Great expectations. The reading habits of year II medical students.
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Books↗
Biomedical subjects
C R Taylor
Publications and source records attributed to C R Taylor.
Estimating transit time for capillary blood in selected muscles of exercising animals.
The mean minimal capillary transit time was estimated in muscles of various animals using a combination of physiological and morphometric methods. Radioactive microspheres were injected intravascularly in various animals running on a treadmill at maximum oxygen consumption rate (VO2,max) to label blood flow to individual muscles. The muscles were then removed and preserved by standard methods for electron microscopy. The volume density of mitochondria was measured to assess muscle oxidative capacity. Capillary densities in muscle cross-sections, capillary diameters and tortuosities were incorporated into an estimate of capillary volume per unit muscle mass. Mean capillary transit time (tc) in the exercising muscles was estimated by dividing mass-specific capillary volume by mass-specific blood flow. Estimates of tc ranged from values near 1 s in horse heart and thigh muscles to 0.2 s in duck gastrocnemius. The relationship between muscle blood flow and tc was hyperbolic. The experimental data indicate a limiting value of 0.2 s for transit times at very high blood flows. There was no correlation between tc and body-mass-specific VO2,max.
Animals↗
Variations in function and design: testing symmorphosis in the respiratory system.
We explore the question of whether and to what extent the large variation in energy requirements observed among mammals is related to variations in the design of the respiratory system, from the lung to the mitochondria in muscle cells. Resting metabolic rate is determined by body size (allometric variation). Maximal rates of O2 consumption (VO2 max) also vary in a regular manner with body size, but adaptive variation allows some species to achieve much higher values than others of the same body size. We, therefore, consider adaptive variation as modulation of structures and functions above those determined by allometric variation. A model is presented that separates functional and design parameters at four steps of the respiratory cascade: the pulmonary gas exchanger, heart and blood, microvasculature, and mitochondria. The variations observed in these parameters are analyzed with respect to those in energy demand and are discussed in relation to the hypothesis of symmorphosis. We conclude that the design of the internal steps of the respiratory system (mitochondria, capillaries, blood, and heart) is matched to functional demand, whereas the lung maintains a variable excess of morphometric diffusing capacity which may be related to the facts that the lung has limited malleability and that it forms the interface with the environment.
Animals↗
Monocytoid B-cell lymphomas: an assessment of diagnostic criteria and a perspective on histogenesis.
To determine which morphologic criteria are most useful in distinguishing reactive from malignant monocytoid B cells (MBCs), we compared 16 monoclonal cases (11 nodal, five extranodal) of monocytoid B-cell lymphoma (MBCL) with 12 cases of various reactive diseases in which MBCs were polyclonal. The results of our study showed that in MBCL the MBC component was the predominant architectural finding and that there was confluence of MBCs in all but one case. In contrast, the MBC component did not predominate in the reactive group (P less than .000001) and focal confluence was seen in only one case. A cytologic comparison showed that in MBCL areas there were more large transformed (prominent nucleolated) MBCs (P = .003), a higher mitotic rate (P = .03), and more nuclear irregularities (P = .007) than were present in the reactive group. In addition, evolution to an aggressive histologic type was found in four cases of MBCL. Our results also revealed concomitant multiple, monoclonal, morphologically distinct populations in other compartments (follicular center cells in seven, mantle cells in five, small lymphocytes in five, and plasma cells in 11). These unique findings can be reconciled by postulating (1) that the simultaneous presence of these diverse cytologic types represents morphologic expressions of a B cell whose population is in different phases of its cell cycle and/or its evolution or (2) that the histogenesis of MBCL is possibly from a nodal pluripotent B-stem cell that can differentiate directly into these various cytologic types.
Adult↗
Computed tomography in the evaluation of the portal venous system.
Computed tomography has widespread clinical application in the evaluation of the portal venous system, even though quantitative methods are impractical due to the inability to measure portal flow discrete from hepatic arterial flow, morbidity associated with the use of large volumes of iodinated contrast, and technical limitations. This represents a major disadvantage compared to Doppler ultrasound and magnetic resonance angiography. Qualitative applications include evaluation of portal vein patency, diagnosis of portal vein thrombosis, underlying inflammatory or neoplastic conditions, and evaluation of surgically created portosystemic shunts and collateral flow. Diagnostic criteria for portal venous thrombosis include nonopacification of the central portion of the portal vein, peripheral enhancement of the vein, and irregular periportal hepatic parenchymal enhancement. However, misdiagnosis is common, occurring in 16% of cases analyzed in one limited series, and periportal vein enhancement is now recognized as a nonspecific finding associated with underlying endothelial injury. Cavernous transformation of the portal vein and neoplastic invasion of the portal system are more reliably recognized. Computed tomography arterial portography demonstrates collateral pathways and arteriovenous shunts. Computed tomography has a sensitivity of 85% in detection of esophageal varices compared to endoscopy, but has the advantage of demonstrating splenorenal, gastrorenal, peripancreatic, pericholecystic, retroperitoneal and omental collateral vessels, and spontaneous large portosystemic shunts, with greater sensitivity than angiography. Computed tomography combined with Doppler ultrasound angiography remains popular, despite a lack of large-scale prospective efficacy studies demonstrating diagnostic superiority over other imaging techniques, largely because of its accessibility, and its detailed axial anatomic images providing an overview of multiple organ systems, and patency of major vessels.
