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Biomedical subjects

A Brock

Publications and source records attributed to A Brock.

At least 19 recordsLinked to original sources

[The initial results on the radiobiological comparability of continuous LDR irradiation and PDR irradiation using a guinea pig skin animal model].

AIMS: The classic continuous low dose rate (LDR) brachytherapy was very important in such cases with a higher risk of severe especially late radiation reactions. From clinical experiences and radiobiological considerations it is known, that the therapeutic ratio of LDR is higher than HDR. Another way to combine the therapeutic ratio of LDR and the possibility of optimisation is the use of pulse dose rate (PDR) technique. The PDR-technique is a method, which can be compared with continuous LDR-therapy. PDR should have biological effects equivalent to conventional LDR. MATERIAL AND METHODS: We have tried to compare the classic continuous LDR-technique with 2 PDR-regimes by means of the guinea pig skin model. In this test series we involved 20 female animals with an initial weight of 400 to 500 g. We compared radiation reactions of following regimes: 1. Continuous LDR regimen with a cobalt-60 source with an activity of 5.5 mCi 30 Gy in 60 hours. 2. PDR regimen 0.5 Gy hourly, pulse length minimal 10 minutes, 30 Gy in 60 hours with an Ir-192 source with an activity of nearly 40 mCi. 3. PDR-regimen 0.8 Gy hourly with 9 hours night break (10.00 p. m. to 7.00 a. m.). The radiation reaction was controlled by the help of an evaluation table in which the criteria of radiation reaction were classified according to the degree of seriousness. The observation time is now minimal 14 and maximal 24 months. RESULTS: The findings shows a significant coincidence of early and late radiation reactions of the skin fields irradiated with the continuous LDR-technique and fields irradiated with the PDR-technique. There was not a difference of the radiation reactions between PDR-irradiation with and without night break. CONCLUSIONS: Generally it is possible to compare the radiation reactions of PDR-irradiation and the classic continuous LDR-brachytherapy. It is also possible to use a PDR-regimen with a night break of 9 hours. But results must be calculated for each tissue of interest, in our test consequently for guinea pig skin.

Animals

Parathyroid hormone in blood pressure and volume homeostasis in healthy subjects, hyperparathyroidism, liver cirrhosis and glomerulonephritis. A possible interaction with angiotensin II and atrial natriuretic peptide.

In order to elucidate a participation of intact parathyroid hormone (PTH(1-84)) in blood pressure (BP) and body fluid homeostasis, we studied fluctuations of PTH(1-84) during manipulations of BP in hyperparathyroid and healthy subjects, and during manipulations of blood volume in patients with glomerulonephritis or liver cirrhosis and in controls. Angiotensin II induced BP elevation was associated with increased values of PTH(1-84) both in healthy subjects (12-25 ng l-1, medians, p < 0.01), in patients with primary hyperparathyroidism (94-125 ng l-1, p < 0.01), in patients with low calcium due to end stage renal disease before requirement of dialysis (95-151 ng l-1, p < 0.02), and in patients with tertiary hyperparathyroidism (221-264 ng l-1, p < 0.05), but not in dialysis patients without hypercalcaemia (126-174 ng l-1, NS). The changes could not be attributed to reduction of serum calcium, but probably to the increase of plasma angiotensin II, which was positively correlated to the increase of serum PTH(1-84) in the healthy subjects (p = 0.619, n = 15, p < 0.05) and in the patients with primary hyperparathyroidism (p = 0.549, n = 18, p < 0.05). Noradrenaline induced BP elevation did not have a similar effect on PTH(1-84), and changes of PTH(1-84) were not related to changes of BP. Volume depletion after furosemide injection, also accompanied by increased levels of angiotensin II, resulted in elevation of PTH(1-84) in controls, cirrhotics, patients with glomerulonephritis without the nephrotic syndrome, but not in nephrotic patients. Volume depletion induced by bolus injection of atrial natriuretic peptide (ANP) was associated with decreased PTH(1-84) in healthy subjects (20-18 ng l-1, p < 0.02), but not in patients with nephrotic syndrome and liver cirrhosis. Volume expansion induced by albumin infusion caused increased plasma levels of ANP, but PTH(1-84) was unaltered. Thus, angiotensin II may be able to stimulate, and ANP to inhibit release of PTH(1-84), and PTH(1-84) may be involved in the regulation of BP and body fluid homeostasis. BP changes or changes in blood volume per se do not seem to influence PTH(1-84) levels.

