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Biomedical subjects

G L Wright

Publications and source records attributed to G L Wright.

At least 109 records · Page 6Linked to original sources
PubMed1989

An endogenous 'hypertensive factor' enhances the voltage-dependent calcium current.

The effects of an immunoaffinity-purified putative endogenous hypertensive factor (HF) on voltage-dependent calcium current in frog cardiac myocytes were assessed. In 9 out of 10 cells, HF reversibly increased the peak amplitude of the calcium current. HF increased peak calcium current density at -5 mV from a control level of 1.8 +/- 1.3 pA/pF (mean +/- SD) to 4.4 +/- 2.0 pA/pF. HF shifted the peak of the calcium current-voltage relationship in the hyperpolarizing direction. HF shifted the voltage dependence of the inactivation of the calcium current to more negative potentials with prepulses from -80 to 0 mV, but the inactivation was not affected with prepulses more positive than 0 mV. Modulation of the voltage-dependent calcium current by HF may be the mechanism underlying its pressor effects.

Action Potentials↗
PubMed1989

Flow cytometric study comparing paired bladder washing and voided urine for bladder cancer detection.

Paired bladder washings and voided urines from bladder cancer patients were compared as sources of exfoliated cells for detection of bladder carcinoma by flow cytometry (FCM). Bladder specimens fixed in 25% ethanol within sixty minutes of collection were found to be superior to unfixed bladder specimens. The percentage of specimens with good DNA resolution was greater for bladder washings (67% unfixed, 90% fixed) than voided urines (41% unfixed, 66% fixed). There was no difference in DNA resolution between specimens that remained unfixed less than one day, one day, or two days suggesting that the cells undergo the majority of degradation within a critical period soon after collection. Once fixed, there was no difference in DNA resolution for up to nineteen days, which suggests the feasibility of specimen transport to central FCM laboratories. Eighteen percent of unfixed bladder washings and 33 percent of unfixed voided urine specimens contained an insufficient number of cells (less than 5,000) at the time of analysis compared with 6 percent bladder washings and 17 percent voided urines fixed in 25% ethanol. Flow cytometry and cytology results were concordant in 28/43 (65%) of fixed bladder washings and 9/13 (69%) of fixed voided urine. Voided urine was unreliable in providing consistent FCM data due to the high number of specimens with poor resolution or insufficient cells and is not recommended as a substitute for bladder washing when screening high-risk populations or monitoring patients with past history of bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1989

Isolation and characterization of collagen in Peyronie's disease.

Peyronie's disease is characterized histologically by excessive collagen deposition in the lesion. We examined the collagen types in Peyronie's disease plaque tissues compared to unaffected tissues from the same patient, other control tissues, and Dupuytren's contracture. Gel electrophoresis of pepsin-solubilized collagen demonstrated the presence of type I collagen and an increased content of type III collagen in plaque tissue. Increased type III collagen was detected in apparently normal tissue adjacent to the plaque and in Dupuytren's lesion, confirming previous findings. Although the cause of excessive collagen accumulation of Peyronie's disease is unknown, the results suggest an imbalance in the regulation of extracellular matrix production leading to pathologic fibrosis.

Collagen↗
PubMed1989

Further investigation of a potential calcium channel modulator isolated from rat erythrocytes.

