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Biomedical subjects

H Schatz

Publications and source records attributed to H Schatz.

At least 145 records · Page 8Linked to original sources
PubMed1995

Expression of functional stimulatory guanine nucleotide binding protein in nonfunctioning thyroid adenomas is not correlated to adenylate cyclase activity and growth of these tumors.

In thyroid cells, the alpha-subunit of the stimulatory guanine nucleotide binding protein (Gs alpha) acts as signal transducer between the TSH receptor and the adenylate cyclase (AC), and it regulates both growth and function. In order to analyze Gs alpha expression by both Western blot analysis and in situ, we generated an antibody raised against a recombinant human Gs alpha protein. With this antibody, a strong cytoplasmic Gs alpha-immunostaining was detectable in cultured human thyroid cells and in TSH-stimulated rat thyroids, in contrast to normal human thyroids and to T4-treated rat thyroids, which showed only weak immunoreactivity. We obtained the following results by immunohistochemistry and Western blot analysis of 32 actively growing human thyroid adenomas: 1) strong Gs alpha expression in 11 adenomas, including 4 hyperfunctioning nodules, 1 of these with a point mutation in codon 201 of the Gs alpha gene; 2) no expression or only weak Gs alpha expression in 13 adenomas; and 3) a pattern of Gs alpha-positive and Gs alpha-negative cells in the remaining 8 adenomas. In addition, we analyzed ADP-ribosylation of Gs alpha and AC activity in 9 nonfunctioning adenomas and found a significant correlation between Gs alpha immunoreactivity and ADP-ribosylation and no correlation of both with basal and TSH-stimulated AC activity. In both types of adenomas, i.e. those with high as well as low Gs alpha, an indistinguishably high fraction of proliferating cells was detectable. We conclude that expression of functional Gs alpha protein in nonfunctioning thyroid adenomas is neither correlated to the basal or TSH-stimulated AC activity nor to the proliferation rate of these tumors.

Adenoma↗
PubMed1994

[Regression of hard exudates in diabetic background retinopathy in therapy with etofibrate antilipemic agent].

BACKGROUND: The aim of this pilot study was to investigate the influence of a lipid lowering therapy with etofibrate on the progression of diabetic background retinopathy in patients with diabetes mellitus and combined hyperlipoproteinemia. In addition to the well known correlation between the duration of diabetes and the quality of blood glucose control, a correlation between diabetic microangiopathy and elevated triglyceride levels is discussed for many years. The most important pathogenic mechanisms in this respect seem to be an elevation of blood viscosity and alterations in the fibrinolytic system. Fibrinogen and triglycerides are the main determinants of plasma viscosity. As lipid lowering drugs containing fibrates and nicotinic acid are able to lower triglycerides and fibrinogen effectively, a favourable therapeutic effect on the progression of diabetic retinopathy may be expected. PATIENTS AND METHOD: 11 type II diabetics with combined hyperlipoproteinemia (Fredrickson type IIb) and mild to moderate background retinopathy detected by fundus photography were treated with etofibrate (2 x 500 mg/day) for a period of 6 months. RESULTS: In 7 of 10 patients hard exudates, which had been present at the beginning of treatment, showed clear regression at the end of the treatment period. Among the laboratory test parameters a significant 30% reduction of triglycerides (p < 0.010) was observed. There was also a clear 25% increase in HDL cholesterol and a 12% fibrinogen reduction. Considerable changes of the quality of blood glucose control were not evident during the treatment period. CONCLUSION: Treatment with the lipid lowering drug etofibrate seems to produce favourable therapeutic effects on hard exudates in diabetic background retinopathy in patients with diabetes mellitus and combined hyperlipoproteinemia. The mechanisms of this effect are not yet clearly understood, in addition to positive effects on the microcirculation of the retina by lowering blood viscosity there is a direct lipolytic effect in the area of hard exudates to be discussed, too. It is important to point out that we did not see any positive effect of etofibrate therapy concerning other morphological changes of diabetic background retinopathy, i.e. microaneurysms or hemorrhages in our pilot study.

