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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 469 records · Page 26Linked to original sources

Different effects of hypercalcemic state induced by Walker tumor (HWCS 256) and 1,25 (OH)D3 intoxication on rat thyroid C cells. An ultrastructural, immunocytochemical, and biochemical study.

Two different models of chronic C cell stimulation by the hypercalcemic state were compared with respect to their morphology, immunocytochemistry, and biochemistry. In the chronic hypercalcemic state due to the HWCS 256 strain of the Walker tumor C cells show signs of degeneration such as vacuolation, on day 7 after tumor implantation. On day 10 tumor induced hypercalcemia leads to irreversible cell damage with karyopyknosis and karyorrhexis. These morphological changes are accompanied by a decline in radioimmunologically measurable calcitonin content of the thyroid and by the loss of response to acute stimulation of C cells. In contrast, in the hypercalcemic state due to 1,25(OH)2D3 intoxication we find an almost complete degranulation of C cells but no signs of degeneration or cell damage, although the thyroid calcitonin content and the calcitonin secretion capacity is greatly reduced. Tumor induced cachexia as a reason for C cell damage in tumor bearing rats could be excluded. Other possible reasons, such as acute overstimulation and tumor factors acting directly on C cells are discussed.

Animals↗

Neuritic uptake and transport of antiviral drugs modifying herpes simplex virus infection of rat sensory neurons.

The neuritic uptake and transport of three antiviral drugs were studied in a cell culture system with dissociated cells of rat dorsal root ganglia. Cultured sensory neurons extended neuritic projections which penetrated a vacuum grease sealed diffusion barrier in the culture. The peripheral infection with herpes simplex virus (HSV) type 1 (McIntyre) resulted in uptake and transport of HSV by neuritic extensions causing a neuronal infection inside the diffusion barrier. By varying the route of administration and concentration of drug and by manipulating the nerve cell culture system, neuritic uptake and transport also of the antiviral drugs (acyclovir, adenine-arabinoside and foscarnet) were demonstrable. The findings are discussed in relation to axonal transport and antiviral treatment of HSV infections of the nervous system.

Acyclovir↗

Gynecomastia caused by estrogen containing hair lotion.

Two men at the age of 48 and 54 yr developed gynecomastia and lost their potency after the use of estrogen containing hair lotions. During exposure to the lotion the levels of 17-beta estradiol were increased, whereas the levels of testosterone and gonadotropins were depressed. Thus, a previous application of such hair lotions should be considered in the differential diagnosis of gynecomastia.

Diagnosis, Differential↗

Developmental changes in the response of the fat body of Manduca sexta to injections of Corpora cardiaca extracts.

The Corpora cardiaca of larval and adult Manduca sexta contain glycogen phosphorylase-activating and adipokinetic activity. Depending on the age of the injected animal, injection of Corpora cardiaca extracts induces different responses. In larvae of the 1st and 2nd day of the Vth instar, phosphorylase is activated strongly by injections of Corpora cardiaca extracts, whereas in older animals it is only slightly activated. Mobilization of lipids in response to Corpora cardiaca extract injections is found only in animals injected after the imaginal molt; in younger animals this response is absent. It is argued that this difference in responsiveness may be due to a change in the properties of the target organ fat body.

Adipose Tissue↗

Uptake and transport of herpes simplex virus in neurites of rat dorsal root ganglia cells in culture.

Attachment and neuritic transport of herpes simplex virus (HSV) type 1 (McIntyre) were studied in a cell culture system with dissociated cells of rat dorsal root ganglia. The two-chamber cell culture system containing a diffusion barrier penetrated by neurites of cultured sensory neurons permitted infection of neurites extending outside the diffusion barrier without exposure of the neuronal cell soma. HSV adsorbed to neuritic extensions and reached the neuronal soma within 1.5 h post-inoculation. Neuritic uptake and transport of HSV were inhibited in the presence of cytochalasin B. Internalization of virus in neurites was preceded by attachment of virus to the neurite plasma membrane. Neurites transported viral nucleocapsids (NC) through the diffusion barrier of the cultures. Destruction of the neuritic extensions before or shortly after peripheral virus inoculation blocked spread of infection to the cell soma. No infection was established when neuritic extensions were exposed to viral NC and NC were then not observed inside the neurite plasma membrane. Virus produced in neurons, when HSV was inoculated into the inner culture chamber containing the neuronal cell bodies, was transported as enveloped virus in cytoplasmic vesicles from the neuronal cell body towards the periphery. Schwann cells were infected by viropexis. Shortly after infection virions were observed in vacuoles of the cytoplasm.

