Acid Phosphatase Content Research Articles

Lipid composition of subcellular membranes from larvae and prepupae of Drosophila melanogaster.

Subcellular membranes were analyzed for their lipid composition and protein content at two developmental points representing the third instar wandering larvae and prepupal stages of Drosophila. At both stages, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were the major constituents with phosphatidylinositol (PI), phosphatidylserine (PS), diphosphatidylglycerol (DPG) and phosphatidic acid (PA) being relatively minor components. In total homogenates and in the nuclear-enriched fraction there was no significant difference in the phospholipid composition of the wandering larvae and prepupae. In mitochondria only a significant increase in the minor component PS was observed in the prepupae. In lysosomal membranes on the other hand, the relative abundance of the major components PE and PC increased in the prepupae although the molar ratios of the two lipids remained almost constant. The fatty acid composition of the phospholipids remained virtually unchanged in all of the fractions examined, including the lysosomes, and there was no evidence of lipid peroxidation. With regard to cellular degeneration and the involvement of lysosomes, we conclude that mechanisms other than gross modification of the lipid and/or lipid/protein ratio of their membranes are involved in the liberation of the acid phosphatase contents.

Isolation of phenotypically and functionally distinct macrophage subpopulations from human bronchoalveolar lavage

Bronchoalveolar lavage was used to obtain alveolar macrophages (AM) from the lower respiratory tract of healthy normal volunteers. Monoclonal antibody (MoAb) probes specific against macrophage determinants were then applied, in conjunction with density separation techniques, to identify and isolate three relatively homogeneous subpopulations from the AM pool. The MoAbs used, RFD1 and RFD7, have previously been shown to differentiate between "dendritic" cells and mature macrophages, respectively, in normal tissue. In addition to these two phenotypically distinct AM subsets (RFD1+D7- and RFD1-D7+ AM), a third AM subpopulation was isolated, which appeared to express both markers (RFD1+D7+). All three separated macrophage subsets were morphologically similar but exhibited distinct differences in surface receptor expression, enzyme content and physiology. Isolated RFD1+D7- AM (the phenotype of "dendritic" cells) did not adhere to the glass, had weak expression of C3b and FcR1 receptors, low fibronectin content and lysosomal activity; only a small proportion of these cells exhibited phagocytosis. The other two isolated AM subsets adhered to glass, expressed C3b and FcR1 receptors, had high fibronectin and acid phosphatase content, and a large majority exhibited phagocytic capacity; qualitative and quantitative differences in these features existed between the two AM subtypes. Furthermore, a diverse spectrum of hexose monophosphate shunt activity was observed throughout all three AM subpopulations, with the highest activity being recorded in the non-adherent AM. These data support the concept of a dynamic heterogeneity within the AM population. The variation in surface antigen expression and physiological capabilities observed amongst the three isolated AM subsets implies the presence of functionally distinct AM within the human lung, which, during steady-state conditions, may be critically balanced under the influence of stimuli in their local microenvironment. In support, proportional and functional shifts have been witnessed amongst these three AM subpopulations with the advent of disease.

Evaluation of hypoxic brain injury with spinal fluid enzymes, lactate, and pyruvate.