The contractile effects of a peptide isolated from rat erythrocytes were further studied in rat aortic rings. Previous data showed that preincubation of aortic tissue with the peptide had no effect on resting tension, but significantly enhanced K+ and norepinephrine (NE) induced contraction. The calcium channel antagonist verapamil noncompetitively blocked the effect of the peptide, whereas nifedipine blockage appeared to be competitive. In the present study the peptide enhanced K+, NE, and phenylephrine (PE) induced contraction in a concentration-dependent manner, with a maximum enhancement at peptide concentrations of 10(-7)-10(-6) M. At a concentration as low as 10(-9) M, the peptide significantly enhanced K(+)-induced, but not NE- or PE-induced, contraction. The magnitude of maximal enhancement was greater for K(+)-induced contraction than that for NE- or PE-induced contraction. Preincubation of the tissues with the peptide caused a leftward shift of cumulative concentration-response curves to K+ and NE. The peptide enhancement of contraction increased with increasing K+ and NE concentration. The peptide potentiated the contractile response to Ca2+ in K(+)-depolarizing medium. It also enhanced the contractile response to NE in intracellular Ca2(+)-pool-depleted tissue following the replenishment of extracellular Ca2+, but had no apparent effect on the mobilization of intracellular calcium. Addition of nifedipine caused a rightward shift of both the peptide and Bay K 8644 concentration-response curves.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Hypotensive properties of antibodies directed against an endogenous pressor peptide isolated from rat blood.

Hypertensive factor (HF), a compound isolated from the erythrocytes of rats and tentatively identified as a peptide, has been shown to influence tissue calcium metabolism and induce prolonged blood pressure elevation. In the present study, we investigated the biological properties of antibodies directed against this peptide. Partially purified antibody preparations significantly decreased HF stimulation of lanthanum-resistant calcium uptake in rat aortic tissue in vitro. Infusion of the antibody preparation into spontaneously hypertensive (SH) or normotensive Sprague-Dawley rats resulted in a rapid decline in mean blood pressure of 54 and 34 Torr (1 Torr = 133.332 Pa), respectively. In contrast, infusion of the serum immunoglobulin preparations from controls (unimmunized and ovalbumin-immunized rabbits) had no significant effect on the blood pressure of SH or normotensive rats. The systolic blood pressure of SH rats was reduced for at least 72 h following a single injection of the antibody preparations, whereas the blood pressure of normotensive rats had returned to normal levels within 24 h following antibody injection. The results indicate that the anti-HF antibody preparation antagonizes the stimulation of calcium uptake by the peptide and acutely lowers blood pressure in SH and normotensive rats.

Animals↗
PubMed1989

Aortic cyclic AMP levels in hypertensive rats.

The levels of adenosine 3':5' cyclic monophosphate (cyclic AMP) were measured in aortae from 2-kidney, 1-clip renovascular hypertensive and DOCA-salt hypertensive rats. Cyclic AMP concentration and content were increased in the arteries from the hypertensive animals compared to their normotensive controls. There was a significant positive linear correlation between aortic cyclic AMP concentration and blood pressure and between aortic cyclic AMP content and blood pressure. Since cyclic AMP has been shown to be involved in cellular proliferation and protein synthesis, a perturbation in the normal functioning of this second messenger system could be related to some of the vascular changes associated with the hypertensive process.

Animals↗
PubMed1988

Skull metastases from follicular thyroid carcinoma.

Distant metastatic disease from thyroid carcinoma is becoming a rare problem. Physicians and the public are increasingly aware of minimally invasive methods of early diagnosis of thyroid malignancy, such as fine-needle aspiration with cytologic examination. Total thyroidectomy itself has become less associated with morbidity than it once was. We describe three patients with follicular thyroid carcinoma metastatic to the skull who were seen recently. Two of these patients had masses neglected for 20 and 50 years, respectively. The management of this disease entity is discussed.

Adenocarcinoma↗
PubMed1988

An endogenous peptide that induces long-term blood pressure elevation.

A peptide was recently isolated from the blood of spontaneously hypertensive (SH) rats that stimulated an increase of calcium uptake by vascular tissue in vitro. In the present study normotensive rats were given nanomolar amounts of this peptide by intravenous or picomolar amounts by intracerebral injection and the effect on blood pressure was recorded. Injection of the peptide into the circulation had no significant effect on the elevation of blood pressure. By comparison, the injection of the compound into the third ventricle of the brain resulted in the elevation of blood pressure to hypertensive levels. The blood pressure response was characterized by a prolonged period of onset with maximal elevation observed several days after the beginning of treatment. Subsequently, the increase in blood pressure was well maintained with significant elevation noted days following the cessation of treatment.

