

At least 73 records · Page 4Linked to original sources
PubMed1996

Medicine--a healing or a dying art?

That medicine is a science is the popular belief, and this has been reinforced by the advent of 'evidence-based medicine', which assumes that scientific proof is required to support medical practice. However, the view of science implied is a narrow one, foreign both to pure scientists and to artists, and the art of medicine is devalued by the approach. There are both important differences and important similarities between science and the arts. The arts should contribute to evidence-based practice and education along with science, and have a role in many aspects of medical practice.

Art↗
PubMed1995

Retrievable, replaceable, macroencapsulated pancreatic islet xenografts. Long-term engraftment without immunosuppression.

Prevention of rejection and prolongation of graft survival are critical to achieving successful islet cell transplantation. Various techniques have been utilized to prolong graft survival. Recently, protection of pancreatic islets from host immune mechanisms by isolating the islets in artificial membranes has emerged as an attractive alternative to the use of immunosuppression. In this Rapid Communication, we describe a novel method for macroencapsulation of rat islets in hydrophilic macrobeads made with various combinations of agarose, collagen, and Gelfoam. Encapsulated xenotypic islets were placed intraperitoneally in mice in which diabetes was induced by streptozotocin. The encapsulated xenografts maintained normoglycemia > 170 days. Recipients mice had normal glucose tolerance tests, which indicates that the islets in the macrobeads were functioning as they would in an intact pancreas. Macrobeads retrieved up to 103 days after transplantation showed no evidence of tissue reaction or local inflammation. These retrieved macrobeads could also be retransplanted and replaced. Our studies indicate that the agarose-collagen/Gelfoam macrobeads we have developed serve both to protect islet xenografts from rejection and to provide a microenvironment in which the islets maintain and support their normal function in vivo. Because they may be retrieved after implantation and replaced, these macrobeads may be suitable for human clinical islet cell xenotransplantation.

Animals↗
PubMed1994

Patterns of dental development in Homo, Australopithecus, Pan, and Gorilla.

Smith ([1986] Nature 323:327-330) distinguished patterns of development of teeth of juvenile fossil hominids as being "more like humans" or "more like apes" based on statistical similarity to group standards. Here, this central tendency discrimination (CTD) is tested for its ability to recognize ape and human patterns of dental development in 789 subadult hominoids. Tooth development of a modern human sample (665 black southern Africans) was scored entirely by an outside investigator; pongid and fossil hominid samples (59 Pan, 50 Gorilla, and 14 fossil hominids) were scored by the author. The claim of Lampl et al. ([1993] Am. J. Phys. Anthropol. 90:113-127) that Smith's 1986 method succeeds in only 8% of human cases was not sustained. Figures for overall success of classification (87% humans, 68% apes) mask important effects of teeth sampled and age class. For humans, the power of CTD varied between 53% and 92% depending on the number and kind of teeth available--nearly that of a coin toss when data described only two nearby teeth, but quite successful with more teeth or distant teeth. For apes, only age class affected accuracy: "Infant" apes (M1 development < or = root cleft complete, unemerged) were usually classed as humans, probably because the present developmental standard for great apes is in substantial error under 3 years of age. "Juvenile" apes (M1 > or = root 1/4), however, were correctly discriminated in 87% of cases. Overall, CTD can be considered reliable (accuracy of 92% for humans and 88% for apes) when data contrast development of distant dental fields and subjects are juveniles (not infants). Restricting analysis of fossils to specimens satisfying these criteria, patterns of dental development of gracile australopithecines and Homo habilis remain classified with African apes. Those of Homo erectus and Neanderthals are classified with humans, suggesting that patterns of growth evolved substantially in the Hominidae. To standardize future research, the computer program that operationalizes CTD is now available.

Aging↗
PubMed1994

The olfactory memory of the honeybee Apis mellifera. II. Blocking between odorants in binary mixtures.

Proboscis extension conditioning of honeybee workers was used to study the processing of odorants when bees were conditioned to binary mixtures. Responses to a set of pure floral odors and pheromones after conditioning have already been described. When bees are conditioned to certain mixtures of odorants, the response to both components is equal to that when they are tested alone. However, mixtures of an aliphatic aldehyde and an alcohol elicit asymmetric response patterns; that is, the response to the aldehyde is much stronger than that to the alcohol. A bee's response to the alcohol after it had been trained in an aldehyde background is significantly lower than when the bee is trained to respond to the same alcohol in the background of another odorant. Such response patterns are not necessarily caused by a behavioral decrement resulting from a compound-unique perceptual effect produced by the mixture. Furthermore, studies of blocking show that behavioral acquisition in response to one component can be hindered or blocked by pretraining with the other component. These results suggest that honeybees can perceive the individual components of some binary mixtures. The similarities in neural processing in olfactory systems of vertebrates and invertebrates mean that such studies could elucidate behavioral mechanisms of olfaction in a wide phylogenetic spectrum of animals.

Alcohols↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