Biomedical subjects
Publications and source records attributed to R E Taylor.
The effect of physostigmine on plasma angiotensin converting enzyme activity in rat was studied. Following administration of the drug (0.3 mg/kg), plasma angiotensin activity fell significantly at 45 min (P less than 0.05) and continued to decline during the course of the experiment. These data demonstrate that physostigmine inhibits plasma angiotensin converting enzyme activity in rat.
Trichomonas cultures taken from 2389 bulls showed that approximately 4.7% of them were infected. Correlation of these data with the ranches from which diagnostic samples were obtained indicated that in the period of 1984 through 1987 26.7 to 44.1% of ranches had at least one infected bull. Thirty-four 18-month-old Holstein heifers were assigned to one of three groups, controls n = 12 animals, soluble vaccine n = 11 animals, and whole vaccine n = 11 animals to determine the effect of Tritrichomonas foetus vaccines on the reproductive performance of T . foetus infected animals. Heifers were bred with T . foetus infected bulls beginning two weeks after the second T . foetus vaccination. All immunized animals developed antibody titers of at least 1:1000 following vaccination. In addition, all control and immunized animals became infected with T . foetus . However, the duration of infection was approximately two weeks shorter in immunized animals. Approximately 42% (5 of 12) of control heifers remained infected with T . foetus for the duration of the experiment, while only 18% (2 of 11) of each of the vaccine groups remained infected for the duration of the experiment. Finally, 27% (3 of 11) of heifers in each of the vaccine groups were pregnant at slaughter, while none of the control heifers were pregnant at slaughter. Therefore, both vaccine formulations appeared to protect heifers (P<0.05) from fetal loss due to trichomoniasis.
Rhabdomyosarcoma is a rare primary bladder tumor, with the majority occurring in children. A case arising in a 75-year-old woman is reported. Complete tumor regression occurred after radiation therapy.
Different calcium-dependent mechanisms may be involved in mediating stimulus-induced aldosterone secretion. Using isolated perfused canine adrenal glands, we determined the effect of reductions in extracellular [Ca2+] and of infusion of a voltage-dependent calcium channel antagonist, nifedipine, on aldosterone secretion induced by decreases in osmolality, by increases in [K+], or by infusion of angiotensin II (ANG II). Aldosterone secretion was stimulated to a similar level by reducing osmolality, by increasing [K+], or by infusing ANG II. After 50 min of stimulation, lowering [Ca2+] from 1.25 to 0.10 mM caused a marked and similar inhibition of osmolality- and [K+]-induced aldosterone secretion that was significantly greater than inhibition of ANG II-induced aldosterone secretion. Similarly, nifedipine at 3.3 X 10(-8) M caused marked and similar inhibition of osmolality- and [K+]-induced aldosterone secretion that was significantly greater than the inhibition of ANG II-induced aldosterone secretion. These data demonstrate that calcium-dependent processes are involved in osmolality-, [K+]-, and ANG II-induced aldosterone secretion. However, the calcium-dependent process(es) evoked by reductions in osmolality or increases in [K+] are considerably different from that evoked by ANG II. Osmolality and potassium appear to induce aldosterone secretion primarily by activating voltage-dependent calcium channels.
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This study describes 11 monoclonal antibodies (Mabs) against human fibroblast collagenase that (i) inhibit the specific catalytic activity of the enzyme and/or (ii) react with one or more forms of the enzyme on Western blots. Each of the Mabs specifically immunoprecipitated the Mr 57,000/52,000 procollagenase from [35S]methionine-labeled culture medium. Five Mabs, designated VI-3, VI-4, 2C5, 4A2, and 7C2, inhibited the activity of fibroblast-type collagenase against soluble monomeric collagen and against reconstituted collagen fibrils but did not inhibit the genetically distinct human PMN leukocyte collagenase. The interstitial collagenase produced by human mucosal keratinocytes (SCC-25) was also inhibited, whereas the corresponding enzyme from rat was not. Assignment of epitopes to structural domains within the molecule based on immunoperoxidase staining of Western blots of collagenase and its autocatalytic fragments revealed that 9 of 11 epitopes, including those recognized by 4 inhibitory Mabs, were clustered in a 169-residue domain, which constitutes the NH2-terminal part of the Mr 46,000/42,000 active enzyme. One Mab (X-2a) specifically recognized the Mr 57,000/52,000 zymogen species and failed to react with the active Mr 46,000/42,000 form. The inhibitory Mab VI-3 was used for immunoaffinity purification of procollagenase from culture media with a recovery better than 80% and a yield of approximately 1.4 mg of enzyme/L of medium.