Adult↗
PubMed1994

Two cases of intraocular infection with Alaria mesocercaria (Trematoda)

We encountered two cases of human intraocular infection with mesocercariae of Alaria (Trematoda), involving unrelated Asian men who had unilateral decreased vision. Both patients had pigmentary tracks in the retina, areas of active or healed retinitis, or both, and other signs of diffuse unilateral subacute neuroretinitis. Similar, nonnematode worms were seen in the patients' retinas and vitreous, respectively, several years after apparent infection. The worm in Case 1 was analyzed from projected fundus photographs and diagnosed as an Alaria mesocercaria on the basis of its shape, size (500 x 150 microns), and movement; it was successfully killed with laser. The worm in Case 2 was removed surgically from the vitreous and identified as A. mesocercaria, 555 x 190 microns, most likely A. americana. The probable source of infection in the patients was ingestion, in local restaurants, of undercooked frogs' legs containing A. mesocercaria. In addition to causing prolonged intraocular infection, A. mesocercaria was found to be a cause of diffuse unilateral subacute neuroretinitis, a condition previously attributed only to intraocular nematode larvae.

Adult↗
PubMed1994

Severe diabetic retinopathy after cataract surgery.

We retrospectively compared the visual acuity and degree of background diabetic retinopathy in 32 consecutive patients with diabetes who had cataract surgery in one eye (study group) and compared them with the visual acuity and degree of diabetic retinopathy in 32 patients with diabetes who had not had cataract surgery (control group) to determine if the retinopathy was asymmetric and worse in the operated-on eye. Twenty-three (72%) of the 32 study patients had asymmetric retinopathy (with the more severe retinopathy in the eye that underwent cataract surgery in each case) compared with three (9%) of the control group (P < .0005). The eyes that had cataract surgery did poorly in terms of visual acuity with no eyes achieving 20/20 or 20/25, only three eyes achieving 20/30 or 20/40, and 16 achieving 20/100 or worse.

Aged↗
PubMed1994

Characterization of gamma- and delta-subunits of Ca2+/calmodulin-dependent protein kinase II in rat gastric mucosal cell populations.

We searched for the occurrence of a Ca2+/calmodulin-dependent protein kinase in rat gastric cell types as a likely member in the chain of gastrin- and muscarinic-receptor-mediated signal transmission. A Ca(2+)- and calmodulin-dependent phosphorylation of major 50, 60 and 100 kDa substrates was observed in parietal cell cytosol and a major 60 and 61 kDa protein doublet was found to bind 125I-calmodulin in 125I-calmodulin-gel overlays. A specific substrate of the multifunctional Ca2+/calmodulin-dependent protein kinase II, autocamtide II, was phosphorylated in a calmodulin-dependent manner. The specific inhibitor of this enzyme, KN-62, antagonized protein kinase activity. RNA extracted from gastric mucosal cells was shown to contain sequences of the gamma- and delta- but not alpha- and beta-subunits of the calmodulin-dependent kinase II, and mRNA of both subtypes was demonstrated in highly purified parietal, chief and mucous cells. A calmodulin-dependent kinase II composed of gamma- and delta-subunits is a likely mediator of Ca(2+)-dependent signal transmission in these populations of gastric cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Long-term compliance of intensified insulin therapy.

Results of the DCCT trial (N. Engl. J. Med. 329, 977-986) demonstrate that therapy in insulin-dependent diabetes mellitus (IDDM) should aim at near-normoglycemia. For reaching this standard, intensified insulin therapy--either intensified conventional therapy (ICT) or continuous subcutaneous insulin infusion (CSII)--is mandatory. These regimes demand much long-term motivation and discipline from the diabetics. With > 95%, long-term compliance of ICT is good, according to the few published data available and our own experience. For CSII, on the other hand, cumulated studies reveal discontinuation rates ranging from 0% to 36%, averaging 20.4% and being significantly correlated with metabolic control before start of CSII in terms of glycosylated hemoglobin levels (r = 0.66; P < 0.05). The major reasons for discontinuation of CSII were skin problems (22.1%), inconvenience of the pump (21.4%) and lack of metabolic improvement (9.6%). A conclusion drawn from these meta-analytical data is that a stepwise approach to CSII is recommended for increasing compliance. A period of ICT long enough to gain experience with blood glucose self-control and self-adjustment of meal-related insulin should precede CSII. Furthermore, a general increase of CSII among IDDM patients is necessary to come closer to the standard of near-normoglycemia for these diabetics. Therefore, diabetes treatment and education resources must be improved, especially concerning psychosocial problem solving and cooperation between diabetologists and general practitioners.

