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Biomedical subjects

C R Taylor

Publications and source records attributed to C R Taylor.

At least 289 records · Page 16Linked to original sources

Immunopathology of B-cell lymphomas induced in C57BL/6 mice by dualtropic murine leukemia virus (MuLV).

Combined clinicopathologic and immunomorphologic evidence is presented that would indicate that a murine leukemia virus (MuLV) with the dualtropic host range is capable of producing a clinically malignant lesion composed of immunoblasts and associated plasma cells in C57BL/6 mice. This process, morphologically diagnosed as an immunoblastic lymphoma of B cells using standard histopathologic criteria, was found to be distinctly polyclonal with regard to immunoglobulin (Ig) isotype when analyzed for both surface and cytoplasmic Ig. Further studies demonstrated that this clinicopathologically malignant, dualtropic MuLV-induced, polyclonal immunoblastic lymphoma of B cells in C57BL/6 mice was normal diploid and unable to be successfully transplanted to nonimmunosuppressed syngeneic recipients. Although all serum heavy and light chain components were found to be progressively elevated as the tumor load increased, the polyclonal increase in serum immunoglobulins was most pronounced for mu heavy and kappa light chains (ie, mu greater than gamma 2A greater than alpha greater than gamma 2B greater than gamma 1; kappa greater than lamba). The dissociation of clinicopathologic and biologic criteria for malignancy in the presently described dualtropic (RadLV) MuLV-induced B-cell lesion is sharply contrasted with the thymotropic (RadLV), MuLV-induced T-cell lymphoblastic lymphoma in C57BL/6 mice. This process is also a clinicopathologically malignant lesion but, when one uses biologic criteria, is found to be distinctly monoclonal, aneuploid, and easily transplanted to nonimmunosuppressed syngeneic recipients. The close clinicopathologic and biologic similarities of the dualtropic MuLV-induced animal model to corresponding human B-cell lymphoproliferative diseases are stressed.

Animals↗

Emergence of B-immunoblastic sarcoma in patients with multiple myeloma: a clinicopathologic study of 10 cases.

Immunologic and histologic studies were performed in 10 cases of myeloma that showed progression to a more aggressive proliferation, designated as immunoblastic sarcoma of B-cell type (B-IBS). Several patterns of clinical presentation were observed: eight patients showed typical multiple myeloma, four developed B-IBS within the bone marrow, and four developed B-IBS in multiple extramedullary sites; the remaining two patients had relatively localized myeloma, but also showed development of extramedullary B-IBS. The implications of these findings are discussed with regard to their prognostic import and their relationship to current concepts of plasma cell development.

Adult↗

Alloantibody-induced impaired neonatal expression of a red blood cell antigen associated with maternal alloimmunization.

Animals genetically capable of making certain gene products have been shown to have the production of such products completely or partially suppressed by exposure in utero or neonatally to antibodies specific for that gene product. This alloantibody-induced depression of expression of a specific antigenic determinant has yet to be shown to occur in man. The McCoya red blood cell antigen is reported to be well developed at birth. However, 2 children born to mothers with high-titer McCoya antibodies in their serum, phenotyped as McCoy (a-) at birth and, on retesting their red blood cells, 1 at 5 months and the 2nd at 11 months, both phenotyped as McCoy (a+). It is possible that this lack of expression of the McCoya antigen at birth represents a characteristic of an obligate heterozygote. However, on testing 50 random umbilical cord red blood cell samples with two potent McCoya antisera, only 1 was found to be negative. If the negative phenotype were a characteristic of an obligate heterozygote at birth, then the neonatal incidence of the McCoy (a-) phenotype should have been significantly (p less than 10(-4)) high in our random cord blood sample than observed (expected 11). The impaired expression of the McCoya antigen on the red blood cells of these 2 infants at birth, in conjunction with evidence of maternal alloimmunization, strongly suggests alloantibody-induced antigenic suppression of the McCoya antigen as a probable cause.

