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Biomedical subjects

P Pietschmann

Publications and source records attributed to P Pietschmann.

At least 19 recordsLinked to original sources

Identification of subsets of human T cells capable of enhanced transendothelial migration.

A critical step in immunologically mediated inflammation is the migration of T cells between endothelial cells of postcapillary venules and into the tissues. To determine whether specific cells are capable of transendothelial migration, T cells that had migrated through endothelial monolayers were retrieved and analyzed. To accomplish this, human umbilical vein endothelial cells (EC) were cultured to confluence on collagen gels and incubated with human T cells. T cells that were nonadherent to the EC, those that bound to the endothelium, and cells that had migrated through the endothelial monolayer and into the collagen were individually harvested and characterized. After a 4-h incubation with EC, T cells distributed themselves such that 77 +/- 2% were nonadherent, 13 +/- 2% were bound to EC, and 10 +/- 1% had migrated into the collagen. The CD4+ T cells that had migrated into the collagen were predominantly CD29bright/CD45RObright and CD45RA-. CD8+ T cells demonstrated a greater transendothelial migratory capacity than the CD4+ T cells. The migrated CD8+ T cells were mainly CD29bright but CD45RA+. Additional phenotypic analysis of the migrating cells indicated that they contained fewer cells that expressed L-selectin. Moreover the surface expression of CD7 was less dense in the T cells that had migrated than in the nonadherent T cells. Finally the T cells that migrated were not enriched for CD45RBdim T cells. Prolonging the incubation with EC to 36 h increased the number of T cells that migrated but did not alter the predominance of CD29bright T cells in the migrated population. Stimulation of EC with IL-1 or IFN-gamma also increased the number of adherent and migrating T cells, respectively, but did not alter the phenotype of the migrating cells. These results indicate that the capacity for transendothelial migration is an intrinsic ability of certain subpopulations of T cells and is related to their stage of differentiation as identified by their surface phenotype.

Antigens, CD

The intrinsic migratory capacity of memory T cells contributes to their accumulation in rheumatoid synovium.

OBJECTIVE: Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites. METHODS: The characteristics of in vivo migrating cells were studied by dual-immunofluorescence FACS (fluorescence-activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed. RESULTS: Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA-, CD29bright, CD11abright, L-selectin-, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA-DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA-DR and VLA-1. RA synovial lymphocytes exhibited a 2-3-fold increase in migratory capacity over normal and RA PBTL: CONCLUSION: These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29bright, CD11abright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L-selectin-. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium.

Adult

The influence of partial gastrectomy on biochemical parameters of bone metabolism and bone density.

Since it has been suggested that gastric resections are followed by changes in bone metabolism, the aim of our study was to determine the biochemical parameters of bone metabolism and radial and lumbar bone density in 15 male ulcus patients treated by partial gastrectomy (Billroth II). Comparing the data with those of a corresponding control group, the lumbar bone density measured by quantitative computed tomography was statistically significantly lower (P less than 0.04) in the patient group, whereas the peripheral bone mass of the distal part of the nondominant forearm measured by single-photon absorptiometry showed no statistically significant difference. In addition, a marked increase in alkaline phosphatase (P less than 0.002) and urinary excretion of hydroxyproline (P less than 0.003) was found in gastrectomy group, whereas the 25-hydroxy-vitamin D levels were found to be significantly decreased (P less than 0.04). Osteocalcin, a biochemical marker for osteoblast activity, and the carboxy-terminal propeptide of type I procollagen (PICP), a marker of collagen formation, were slightly but not significantly higher in gastrectomy-treated patients. The serum parathyroid hormone levels were similar in both groups. As none of the patients had any radiologic evidence of osteopenia, the changes in biochemical parameters of bone metabolism and bone mass in patients who had undergone partial gastrectomy could be a marker of latent bone loss.

Absorptiometry, Photon

Increased serum osteocalcin levels in patients with paraplegia.