Animals↗

Inflammation-mediated osteopenia in the rat: a new animal model for pathological loss of bone mass.

We have developed a rat model of inflammation-mediated osteopenia. Generalized loss of trabecular bone occurs in the rat after sc injection of nonspecific irritants such as talcum (magnesium silicate) and cotton wool (Cellulose). Although it appears likely that a systemic mediator of bone resorption is responsible for these effects, the loss of bone was not due to increased PTH secretion, since it occurred in parathyroidectomized rats, nor due to excessive 1,25-dihydroxyvitamin-D3 production. In parathyroidectomized rats, this inflammation was associated with significant increase in serum calcium within 4-7 days independent of its cause. Identification and characterization of this mechanism may provide insight into the bone loss associated with chronic inflammatory diseases such as rheumatoid arthritis and periodontal disease.

Animals↗

Reversible diminished calcitonin secretion in the rat during chronic hypercalcemia.

A transient increase in serum calcitonin (CT) concentration is induced by an acute iv calcium (Ca) load, whereas in the chronic hypercalcemic state, serum CT levels, as well as CT content of the thyroid, are equivocal. The secretion of CT was tested in three models of hypercalcemia in rats: tumor induced by the hypercalcemic Walker carcinosarcoma 256 (HWCS 256), chronic parenteral Ca administration, and chronic 1,25(OH)2D3 administration. In rats with HWCS 256, serum CT levels increased from basal values of 0.21 +/- 0.11 ng/ml to a maximum of 0.42 +/- 0.20 ng/ml on day 4 after tumor transplantation, 1 day before serum Ca increased. The serum CT levels declined again the following day (day 5). In thyroidectomized, parathyroid autotransplated rats with HWCS 256, serum Ca increased 1 day earlier than in intact rats. Substitution of CT by exogenous CT injections delayed the hypercalcemia for one day. Ca loading was followed by a decreased serum CT level (delta CT); the CT content of the thyroid fell from 9.4 +/- 1.1 ng/mg wet wt to 1.0 +/- 0.3 ng/mg wet wt. While hypercalcemia was present. Also chronic intraperitoneal Ca administration induced a decrease in the CT response to a Ca load (delta CT) and a decrease in thyroid CT content from 9.32 +/- 0.58 ng/mg wet wt to 3.84 +/- 0.33 ng/mg wet wt. These changes were no longer present 4 days after stopping Ca administration. In chronic hypercalcemia induced by 1,25(OH)2D3 administration, basal serum CT levels did not vary significantly, whereas serum Ca increased to 11.8 +/- 0.46 mg/dl on day 4. CT after an acute Ca load was diminished, as was CT content of the thyroid during 1,25(OH)2D3 administration. These changes were reversible after stopping 1,25(OH)2D3 administration. During chronic hypercalcemia a reversible exhaustion of CT content of the thyroid and a diminished CT response to acute Ca stimulation was observed, while basal serum CT levels remained unchanged.

Animals↗

Isolation and amino-acid composition of the adipokinetic hormone of Manduca sexta.

An adipokinetic hormone was purified from corpora cardiaca of au adult Manduca sexta (tobacco hornworm)by reversed-phased high performance liquid chromatography. The following amino-acid composition was determined: 2 Thr, 2 Ser, Glx, Gly, Leu, Phe, Trp. The adipokinetic activity was tested in adult Manduca. In a bioassay in which activation of fat body glycogen phosphorylase was measured in ligated larvae, the hormone elicited a maximal response at the same concentration as it did in the bioassay for hyperlipaemic activity.

Amino Acids↗

[Paget disease of the skeleton. Internal medicine aspects].