Adult↗

Detection of estrogen receptor in breast and endometrial carcinoma by the immunoperoxidase technique.

Paraffin-embedded tissues from 15 women with breast or endometrial carcinomas were analyzed in a study designed to explore the possible value and validity of an immunoperoxidase method for the detection of estrogen receptor in formalin-fixed paraffin-embedded tissue. Results were compared with biochemical assays for estrogen receptor performed on cytosols of fresh tissue from the same patients. There was complete correlation in nine of 15 (60%) of the tumors analyzed. Four cases (26.7%) were judged positive for estrogen binding sites by immunoperoxidase but were negative for estrogen receptor by biochemical assays; in two cases the converse was observed. The immunohistologic technique is relatively rapid and utilizes fixed paraffin sections of the same tissue that is used for standard histologic diagnosis. The provision of a permanent record that can be kept for future reference provides an advantage over immunofluorescence methods that have been advanced for the detection of estrogen receptors. The excellent morphology achieved permits an assessment of the staining of individual cells in relation to the usual histologic criteria employed in the diagnosis of breast and endometrial cancer. This stands in contrast to biochemical cytosol-based assays that take no account of variations in receptor expression by the tumor cells or variations in the proportion of the assayed material that is in fact neoplastic as distinct from supporting stroma and connective tissue.

Adenocarcinoma↗

Immunoperoxidase staining for carcinoembryonic antigen in colonic carcinoma, osteosarcoma, and chordoma.

An indirect immunoperoxidase method was used in an attempt to detect carcinoembryonic antigen (CEA) in 17 well-differentiated colonic adenocarcinomas, five osteosarcomas, and four chordomas. Fifteen of the adenocarcinomas were positive, and five of them had been fixed and embedded in 1952 and one in 1942. Two other adenocarcinomas from 1942 were not positive. CEA was not demonstrated in any of the osteosarcomas or chordomas.

Adenocarcinoma↗

Comparative pharmacology and clinical efficacy of newer agents in treatment of heart failure.

The animal and human pharmacology of several new drugs (prazosin, trimazosin, pirbuterol, and carbazeran) useful in the treatment of congestive heart failure (CHF) is delineated in relation to the pharmacology of other agents employed for CHF management. Prazosin and trimazosin are selective alpha 1-blockers that cause a balanced increase in cardiac output (CO) and reduction in left ventricular filling pressure (LVFP); the reduction in diastolic blood pressure with these drugs is significantly related to increase in treadmill exercise, fall in LVFP, and increase in CO. Pirbuterol is a relatively selective beta 2-agonist with somewhat greater effects on CO than on LVFP. Early promise in CHF therapy is being shown by a novel series of cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitors with combined direct inotropic and vasodilator effects. Double-blind long-term studies demonstrate persistent efficacy of prazosin and trimazosin in CHF as measured by improvement in New York Heart Association functional class, treadmill exercise performance, and noninvasive measures of cardiac function; these data are supported by studies in which repeat cardiac catheterization has been performed after several months of therapy. Double-blind studies of other CHF drugs are in progress.

Animals↗

Pirbuterol: a new oral sympathomimetic amine for the treatment of congestive heart failure.

Fourteen patients with refractory congestive heart failure (CHF) were given a single oral dose ranging from 5 to 30 mg of the new sympathomimetic drug pirbuterol. Hemodynamic measurements and plasma pirbuterol levels were obtained at control and then serially for 6 hours following drug administration. The optimal pirbuterol dose range was determined to be 20 to 30 mg. Ten patients received 20 to 30 mg pirbuterol. In this group cardiac index was significantly increased (1.9 to 2.6 L/min/m2, p less than 0.001). Pulmonary artery wedge pressures fell significantly (24 to 20 mm Hg, p less than 0.02). Decreases were also noted in mean pulmonary artery pressure (36 to 31 mm Hg, p less than 0.02), aortic diastolic pressure (71 to 65 mm Hg, p less than 0.05), systemic vascular resistance (1782 to 1201 dynes. sec. cm-5, p less than 0.001), and pulmonary vascular resistance (265 to 175 dynes.sec.cm-5, less than 0.001). Systolic and mean aortic pressure and heart rate showed no significant change from control. Hemodynamic effects persisted for 5 hours. Pirbuterol was clinically well tolerated. The mechanism of action is unclear at this time, but both inotropic and vasodilator effects are possible. Pirbuterol orally has a marked and prolonged salutary hemodynamic effect and offers promise in CHF treatment.

