Biomedical subjects

C R Taylor

Publications and source records attributed to C R Taylor.

At least 145 records · Page 8Linked to original sources

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

The circadian rhythm of angina pectoris.

Analysis of diary card data from 33,999 angina attacks recorded in 1,022 patients with chronic stable angina showed a clear circadian pattern to the frequency of angina that resembles patterns previously described for myocardial infarction and sudden cardiac death, with a peak in the morning. The majority of angina attacks were preceded by physical exertion and the circadian pattern was more pronounced for exertional angina than nonexertional angina. In this study, treatment with beta-blockers did not prevent the morning peak of angina attacks.

Adrenergic beta-Antagonists↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

The circadian rhythm of angina pectoris. Amlodipine Angina Studies Group.

A clear circadian rhythm exists for angina, with the frequency of attacks increasing during the mid-morning and mid-afternoon hours. This pattern is comparable to circadian rhythms previously reported for the incidence of myocardial infarction and sudden cardiac death. The frequency of angina attacks precipitated by physical exertion showed a more pronounced circadian pattern compared to non-exertional angina. Beta-adrenergic blocking agents did not abolish the circadian rhythm of total angina and exertional angina attacks.

Angina Pectoris↗

PubMed1991

Magnitude and duration of UV-B-induced tolerance.

Using repeated minimal erythema dose (MED) testing, we investigated the magnitude and duration of tolerance to short-wave UV radiation in the B range (UV-B) in 37 patients with psoriasis who received at least 12 UV-B phototherapy treatments. Without substantial erythema developing, half of the patients received UV-B doses in excess of 13 times their pretreatment MED dose and a fourth received UV-B doses in excess of 28 times their pretreatment MED dose. On average, tolerance faded to about half that present at the last UV-B treatment in 3 weeks. Six weeks after therapy was stopped, most posttreatment MEDs were less than twice the pretreatment MED. The magnitude of tolerance achieved and the rate of decay did not vary with skin type. Our findings indicate that repeated exposures to suberythemal or mildly erythematous doses of UV-B can induce exceptional degrees of tolerance to UV-B radiation. The duration of this increase in tolerance is, however, short.

Adult↗

PubMed1990

Energetics of running: a new perspective.

The amount of energy used to run a mile is nearly the same whether it is run at top speed or at a leisurely pace (although it is used more rapidly at the higher speed). This puzzling independence of energy cost and speed is found generally among running animals, although, on a per gram basis, cost is much higher for smaller animals. Running involves little work against the environment; work is done by muscles and tendons to lift and accelerate the body and limbs. Some of the work is recovered from muscle-tendon springs without metabolic cost and work rate does not parallel metabolic rate with either speed or size. Regardless of the amount of work muscles do, they must be activated and develop force to support the weight of the body. Load-carrying experiments have shown that the cost of supporting an extra newton of load is the same as the weight-specific cost of running. Size differences in cost are proportional to stride frequency at equivalent speeds, suggesting that the time available for developing force is important in determining cost. We report a simple inverse relationship between the rate of energy used for running and the time the foot applies force to the ground during each stride. These results support the hypothesis that it is primarily the cost of supporting the animal's weight and the time course of generating this force that determines the cost of running.

Animals↗

PubMed1990

Characterization of a cell surface molecule expressed on B-lymphocytes and Hodgkin's cells.

