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T Merz

Publications and source records attributed to T Merz.

At least 19 recordsLinked to original sources
PubMed1999

Clinical correlates in acromegalic patients with pituitary tumors expressing GSP oncogenes.

We herein review published findings on the clinical characteristics of acromegalic patients harboring pituitary somatotrophinomas expressing adenylyl cyclase activating gsp mutations and present an update of our own data on a large series of 176 patients with and without these oncogenes. Gsp oncogenes are the result of point mutations in either codon 201 or 227 of the Gs-alpha subunit of the Gs-protein which controls adenylyl cyclase. They result ultimately in increased intracellular cAMP levels and thus in excessive growth hormone (GH) secretion. Our large series has allowed us to characterise patients with mutations in codon 201 and the far rarer group possessing codon 227 defects. Both groups were compared with patients without gsp oncogenes. In accordance with previous findings, there was no statistically significant difference in age of the patients belonging to each group, the overall average tumor diameter nor in pre-operative serum GH levels, although the latter showed a tendency to be lower in patients with gsp oncogenes. The distribution of different types of response during an oral glucose tolerance test (no change, paradoxical rise or greater than 50% decrease in serum GH levels) did not differ between the 3 groups. However, the incidence of microadenomas was higher in acromegalics expressing gsp oncogenes in patients possessing mutations in codon 227. Additionally, the incidence of invasiveness was much lower (10% v. 33%) in those tumors with mutations in codon 227. Finally, previous in-vitro data indicating that gsp oncogene-expressing tumors may respond more efficiently to the somatostatin analogue, octreotide, have been confirmed by subsequent in-vivo studies showing a better reduction in serum GH levels in patients with gsp oncogenes. These latter findings suggest that presence of gsp oncogenes may be a marker for good reponsiveness to octreotide. Assessment of gsp oncogene status of surgically removed pituitary somatotrophinomas may thus be helpful in designing optimal medical therapies in those acromegalics requiring further post-operative management of the disease.

Acromegaly↗
PubMed1987

Chromosomal aberrations in irradiated Down's syndrome fibroblasts.

We have compared the frequencies of chromosomal aberrations in skin fibroblasts from persons with Down's syndrome (trisomy 21) with those from normal diploid controls exposed to 60Co gamma-radiation in vitro. No difference between the chromosomal radiosensitivities of the two groups was observed, nor did the two groups differ in the background frequency of spontaneous aberrations. These data support the hypothesis that the increased in vitro chromosomal radiosensitivity of lymphocytes reported to be associated with trisomy 21 is not typical of all tissues.

Adult↗
PubMed1986

Technetium-99m-labeled lymphocytes: a radiotoxicity study.

Radiolabeled white blood cells offer a unique clinical diagnostic technique. However, radiotoxicity to these radiosensitive cells must be carefully considered. Indium-111 has been shown to produce significant chromosomal alteration even at subscintigraphic doses. It has been suggested that 99mTc is less radiotoxic and may be desirable even though labeling is less efficient. The radiotoxicity of bound 99mTc was investigated in human lymphocytes by determination of division delay and chromosomal aberration as a function of increasing 99mTc activity concentration. This data revealed that human lymphocytes demonstrate significant division delay above 0.580 mCi/10(7) cells with chromosomal damage equivalent to 1 Gy of 250 keV x-ray at this level.

Cell Division↗
PubMed1983

The influence of cell cycle kinetics on the radiosensitivity of Down's syndrome lymphocytes.

In agreement with previous work, [60Co]gamma-irradiation shortly after phytohemagglutinin (PHA) stimulation, induces higher frequencies of chromosomal aberrations in trisomy 21 lymphocytes compared to normal controls. However, equal frequencies of chromatid aberrations are induced in fully-stimulated trisomy 21 and normal lymphocytes by irradiation during G2. We have observed that trisomic lymphocytes respond more rapidly to PHA stimulation than normal lymphocytes. Furthermore, we have observed that chromosomal radiosensitivity increases as a function of time after PHA stimulation in normal lymphocytes. When normal lymphocytes are irradiated 8 h after PHA stimulation, the frequencies of chromosomal aberrations induced are comparable to those induced in trisomy 21 lymphocytes irradiated 30 min after PHA stimulation.