Animals↗
PubMed1988

Bay K 8644-like contractile effects of a peptide isolated from spontaneously hypertensive rats.

The in vitro contractile effect of a peptide recently isolated from the blood of spontaneously hypertensive rats was assessed on rat aortic rings. Preincubation of aortic rings with the peptide had no effect on resting tension but significantly enhanced K+ or norepinephrine-induced contractile responses. Contractile effects were abolished by removal of extracellular calcium or by additions of the calcium channel antagonists, verapamil and nifedipine. The antagonism of peptide enhancement of contraction by verapamil was noncompetitive, whereas nifedipine blockade was competitive in nature. Moreover, preincubation of aortic rings with the peptide attenuated the contractile response to Bay K 8644, a newly described synthetic calcium channel agonist. We suggest that this peptide has similar effects to Bay K 8644 and may act as an endogenous modulator of voltage-dependent calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Hypertensive factor: calcium stimulatory activity obtained from different tissues and animal species.

It was recently shown that a peptide (hypertensive factor, HF) isolated from erythrocyte hemolysates from spontaneously hypertensive rats induced a prolonged elevation of blood pressure in normotensive rats. In addition, the peptide produced a marked stimulation of the in vitro uptake of lanthanum-resistant calcium by the aortae and enhanced the contractile response of aortic rings to constrictor agents. The present report describes findings of calcium stimulatory activity, enhancement of contractile function, or pressor activity in extracts of homogenates from several tissues of the rat and from erythrocyte hemolysates of several mammalian species. Significant stimulation of calcium uptake in aortic rings was obtained with preparations from rat brain, liver, and kidney. The activity per weight of tissue was similar for brain and kidney (approximately 2 units/g), while liver exhibited somewhat higher concentrations (4 units/g). The diffusate of cardiac tissue did not significantly alter in vitro calcium uptake by aortae. The injection of the cardiac and liver diffusates into normotensive Wistar-Kyoto rats produced slight (10 Torr) (1 Torr = 133.3Pa) and moderate (25 Torr) elevations of blood pressure, respectively. Finally, a peptide purified from homogenates of rat brain by the protocol developed for the purification of HF from erythrocytes was shown to significantly enhance the contractile response of aortic rings to K+ and norepinephrine. Diffusates of erythrocytes from the rat, rabbit, dog, and guinea pig each caused a significant stimulation of calcium uptake and contained approximately the same level of activity (500 units/L of whole blood). Diffusates prepared from outdated human erythrocytes had no significant effect on calcium uptake, whereas those of freshly drawn samples exhibited high levels of activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Chromosome abnormalities in Peyronie's disease.

Peyronie's disease is a localized and progressive fibrosis of unknown etiology that affects the tunica albuginea of the penis. We examined cytogenetically cell cultures derived from plaque, adjacent tunica, dermis and lymphocytes in patients with Peyronie's disease, and compared the results to cell cultures established from the tunica albuginea of control patients. Chromosomal abnormalities were detected in 9 plaque-derived cell cultures from 7 of 12 Peyronie's disease patients (58 per cent). Cells cultured from adjacent tunica, dermis and lymphocytes from the same patients were karyotypically normal, as were cultures derived from control (chordee and penile scar) patients. Chromosomal aberrations consisted of 5 numerical changes and 4 structural rearrangements, and included chromosomal additions (trisomy 7 and trisomy 8), deletions (45X,-Y), reciprocal translocations and inversions or markers. In 2 instances cultures derived from plaque tissue contained 2 independent chromosomal abnormalities. The apparently random chromosomal changes associated with Peyronie's disease suggests that karyotypic instability may be a common feature of cells within the plaque. It presently is unclear whether this finding represents multiple pathways for the development of Peyronie's disease or secondary consequences of Peyronie's disease.