An antigen specifically expressed on the surface of plasma membrane of B-lymphocytes and Reed-Sternberg cells was identified using a newly developed monoclonal antibody produced by immunization by BALB/c mouse with a Hodgkin's cell line (HDLM-3). The antibody was termed anti-BLA.36 (B lymphocyte antigen.36) to indicate its predominant reactivity and the molecular weight of the corresponding antigen. By using immunoperoxidase techniques, expression of BLA.36 was detected on Hodgkin's, B-, and pre-B-cell lines, but not on other hematopoietic, melanoma, or carcinoma cell lines. In normal tissues, BLA.36 was detectable predominantly on cells in the germinal center and mantle zone of reactive follicles in lymph nodes and spleen. In hematopoietic malignancy, BLA.36 was detectable on the surface of Reed-Sternberg cells, mononuclear Hodgkin's cells, and also on malignant cells of B-cell lineage. Under these conditions, T-lymphocytes, histiocytes, granulocytes, macrophages, stromal cells in lymphoid tissue, and both normal and neoplastic epithelial cells were consistently negative for the expression of the antigen, with the single exception of a variable proportion of Kupffer cells in normal liver. Biochemical and immunological analyses indicate that BLA.36 is distinct from previously identified antigens of hematopoietic cell lineage, including CD20 and CD75 (LN2) which have similar molecular weights. When BLA.36-positive cell lines were cultured in the presence of the antibody, cell growth was adversely affected. Such an effect was eliminated by removal of the antibody from the culture, suggesting a possible growth-related function of the antigen. Anti-BLA.36 may serve as a probe to study growth-related functions of the corresponding antigen during normal growth of the B-lymphocyte, as well as in the neoplastic proliferations occurring in Hodgkin's disease and antigen-positive B-cell lymphomas. Finally, the antibody has already demonstrated its usefulness for the identification of Reed-Sternberg and Hodgkin's cells, and also normal and malignant B-lymphocytes in frozen as well as formalin- or B5-fixed/paraffin-embedded tissue sections.

Animals↗

PubMed1990

Photoaging/photodamage and photoprotection.

Exposure to sunlight can produce both acute and long-term effects. Acute changes include erythema, photosensitivity, and immunologic alterations. Long-term consequences include carcinogenesis and photoaging. All effects can be minimized by photoprotection. This article reviews the adverse effects of sun exposure and strategies to reduce photodamage.

Humans↗

PubMed1990

Generation and characterization of a murine monoclonal antibody to cervical glandular epithelium using mice rendered tolerant to cervical squamous epithelium.

Murine monoclonal antibodies that distinguish glandular from squamous epithelia in human tissue were generated using a procedure that involved tolerization prior to immunization. Tolerization was achieved by injection of newborn (24 hrs old) Balb/c mice with extract of normal cervical tissue containing squamous epithelium (the tolerogen). Three weeks later, mice showing no evidence of antibodies to tolerogen in their sera were immunized with an extract of cervical tissue containing both glandular and squamous epithelia. Following immunization, the sera from mice subjected to this treatment showed strong reactivity with glandular cells but not with squamous cells in sections of frozen tissue examined by an indirect immunohistological method. Spleen cells from mice showing this pattern of serum reactivity were used as fusion partners with a mouse myeloma cell line in order to generate monoclonal antibodies. Following extensive screening, one monoclonal antibody (designated anti-GEA.49) was selected for further study on the basis of reactivity with high affinity to glandular epithelium and a complete absence of staining of squamous and connective-tissue cells. Detailed tests of specificity and patterns of reactivity indicate that the antigen detected by the antibody is expressed on the apical plasma membrane of glandular epithelia and is a glycoprotein with an apparent molecular weight of 49 kilodaltons. Both immunohistological and biochemical methods demonstrated the expression of the antigen on glandular epithelia but not on squamous epithelia from several sources, underlining the usefulness of tolerization/immunization approach for generating antibodies with particular specificity requirements.

Animals↗

PubMed1990

Localization of monoclonal antibody TNT-1 in experimental kidney infarction of the mouse.

An experimental kidney infarction model was developed in the mouse to study the uptake of a radiolabeled monoclonal antibody previously shown to bind to degenerating cells in malignant tumors. To determine if this approach is applicable to normal tissue and cell degeneration, kidney infarction was produced by clamping the mouse renal artery for 3 h using surgical procedures. Various groups of mice were injected with 131I-labeled TNT-1 F(ab')2 monoclonal antibody directed against nuclear histone antigens at varying intervals after surgery. Imaging, biodistribution, autoradiography, and histological studies were performed on each group of mice, including sham-operated controls, to quantitate the level of binding and localize the uptake of label in clamped and unclamped (contralateral) kidneys. As additional controls, clamped mice were administered radiolabeled irrelevant monoclonal antibody Lym-1 or mouse albumin. The results showed a marked selective uptake of radiolabeled TNT-1 F(ab')2 in the injured clamped kidney compared with the untreated kidney and other normal organs of the mouse. These studies define a model of normal organ necrosis that may be useful for study of the kinetics of antibody uptake in infarcted tissues.

Animals↗

PubMed1990

S100 immunophenotypes of uveal melanomas.

