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Biomedical subjects

H M Taylor

Publications and source records attributed to H M Taylor.

At least 19 recordsLinked to original sources

Estrogen synthetase inhibitors. 2. Comparison of the in vitro aromatase inhibitory activity for a variety of nitrogen heterocycles substituted with diarylmethane or diarylmethanol groups.

The preparation and in vitro aromatase inhibitory activity of a wide variety of heterocyclic (4,4'-dichlorodiphenyl)methanes and -methanols are described. The choice of the two diaryl-bearing moieties as a vehicle for the evaluation of the heterocycles was made by the comparison of series of imidazole and pyridine-derived compounds with similar pyrimidine compounds reported previously. A structural model for the most active compounds is also presented. The activity of a related series of the compounds which contain two heterocyclic moieties was found to be consistent with the model. Many of the compounds evaluated, including representatives of the pyridine, imidazole, pyrimidine, pyrazole, triazole, thiazole, and isothiazole classes, exhibit EC50 potencies for aromatase inhibition at low nanomolar levels. These compounds are at least as potent as other nonsteroidal aromatase inhibitors reported previously.

Androstenedione

Myelodysplastic syndrome: prospective evaluation of fifty-one patients using the Dutcher scoring system.

Fifty-one patients with primary myelodysplastic syndrome were prospectively evaluated using a scoring system based on the presentation blood and bone marrow findings. Twenty-four patients (47%) evolved to acute nonlymphocytic leukemia. Stepwise regression model showed that the scoring system was the only significant variable for predicting transformation to acute leukemia (p = 0.0007, sensitivity 70.8%, specificity 77.8%). Seventy-six percent of patients with a score of 14 or greater developed acute leukemia compared to 19% with a score of 13 or less. Median survival of the entire group was 10 months. The most important prognostic factor for predicting survival was the scoring system (p = 0.0001). Survival correlated inversely with the score. This scoring system may be useful in the management of patients with myelodysplasia.

Acute Disease

Aromatase inhibition by 5-substituted pyrimidines and dihydropyrimidines.

The inhibition of estrogen biosynthesis has been suggested to be an effective treatment of hormone-dependent diseases, particularly breast cancer. Several series of 5-substituted pyrimidine derivatives have been synthesized and tested for their ability to inhibit the enzyme aromatase (estrogen synthetase). Compounds were evaluated in an in vitro assay that measured the inhibition of rat ovarian microsomal aromatase activity. Greatest inhibitory activity was achieved in the cases of diarylpyrimidinemethanols and diarylpyrimidinyl methanes which were substituted in the 4- and 4'-positions with electron-withdrawing substituents, particularly Cl.

Animals

Fluorescence intensity as a quality control parameter in clinical flow cytometry.

The fluorescence intensity (FI) and percentage of immunostained peripheral blood lymphocytes (PBLs) were tested as parameters for monitoring quality control of monoclonal antibodies (MoAbs) and the staining procedure. Several potential variables were addressed, including optimal dilutions of MoAbs, standardization of instrument functions with fluorescent microspheres, stability of day-to-day fluorescence detection with fluorescent fixed cells, and effects of separation method and storage conditions on FI and PBL antigens. Although some small (but statistically significant) changes were found in certain tests, in general the FI and percentages of MoAB-positive human PBLs provided information useful in a standardized flow cytometry quality control program. This type of standardization and quality control facilities early discovery of methodologic and reagent problems in the clinical laboratory, as well as the ability to routinely evaluate disease states associated with abnormal antigen density.

Adult

Reference values for peripheral blood lymphocytes from Aotus lemurinus ssp. griseimembra (owl monkey).

The reactivities of several monoclonal antibodies that define human lymphocyte cell-surface antigens have been tested with peripheral blood lymphocytes of Aotus lemurinus ssp. griseimembra. Based on reactivity patterns in humans, reactive MoAb were identified that mark pan-T, helper/inducer, suppressor/cytotoxic, pan-B, and natural killer cells. Reference values of these subsets in Aotus are presented. These MoAb should provide a useful tool for further phenotypic and functional dissection of the immune system in this simian model of human disease.

Animals

A rapid, no-wash technic for immunophenotypic analysis by flow cytometry.

With the advent of fluorochrome-labeled monoclonal antibodies, it has now become possible to eliminate the removal of unbound antibodies during immunophenotypic analysis of lymphoid cells by flow cytometry. Suspensions of mononuclear cells from healthy controls and fluoresceinated monoclonal antibodies may be introduced directly into the flow cytometer. The percentage of nonwashed antibody-positive cells from healthy controls as compared with the conventional technic of cell washing shows a good correlation. However, the correlation is not as good when the lymphocytes from certain classes of diseased patients are analyzed. It appears that excessive washing in fact produces erroneous results for certain markers with cells from diseased patients. The no-wash technic is also applicable to various combinations of dual-fluorescence monoclonal antibody staining. This technic substantially reduces the processing time and, more importantly, eliminates some of the cell losses and artifacts induced during the process of cell washing. The shortened processing time has allowed rapid responsiveness in certain urgent clinical situations.