Osteocalcin(OC) is a specific serum parameter of bone formation. Since bone metabolism disturbances, including osteoporosis, are seen in paraplegia, the serum levels of OC, midregional parathyroid hormone(mPTH), intact para-thyroid hormone (iPTH) and calcitonin (CT) serum levels were determined in 13 patients with paraplegia or tetraplegia and 15 control subjects by radioimmunoassay in a cross sectional study. In addition, the urinary hydroxyproline/creatine and the urinary calcium/creatinine ratio was determined. Serum OC levels were significantly increased in the patients with spinal cord injury (p less than 0.02), whereas serum levels of mPTH, iPTH and CT were not statistically different. The urinary hydroxyproline/creatinine ratio was significantly higher in the patients than in the controls (p less than 0.02), and the urinary calcium/creatinine ratio also tended to be higher in the patients. In a follow up study over 6 months after spinal cord injury, serum OC, serum iPTH, urinary hydroxyproline/creatinine ratio and the calcium/creatinine ratio were determined in 6 patients at monthly intervals. Hyperhydroxyprolinuria preceded the gradual increase of serum OC from normal to clearly elevated levels. Our data suggest that increased bone resorption in paraplegia is linked to an enhanced osteoblastic activity.

Adolescent

Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis.

With advancing age both sexes have an increased incidence of osteoporotic fractures, although fractures are more common in women than in men. Whereas in women several potential risk factors have been identified, less is known about osteoporosis in men. A total of 27 Austrian men (mean age: 65 +/- 2 years) with atraumatic spine fractures were studied. In all patients, medical history gave no evidence of disease or medications causing osteoporosis. Peripheral bone mass was determined by single-photonabsorptiometry on the distal non-dominant forearm; lumbal bone density was measured by quantitative computed tomography. Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, testosterone, estrogen, parathyroid hormone and 25-hydroxy-vitamin D as well as 2-h-urinary-OH proline and calcium excretion were measured. All data were compared with those of an age and sex matched control group consisting of 19 healthy males. A significant difference in mean peripheral and axial bone mass (SPA: P less than 0.004; QCT: P less than 0.0001) was observed between osteoporotic men and controls. When compared to controls, serum levels of alkaline phosphatase (P less than 0.012), urinary OH proline (P less than 0.05) and urinary calcium excretion (P less than 0.003) were significantly higher in the osteoporotic males. Additionally, there was a significant positive correlation between serum alkaline phosphatase and urinary OH proline excretion (r = 0.32; P less than 0.04) in the osteoporotics. All other biochemical parameters showed no significant differences. Our results may lead to the assumption that osteopenia in men is related to increased bone turnover.

Aged

The spine deformity index in osteoporosis is not related to bone mineral and ultrasound measurements.

In 34 female patients suffering from osteoporotic vertebral compression fractures, the spine deformity index (SDIM) was determined, according to the method of Minne et al (1988), to reflect the radiological severity of established osteoporosis. Peripheral (single-photon absorptiometry (SPA) of the non-dominant distal forearm) and axial (quantitative computed tomography (QCT) of the lumbar spine) bone mineral measurements, as well as the broadband ultrasound attenuation of the os calcis, were performed in the osteoporotic patients and in a control group of 20 age-matched women. No correlation could be found between bone mineral measurements and radiological severity of osteoporosis, expressed as SDIM. All three densitometry methods showed clearly reduced values in patients with vertebral crush fractures. Correlations established in the control group between peripheral and axial bone mass (SPA versus QCT) could no longer be found in the osteoporotic group, thus indicating changes in bone mineral density of the spine after the occurrence of osteoporotic fractures. Our data show that SDIM is an additional parameter of osteoporotic change in the spine, independent from bone mass measurements. In the management of osteoporotic patients, quantitative radiological methods (i.e. SDIM) in addition to densitometry might be of value for grading and monitoring the progress of disease.

Absorptiometry, Photon

Serum osteocalcin levels in primary hyperparathyroidism.