Cell Cycle↗
PubMed1976

Transformation delay of lymphocytes in patients undergoing radiation therapy.

Two types of assay systems to measure the effect of radiation on immune competence are described. The first, transformation, is measured by blast formation or uptake and incorporation of tritiated thymidine by lumphocytes. This measure is affected by a number of known cell responses to radiation such as division delay and delay in DNA synthesis. The second, called Bactec, is designed to measure lymphocyte metabolic acitivty. Data gathered on 37 patients with lung cancer show that the Bactec system provides a better index of the patient's immune status before and after radiation therapy.

Cell Division↗
PubMed1975

Pathophysiology of chronic communicating hydrocephalus in dogs (Canis familiaris). Experimental studies.

A model designed to produce chronic communicating hydrocephalus in dogs has been developed in our laboratory. The animals tolerate the procedure well and the yield of animals with communicating hydrocephalus is high. Serial cisternograms show ventricular entry first with "clearing" and later with "stasis". CSF pressures are initially increased, but when the ventricles become enlarged the pressure falls into the normal range. Grossly there is generalized ventricular enlargement and, on histological studies, the ependyma is flattened and denuded. Periventricular edema occurs in the white matter. Autoradiographs show transependymal movement of protein. CSF production appears to be normal despite obstruction to flow of CSF to areas where resorption is greatest. Diversionary shunting probably produces relief of many of the neurological symptoms by providing an efficient pathway for the removal of CSF and thus by lessening edema and ventricular enlargement. A more appropriate treatment would appear to be a noninvasive method of decreasing CSF production. Only when the basic pathophysiological alterations of CSF production and absorption are understood will this be possible. We believe that this animal model affords us the opportunity of studying these mechanisms.

Animals↗
PubMed1975

X-ray and UV-induced chromatid aberrations: evidence for polynemic chromosomes?

Ikushima and Wolff have recently interpreted both their observation of chromatid aberrations in second and third mitoses following X-irradiation and the production of chromatid type chromosomal aberrations by UV light administered during the G1 phase of the cell cycle in terms of a polyneme model of eukaryote chromosome structure. They were led to do so, however, largely because of their X-ray data, which the interpreted as evidence for the induction of sub-chromosomal lesions (by G1 irradiation; sub-chromatid for G2 irradiation) which appear as chromatid type aberrations only in later divisions. We here report data from similar X-ray experiments in which synchronized Chinese hamster tissue culture cells were irradiated in either G1 or G2 and then scored for chromatid aberrations in their first, second and third post-irradiation mitoses. Our results do not show the effect reported by Ikushima and Wolff. We conclude that all of the data available of aberration production is compatible with a simple mononeme model of eukaryote chromosome structure.

Animals↗
PubMed1975

A blaze-dry spreading procedure for the electron microscopy of chromosomes from acid alcohol-fixed human lymphocytes.

A procedure is described for the blaze-drying of human lymphocyte chromosomes on carbonized Parlodion film. Films are prepared by applying Parlodion solution to sheets of freshly cleaved mica. Damage to the film during blaze-drying is prevented by chilling the mica sheets on dry ice before flaming. After spreading, the film and metaphases are floated free from the mica and transferred to a slide of Formav-coated electron microscope grids. The resulting preparations yield complete metaphase spreads and banded chromosomes morphologically similar to those observed with the light microscope.

Azure Stains↗
PubMed1975

Iron-induced enhancement of 67Ga uptake in a model human leukocyte culture system.

The addition of iron, either as Fe dextran or FeCl3, to leukocyte tissue culture medium (containing 20% fetal calf serum) significantly increased the cellular accumulation of subsequently added 67Ga-citrate. This effect of iron was dose-related and decreased, after the initial increase, with increasing concentrations of elemental iron. There was a significant negative correlation (P less than 0.025) between the concentrations of gallium and iron in the medium indicating competition between the two elements for the same serum binding sites. Although it is not yet justified to begin clinical trials, these experiments suggest the possibility that prior administration of iron may increase the usefulness of 67Ga scanning for the diagnosis of neoplasms or abscesses. Further testing of this hypothesis in animals with such lesions would seem indicated.

Gallium Radioisotopes↗