To investigate the prognostic importance in neurologic recovery of the lumbar cerebrospinal fluid (CSF) variables creatine kinase (CK) and brain-type creatine kinase isoenzyme (CK-BB), lactate dehydrogenase (LDH) and its isoenzymes (LDH 1-5), CSF acid phosphatase, beta-D-N-acetylglucosaminidase activity, and CSF lactate, pyruvate, sodium, potassium, and calcium concentrations in patients who experienced cardiac arrest. Prospective clinical study with blood and CSF samples collected 4, 28, 76, and 172 hrs after resuscitation. Medical ICU in a university hospital. Twenty consecutive victims of out-of-hospital cardiac arrest. Eight patients recovered neurologically and 12 patients remained comatose or neurologically disabled until death. CSF CK, CK-BB, LDH, and LDH isoenzyme 1-3 concentrations in all disabled patients were markedly increased at 76 hrs after the resuscitation. However, these variables were not changed in the recovered subjects. Patients (n = 7) with a mean CSF CK level of 25 +/- 33 (SD) U/L, CK-BB 23 +/- 33 U/L, and CSF lactate 3.8 +/- 0.9 mmol/L at 28 hrs after cardiac arrest remained unconscious and died. In the recovered patients, the mean CSF CK concentration was 2.0 +/- 1.5 U/L (p less than .001) and CSF lactate concentration 2.5 +/- 0.5 mmol/L (p less than .002). The lactate concentration was highest at 4 hrs after resuscitation, declining thereafter. Patients with a mean CSF total LDH level of 609 +/- 515 U/L and acid phosphatase 2.4 +/- 1.2 U/L 76 hrs after resuscitation died without regaining consciousness. In the recovered patients, the mean total CSF LDH activity was 82 +/- 58 U/L (p = .003) and CSF acid phosphatase was 0.8 +/- 0.5 U/L (p = .01) 76 hrs after resuscitation. CSF CK, CK-BB, and CSF lactate concentrations reflect a patient's outcome most reliably when measured within 28 to 76 hrs of the cardiac arrest. Similarly, CSF LDH, its isoenzymes 1-3, and CSF acid phosphatase concentrations, when measured at 76 hrs, can be used to monitor the patient's outcome after cardiac arrest. When correlated with Glasgow Coma Scale scores, the closest negative correlation was again seen in CSF CK and CK-BB at 28 and 76 hrs, as well as in LDH, LDH1-3, and acid phosphatase values at 76 hrs. The negative correlation between CSF lactate and Glasgow Coma Scale scores was most distinct at 28 hrs.

Protective effect of diosmetin on in vitro cell membrane damage and oxidative stress in cultured rat hepatocytes

Primary cultures of rat hepatocytes were used to study the effects of the flavonoids diosmin and its main metabolite diosmetin on the cell membrane damage caused by erythromycin estolate (EE) and oxidative stress caused by tert-butylhydroperoxide (TBHP). The damage was evaluated by the leakage of intracellular enzymes lactate dehydrogenase, aspartate-aminotransferase and the residual cell content of a lysosomal marker acid phosphatase (AP). After treating the cells for 40 h with diosmetin EE induced less enzyme leakage. The content of AP was kept higher by diosmetin pretreatment after 6 h exposure to EE. Diosmin at the same concentrations had barely any effect. Diosmetin, but not diosmin, also protected against TBHP toxicity and this was related to lower lipid peroxidation and higher glutathione content caused by pretreatment with the flavonoid. When the cells were treated simultaneously with TBHP and diosmetin after 21 h of culture, the protection by the flavonoid was even higher. In fact the antioxidant activity of diosmetin was considerably greater than that of diosmin. After 40 h exposure to both flavonoids diosmin but not diosmetin was detectable in the cell membrane fraction, suggesting that the latter's protective effect is associated with its metabolites.

Serum prostatic acid phosphatase, gamma-seminoprotein and prostatic specific antigen in hemodialysis patients.

Serum concentrations of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PSA) were measured in 31 hemodialysis patients without clinical signs of malignant disease. PAP, gamma-Sm and PSA levels in serum were not significantly different between control and hemodialysis groups. A significant reduction in these tumor markers was not found after dialysis treatment. This indicates that the measurement of PAP, gamma-Sm and PSA in serum is useful for the detection of prostatic cancer in patients undergoing hemodialysis.

Changes in prostate-specific antigen and prostatic acid phosphatase concentration following prostatic examination in benign prostatic hypertrophy and prostate cancer patients.