Adolescent

Ki-S1, a novel proliferative marker: flow cytometric assessment of staining in human breast carcinoma cells.

There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle phase; (ii) investigated the labelling pattern with Ki-S1 on a human breast cell line (ZR75) under varying proliferative conditions induced by serum deprivation and refeeding; (iii) examined in a flow cytometric study Ki-S1 staining in archival, clinical breast carcinoma samples. In exponentially growing cells Ki-S1 showed a marked cell cycle phase-specific variation in staining intensity which increased linearly through the S-phase, was high in G2 and reached its peak in mitosis. Ki-S1 staining intensity mirrored the changes in proliferative activity of ZR75 cells during serum deprivation and refeeding. In a small series of human breast carcinoma, Ki-S1 staining intensity correlated with S-phase fraction (SPF) derived from DNA profiles. The antigen labelled by Ki-S1 is extremely robust, resisting degradation by fixation and by an aggressive enzymic tissue disaggregation method. Ki-S1 warrants further investigation as a proliferation-related marker, particularly for routine clinical application.

Animals

Anti-cholinesterase agents uptake during cultivation of greenhouse flowers.

The cholinesterase (ChE) activities were measured in-season and out-season in a total of 204 greenhouse workers and 360 non-exposed controls. No seasonal ChE variation were observed in the controls, whereas an in-season depression was seen in the workers, indicating an uptake of anti-cholinesterase agents during cultivation of greenhouse flowers in the intervals between sprayings (p = 0.0001). The anti-ChE agents applied seem to persist in the greenhouses and cause continued subtoxic uptake for weeks since last application. Wearing of protective gloves did not prevent the uptake. Thus, chronic percutaneous and oral uptake occurs as a result of cultivation of greenhouse flowers.

Carbamates

Cadmium effects on bone metabolism: accelerated resorption in ovariectomized, aged beagles.

The purpose of this study was to evaluate, in an animal whose skeleton is comparable to humans, the combined effects of estrogen depletion and Cd exposure on bone resorption by monitoring skeletal release of 45Ca and to determine whether Cd-induced bone resorption occurred independent of osteotropic hormone changes and renal dysfunction. Cd exposure following ovariectomy or sham surgery was for 7 months: 1 month by oral ingestion of capsules (1, 5, 15, 50 ppm) and 6 months via drinking water (15 ppm). Serum and fecal 45Ca were increased at 1 week following ovariectomy (OV) (54 +/- 9% and 122 +/- 40%, respectively), but this response was attenuated by 2 weeks. Five of seven exposed dogs had increased serum and fecal 45Ca during the 50-ppm Cd capsule period (15-40% and 15-190%, respectively). Serum 45Ca levels in OV/+Cd dogs showed a significant and consistent increase within 1 week of initiating each of three separate Cd.H2O exposure cycles. Blood Cd levels increased over time from 2 to 15 micrograms/l, coinciding with the elevated serum 45Ca concentrations. No correlation was observed between serum 45Ca increases and parathyroid hormone, 1,25-(OH)2-vitamin D, or calcitonin. No effects of ovariectomy and/or Cd were observed in total serum Ca, calciotropic hormone concentrations, serum or urinary phosphorus and creatinine, creatinine clearance, or urinary specific gravity. Urinary Cd concentrations ranged from 7 to 50 micrograms/l in exposed dogs but were not detectable in nonexposed dogs. Urinary protein concentrations showed no differences between groups. Cd increased bone resorption (skeletal 45Ca release) in ovariectomized and sham-operated dogs without renal dysfunction or calciotropic hormone interaction. Based on our results, Cd is an exogenous factor which exacerbates bone mineral loss in postmenopausal osteoporosis.

Aging

Chronic subclinical intake of dietary anticholinesterase agents during the spraying season.

The dietary intake of anticholinesterase (anti-ChE) agents was estimated in 331 schoolteachers during the spraying season. Summer plasma-cholinesterase (ChE) activity was compared with the baseline value obtained during winter. Intraindividual plasma-ChE activity varied independently of factors such as drugs, non-malignant diseases, alcohol and smoking. A depressed mean plasma-ChE, indicating an intake of anti-ChE agents (P = 0.04), was observed in individuals who consumed exclusively agriculturally-grown fruits and vegetables without an additional intake of unsprayed, home-grown products. It remains to be determined whether a subclinical but chronic intake of anti-ChE agents in the diet can be hazardous to humans.