Administration, Oral↗

Design of the mammalian respiratory system. II. Measuring maximum aerobic capacity.

We describe a simple and reproducible procedure for measuring maximal O2 consumption (Vo2max) that can be used for mammals spanning a wide range of body mass (Mb). Vo2 of trained animals was measured as a function of speed while they ran on a treadmill. Lactate concentration of the blood was determined at the beginning and end of the run. We considered that an animal had achieved Vo2max when Vo2 no longer increased with increasing tread-speed and the additional energy consumed by the muscles could be accounted for by anaerobic glycolysis. We found that Vo2 increased linearly with tread-speed up to a maximal rate and then remained unchanged with further increases in speed in nine species. When the animals ran at speeds faster than that where Vo2max was reached, they refused to continue when blood lactate concentrations reached 18-28 mmol . kg-1. Values for Vo2max obtained with this procedure were found to be about 20% greater than values obtained with the 'cold exposure' procedure for determining Vo2max. We conclude that our treadmill procedure is valid for determining the allometric relationship between Vo2max and Mb.

Aerobiosis↗

Design of the mammalian respiratory system. III Scaling maximum aerobic capacity to body mass: wild and domestic mammals.

The purpose of this study was to determine whether the maximal rate of oxygen consumption (Vo2max) is scaled proportionally to Mb1.0, as the diffusing capacity of the lung, or proportionally to Mb0.75, as the standardized resting rate of oxygen consumption (V02std). We measured Vo2max on a variety of mammalian species (14 wild species and 8 domestic or laboratory species ranging in Mb from 7.2 g to 263 kg) using the same 'treadmill' procedure for all animals. For the wild species we found: Vo2max = 1.94.Mb0.79; r=0.995 where Vo2max has the units ml . sec-1 and mb is in kg. There was a great variability in Vo2max among domestic species of the same size, horse and dog having a Vo2max more than 3 times that of a cow and sheep, respectively. Both the variability in Vo2max with body size and among animals of the same size provide powerful tools for investigating the relationship between structure and function at each step in the respiratory system, from the oxygen in environmental air to the oxygen sink in the mitochondria.

Aerobiosis↗

Design of the mammalian respiratory system. V. Scaling morphometric pulmonary diffusing capacity to body mass: wild and domestic mammals.

This paper utilizes a comparative approach to establish the relationship between morphometric diffusing capacity for oxygen (DLo2) and maximal oxygen consumption (Vo2max). DLo2 and Vo2max were determined on the same 21 individuals in African mammals spanning a range in body mass from 0.4 to 240kg. We confirmed earlier findings that Dlo2 was proportional to Mb0.99 while Vo2max was proportional to Mb0.79. Thus, the ratio of Dlo2/Vo2 is approximately proportional to Mb0.20. We conclude that large animals require a larger pulmonary diffusing capacity to transfer oxygen at the same rate from air to blood.

Aerobiosis↗

Design of the mammalian respiratory system. VII. Scaling mitochondrial volume in skeletal muscle to body mass.