The authors measured serum prostate-specific antigen (PSA) and prostatic acid phosphatase concentration in histologically positive prostate hyperplastic and carcinomatous patients before, and 30-60 min and 24 h after prostate manipulation (rectal digital examination, cystoscopy and perineal punch biopsy). After rectal examination, PSA, and after other interventions, both markers changed significantly, although in different points of time and to a different extent. The authors call the attention to the importance of the point of time of the examination. Examination following prostate manipulation may result in wrong diagnosis or in erroneous therapeutic consequences in the follow-up period.

Experience with prostate-specific antigen in prostatic carcinoma

A total of 71 prostatic tumour patients and 45 prostatic adenoma patients were tested for prostate-specific antigen (PSA), immunological prostatic acid phosphatase (PAP) concentration as well as serum prostatic phosphatase (SPP) and enzymic serum phosphatase. It was found among untreated patients that PSA showed the highest percentage of pathologic affection in each stage. PSA, on the evidence of clearance test in the initial days of therapy and after a follow-up period of several months, gave a good picture of the course that the disease had taken.

Measurement of prostate-specific antigen and prostatic acid phosphatase concentrations in serum before and 1-42 days after transurethral resection of the prostate and orchidectomy

Preoperative intra-individual variation for determinations of prostate-specific antigen and prostatic acid phosphatase concentrations, 15-30% in 92 patients with benign prostatic hyperplasia, limits the diagnostic usefulness of both tumor markers. In benign prostatic hyperplasia (214 patients), concentrations of these tumor markers increased in the initial postoperative period. Prostatic acid phosphatase concentration then decreased by the third postoperative day. Prostate-specific antigen concentration remained above normal in the first postoperative week but had decreased by 42 days. In prostatic carcinoma (46 patients), the concentrations of these tumor markers did not increase postoperatively. During the first week, the concentrations of prostatic acid phosphatase began to fall, but prostate-specific antigen showed a decrease only at 42 days. After orchidectomy (11 patients), the concentrations of both markers had decreased by five days. Concentrations of prostate-specific antigen but not of prostatic acid phosphatase were significantly increased in patients with metastases at 42 days postoperatively. When the concentration of tumor marker did decrease, the magnitude of change was greater for prostatic acid phosphatase than for prostate-specific antigen. These changes were accentuated after an orchidectomy.

Requirement of Innervation for Maintenance of Structural and Functional Integrity in the Rat Prostate1

The rat prostate is innervated by pelvic and hypogastric nerves through a single pelvic ganglion, removal of which would result in complete denervation of the prostatic complex. The present study was conducted to investigate the effect of denervation on the rat prostate. Adult Sprague-Dawley rats of 300 g in body weight were divided into two groups. Bilateral pelvic ganglion denervation was performed in one group of animals; the other group received a sham operation. Three weeks later, animals were killed; and the ventral prostates were removed, weighed, and subjected to routine procedures for light and electron microscopy. The average weight, total protein content, and total content of acid phosphatase of the ventral prostates in the denervated group were significantly less than those in the control group. Total DNA content per prostate, however, was not significantly different between the two groups. Results of histological examination indicated that the prostates from control animals showed normal morphology, whereas those from the denervated animals showed reduced cell height and enlarged vacuoles surrounding the nuclei. Inspection of electron micrographs revealed that the prostates from denervated animals, compared with those of controls, showed a reduced ratio of cell height:cell width, which is associated with a reduced number of microvilli and secretory granules. These results indicate that denervation in the prostate is associated with a lower prostatic weight, decreased cell height, and reduced secretory activity.