The serum levels of osteocalcin, a 49-amino-acid bone-matrix protein, have been found to be a specific biochemical parameter of bone formation. The aim of our study was to compare the sensitivity of serum osteocalcin levels with that of alkaline phosphatase in the evaluation of patients with primary hyperparathyroidism. In 40 patients with biochemically and histologically confirmed primary hyperparathyroidism, the serum levels of osteocalcin, intact parathyroid hormone, alkaline phosphatase, calcium, phosphorus, and creatinine were determined preoperatively. The serum levels of osteocalcin were elevated in 22 patients (55%), whereas the serum levels of alkaline phosphatase were increased in 18 patients (45%). In 10 patients (25%) the serum levels of osteocalcin, but not those of alkaline phosphatase, were increased, whereas in six patients the activity of alkaline phosphatase was high, but the serum osteocalcin levels were normal. When the biochemical data of the patients with increased serum osteocalcin levels were compared with those of the patients with serum osteocalcin levels within the normal range, the serum levels of intact parathyroid hormone and alkaline phosphatase were significantly increased in the group of patients with elevated serum osteocalcin levels. Our data indicate that serum osteocalcin levels might be a clinically useful additional parameter in the evaluation of patients with primary hyperparathyroidism.

Adult

Peripheral and axial bone mass in Austrian free climbers.

The present investigation was carried out in healthy white adult males to determine the effects of exercise, in the form of free climbing, on peripheral and axial bone mass. 13 men who have been regularly engaging in alpine free climbing for a mean period of nine years and, for training purposes, have been performing additional muscle building exercises (4.5 h +/- 1 SEM per week) and 12 age matched controls were included in the study. Bone mineral content of the non-dominant distal forearm was measured by single-photon absorptiometry, and bone mineral density of the lumbar spine was determined by quantitative computed tomography. It was found that consistent exercise in the form of alpine free climbing was associated with increased bone mass of the lumbar spine (162.4 +/- 4.4 vs 184.8 +/- 7.9 mg/ml, p less than 0.025). Peripheral bone mineral content of the distal forearm was slightly but not significantly increased in the free climbers (55.4 +/- 9.0 vs 61.1 +/- 7.4 Units, p less than 0.09 N.S.). The study provides additional evidence that exercise in the form of alpine climbing, is associated with increased lumbar bone mass.

Absorptiometry, Photon

Serum osteocalcin levels are decreased in patients with acute viral hepatitis.

In 16 patients with acute viral hepatitis and 32 sex- and age-matched control subjects the serum levels of osteocalcin, a biochemical parameter of bone formation, as well as the serum levels of parathyroid hormone, 25-hydroxyvitamin D, calcium and phosphorus were measured. The serum levels of osteocalcin (P less than 0.0001) and parathyroid hormone (P less than 0.0001) were significantly lower when measured at the time of maximal aminotransferase levels in the patients with hepatitis than in the control subjects. In contrast, the serum levels of calcium and 25-hydroxyvitamin D were similar in the patients and the controls. In nine patients with acute hepatitis measurements of the biochemical bone metabolism parameters were performed after normalization of the liver enzymes. In these patients a significant increase of serum osteocalcin levels towards normal values (P less than 0.0005) was found, parathyroid hormone levels tended to increase. Our data suggest an alteration of bone metabolism in patients with acute viral hepatitis. Bone formation as reflected by serum osteocalcin levels seems to be decreased in acute hepatitis and returns to normal after recovery from hepatitis.

Acute Disease

Enhanced growth hormone responses to growth hormone releasing hormone in male type I diabetic patients.

In a previous paper we have demonstrated that growth hormone (GH) responses to growth hormone releasing hormone (GHRH) are higher in premenopausal normal women than in age matched healthy men. As in type I diabetes mellitus various disturbances of GH secretion have been reported, the aim of our study was to assess the effect of sex on basal and GHRH stimulated GH secretion in type I diabetes mellitus. In 21 female and 23 male type I diabetic patients and 28 female and 30 male control subjects GH levels were measured before and after stimulation with GHRH (1 microgram/kg body weight i.v.) by radioimmunoassay. GH responses to GHRH were significantly higher in female than in male control subjects (p less than 0.02), whereas the GH levels following GHRH stimulation were similar in female and male type I diabetic patients. GH responses to GHRH were significantly higher in the male type I diabetic patients than in the male control subjects (p less than 0.001); in the female type I diabetic patients and the female control subjects, however, GH responses to GHRH were not statistically different. The absence of an effect of sex on GHRH stimulated GH responses in type I diabetes mellitus provides further evidence of an abnormal GH secretion in this disorder.