To determine whether ocular melanomas are immunophenotypically identical to cutaneous melanomas, 34 primary and metastatic choroidal melanomas representing all major histotypes defined by the Callender's classification, plus one melanoma of the iris and one conjunctival melanoma, were subjected to a panel of immunostains designed to distinguish anaplastic biopsies of cutaneous melanomas from carcinomas and lymphomas. All ocular melanomas were found to express the intermediate filament vimentin but not keratin, and all but 2 were melanotic by immunostaining. Thirty-three of 34 (97%) choroidal melanomas were strongly stained with a rabbit polyclonal antibody (P-S100) developed against the S100 protein family. In contrast, none of 14 spindle cell type primary lesions was stained with a monoclonal antibody (MAB-079) specific for both S100 alpha and S100 beta, the best-characterized S100 polypeptides. Furthermore, only 2 of 5 epithelioid and 3 of 10 mixed-cell-type melanomas were weakly reactive. Overall, 14.7% (5 of 29) were stained. In comparison, MAB079 stained 85% of all cutaneous melanomas. Five metastases of choroidal melanomas (spindle B, epithelioid, and mixed cell types) from different organ sites also were stained by P-S100 but not by MAB079. These findings were corroborated by immunostaining with another monoclonal antibody (MAB4D4) specific for S100 beta. Differential staining by the polyclonal but not the monoclonal antibodies suggests the possible presence of a variant S100 polypeptide(s) in choroidal melanomas. Since S100 alpha, S100 beta, and related proteins appear to be physiologically important, additional studies of these S100 proteins may shed light on the etiology or pathology of choroidal melanomas.

Antibodies, Monoclonal↗

PubMed1990

Diagnostic imaging techniques in the evaluation of drug-induced pulmonary disease.

Although chest radiology is the first imaging option in evaluating patients for pulmonary manifestations of drug toxicity, the limitations of the pattern approach often predicate the use of other imaging techniques in addition to clinical and laboratory evaluation. There is a role for CT and nuclear scintigraphy in selected cases in an attempt to detect bioeffects while still at a reversible stage, or to differentiate drug toxicity from other etiologies. Future applications for MR imaging and in vivo MR spectroscopy are promising.

Humans↗

PubMed1990

A comparative autoradiographic study demonstrating differential intratumor localization of monoclonal antibodies to cell surface (Lym-1) and intracellular (TNT-1) antigens.

Autoradiography was utilized to explore the patterns of distribution of two different monoclonal antibodies (Lym-1 and TNT-1) in tumor-bearing nude mice. Lym-1 is an antibody against a cell surface B-cell antigen. In comparison, TNT-1 represents a novel approach and is an antibody against an intracellular (nuclear) antigen that is selectively revealed in degenerating tumor cells. Experimentally iodine-125-(125I) labeled Lym-1 or TNT-1 was injected intravenously into nude mice bearing either the Raji lymphoma or the ME-180 human cervical carcinoma. Qualitative autoradiographic analyses performed after injection revealed that Lym-1 accumulated at the periphery of the target tumor where vascular permeability is marked and where Lym-1 positive cells are first encountered. By contrast, TNT-1 lost its initial peripheral distribution and demonstrated progressive concentration in the center of the tumor where binding to its nuclear antigen is facilitated by the presence of cell degeneration and necrosis. These studies confirm the ability of TNT-1 to bind areas deep within tumor that traditionally are considered inaccessible to antibodies administered for imaging and therapy.

Animals↗

PubMed1990

Treatment of tattoos by Q-switched ruby laser. A dose-response study.

Tattoo treatment with Q-switched ruby laser pulses (694 nm, 40 to 80 nanoseconds) was studied by clinical assessment and light and electron microscopy. Fifty-seven blue-black tattoos or portions thereof (35 amateur and 22 professional) were irradiated with 1.5 to 8.0 J/cm2 at a mean interval of 3 weeks. Substantial lightening or total clearing occurred in 18 (78%) of 23 amateur tattoos and 3 (23%) of 13 professional tattoos in which the protocol was completed. Response was related to exposure dose. Scarring occurred in one case, and persistent confettilike hypopigmentation was frequent. Optimal fluence was 4 to 8 J/cm2. Clinicohistologic correlation was poor. Q-switched ruby laser pulses can provide an effective treatment for tattoos.

Adult↗