Pharmacodynamics and pharmacokinetics of miloxicam in the horse

The novel non-steroidal anti-inflammatory drug (NSAID) miloxicam was administered intravenously to six New Forest ponies at a dosage rate of 0.6 mg/ kg in a two-part cross-over study. In each part, three horses received miloxicam and three were given a placebo preparation. The actions of miloxicam, compared to placebo, were assessed in a carrageenan-sponge model of acute inflammation. The rise in skin temperature over the site of the acute inflammatory reaction was less in treated ponies, but differences were not statistically significant. Concentrations of the enzymes acid phosphatase (AP) and lysozyme in inflammatory exudates harvested at 4, 8, 12 and 24 h were not significantly different in drug-treated animals compared with those receiving placebo. Concentrations of protein and lactate dehydrogenase (LDH) in exudate and exudate leucocyte numbers were significantly reduced in drug-treated horses when data for all sampling times were pooled. The differences were not significant, however, at each sampling time. Exudate concentrations of the eicosanoids, bicyclic-PGE 2, 6-keto-PGF 1α and TXB 2, were reduced significantly by miloxicam at most sampling times, and serum TXB 2 was also significantly reduced at 4 and 8 h but not at 12 and 24 h after drug administration. These pharmacodynamic findings correlated with the pharmacokinetic properties of miloxicam. The plasma concentration-time curve was defined by a three-compartment open model in one pony and by a two-compartment model in five ponies. Mean values for pharmacokinetic parameters for the five ponies were: t 1 2 α 0.40 h; t 1 2 β 2.70 h; Vdarea 0.158 l/kg; Cl B 41.87 ml/kg/h. Exudate concentrations of miloxicam were initially similar to and eventually greater than concentrations in plasma, and this may explain the more prolonged inhibition of eicosanoid synthesis in exudate than in serum. These findings demonstrate the value of relating, in a single experimental study, drug action on a range of variables to drug fate in the body.

Effect of Suramin on Human Prostate Cancer Cells in Vitro

Suramin, a polyanionic compound with known antiparasitic activity, has been shown to be adrenocorticolytic in primates and to have clinical efficacy in the treatment of patients with metastatic prostate cancer refractory to conventional hormonal manipulation. To better characterize the activity of suramin on prostate cancer biology, we studied the effect of the drug on plasma adrenal androgens of patients and on the human prostate adenocarcinoma cell lines PC-3, DU 145 and LNCaP-FGC. Five cancer patients treated with suramin had an approximate 40% decline in circulating androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate levels. The drug inhibited the colony formation in two of the three cell lines at concentrations clinically achievable in humans without excessive drug-related toxicity. The presence of suramin 300μg./ml. partially inhibited the growth stimulatory effect of testosterone and basic fibroblast growth factor, but not that of epidermal growth factor. The cellular concentration of suramin following exposure to a single dose increases linearly over time in each of the cell lines with LNCaP-FGC accumulating the highest levels of the drug; cellular levels of suramin, not androgen or growth factor sensitivity, correlated with the sensitivity to the drug. The concentrations of prostatic acid phosphatase and prostatic specific antigen released by LNCaP-FGC cells in cell culture medium declined in the presence of increasing levels of suramin in a manner which exceeded the decrease in cell number. We conclude that suramin, aside from decreasing circulating androgens through its adrenocorticolytic effect, is also capable exerting a direct inhibitory effect on cell proliferation of prostate cancer cells, and interfere at a cellular level with the growth stimulatory effects of exogenous testosterone and basic fibroblast growth factor.

The Histological and Histochemical Effects of Ketotifen in Allergic Rhinitis

The effects of a three-month course of oral ketotifen on the histology and histochemistry of nasal mucosa, assessed on punch biopsy material, were studied in 30 adults with perennial allergic rhinitis. Ketotifen treatment was associated with reversal of the histopathology and enzyme changes in every case. Two months after stopping therapy, the rhinitis changes had returned in all 10 patients from whom posttreatment punch biopsies were taken. Other patients whose symptoms were relieved declined a third biopsy. Five normal volunteers were included as controls. The pretreatment mucosal biopsies showed variations in goblet cell population, thickened basement membranes, hypertrophied serous glands, diminished or absent mucus glands, and varying degrees of cellular infiltrates. There was marked edema with separation of collagen fibers and epithelial metaplasia especially in patients with long-standing allergy and nasal polyps. Ketotifen therapy was linked with reversal of the epithelial changes to normal, marked reduction in edema and cellular infiltration, and the retention of granules by mast cells. Changes in mucosal content of succinic dehydrogenase and acid phosphatase; high tissue levels of both which are associated with allergic rhinitis, also diminished towards the control levels during ketotifen therapy, only to return after its cessation.