Cholinesterase Inhibitors

Flow cytometric characterisation of proliferating cell nuclear antigen using the monoclonal antibody PC10.

Anti-PCNA antibodies have aroused considerable interest recently as potential immunohistochemical markers of proliferation for use on clinical samples. PC10 is a monoclonal antibody which has been shown to recognise its epitope on formalin-fixed, paraffin-embedded, archival material. However, whilst PC10 gives the expected labelling pattern for growth fraction in normal tissues and some tumours, discrepant results have been obtained, for example, in carcinoma of the breast. By means of flow cytometry, we have attempted to characterise the different staining patterns that can be obtained with PC10. Intact fixed cells from proliferative mammalian cultures show 100% labelling, consistent with a growth fraction estimate. In contrast, detergent-extracted nuclei show S-phase specific staining. Nuclei extracted by treatment of fixed cells with pepsin show a different staining pattern again, with many G1 cells weakly stained and staining intensity increasing through S-phase into G2. The results demonstrate that multiparametric flow cytometry can define the cell populations which label with proliferation-related antibodies, such as PC10, under a variety of experimental conditions.

Animals

A new automated method for phenotyping arylesterase (EC 3.1.1.2) based upon inhibition of enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate.

A new method for phenotyping human serum arylesterase (EC 3.1.1.2) is described and evaluated. The aromatic esters, phenyl acetate and 4-nitrophenyl acetate, were compared as substrates for spectrophotometric measurement of arylesterase activity. A method for arylesterase phenotyping, based upon inhibition of the enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate, was developed. The method was applied to serum samples from 158 blood donors and showed a distinct separation of the three phenotypes defined by a reference method based on the ratio of paraoxonase activity to arylesterase activity using paraoxon and phenyl acetate as substrates. The method was adapted to a Cobas-Fara centrifugal analyser.

Alleles

Atrial natriuretic peptide and parathyroid hormone (1-84) in relation to noradrenaline induced changes in blood pressure in uraemic and healthy subjects.

In order to evaluate the hormonal regulation of blood pressure (BP) in uraemia 12 patients on chronic maintenance dialysis and 14 healthy controls were studied. BP and plasma concentrations of atrial natriuretic peptide (ANP), cyclic 3',5'-guanosine monophosphate (cGMP), and intact parathyroid hormone (PTH(1-84)) were determined before, during, and after a 60 min noradrenaline infusion 0.1 micrograms kg-1 body wt. min-1. Mean BP increased to the same extent in the uraemic patients (median 15 mmHg, range 6-25 mmHg) as in the controls (12 mmHg, 5-25 mmHg). ANP increased during noradrenaline infusion both in patients (7.2 to 8.3 pmol/l, medians, p < 0.01) and in controls (4.4 to 6.0 pmol/l, p < 0.01), and so did cGMP (patients: 31.6 to 35.9 nmol/l, p < 0.05; controls: 6.6 to 8.7 nmol/l, p < 0.01). PTH(1-84) was higher in the uraemic patients than in the controls, but was unchanged during noradrenaline infusion in both groups. Correlation analyses gave no evidence of a direct relation between BP and ANP, but basal PTH(1-84) was negatively correlated to basal mean BP in the patients (rho = -0.615, p < 0.05), but not in the controls. In conclusion, noradrenaline induced similar elevations of BP in dialysis patients as in healthy controls despite elevated ANP and PTH(1-84) in the patients, and ANP release was stimulated in both groups. PTH(1-84) may participate in blood pressure regulation in uraemic patients.

Adult

[Radiobiological research to optimize high-dose-rate afterloading therapy with Ir-192 in extragenital tumors].

Since the introduction of the high-dose rate afterloading therapy a higher biological effectivity of this method has been well known in comparison with the low-dose contact therapy. This will practically taken into account by reducing the dose and more fractionating of the total dose. With our test we want: firstly to prove the influence of the therapy break on the duration of the radiation reaction. Secondly we want to prove the influence of the dose rate on the efficiency of the radiation reaction. We have tried to answer the question by the animal model guinea pig skin. We examined early reactions as well late reactions.

Animals

Otto Fenichel and the left opposition in psychoanalysis.