Adult

Decreased peripheral bone mineral content in patients under anticoagulant therapy with phenprocoumon.

In experimental and clinical studies, conflicting results regarding the effect of oral anticoagulant therapy on bone metabolism have been reported. To measure a possible influence of long-term anticoagulant therapy with phenprocoumon on peripheral bone mass, measurements of peripheral bone mineral content (BMC) and serum osteocalcin levels were performed with single photon absorptiometry in a total of 78 patients on anticoagulant treatment. We studied 43 women (mean age 66 years +/- 2 SEM) and 35 men (mean age 65 years +/- 2 SEM) with a median duration of phenprocoumon therapy of 1 year (1-9 years). In all patients, the medical history gave no symptoms of metabolic bone disease, or diseases or medications causing osteoporosis. Both in the male and female groups, mean peripheral BMC was significantly decreased (male: P less than 0.01, female: P less than 0.003) when compared with corresponding controls. Serum OC-levels measured in 16 patients were also significantly lower than those of the controls (P less than 0.02). Our data of decreased BMC and low serum OC-levels indicate reduced bone mass in patients on long-term anticoagulant therapy with phenprocoumon. This may imply an influence of anticoagulants on bone metabolism resulting in decreased bone formation.

Aged

Bone metabolism in patients with functioning kidney grafts: increased serum levels of osteocalcin and parathyroid hormone despite normalisation of kidney function.

In order to study bone metabolism after renal transplantation we measured serum levels of parathyroid hormone (PTH) and osteocalcin (OC), a specific biochemical parameter of bone formation, in 30 patients with functioning kidney grafts and 30 sex- and age matched control subjects. Serum levels of OC and PTH were markedly elevated in the kidney transplantation patients when compared with the control subjects (p less than 0.0001). Elevated levels of OC and PTH were present even in patients with very well functioning transplants. In the kidney transplantation patients, a significant positive correlation between serum OC and serum PTH levels could be found. Our data give evidence of persistent hyperparathyroidism and increased bone turnover in patients after renal transplantation.

Adult

Decreased serum osteocalcin levels in patients with postmenopausal osteoporosis.

Osteocalcin is a 49 amino acid non collagenous bone matrix protein which is synthesized by the osteoblasts. The serum levels of osteocalcin have been found to be a specific biochemical parameter of bone formation. We determined the serum levels of osteocalcin, parathyroid hormone, calcitonin and alkaline phosphatase as well as the 2 hour fasting hydroxyproline excretion in 26 patients with postmenopausal osteoporosis and in 24 postmenopausal control subjects. Serum levels of osteocalcin were significantly lower in the patients with postmenopausal osteoporosis than in the control subjects (p less than 0.002). In contrast, serum levels of parathyroid hormone, calcitonin, alkaline phosphatase and the 2 hour hydroxyproline excretion in the patients with postmenopausal osteoporosis and the control subjects were not statistically different. Our data give evidence of a decreased bone formation in patients with postmenopausal osteoporosis.

Aged

Bone mass and bone diminution of the axial and peripheral skeleton in normal and osteoporotic Austrian females.