In a consecutive series of 113 patients with localized (Stage I and II) intermediate and high grade non-Hodgkin's lymphoma we have retrospectively analysed patterns of survival and relapse in relation to presenting features and therapy. Two patients were treated by complete surgical excision. Seventy-two were treated by radiotherapy (RT), 19 by chemotherapy (CT) and 20 by combined CT and RT. A number of different chemotherapy combinations were employed. Overall survival for Stage I patients was 68.3% at 5 years and 65.5% at 10 years; for Stage II patients it was 61.2% at 5 years and 52.2% at 10 years. Recurrence-free survival for Stage I patients was 51.4% at 5 years and 42.1% at 10 years; for Stage II patients it was 46.2% at both 5 and 10 years. Local control by radiation was achieved in 59/72 (82%) patients treated with less than 40 Gy and 19/20 (95%) treated with 40 Gy or more. There was no advantage for extended field irradiation when compared with involved field. Eleven of 19 (58%) patients treated by CT alone achieved complete response (CR). For patients responding completely to CT there was no clear advantage for irradiation of originally involved bulky sites. For patients with Stage II and bulky Stage I disease there was a significant (P = 0.05) improvement in recurrence-free survival (RFS) and a trend (P = 0.192) towards improved overall survival for patients treated by CT alone or together with RT compared with RT alone. Independent variables identified by multivariate analysis were age, with better survival for younger patients (P = 0.034) and histopathological group, with better survival for DPDL compared with DH (P = 0.015).
Sixty-four patients (37 stage I and 27 stage II) with low grade non-Hodgkin's lymphoma were treated by surgical excision alone (two patients) or with radiotherapy (53 patients), chemotherapy (five patients) or both (four patients). Actuarial survival was 80.7% at 5 years and 77.9% at 10 years. Actuarial recurrence-free survival at 10 years was 49.4% for stage I and 38.0% for stage II patients. Local control was achieved in 52 out of 56 (93%) patients treated with a radiation dose of 30 Gy or greater. There was no advantage for extended compared with involved, field irradiation. A multivariate analysis identified age, sex, stage and disease site as independent prognostic variables for survival.
We report a case of malignant mesothelioma of the testicular tunica vaginalis. A preceding hydrocele showed mesothelial hyperplasia of its lining. The tumor was treated surgically as well as with a combination of radiotherapy and chemotherapy but it progressed, resulting in death within 21 months from the diagnosis. The relationship of the tumor to mesothelial hyperplasia and to previous exposure to asbestos is discussed.
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Although other investigators have suggested that reductions in either Na or chloride concentration stimulate aldosterone secretion, we previously found that small reductions in NaCl (3-7 mM) that enhanced angiotensin II-(ANG II) and [K]- but not adrenocorticotropic hormone (ACTH)-stimulated aldosterone secretion are due to a change in osmolality. In the present study, aldosterone secretion by an isolated perfused canine adrenal gland was stimulated by low doses of ANG II or ACTH or by small increases in perfusate [K], and during this stimulation, replacing 25 mM NaCl with an isosmotic amount of mannitol enhanced aldosterone secretion induced by each of the above secretagogues. Choline chloride significantly enhanced ANG II-stimulated aldosterone secretion when used in place of 25 mM NaCl, but sodium methylsulfate did not. Large isosmotic reductions in [NaCl] failed to alter ACTH-stimulated cortisol secretion or the conversion of either exogenous corticosterone or 11-deoxycorticosterone to aldosterone. Thus, reductions in Na, but not in chloride concentration, specifically enhance the ability of the adrenal glomerulosa to secrete aldosterone in response to ANG II, K, and ACTH by an action on some site in the steroidogenic cascade that is sensitive to ANG II, potassium, and ACTH.
Feeder-cell-independent serially propagating keratinocytes from rat oral mucosa (tongue) dissolved reconstituted type I [3H]collagen fibrils, although rather slowly. Analysis of the conditioned medium from such cultures revealed secretion of a Mr = 65,000 collagenase which remained almost entirely latent in the absence of exogenous protease activity. Addition of trypsin (0.1-1.0 microgram/ml) or plasmin (1.0-4.0 micrograms/ml) resulted in substantial acceleration of the collagenolytic process in stimulated secretion of latent collagenase and, at higher concentrations, in conversion of the latent enzyme to the catalytic form. The keratinocyte collagenase was indistinguishable from interstitial, fibroblast-type collagenases by several criteria including: cleavage of native type I collagen in solution at the characteristic collagenase-sensitive locus at 22 degrees C and dissolution of reconstituted type I collagen fibrils at 35 degrees C; activation by trypsin and by organomercurials and inhibition by Zn2+ and Ca2+ chelators; and cross-reaction with antibody to fibroblast-type procollagenase. Expression of collagenolytic activity in keratinocyte cultures was effectively regulated by cell density. The activity (on a per cell basis) was maximal at 10-20% confluence and was more than 95% "contact-inhibited" at subconfluent and early confluent densities (2-4 X 10(5)/cm2). Our findings show that mucosal keratinocytes possess a potent enzymatic apparatus for degradation of interstitial collagen fibrils which includes a classical vertebrate collagenase.