Collateral Circulation↗
Magnetic resonance imaging in the evaluation of the portal venous system.
Magnetic resonance (MR) imaging is used in assessing the portal venous system through qualitative and quantitative methods. Magnetic resonance angiography can be performed using time-of-flight or phase-contrast techniques. Time-of-flight techniques (which use gradient echo images to display bright blood or spin echo images to display black blood) are relatively standardized and commercially available. These techniques are used to display liver morphology, portal vein patency, portal venous collaterals, and surgically created portosystemic shunts. Magnetic resonance is equivalent to angiography in the detection of varices, according to a preliminary study. Time-of-flight flow imaging using gradient echo techniques (in which a thrombus appears as absence of bright signal in the portal vein) and spin-echo techniques (where thrombus appears as a bright signal) can become combined to increase specificity for diagnosis of portal vein thrombosis. Phase-contrast techniques provide flow information based on phase shifts induced by flow through magnetic gradients. Phase-contrast angiography is less widely available than time-of-flight angiography. However, phase-contrast methods allow imaging of very slow flow that is not possible using time-of-flight methods. Quantitation of flow is possible, both with time-of-flight techniques using bolus tracking and with phase-contrast techniques using quantitative measurement of phase shifts. Calculations of flow velocity correlate well with Doppler ultrasound estimations, MR flow quantitation does not, at present, rival ultrasound in terms of cost or availability. However, MR is not limited by obesity or overlying bowel gas which can prevent adequate ultrasound evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)
Humans↗
O2 delivery at VO2max and oxidative capacity in muscles of standardbred horses.
The purpose of this study was to describe the relationships between 16 physiological, biochemical, and morphological variables presumed to relate to the oxidative capacity in quadriceps muscles or muscle parts in Standardbred horses. The variables included O2 delivery (blood flow) and mean capillary transit time (MTT) during treadmill locomotion at whole animal maximal O2 consumption (VO2max, 134 +/- 2 ml.min-1 x kg-1), capillary density and capillary-to-fiber ratio, myoglobin concentration, oxidative enzyme activities, glycolytic enzyme activities, fiber type populations, and fiber size. These components of muscle metabolic capacity were found to be interrelated to varying degrees using correlation matrix analysis, with lactate dehydrogenase activity showing the most significant correlations (n = 14) with other variables. Most of the "oxidative" variables occurred in the highest quantities in the deepest muscle of the group (vastus intermedius) and in the deepest parts of the other quadriceps muscles where the highest proportions of type I fibers were localized. The highest blood flow measured with microspheres in the muscle group during exercise was in vastus intermedius muscle (145 ml.min-1 x 100 g-1), and the lowest was in the superficial part of rectus femoris muscle (32 ml.min-1 x 100 g-1). Average muscle blood flow during exercise at whole animal VO2max was 116 ml.min-1 x 100 g-1. Because skeletal muscle comprised 43% of total body mass (453 +/- 34 kg), total muscle blood flow was estimated at 226 l/min, which was approximately 78% of total cardiac output (288 l/min).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A technique for retrieving antigens in formalin-fixed, routinely acid-decalcified, celloidin-embedded human temporal bone sections for immunohistochemistry.
The application of immunohistochemistry to routinely decalcified, celloidin-embedded human temporal bone sections has been hampered because of antigen loss during processing of the specimens. To our knowledge, there has been no published report to date describing immunohistochemical staining of such tissues suitable for examination by light microscopy. Here we report a novel antigen retrieval technique which can be successfully used to stain a variety of antigens in routinely formalin-fixed, trichloroacetic acid-decalcified, celloidin-embedded human temporal bone sections. The new procedure reported here for decalcified human temporal bone tissues simply requires immersing slides for 30 min at room temperature in an antigen retrieval solution. A total of 60 decalcified, celloidin-embedded human temporal bone tissues were tested with monoclonal antibodies (MAb) to 15 different antigens. Of these, 12 MAb showed definite positive staining, while three were negative. This technique may prove very useful in studying the expression of various antigens by immunohistochemistry in formalin-fixed, acid-decalcified, celloidin-embedded tissues.