Aged↗
PubMed1987

An endogenous peptide that stimulates lanthanum-resistant calcium uptake in vascular tissue.

A recent report has described the preparation of an extract from hemolyzed erythrocytes that has a stimulatory effect on lanthanum-resistant calcium uptake by vascular tissue in vitro and a hypertensive effect when injected into normotensive rats. The compound having a stimulatory effect on calcium uptake was further fractionated by molecular sieve and ion exchange chromatography, precipitation with CaCl2, high voltage paper electrophoresis, and high performance liquid chromatography (HPLC). HPLC yielded only a single fraction containing biological activity. This fraction was ninhydrin positive and acid labile. The amino acid composition was as follows: Asp/Asn (1.41), Ser (1.02), Glu/Gly (1.00), and Gly (2.00). Based on the assumption that the compound contains a single glutamic acid or glutamine residue, concentration-response data indicated that only nanomolar amounts of material were necessary to achieve significant stimulation. There was a marked increase in stimulatory activity of the resolubilized compound following calcium precipitation. The compound became inactive or showed a reduction in activity after being applied to a cation exchange column to remove calcium. Subsequent reprecipitation with CaCl2 and resolubilization restored the lost activity. Thus, we conclude that the compound is a small, acidic, calcium-dependent peptide that is extremely potent in stimulating lanthanum-resistant calcium uptake in vascular tissue.

Amino Acids↗
PubMed1987

Spontaneous hypertension: a humoral component.

A hypertensive factor (HF) has been partially purified from the erythrocytes of spontaneously hypertensive rats. Injection of the factor produces a sustained elevation of the blood pressure of normotensive rats. The blood pressure response following intravenous injection of the factor is characterized by a prolonged period of onset with maximal elevation obtained several days following the beginning of treatment. Subsequently, the elevation of blood pressure is well maintained and may be observed days or weeks following the cessation of treatment. In addition to its pressor effects, the preparation stimulates an increase in the concentration of "lanthanum-resistant" calcium in aortae excised from normotensive or hypertensive rats. In contrast, the efflux of calcium from aortae in the presence of the factor is enhanced suggesting that the factor involved may induce a change in the lability and exchangeability of calcium stores in aortic tissue. Secondarily, the efflux data indicate that the increase in "lanthanum-resistant" calcium noted in aortae exposed to the erythrocyte extract is due to an increase in calcium uptake by the tissue as opposed to a decrease in the extrusion of the ion.

Animals↗
PubMed1987

Binding of human IgG to cultured urogenital tumor cells.

Binding of human IgG by the Fc portion of the immunoglobulin molecule was detected on established human tumor cell lines by indirect immunofluorescence microscopy, cytofluorography, quantitative absorption, and rosette formation with the use of antibody-coated erythrocytes. Of the nonlymphoid tumors tested, IgG binding was restricted to the cell membranes of certain prostate and urinary bladder tumor cell lines. Although most cell lines tested shared a common antigenic determinant with monocytes and granulocytes, these cells did not express T- and B-cell antigens, the complement 3b receptor, or bind a monoclonal antibody specific for the Fc receptor expressed on human neutrophils. The facts that IgG binding was present on long-term established tumor lines and was not influenced by in vitro passage provide evidence that these properties are intrinsic to the tumor cells and may play some role in the pathophysiology of these tumors.

Adenocarcinoma↗
PubMed1986

An antihypertensive extract of erythrocytes: effects on 45Ca uptake and efflux.

