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Biomedical subjects

R Maurer

Publications and source records attributed to R Maurer.

At least 91 records · Page 5Linked to original sources

[Primary non-Hodgkin's lymphoma of the muscles].

On the basis of two personal observations and of 18 published cases, a review of primary non-Hodgkin lymphoma originating in the skeletal muscle is presented. The disease mainly affects persons in the seventh decade. Ninety-five percent of the tumors occur in the extremities, with 75% in the lower extremities. Most lymphomas were of low grade malignancy, with intermediate and high grade tumors accounting for 45% of cases. Reliable differentiation of NHL from other small round cell tumors of the soft tissues, such as rhabdomyosarcoma or Ewing sarcoma, and from metastatic carcinoma, is mandatory for therapeutic purposes. Diagnosis can be established by light microscopy alone in most patients. In doubtful cases immunohistochemistry may be required.

Combined Modality Therapy↗

CY 208-243: a unique combination of atypical opioid antinociception and D1 dopaminomimetic properties.

Here we describe the potent antinociceptive action of the indolophenanthridine, CY 208-243, which has high affinities to the dopamine D1 binding and the opioid sites as well as to the 5-HT1A site. The antinociceptive action was comparable to that of morphine in most, but not all models of nociception, nevertheless, basic differences exist in its overall profile. Antagonism of CY 208-243's antinociceptive action was only possible with either high doses of naloxone or not at all and no cross-tolerance with morphine in CY 208-243 tolerant rats occurred. The biochemical basis for dependence liability may be absent and no opioid activity was observed in cultured hippocampal cells. Physical dependence did not occur after programmed administration in the rhesus monkey, nor did CY 208-243 cause respiratory depression in the rat (rather a stimulation). Lack of generalization in fentanyl-trained rats strongly suggests that CY 208-243 lacks opioid-like subjective cues. The coexistence of D1 dopaminergic and atypical opioid agonist properties represents a unique pharmacodynamic combination which is not shared with any other analgesic, and may provide safe and innovative pain therapy.

Analgesics↗

Sequence of the dnaB gene of Salmonella typhimurium.

The dnaB gene of Escherichia coli encodes a helicase that operates at replication forks of the bacterium and certain of its bacteriophages to produce separated strands suitable for subsequent use by primase and DNA polymerase III. Here, we present the sequence of the dnaB gene of Salmonella typhimurium, a functionally interchangeable analog of the E. coli dnaB gene. The DnaB proteins of these two organisms, inferred from the DNA sequences, are identical in length and in 93% of amino acid residues. Extended portions of the DnaB proteins are also similar to two phage-encoded DNA replication proteins: the gene 4 helicase-primase of coliphage T7 and, as reported previously (H. Backhaus and J. B. Petri, Gene 32: 289-303, 1984), the gene 12 protein of Salmonella phage P22. In contrast, little similarity was found between DnaB and either the UvrD repair helicase or transcription termination factor Rho (an RNA-DNA helicase). These results identify S. typhimurium DnaB as a member of the DnaB family of proteins by structural, as well as functional, criteria and provide the basis for the eventual identification, by mutational studies, of residues in DnaB critical for its function.

Amino Acid Sequence↗

Dominant lethal mutations in the dnaB helicase gene of Salmonella typhimurium.

A class of dominant lethal mutations in the dnaB (replicative helicase) gene of Salmonella typhimurium is described. The mutated genes, when present on multicopy plasmids, interfered with colony formation by Escherichia coli host strains with a functional chromosomal dnaB gene. The lethal phenotype was expressed specifically in supE (glutamine-inserting) host strains and not in Sup+ strains, because the mutant genes, by design, also possessed an amber mutation derived from a glutamine codon. Mutations located at 11 sites by deletion mapping and DNA sequence analysis varied in the temperature dependence and severity of their lethal effects. None of the mutations complemented a dnaB(Ts) host strain at high temperature (42 degrees C). Therefore, these nonfunctional DnaB proteins must engage some component(s) of the DNA replication machinery and inhibit replication. These mutations are predicted to confer limited, specific defects in either the catalytic activity of DnaB or the ability of DnaB to interact with one of its ligands such as DNA, nucleotide, or another replication protein. The variety of mutant sites and detailed phenotypes represented in this group of mutations may indicate the operation of more than one specific mechanism of lethality.

Bacterial Proteins↗

Somatostatin receptors in normal and tumoral tissue.