Biomarkers↗
PubMed1994

Surgical results in the vitreomacular traction syndrome.

PURPOSE: The vitreomacular traction syndrome is a distinct clinical entity in which partial posterior vitreous detachment is present in combination with persistent macular adherence, causing traction-induced visual deficit. The authors evaluate the results of vitreous surgery for this syndrome. METHODS: The authors reviewed 20 consecutive eyes that underwent vitrectomy and posterior hyaloid/epiretinal membrane stripping to better define the clinical features, visual results, and complications of surgery for the vitreomacular traction syndrome. FINDINGS: Eyes were categorized anatomically as having either "classic" vitreomacular traction syndrome (8 [40%] eyes had 360 degrees midperipheral vitreous detachment) or "variable" vitreomacular traction syndrome (12 [60%] eyes had a variety of midperipheral areas of vitreous separation). Release of vitreomacular traction resulted in improvement in vision of two or more lines in 15 (75%) eyes, with 8 (40%) obtaining 20/50 visual acuity or better. All eyes were followed for at least 6 months. Complications of vitreous surgery included progression of nuclear sclerosis (83% of phakic eyes), epiretinal membrane formation (40%), and retinal breaks (20%). CONCLUSION: The vitreomacular traction syndrome represents a wide spectrum of vitreoretinal anatomic configurations that can produce visual deficit. Vitrectomy surgery to release macular traction may improve visual acuity.

Aged↗
PubMed1994

Okadaic acid indicates a major function for protein phosphatases in stimulus-response coupling of RINm5F rat insulinoma cells.

Stimulus-induced insulin secretion involves the activation of several protein kinases within the beta cell. Most prominent are protein kinase A, protein kinase C and calcium/calmodulin-dependent protein kinases. Protein kinase action is functionally antagonized by protein phosphatases. The four ubiquious serine/threonine protein phosphatases are termed PP-1, PP-2A, -2B and -2C. PP-1 and PP-2A are in vivo parts of major protein complexes. These complexes presumably regulate the phosphatase activity and direct the enzyme to its site of action. Therefore, PP-1 and -2A could play an important role in controlling intracellular signal transmission. Two different toxins, okadaic acid and calyculin A, both from marine invertebrates, were recently discovered and identified as potent and highly specific inhibitors of PP-1 and PP-2A. Both compounds emerged as very useful tools for studying intracellular phosphorylation events. We took advantage of these substances to investigate the significance of protein phosphatase action in stimulus-induced insulin secretion. To avoid major complexity, we confined our study to the cAMP and the phosphoinositide signal pathway. Okadaic acid alone evoked virtually no secretory response. cAMP-dependent secretion was markedly enhanced by 1 microM okadaic acid. The stimulatory effect of okadaic acid was strongly dependent on the concentration of cAMP analoga. In contrast, insulin release caused by the cholinergic agonist carbachol was not influenced by okadaic acid. Calyculin A (10 nM) slightly increased cAMP-induced secretion, but its high toxicity prohibited accurate interpretation of the data. Our findings support the idea that serine/threonine phosphatases act as important regulators in stimulus response coupling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

New isoforms of multifunctional calcium/calmodulin-dependent protein kinase II.

Calcium/calmodulin dependent protein kinase II (CaM kinase II) seems to act as an important regulator of intracellular signal transmission. Four subtypes, termed alpha to delta, have been cloned; some of them can exist as different splicing variants. All these isoforms share a great overall homology, and they contain 3 areas of low homology. We have identified 5 new variants of subtype delta so that the total number of different isoforms now adds up to 12. These variants are probably a result of different splicing and show several deletions in regard to subtype delta. The deletion sites do exactly match regions of low homology between the subtypes. This suggests a functional division of the CaM kinase II molecule into homologous and variable domains. The homologous domains are highly conserved. Therefore, it might be the case that the constitution of the variable domains is more significant for a certain isoform than its belonging to one of the 4 subtypes alpha to delta.