The present report describes some aspects of the effects of a recently described antihypertensive extract of erythrocytes (AHF) on calcium uptake and efflux in rat aortae. AHF was found to be present in the erythrocytes of both spontaneously hypertensive rats and normotensive rats. Furthermore, AHF obtained from erythrocytes of SH rats was shown to be equally effective in suppressing lanthanum-resistant calcium uptake in aortae from hypertensive and normotensive rats. AHF treatment prior to incubation of aortae with 45Ca caused an apparent increase in the total 45Ca uptake. The analysis of calcium washout curves obtained for tissue in calcium-free or lanthanum-containing media indicated that AHF had no significant effect on the rate of calcium loss from the slow component of efflux, though this compartment tended to be reduced in size. This indicated that the increase in the 45Ca content of AHF-exposed aortae prior to rinsing was confined to the rapid component of efflux. The loss of calcium from the rapidly exchanging compartment was enhanced in either of the efflux media used. The results suggest that a principal action of AHF involves an increase in the lability and exchangeability of calcium stores. In addition to its effects in resting tissue, AHF abolished the increase in lanthanum-resistant calcium uptake induced in rat aortae by the addition of high K+ or norepinephrine to the incubation media. In a second part of the study, the effect of AHF on blood pressure and in vitro calcium uptake were compared with that of phosphatidylethanolamine (PEA), the probable identity of another endogenous antihypertensive (renin preinhibitor) compound earlier shown to share important functional similarities with AHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Stimulation of aortic tissue calcium uptake by an extract of spontaneously hypertensive rat erythrocytes possessing hypertensive properties.

In earlier reports we have described the isolation of a fraction from the erythrocytes of spontaneously hypertensive rats that produced hypertension when administered to normotensive rats. In addition, it was found that the fraction stimulated the uptake of "lanthanum-resistant" calcium by aortic rings excised from normotensive rats. In these studies we have found that the fraction causes a greater increase in the in vitro uptake of calcium by aortic tissue than that produced by depolarization of the tissue with high K+ or the receptor-mediated influx of calcium induced with norepinephrine. The hypertensive fraction appeared to be more effective in promoting increased calcium uptake in rabbit than in rat aortic tissue, suggesting that significant differences in tissue sensitivity to the active compound(s) may exist between species. In addition, we obtained evidence indicating that the tissue sensitivity to the action of the hypertensive fraction was greater in aortae from spontaneously hypertensive rats than from those of normotensive animals. Attempts to block the action of the hypertensive fraction with verapamil, nifedipine, and sodium nitroprusside had no significant effect on the elevation in tissue calcium. It was found, however, that the action of the hypertensive fraction was temperature dependent with reduced activity at lower temperatures. The data suggest that a compound(s) is present in the erythrocytes of rats that may have a marked effect on vascular tissue metabolism of calcium.

Animals↗
PubMed1986

Human prostate tissue antigens defined by murine monoclonal antibodies.

BALB/c mice were hyperimmunized against a membrane preparation derived from a pool of transurethral resection specimens which included three benign prostatic hyperplasia and one prostate adenocarcinoma tissue samples. The activated lymphocytes were fused with the NS-1 mouse myeloma cell line, and supernatants from immunogen-reactive hybridomas were screened for antibody binding activity using a solid-phase radioimmunoassay against the Calu-1 human lung adenocarcinoma cell line and several membrane preparations derived from various normal human tissues. Hybridoma cultures secreting antibodies which did not appear cross-reactive were doubly cloned by limiting dilution and screened against a large panel of membrane preparations derived from normal prostate, benign prostatic hyperplasia, and prostate adenocarcinoma tissues as well as samples obtained from a variety of normal human tissues. The monoclonal antibodies were also evaluated against 24 normal, virally transformed, and malignant human cell lines. Two monoclonal antibodies were isolated which demonstrated a restricted binding activity to prostate antigens and were not widely cross-reactive with nonprostate normal tissues or cell lines. These antibodies were designated TURP-27 (IgG3, k) and TURP-73 (IgG2a, k). Both of these monoclonal antibodies were reactive against formalin-fixed, paraffin-embedded tissues in the immunoperoxidase assay and were subsequently tested against a variety of normal, hyperplastic, and malignant human tissues. These studies indicated that TURP-27 may be directed against a new prostate organ-associated marker and that TURP-73 is directed against an antigen expressed on prostate and a limited number of other tissues.

Antibodies, Monoclonal↗