David Rapaport's collection of Otto Fenichel's Rundbriefe (1934-1945) is described as a recently rediscovered, 2,500-page primary source for studying the intellectual and organizational history of European-American psychoanalysis. Beginning as the confidential newsletter of the Reich-Fenichel "Left opposition" within the International Psychoanalytic Association, its function became primarily intellectual as Fenichel's group ceased to function as a caucus. It ended when its editor decided to devote himself to the struggle against neo-Freudianism within psychoanalysis, and to practice as a licensed physician.

Freudian Theory

Inter and intraindividual variations in plasma cholinesterase activity and substance concentration in employees of an organophosphorus insecticide factory.

During a period of 10 months, inter and intraindividual variations in plasma cholinesterase (ChE) activity were studied in 331 employees of an organophosphorus insecticide factory, and in 193 healthy volunteers without occupational exposure to known ChE inhibitors. Repeated (n = 6) measurements of ChE activity and ChE substance concentration were performed in 410 subjects. The study showed substantial intraindividual variations of ChE activity and ChE substance concentration (up to 40%) in the employees and in the reference group. When effects due to sex, ChE-1 phenotype, body weight, and height were considered, one subgroup of employees of the organophosphorus insecticide factory showed a significantly lower average ChE activity than other subgroups; as ChE substance concentrations were found to be proportionally decreased, it was concluded that the low ChE activity was unrelated to occupational exposure. A combined determination of ChE activity and ChE substance concentration is recommended as a rational diagnostic tool when an unexpected decrease of plasma ChE activity is registered in people joining organophosphorus insecticide health surveillance programmes.

Adult

[Cholinesterase in healthy adults. Significance of sex, age, weight and height for activation of P-cholinesterase].

On the basis of an investigation og 193 healthy adults without occupational exposure to known cholinesterase-inhibitors, it was found that in addition to being related to the sex and ChE-fenotype, the cholinesterase activity is correlated to the weight and height of the individual concerned. Compared with the great interindividual variations, the intraindividual variations are of marginal significance for the total variation. Where dissimilar groups are concerned, comparison of the cholinesterase values corrected for variations which may be ascribed to the factors: sex, ChE-fenotype, weight and height is recommended.

Adult

Immunoreactive plasma cholinesterase (EC 3.1.1.8) substance concentration, compared with cholinesterase activity concentration and albumin: inter- and intra-individual variations in a healthy population group.

Substance concentrations of plasma cholinesterase (EC 3.1.1.8) were measured in 94 healthy individuals without occupational exposure to known inhibitors (six samples from each individual). Immunoreactive cholinesterase substance concentrations showed an inter-individual variation corresponding to CVtotal = 22% (mean: 5.01 mg/l, SD: 1.11 mg/l). Intra-individual variations of immunoreactive cholinesterase substance concentration were correlated (r = 0.36) to intra-individual variation of albumin. Estimated by a repeated-measures analysis of variance, the observed intra-individual variation of cholinesterase substance concentration corresponded to CV = 8.8% (SD: 0.44 mg/l), which together with a CVerror = 6% (within and between runs), implies a biological intra-individual variation of cholinesterase substance concentration corresponding to CVintra = 6.4%. Specific catalytic activity (kU/mg immunoreactive cholinesterase) was influenced by the ChE-1 phenotype (phenotype U: 1.58 kU/mg, phenotype UA: 1.22 kU/mg), but not by body weight, height, age, and sex. Observed intra-individual variation of specific catalytic activity corresponded to 6.4% (SD: 0.10 kU/mg), which together with an estimated CVerror = 6.2% implies the biological intra-individual variations of specific catalytic cholinesterase activity to be insignificant. The insignificant CVintra makes specific catalytic cholinesterase activity a rational quantity for evaluation of unexpected fluctuations of cholinesterase activity concentrations.

Adult

Enzyme immunoassay of human cholinesterase (EC 3.1.1.8). Comparison of immunoreactive substance concentration with catalytic activity concentration in randomly selected serum samples from healthy individuals.

We developed an enzyme immunoassay (ELISA) for quantitation of plasma cholinesterase substance concentrations in native plasma or serum samples. The ELISA assay is based on polyclonal (rabbit) antihuman cholinesterase and a highly specific monoclonal (mouse) antibody, with a commercially available peroxidase-conjugated (rabbit) antibody directed against mouse immunoglobulins as the signal carrier. The detected serum cholinesterase substance concentrations (mean: 4.51 mg/l, SD: 0.90 mg/l) in randomly selected serum samples from 33 healthy individuals were closely and linearly related to the corresponding catalytic activity concentrations.

Calibration