Measurements of bone mass were performed in 133 healthy Austrian women using the quantitative computed tomography technique of the lumbar spine and single photon absorptiometry of the distal forearm. The data were compared with those of 110 Austrian females with osteoporotic spine fractures. A significant difference in mean bone density of the lumbar spine was observed between normal and osteoporotic patients in every decade, whereas forearm measurements showed statistical differences in the seventh and eighth decade but not in the sixth decade. Compared to age matched controls, bone mass of osteoporotic women showed the following diminution: sixth decade: distal forearm: -12.7%, spine: -46.8%; seventh decade: distal forearm: -19.0%, spine: -36.7%, eighth decade: distal forearm: -15.4%, spine: -33.7%. It appears that postmenopausal osteoporosis involves greater loss of bone in the spine in the first decade after menopause and slows down after this period, whereas loss of forearm bone mineral density (BMD) increases with advancing age.

Absorptiometry, Photon

Increased serum osteocalcin levels in patients with lactase deficiency.

Serum levels of osteocalcin, a noncollagenous bone matrix protein, have been found to be a specific biochemical parameter of bone formation. In the literature in subjects with osteoporosis, an increased incidence of lactase deficiency has been described. We therefore determined the serum levels of osteocalcin in 10 patients with lactase deficiency and in 20 control subjects by radioimmunoassay. The patients with lactase deficiency were dietary treated and had a very low daily calcium intake. Serum osteocalcin levels were significantly higher in the patients with lactase deficiency than in the control subjects. In contrast, serum levels of parathyroid hormone, alkaline phosphatase, calcium, and phosphorus were not statistically different in the two groups. Our data suggest an increased rate of bone turnover in patients with lactase deficiency on a low calcium diet; possibly calcium supplementation is indicated in dietary-treated patients with lactase deficiency.

Adult

[Osteocalcin].

The serum levels of osteocalcin, a 49 amino acid bone matrix protein have been found to represent a specific biochemical parameter of bone formation. The serum osteocalcin levels are influenced by age, sex and the time of blood sampling. In various studies on osteoporosis, endocrinopathies and other diseases which might be associated with bone disorders, the determination of serum osteocalcin levels has been proved to be an interesting research tool. However, further studies are necessary to clarify, whether the measurement of serum osteocalcin levels should be recommended in general clinical praxis.

Age Factors

Decreased serum osteocalcin levels in patients with liver cirrhosis.

Serum levels of osteocalcin (OC) have been found to be a specific biochemical parameter of bone formation. We measured serum levels of osteocalcin, parathyroid hormone (PTH) and 25-hydroxyvitamin D (25(OH)D) in 49 patients with liver cirrhosis, who are known to have an increased prevalence of metabolic bone disease, and a matched control group (n = 35). Serum levels of OC were significantly decreased in the patients with liver cirrhosis when compared to control subjects (P less than 0.001). Serum levels of 25(OH)D were decreased (P less than 0.001), whereas no statistical difference was found between the serum levels of PTH in the patients with liver cirrhosis and those of the controls. In a subgroup of 23 patients with cirrhosis of the liver and 34 control subjects, the bone mineral content (BMC) of the non-dominant forearm was determined by single photon absorptiometry. BMC was significantly lower in the patient with liver cirrhosis than the control subjects (P less than 0.04). Our data demonstrate vitamin D deficiency, decreased bone formation and a decreased BMC in patients with liver cirrhosis.

Bone Density

Increased serum osteocalcin levels in elderly females with vitamin D deficiency.

Serum levels of osteocalcin (OC), a 49 amino acid bone matrix protein, have been found to be a biochemical parameter of bone formation. In order to study bone metabolism in aging subjects we measured serum levels of OC, parathyroid hormone (PTH) and 25 hydroxy-vitamin D (25 OH Vit D) in 36 institutionalized elderly females (age range: 80-93 years) and in 21 premenopausal control subjects. Serum levels of 25 OH Vit D were significantly decreased in the elderly subjects (p less than 0.0001), whereas serum levels of OC and PTH were significantly higher in the elderly subjects than in the controls (p less than 0.0025 and p less than 0.0001, respectively). Serum OC levels correlated significantly with the serum PTH levels (p less than 0.009). Our data demonstrate that in elderly females with vitamin-D deficiency secondary hyperparathyroidism is associated with increased serum OC levels indicating an increased bone formation; these conditions might contribute to the bone disease of geriatric patients.

Aged