Serum Tumour Markers in Human Prostatic Carcinoma: The value of a marker panel for prognostic information

Serum from 102 patients was analysed with regard to its content of prostatic acid phosphatase (PAP), prostate specific antigen (PSA), neopterin, osteocalcin, thymidine kinase, C-reactive protein, and of tissue polypeptide antigen (TPA). The levels were related to the short-term survival (death from cancer within 3 years) and compared by statistical means. A comparison was also made with tumour grade and stage and the presence or not of metastatic lesions. In this study neopterin was found to be most closely related to the clinical course followed by tumour grade, thymidine kinase and PSA. When all these four variables were in the equation no other parameter added any information of statistical significance. The importance of selecting appropriate cut off values ('normal' vs 'elevated') when using the serum marker as a prognostic indicator is also discussed.

Hydrochlorothiazide inhibits parathormone-stimulated increase in plasma tartrate-resistant acid phosphatate in mice

The inhibitory effect of hydrochlorothiazide (HTZ) on parathormone-induced bone changes in mice was studied with the aid of the analysis of plasma calcium and tartrate-resistant acid phosphatase. We have found that HTZ alone had no effect on plasma tartrate-resistant acid phosphatase (Tr-ACP), phosphate, and creatinine concentration. Parathormone (PTH) administration increased plasma Tr-ACP from 15.00 +/- 1.50 to 20.62 +/- 2.35 U/liter in intact mice. The increase of plasma Tr-ACP in HTZ-treated mice after PTH administration was not significant. The plasma calcium was affected in a way similar to Tr-ACP. HTZ reduced the sensitivity of bone to resorbing effects of PTH, using Tr-ACP as a useful biomarker of bone resorption.

Lysosomal Changes in Renal Proximal Tubular Epithelial Cells of Male Sprague Dawley Rats following Decalin Exposure

A histochemical stain for acid phosphatase served as a marker for lysosomal alterations in renal tubular cells associated with male rat hyaline droplet nephropathy. Morphometric analysis and quantitative histochemistry were used to compare the size and acid phosphatase stain reaction of lysosomes in tubular epithelial cells of treated and control animals. Decalin exposure increased the size and significantly ( p < 0.01) reduced the acid phosphatase stain intensity of individual lysosomes. However, there was no significant different ( p > 0.05) between the acid phosphatase stain intensity of treated and control animals when analyzed on a whole cell basis. The increase in size of the lysosomes without a proportional increase in whole cell acid phosphatase stain intensity indicates a dilution or a failure to accommodate in the acid phosphatase concentration (stain intensity/μm2) per lysosome. All acid phosphatase stain reaction product was contained within intact lysosomes, mitigating against the hypothesis of lysosomal enzyme leakage as the cause of cell death in decalin-induced alpha 2U globulin nephropathy.

Effect of season on seminal traits and serum hormone concentrations in captive male Siberian tigers (Panthera tigris)

Electroejaculates and serum samples were collected throughout the year from 5 male Siberian tigers. Semen quality, seminal plasma chemistry and serum hormone concentrations were evaluated and analysed as a function of season. Semen volume, concentration, motility, viability and morphology were not influenced by season. The ability of spermatozoa to undergo capacitation and penetrate zona-free hamster eggs did not differ due to season. Season had no influence on seminal plasma concentrations of acid phosphatase, calcium, glucose, potassium and phosphorus. Serum values of thyroxine and triiodothyronine were lowest (P = 0.002 and P = 0.03, respectively) during the summer months while cortisol showed no seasonal variation. Serum testosterone concentrations were higher in fall and early winter (P less than 0.001) than at other times of the year but were not correlated with semen quality. These results demonstrate that season has no effect on the semen production and quality of captive male Siberian tigers.