Paget's disease of bone seems to be a slow virus infection of a single or several areas of the skeleton. Pagetic lesions are rather common among elderly people, but the disease does not manifest itself very often. Compared to the incidence of Paget's disease in England it seems to be rarer in this country. The pelvis is most frequently involved, followed by bones of the leg, skull, lumbar spine. The patients suffer from pain and deformities, arthroses of the adhering ankles, increased temperature of the area, nerve irritation and nerve damage due to increased bone growth (e.g. hearing loss due to Paget's disease of the skull). The development of sarcoma is rare and is only seen in severe cases. Diagnosis is made by X-ray, confirmed by bone biopsy, if necessary. Asymptomatic lesions are detected by bone scintigraphy. The activity of the disease is expressed by increased alkaline serum phosphatase and urinary hydroxyproline excretion. For treatment calcitonins and diphosphonates (especially EHDP, Diphos) are used. Both inhibit the overactive osteoclasts, and the increased bone turnover is normalized. The patients feel considerable relief; the elevated biochemical parameters fall to about 50% of initial values after calcitonin or EHDP monotherapy. In severe cases the combination of both substances may be profitable. The cytostatic drug mithramycin which can also be effective is only needed in exceptional cases.

Alkaline Phosphatase↗

[Paget's osteitis deformans. Significance and control].

Follow-up observation of patients with Paget's disease by conventional radiology is useful to evaluate the spontaneous course of the disease in untreated cases and to determine the regeneration of the affected bone after therapy. This also includes complications of the otitis deformans Paget--mainly complete or incomplete fractures, severe deformations as well as rare malignant changes.

Arthritis↗

Variations of plasma calcitonin levels measured by radioimmunoassay systems for human calcitonin.

Radioimmunoassay systems of different characteristics are available for routine determination of human calcitonin (hCT). The purity and calcitonin content of the used standards has to be observed, different antisera may yield discrepant absolute values from the same plasma samples. HCT measurements permit blood level control during treatment with this hormone. In most thyroidectomized patients hCT is not measurable--it is supposed that there is no relevant extrathyroidal calcitonin production in man. HCT RIA systems also recognize rat calcitonin. In this species, chronic hypercalcemia first leads to increased calcitonin secretion which is soon followed by a decrease. Presumably, this fall reflects down-regulation of calcitonin secretion which is more a calcium conserving than an anti-hypercalcemic hormone.

Animals↗

[Etidronic acid therapy in Paget's disease of bone].

Treatment of Paget's disease of bone was done in 32 patients using monotherapy with disodium etidronate (Diphos). A further 19 patients underwent combined treatment with etidronate and human calcitonin. Both monotherapy and combined treatment led to marked regression of disease activity in most patients as measured be decreased activity of alkaline phosphatase. In most cases this coincided with improvement of complaints. In two cases with initial monotherapy and in six with combined treatment success of treatment remained unsatisfactory. The latter group comprised patients with very serious illness. Our experience suggests that etidronic acid is an effective and well tolerated drug relatively free of side-effects for the treatment of Paget's disease of bone.

Alkaline Phosphatase↗

[Tumor markers in C-cell cancer].

C-cell carcinoma (medullary thyroid carcinoma) is associated with increased serum calcitonin levels. In addition, increased serum levels of other tumour markers are also found: carcinoembryonic antigen (CEA), adrenocorticotrophic hormone (ACTH) and tissue polypeptide antigen (TPA). The relevance of these tumour markers as compared to calcitonin was evaluated in 46 patients with C-cell carcinoma. With decreasing frequency pathologically increased levels were found: calcitonin 93%, CEA 73%, TPA 17% and ACTH 8%. There was a positive correlation between calcitonin and CEA values. Calcitonin and CEA levels correlated with the clinical tumour stage. In selective venous catheterisation estimation of calcitonin is superior to estimation of CEA. Assessment of CEA supplements calcitonin measurements in follow-up controls and evaluation of success of treatment. As regards specificity and sensitivity calcitonin is superior to all other tested tumour markers in C-cell carcinoma.

Adrenocorticotropic Hormone↗