Acquired Immunodeficiency Syndrome

Sequential analysis of HLA-class II antigen expression in human renal allografts. Induction of tubular class II antigens and correlation with clinical parameters.

The expression of HLA-class II antigens was assessed in 142 biopsies from 29 recipients of cadaveric renal allografts who received either short-term cyclosporine (n = 12) or azathioprine and low-dose prednisolone (n = 17). Biopsies were obtained before transplantation, routinely at days 7, 21, 90, and 365 after transplantation, and at other times as clinically indicated. Cryostat sections were labeled with monoclonal antibodies using an indirect immunoperoxidase technique. In all biopsies HLA-class II antigens were expressed on glomeruli and intertubular structures. In pretransplant biopsies proximal tubules expressed class II antigens, whereas distal tubules were always negative. After transplantation three patterns of class II expression were recognized based on renal tubular class II staining: normal, focal increased, and generalized increased expression. Sequential biopsy analysis showed fluctuating levels of expression in individual patients, which correlated with cellular infiltration and was associated with allograft rejection. 71% of biopsies obtained at day 90 from patients on conventional therapy showed increased class II expression compared with only 9% of biopsies from patients on cyclosporine immunosuppression. All patients with normal class II antigen expression in day 90 biopsies had well-functioning grafts two years after transplantation, whereas 3 of 9 with increased class II antigen expression had failed. Furthermore, all grafts failing from irreversible rejection before 90 days showed marked increase of class II antigen expression. The increased class II antigen expression in renal allografts may be merely a marker of rejection or may have a role in the augmentation of the response, either in its induction or as a target for the effector arm of the reaction.

Azathioprine

Morphometric analysis of cellular infiltration assessed by monoclonal antibody labeling in sequential human renal allograft biopsies.

The mononuclear cell infiltrate in a total of 279 human renal allograft biopsies was determined by a panel of monoclonal antibodies using an indirect immunoperoxidase technique. Two hundred and seventy-two biopsies were obtained from 83 patients randomly allocated to receive short-term cyclosporine (CsA) or conventional azathioprine and low-dose prednisolone (AP). Biopsies were obtained routinely at days 0 (control biopsies), 7, 21, 90, and 365, as well as at other times when clinically indicated. A further 7 patients on AP therapy were biopsied several years after transplantation (median: 6 years 1 month). Morphometric analysis of cryostat tissue sections using a point-counting technique has shown that the infiltration in rejecting grafts is significantly greater than in grafts with stable function. However, significant infiltration also occurs within the first week after transplantation in grafts with stable function. While this infiltrate diminishes with time, it remains significant even in grafts biopsied several years after transplantation. The infiltration with CsA treatment is significantly less than with AP therapy. The magnitude of the infiltrate therefore varies with time, graft status, and immunosuppression. In contrast the phenotypic composition of the infiltrate remains relatively constant in all biopsies after transplantation with T lymphocytes (CD3+), accounting for approximately 35% of infiltrating cells and CD8+ cells more common than CD4+. Monocytes and macrophages account for most of the remainder of the infiltrate.

Antibodies, Monoclonal

Control of hypertension after renal transplantation by embolisation of host kidneys.

A percutaneous embolisation technique was used for host kidney ablation in 13 patients with renal allografts and hypertension. Markedly improved blood pressure control was achieved in 9 of them, and morbidity was minimal. All patients have been followed from 12 to 25 months. Embolisation of the host kidneys appears to be a simple, effective, and less hazardous alternative to surgery in the treatment of drug-resistant hypertension after renal transplantation in some patients.

Adult

Granulomatous bone marrow disease. A review of the literature and clinicopathologic analysis of 58 cases.

We have reviewed 58 cases of bone marrow granuloma at a single institution over a 20-year time span, and have summarized the available English literature. We conclude that bone marrow granulomas are an infrequent pathologic finding which, when found, require definition as to an underlying etiology. Undoubtedly, the illnesses associated with marrow granuloma are similar to those causing granulomatous hepatitis. The following additional statements may justifiably be made based on this review. There are no morphologic features which allow reliable differentiation between the causes of bone marrow granuloma. By combining careful histologic, microbiologic, and serologic techniques, an etiology can be documented in most (87%) patients with marrow granulomas. A medication history is an important element of this evaluation. Rocky Mountain spotted fever, cytomegalovirus infection, ibuprofen, acute lymphocytic leukemia, and various collagen vascular diseases should be added to the list of causes of marrow granuloma. The prognostic significance of marrow granuloma in patients without an ascertainable underlying illness remains unclear.

Adolescent

Container blow molding noise.

Evaluation of the environmental noise within a blow mold plant revealed borderline acceptability for hearing conservation. However, audiometric examinations did not appear to reveal appreciable work-related hearing loss. Octave band analysis of this nuisance noise provided the base for feasible engineering controls.

Adolescent