Tumour Markers as Prognostic Aids in Prostatic Carcinoma

Of 102 patients suffering from prostatic carcinoma, complete data on the serum concentration of 7 tumour markers were available from 90 patients, together with tumour grade, local stage and the presence or absence of skeletal metastases. The serum content of prostatic acid phosphatase, prostate specific antigen, neopterin, thymidine kinase, osteocalcin, C-reactive protein and tissue polypeptide antigen was measured. By means of Cox's regression and multivariate analysis the ability of these variables to predict prognosis, i.e. death from prostatic cancer, was studied. Neopterin appeared to be the most efficient marker, followed by tumour grade, thymidine kinase and prostate specific antigen. No other variable provided information of statistical significance. In multivariate analysis thymidine kinase performed best, followed by neopterin, tumour grade and prostate specific antigen. Several serum tumour markers reflect the biological activity of human prostate cancers and their value should be further explored. They may become useful in the management of individual patients.

Lysosomal Changes in Renal Proximal Tubular Epithelial Cells of Male Sprague Dawley Rats Following Decalin Exposure

A histochemical stain for acid phosphatase served as a marker for lysosomal alterations in renal tubular cells associated with male rat hyaline droplet nephropathy. Morphometric analysis and quantitative histochemistry were used to compare the size and acid phosphatase stain reaction of lysosomes in tubular epithelial cells of treated and control animals. Decalin exposure increased the size and significantly (p less than 0.01) reduced the acid phosphatase stain intensity of individual lysosomes. However, there was no significant different (p greater than 0.05) between the acid phosphatase stain intensity of treated and control animals when analyzed on a whole cell basis. The increase in size of the lysosomes without a proportional increase in whole cell acid phosphatase stain intensity indicates a dilution or a failure to accommodate in the acid phosphatase concentration (stain intensity/microns 2) per lysosome. All acid phosphatase stain reaction product was contained within intact lysosomes, mitigating against the hypothesis of lysosomal enzyme leakage as the cause of cell death in decalin-induced alpha 2U globulin nephropathy.

In Vitro Cytotoxicity of 26 Coded Chemicals to HEp-2 Cells: A Validation Study

Twenty-six chemicals supplied coded by FRAME, were tested on HEp-2 cells. Three endpoints were used to measure the cytotoxicity of these compounds: total protein content, LDH release and total acid phosphatase content. The sensitivity of these parameters is discussed. The results are compared with those obtained by other groups participating in the validation scheme organised by FRAME.

Prostatic acid phosphatase in the serially transplantable human prostatic tumor lines PC-82 and PC-EW

The correlation between tumor volume of untreated tumor-bearing nude mice and serum concentration of prostatic acid phosphatase (PAP/RIA) was studied in the hormone-dependent serially transplantable human prostatic tumor models PC-82 and PC-EW. The normal serum level of PAP in control male nude mice without tumor was found to be 0.9 +/- 0.3 ng/ml. Elevated PAP serum concentrations were never found in animals without tumor (a highly specific diagnostic technique). A close correlation was observed between the concentration of PAP in the serum (range 0.3 to 154 ng/ml) and the tumor volume (range 10.0 to 6,530 mm3) of 104 untreated mice bearing a PC-82 or PC-EW human prostatic tumor. This correlation was comparable in both tumor lines (p less than 0.001). The positive effect of endocrine manipulation which resulted in tumor diameter decrease or growth arrest with regressive histological patterns, showed the normal PAP serum level, too. After successful treatment PAP was found to be normal, independent from the residual tumor mass. By contrast, in the event of only retarded tumor growth, the PAP level still correlated with the tumor burden.