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A series of 243 patients with adenocarcinoma of the rectum treated with radiotherapy is presented. In the early part of the study radiotherapy was combined with 5-fluorouracil (5FU). Later, radiotherapy was given alone. Seventy-four patients were treated with radical external beam radiotherapy for recurrent or inoperable rectal adenocarcinoma. One hundred and forty-five patients with advanced pelvic tumours or with metastases were treated with palliative pelvic radiotherapy. Twenty-four patients who had small-volume residual pelvic tumour or who were felt to be at high risk of pelvic recurrence following radical resection received postoperative radiotherapy. Complete tumour regression was seen in 38 per cent of radically treated patients, and 24 per cent of palliatively treated patients. Partial regression was observed in 56 per cent of radically treated patients, and 58 per cent of palliatively treated patients. Long-term local tumour control was more commonly observed for small tumours (less than 5 cm diameter). Fifty-eight per cent of patients treated with postoperative radiotherapy remained free of local recurrence. Survival was significantly better in patients with small tumours. The addition of 5FU did not appear to improve survival or tumour control. The value of radiotherapy in the relief of distressing symptoms related to the presence of pelvic tumour has been confirmed.
A case of seminoma testis with metastases to periurethral tissue and gastric submucosa is described. Response to treatment with irradiation and chemotherapy was good. Regression of the unusually sited tumour masses is demonstrated by barium meal and computed tomography. A brief review of gastric metastases is presented.
There has been some uncertainty in the past as to the origin of the rising phase of the gating current. We present evidence here that proves that the gating current does not have a rising phase and that the observed rising phase is due to an uncompensated series resistance in the Frankenhaeuser-Hodgkin (F-H) space. When a squid giant axon is bathed in a solution that is 10-20% hyperosmotic with respect to the internal solution, the rising phase of the gating current is eliminated. In parallel with this, a component of the capacity transient (time constant, 20 microseconds) is reduced so that the capacity transient now appears to be closer to a single fast (5-10 microseconds) component. These changes in the capacity transient and gating current occur without altering the amount of charge moved in either. This indicates that the charge is simply redistributed in time. The gating current without a rising phase can still be immobilized by inactivation. Supporting evidence is provided by measuring the accumulation and washout of K+ from the F-H space. It was found that K+ washes out 35% faster when the axon is bathed in hyperosmotic solution. It was estimated that the F-H space thickness (theta) increased 2.5 +/- 0.4-fold (mean +/- SEM) in hyperosmotic solution. Similarly, K+ accumulation in the F-H space was decreased, leading to an estimate of a 5 +/- 1.4-fold increase in theta in hyperosmotic solution. These results are consistent with the simple structural model presented.
Small (3-7 mM) changes in [NaCl] have a marked inverse effect on angiotensin II- or K-stimulated aldosterone secretion by the isolated, perfused canine adrenal gland. The effect is due to the accompanying changes in osmolality rather than to the changes in [Na] or [Cl]. The present study was undertaken to determine whether osmolality is a specific and discrete signal that modulates the secretion of aldosterone only or is simply a nonspecific physical factor that alters the secretion of other adrenocortical hormones as well. The study also determined whether small changes in osmolality affect the conversion of corticosterone to aldosterone. The secretion of both cortisol and aldosterone by isolated canine adrenal glands responded in a dose-dependent fashion to adrenocorticotropin (ACTH), but in contrast to the rapid and potent modulating action of osmolality reported previously for angiotensin II- or K-stimulated aldosterone secretion, changes in osmolality at the midpoint of ACTH infusion had no detectable effect on either cortisol secretion or, unexpectedly, aldosterone secretion. This indicates that osmolality is a highly specific signal that modulates responsiveness of the zona glomerulosa to the factors, angiotensin II and K, which are considered to be most important in the acute regulation of aldosterone secretion, but does not influence secretion of cortisol by inner zones of the adrenal cortex. In glands treated with agents that block aldosterone production from endogenous precursors, small changes in osmolality had no detectable effect on the conversion of exogenous corticosterone to aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)