Alternative Splicing↗
PubMed1993

Expression of the human TSH receptor in a human thyroid carcinoma cell line that lacks an endogenous TSH receptor: growth inhibition by cAMP.

The role of TSH and its receptor in controlling growth of thyroid carcinomas is far from well understood. In order to study this subject further we established a new human thyroid carcinoma cell line. We transfected human thyroid carcinoma cells lacking an endogenous TSH receptor with the human TSH receptor cDNA. Transfected cells, designated HTC-TSHr, expressed the TSH receptor mRNA and synthesized a functional TSH receptor with a TSH binding affinity in the order of magnitude of normal thyroid cells. In response to TSH stimulation HTC-TSHr cells accumulated cAMP, indicating a functional TSH receptor-adenylate cyclase system. However, HTC-TSHr cells did not concentrate iodide and lacked thyroglobulin immunoreactivity, although they did express low amounts of thyroglobulin mRNA. Proliferation of HTC-TSHr cells was inhibited by dibutyryl-cAMP and forskolin and also by TSH via the re-expressed TSH receptor.

Base Sequence↗
PubMed1993

A local education campaign on early diagnosis of malignant melanoma.

The growing incidence of all kinds of skin cancer is a worldwide phenomenon observed in the last decades. Malignant melanoma is of special concern because of its high death rate when in an advanced stage, poor therapeutic response and fast growing incidence. Malignant melanoma is primarily located on the skin and therefore well suited for early cancer detection. The "Deutsche Dermatologische Gesellschaft" carried out a highly successful information campaign in Germany. Under this roof we organised different campaigns. Following considerable success in a campaign in 1989, a total of 1467 patients were examined and advised in the course of a local initiative (Education Campaign "Black cancer") in the city of Bochum (approximately 400,000 inhabitants) in the summer of 1991. In addition to full body examinations, important data were collected concerning the degree of knowledge about skin cancer, epidemiology, and the risk of skin cancer in general. As a result of the clinical examinations, 73 patients with strongly suspected skin cancer have been treated. Within this group, 14 malignant melanomas (1.0%) as well as 34 basal cell carcinomas (1.9%) were diagnosed. These numbers highly exceed the assumed risk incidence of skin cancer in Germany. Even on the assumption that the population was selective it is to be feared that a high number of individuals with skin cancer remain undetected and untreated. The majority of persons seeking advice had been motivated by the local media. The response and results of this local campaign indicate that further preventive measures for the general population in Europe are conceivable, meaningful and urgently needed.

Adolescent↗
PubMed1993

Function tests on the neuroendocrine hypothalamo-pituitary system following acute midbrain syndrome, with special reference to computertomographical and magnetic resonance imaging results.

Seventeen patients underwent a neuroendocrinological function test at a mean 6.3 years following a severe craniocerebral trauma (CCT) accompanied by midbrain syndrome. An insulin hypoglycaemia test (IHT) and the combined pituitary anterior lobe test (CPALT) were applied. Whereas the IHT as maximum stimulator of the hypothalamo-pituitary system (HPS) showed an adequate reserve capacity, the CPALT yielded a partial limitation of the secretion dynamic in the somatotropic, adrenocorticotropic axis as well as a dysfunction in the FSH secretion. Neuroradiological tests could not establish substantial injury in the regio hypothalamica in any patient.

Adolescent↗
PubMed1993

Central retinal vein occlusion associated with retinal arteriovenous malformation.

PURPOSE/BACKGROUND: Retinal arteriovenous malformations can be seen in a variety of ways and have multiple, associated, ocular changes that can affect vision. The authors report two cases of retinal arteriovenous malformation. In each case, a central retinal vein occlusion developed. METHODS: Each patient underwent clinical examination and fluorescein angiography. One patient was followed over a long period of time. CONCLUSION: The authors propose that a turbulent flow, high intravascular volume, and arteriolar pressure in the venous side of the retinal arteriovenous malformation may lead to vessel wall damage, thrombosis, and occlusion. They also suggest that compression of the central retinal vein by the mass effect of the arteriovenous malformation on the optic nerve further leads to turbulence and thrombosis.

Arteriovenous Malformations↗