Antibodies, Monoclonal↗
Quality assurance and standardization in immunohistochemistry. A proposal for the annual meeting of the Biological Stain Commission, June, 1991.
Quality assurance, quality control, proficiency testing, reagent documentation and validation are standard parts of everyday practice in clinical laboratories throughout the United States. Immunohistochemical stains employ reagents and principles in common with immunoenzyme methods utilized in the clinical laboratory. However, immunohistochemistry has not routinely been subjected to similar standardization and quality assurance procedures that manufacturers and pathologists alike have applied to essentially the same techniques in the clinical laboratory environment. The current proposal was invited by the Biological Stain Commission with the charge of incorporating the findings of previous workshops on quality control in immunohistochemistry into a practical design for implementation. The status of quality assurance, quality control and standardization in immunohistochemistry is reviewed and a phased strategy for implementation is proposed.
Immunohistochemistry↗
Report of the Immunohistochemistry Steering Committee of the Biological Stain Commission. "Proposed format: package insert for immunohistochemistry products".
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Immunohistochemistry↗
Clinical use of tumor markers.
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Antigens, Neoplasm↗
The concept of symmorphosis: a testable hypothesis of structure-function relationship.
The hypothesis that, in biological organisms, structural design is matched to functional demand is difficult to test because it is largely based on anecdotal evidence suggesting economic design. The hypothesis of symmorphosis postulates a quantitative match of design and function parameters within a defined functional system; because of its stringency it is refutable and can, therefore, be subjected to empirical test, for example, by assessing whether the structures that support the pathway for oxygen from the lung to the consumer in muscle cells are quantitatively adjusted to the limit of functional performance of the respiratory system. The study of allometric and adaptive variation leads to the conclusion that the hypothesis of symmorphosis is acceptable for all internal compartments of the respiratory system (blood, heart, muscle capillaries, and mitochondria), whereas it must be refuted for the lung that forms the interface to the environment.
Adaptation, Physiological↗
A mechanical trigger for the trot-gallop transition in horses.
It is widely thought that animals switch gaits at speeds that minimize energetic cost. Horses naturally switched from a trot to a gallop at a speed where galloping required more energy than trotting, and thus, the gait transition actually increased the energetic cost of running. However, by galloping at this speed, the peak forces on the muscles, tendons, and bones, and presumably the chance of injury, are reduced. When the horses carried weights, they switched from a trot to a gallop at a lower speed but at the same critical level of force. These findings suggest that the trot-gallop transition is triggered when musculoskeletal forces reach a critical level.
Animals↗
Diffusion and binding of monoclonal antibody TNT-1 in multicellular tumor spheroids.
Tumor spheroids of HT-29 human colon adenocarcinoma and A375 melanoma were established to investigate the uptake and clearance kinetics of TNT-1, a monoclonal antibody that targets necrotic cells of tumors. Our data reveal that there was rapid uptake of TNT-1 and its F(ab')2 fragment in both spheroid models, whereas an antibody of irrelevant specificity, Lym-1, and its F(ab')2 fragment bound poorly to the spheroids. Unlike previously reported monoclonal antibodies to tumor cell-surface antigens, TNT-1 showed 1) a linear uptake that increased over time without saturation in tumor spheroids and 2) an unexpected uptake by a subpopulation of cells in the viable outer rim of the spheroids. These preclinical studies provide important information concerning the therapeutic potential of TNT monoclonal antibodies for the treatment of cancer and micrometastases.
Adenocarcinoma↗
2-Phenyl-3H-imidazo[4,5-b]pyridine-3-acetamides as non-benzodiazepine anticonvulsants and anxiolytics.
A series of 2-phenyl-3H-imidazo[4,5-b]pyridine-3-acetamides were designed and synthesized as non-benzodiazepine anxiolytics based on a molecular disconnection of a typical 1,4-benzodiazepine (BZD). A number of these compounds showed submicromolar potency in a [3H]benzodiazepine binding assay in vitro and good potency in protecting rodents against pentylenetetrazole-induced seizures. Compound 84 appears to be a selective anticonvulsant (pentylenetetrazole) agent when tested against a profile of chemically and electrically induced seizures in mice. In addition, compound 148 appears to be a selective anxiolytic/hypnotic agent on the basis of biochemical and pharmacological characterization. It appears to be a full BZD agonist as assessed by GABA shift ratio and to be effective in punishment and nonpunishment animal models of anxiety. In addition, it shows a lower side-effect profile than diazepam as assessed by rotorod neurotoxicity and potentiation of ethanol-induced sleep time in mice. The chemistry and structure-activity relationships of this series is discussed.