Somatostatin receptors have been visualized with autoradiography and characterised biochemically in various somatostatin target tissues, such as brain, pituitary, pancreas and gastrointestinal tract, where they are likely to mediate the somatostatin actions. With the same methods, somatostatin receptors have been detected also in tumors originating from somatostatin target tissues: high receptor incidence is found in GH-producing pituitary adenomas as well as in some hormone-producing gastrointestinal tumors. These tumors are often highly responsive to somatostatin analogs in vivo. Among brain tumors, meningiomas usually contain a high density of receptors, suggesting a novel function for somatostatin in the human meninges. Among other human tumors tested, prostate, ovarian and endometrial carcinomas were free of receptors whereas 3 out of 39 mammary tumors contained somatostatin receptors.

Adenoma↗

Distribution and biochemical characterization of somatostatin receptors in tumors of the human central nervous system.

Fifty-two brain tumors, consisting of 17 astrocytomas, 4 oligodendrogliomas, 20 glioblastomas, 3 neurinomas, 2 ependymomas, 1 neurofibroma, 1 ganglioneuroblastoma, 1 medulloblastoma, 1 plexus papilloma, 1 teratoma, and 1 germinoma, were tested for their content of specific somatostatin receptors using autoradiographic techniques or in vitro binding assays with membrane homogenates. Somatostatin receptors were found in most of the differentiated glia-derived tumors such as astrocytomas and oligodendrogliomas whereas the poorly differentiated glioblastomas were usually free of receptors. Tumors originating from neuroblasts, i.e., ganglioneuroblastoma and medulloblastoma, contained a high density of somatostatin receptors, whereas neurinomas and neurofibromas as well as the ependymomas, one teratoma, and one plexus papilloma were lacking such receptors. In one germinoma, low amounts of somatostatin receptors were observed over the lymphocytic elements. Receptor-positive tumors had saturable and high affinity receptors with pharmacological specificity for somatostatin and somatostatin analogues resembling that of normal human central nervous system tissue. In most instances, they could be labeled with two different iodinated radioligands, a somatostatin octapeptide derivative (204-090) or a somatostatin-28 analogue. This is the first time that somatostatin receptors have been shown to exist not only on neuronal structures of the central nervous system but also on glial elements. The precise function of such somatostatin receptors on glial cells, which may be different from neurotransmission, remains to be determined.

Adolescent↗

[Somatostatin-producing endocrine pancreatic tumor in Recklinghausen's neurofibromatosis. Case report and literature review].

Somatostatin-producing tumors of the pancreas were first described in 1977. In 1983 a syndrome involving multiple endocrine neoplasias (MEN) was named type III A. This syndrome consists of carcinoid of the duodenum, often producing somatostatin, and von Recklinghausen's disease (neurofibromatosis) or pheochromocytoma. The case is reported of a 62-year-old man with familial neurofibromatosis and a tumor of the head of the pancreas spreading into pars II of the duodenum. After Whipple's duodenopancreatectomy the patient exhibited no further symptoms. Immunohistochemistry served to prove the production of somatostatin and small amounts of calcitonin in the tumor.

Adenoma, Islet Cell↗

Primary aldosteronism by carcinoma of the adrenal cortex.

A 58-year-old white woman with hypertension and severe hypokalemia was found to have a carcinoma of the left adrenal gland. Plasma renin activity was constantly under the normal limit, while plasma aldosterone levels were pathologically elevated. Plasma cortisol (8:00 a.m.) and excretion rates of urinary free cortisol were within the normal range. After an adrenalectomy, relapsing excessive aldosterone secretion was successfully treated with opDDD (Lysodrene). Ten months after the diagnosis was established, the patient died from a bleeding liver metastasis.

17-Hydroxycorticosteroids↗

Somatostatin receptors in human endocrine tumors.

A selection of 90 mainly endocrine but nonpituitary tumors have been tested for their content of specific somatostatin receptors using receptor autoradiography. Somatostatin receptors were detected in the following tumors: in all 5 meningiomas tested; in 3 of 39 malignant breast tumors; and in 3 growth hormone releasing factor-producing tumors, i.e., one mediastinal carcinoid, one intestinal carcinoma, and its liver metastasis. Receptor density varied greatly among individual tumors. Some of the positive tumors were biochemically characterized using in vitro binding assay and were shown to have saturable and high affinity receptors with pharmacological specificity for somatostatin. The following tumors did not contain somatostatin receptors: prostate carcinomas (n = 17); prostate hyperplasia (n = 2); ovarian carcinomas (n = 6); endometrial carcinomas (n = 4); primary liver cell carcinomas (n = 3); pheochromocytomas (n = 3); aldosteronomas (n = 2); medullary thyroid carcinomas (n = 2); one adrenocorticotropic hormone-secreting pulmonary carcinoid; one astrocytoma; one neurofibroma; one lung tumor; and one bladder tumor. Somatostatin receptors can be found in benign or malignant tumors, originating in part from tissue not primarily known as a somatostatin target. The biological function of such receptors is, therefore, partly unknown. If they can mediate antiproliferative properties, as has been suggested to be the case for somatostatin receptors in selected endocrine tumors in rats and humans, the present data could be of potential therapeutic interest.