Since O2 is mainly consumed in muscle mitochondria during heavy physical work, one would expect to find a relationship between the volume density of mitochondria in skeletal muscles and maximal O2 uptake. We analyzed the volume density of mitochondria, Vv(mt,f) in four muscles of a series of African mammals ranging in body mass from 0.4 to 251 kg. Vv(mt,f) scaled as Mb-0.231, Mb-0.163, Mb-0.139 and Mb-0.055 in Mm. semitendinosus, longissimus dorsi, vastus medialis and diaphragm, respectively. The mass or volume of diaphragm was found to scale as Mb0.865, whereas for Mm. semitendinosus and vastus medialis, muscle volume (Vmu) scaled as Mb1.030 and Mb0.956 respectively. Scaling the absolute volume of mitochondria Vmt, in these muscles (Vmt = Vv (mt,f) x Vmu) against Mb gives regression lines whose slopes closely parallel that obtained for Vo2max against body mass. Therefore the ratio of volume of mitochondria in these muscles to Vo2max is body mass independent.

Africa↗

Design of the mammalian respiratory system. VIII Capillaries in skeletal muscles.

The relationship between capillary density and mitochondrial volume density in skeletal muscle tissue is investigated on 25 African mammals ranging in body mass from 0.4 to 251 kg. As a general trend higher capillary densities, NA (c,f) are found in muscles with higher volume densities of mitochondria, Vv(mt,f). The individual data however show considerable scatter. Part of this scatter can be explained by the fact that NA (c,f) alone is not a sufficient parameter to account for functional properties of the vascular supply. The regional variability of the capillary network from arterial to venous end also contributes to the data spread. A number of physiological variables of the vascular compartment may also influence the relationship of capillary counts to the mitochondrial densities of muscle fibers. This relationship therefore cannot be expected to be a simple one.

Africa↗

Design of the mammalian respiratory system. IX. Functional and structural limits for oxygen flow.

This paper presents the synthesis and interpretation of a series of correlated studies of the mammalian respiratory system--measurements of maximal rate of O2 consumption, the lung's diffusing capacity, the mitochondrial volume, and the capillary number and length in skeletal muscle. It discusses the results with respect to the principle of symmorphosis, i.e. of morphogenesis adapted to functional needs. We find that the accumulated evidence supports this principle at all organizational levels considered, although the models used for structure-function correlation need further refinement.

Aerobiosis↗

Panting in dogs: paths of air flow in response to heat and exercise.

Panting is the major avenue of evaporative cooling in dogs exposed to heat and/or exercise. We found modulation of evaporation was achieved by varying the paths of airflow during inhalation and exhalation. The direction of airflow through the nose and mouth was determined by measuring pressure changes and temperature at the openings of one nostril and the mouth in three dogs (av. weight 22 kg). Rates of oxygen consumption and respiratory evaporation were measured simultaneously. Three patterns of panting were observed as the demand for respiratory evaporation increased: (I), inhalation and exhalation through nose; (II), inhalation through nose, exhalation through nose and mouth; and (III), inhalation through nose and mouth, exhalation through nose and mouth. Pattern I was observed in resting dogs when ambient temperature was below 26 degrees C and when animals ran at slow speeds in the cold (e.g. 0.8 m . s(-1) at 10 degrees C). Patterns II and III were observed when dogs rested quietly at ambient temperatures above 30 degrees C and during exercise except when dogs ran slowly at very low temperatures. Patterns II and III rarely occurred independently for long periods of time. Instead, there was normally a continual oscillation between the two. The proportion of the time that the dog used Pattern III instead of Pattern II increased as temperature and/or speed were increased; but the correlation between rate of respiratory evaporation and the percentage of time Pattern III was utilized was weak (r2=0.63).

Animals↗

Immunohistologic techniques in surgical pathology - a spectrum of "new" special stains.

Immunoperoxidase techniques, applied to fixed paraffin sections, provide a wide range of highly specific special stains of value to the surgical pathologist in diagnostic practice and in investigative studies. The application of "immunostains" provides an independent method of cell identification against which traditional subjective morphologic criteria may be compared: histopathology may thereby be transformed from something of an art to more of a science.

Biopsy↗