Animals↗
Detection by a human monoclonal antibody of a glycoprotein associated with malignant proliferation of mammary epithelial cells.
A tumour-associated antigen (TAA.62) with an apparent mol. wt. of 62 kd, identified by a human monoclonal antibody (IgG2, kappa-light chain), was found to be expressed at elevated levels in the cytoplasmic compartment of malignant as compared with normal mammary epithelial cells in both tissues and cultured cells. Increased levels of cytoplasmic expression of the antigen were also observed in malignant cells of cervix, colon, kidney, lung, and stomach. The patterns of expression of TAA.62 in cultured cells mirrored those of tissues and the antigen was expressed at elevated levels in the established breast cancer lines or oncogenically transformed mammary carcinoma cell line (tumourigenic) compared with the immortalised mammary epithelial cell line (non-tumourigenic). Aliquots of TAA.62 were purified to homogeneity from the conditioned-medium of malignant and immortalised breast cells by immunoaffinity chromatography using immobilised anti-TAA.62 antibody, and gel filtration. Both preparations of TAA.62 yielded a single band with an apparent molecular weight of 62 kd under reducing condition on sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and both were identical in terms of size and immunoreactivity to anti-TAA.62 antibody. However, TAA.62(T) isolated from tumourigenic cell lines itself interacted with a cell surface molecule having an apparent molecular weight of 160 kd on both the malignant and immortalised cells: TAA.62(I) isolated from immortalized cell lines, showed no comparable interaction. Scatchard analysis of the concentration-dependent binding of TAA.62(T) to 160 kd-receptor molecule revealed a 2.6 x 10(4) binding sites per cell. The association constant of such binding was determined to be approximately 16.6 nM. Finally, addition of anti-TAA.62 antibody to culture medium resulted in the inhibition of proliferation of the malignant cells, but showed no effect on the normal cells. The results suggest that TAA.62 may interact as a ligand with its 160 kd cell surface receptor with a possible growth related function.
Antibodies, Monoclonal↗
Light and electron microscopic analysis of tattoos treated by Q-switched ruby laser.
Short-pulse laser exposures can be used to alter pigmented structures in tissue by selective photothermolysis. Potential mechanisms of human tattoo pigment lightening with Q-switched ruby laser were explored by light and electron microscopy. Significant variation existed between and within tattoos. Electron microscopy of untreated tattoos revealed membrane-bound pigment granules, predominantly within fibroblasts and macrophages, and occasionally in mast cells. These granules contained pigment particles ranging from 2-in diameter. Immediately after exposure, dose-related injury was observed in cells containing pigment. Some pigment particles were smaller and lamellated. At fluences greater than or equal to 3 J/cm2, dermal vacuoles and homogenization of collagen bundles immediately adjacent to extracellular pigment were occasionally observed. A brisk neutrophilic infiltrate was apparent by 24 h. Eleven days later, the pigment was again intracellular. Half of the biopsies at 150 d revealed a mild persistent lymphocytic infiltrate. There was no fibrosis except for one case of clinical scarring. These findings confirm that short-pulse radiation can be used to selectively disrupt cells containing tattoo pigments. The physial alteration of pigment granules, redistribution, and elimination appear to account for clinical lightening of the tattoos.
Biopsy↗
Hopping frequency in humans: a test of how springs set stride frequency in bouncing gaits.
The storage and recovery of elastic energy in muscle-tendon springs is important in running, hopping, trotting, and galloping. We hypothesized that animals select the stride frequency at which they behave most like simple spring-mass systems. If higher or lower frequencies are used, they will not behave like simple spring-mass systems, and the storage and recovery of elastic energy will be reduced. We tested the hypothesis by having humans hop forward on a treadmill over a range of speeds and hop in place over a range of frequencies. The body was modeled as a simple spring-mass system, and the properties of the spring were measured by use of a force platform. Our subjects used nearly the same frequency (the "preferred frequency," 2.2 hops/s) when they hopped forward on a treadmill and when they hopped in place. At this frequency, the body behaved like a simple spring-mass system. Contrary to our predictions, it also behaved like a simple spring-mass system when the subjects hopped at higher frequencies, up to the maximum they could achieve. However, at the higher frequencies, the time available to apply force to the ground (the ground contact time) was shorter, perhaps resulting in a higher cost of generating muscular force. At frequencies below the preferred frequency, as predicted by the hypothesis, the body did not behave in a springlike manner, and it appeared likely that the storage and recovery of elastic energy was reduced. The combination of springlike behavior and a long ground contact time at the preferred frequency should minimize the cost of generating muscular force.
Adult↗