Autoradiography↗

Diazepam and N-desmethyldiazepam are found in rat brain and adrenal and may be of plant origin.

Benzodiazepine-binding inhibitory (BBI) activity was detected in aqueous extracts of brain and peripheral tissues of rats. The BBI activity in brain and in adrenals was, at least partially, due to the presence of N-desmethyldiazepam and diazepam as shown by HPLC, UV-spectroscopy and mass spectrometry. In addition, BBI activity was found in standardized rat food, as well as in a variety of cereals and in other nutritive plant products. In wheat grains diazepam and N-desmethyldiazepam could be identified by HPLC and analysis by gas chromatography combined with mass spectrometry. The estimated amounts of the two benzodiazepines present in rat brain and adrenals and in wheat grains were in the low ppb range. Since laboratory contamination was rigorously excluded we conclude that diazepam and N-desmethyldiazepam are naturally occurring compounds. These findings may explain their occurrence in the brain and adrenals of animals.

Adrenal Glands↗

Specific luteinizing-hormone-releasing hormone receptor binding sites in hippocampus and pituitary: an autoradiographical study.

Using the iodinated luteinizing-hormone-releasing hormone analogue [D-Ala6, N alpha MeLeu7, Pro9 NEt]-luteinizing-hormone-releasing hormone as radioligand, specific binding sites have been visualized in the rat both in the pituitary and the hippocampal formation of the brain. In the hippocampus, the CA1, CA2 and particularly CA3 regions were heavily labelled. These hippocampal sites have a pharmacological specificity resembling that of luteinizing-hormone-releasing hormone receptors in pituitary homogenates and could therefore represent true luteinizing-hormone-releasing hormone receptors. The luteinizing-hormone-releasing hormone superagonist [D-Ala6, Pro9 NEt]-luteinizing-hormone-releasing hormone and the potent antagonist [D-pGlu1, D-Phe2, D-Trp3,6]-luteinizing-hormone-releasing hormone were highly potent in displacing the iodinated luteinizing-hormone-releasing hormone analogue. The weak agonist [Gln8]-luteinizing-hormone-releasing hormone, however, was at least two orders of magnitude less potent. Somatostatin was inactive. Hippocampal luteinizing-hormone-releasing hormone receptors were species-specific, being present in the rat but not in the mouse, guinea-pig, hamster, rabbit and human brains. In order to identify the cellular location of these hippocampal receptors, various lesions were performed. Electrolytic lesions of the septal afferents did not reveal any receptor density change. Colchicine as well as kainic acid injections did, however, reduce considerably the number of hippocampal receptors. Interestingly, in the electrolytically and kainic-acid-lesioned animals, the appearance of non-displaceable luteinizing-hormone-releasing hormone binding sites within a well-defined area corresponding to the lesioned, gliosis-rich area was observed. The present results suggest the presence of pharmacologically specific, species-dependent, luteinizing-hormone-releasing hormone receptors located, at least partly, on intrinsic hippocampal neurons, in particular granule and pyramidal cells.

Animals↗

Diagnostic and prognostic value of monoclonal antibodies in immunophenotyping of angioimmunoblastic lymphadenopathy/lymphogranulomatosis X.

Immunophenotyping of frozen lymph node sections from seven patients with morphologically defined angioimmunoblastic lymphadenopathy (AILD) was performed with a panel of 20 monoclonal antibodies (MoAb). MoAb for identification of dendritic reticulum cells showed remnants of follicular structures in all cases. In four cases these 'burnt out' follicular structures were associated with clusters of polyclonal B-cells. Vascular proliferation and small amounts of intercellular collagenous fibrils were reliably revealed by MoAb CIV22 against basement membrane collagen. Cellular infiltrates of T4+ cells prevailed in four cases, of T8+ cells in one case. In one case conventionally identified blasts were of T- and B-cell origin. Expression of cell proliferation associated nuclear antigen identified by MoAb Ki-67 was present in more than 25% of lymph node cells in three patients with fatal outcome, but in less than 10% of cells in two patients with a better clinical course. Therefore MoAb Ki-67 may represent a valuable prognostic marker in AILD.

Adolescent↗

Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. II. Chemistry and structure elucidation.

The structure of a new pancreatic lipase inhibitor, lipstatin, produced by Streptomyces toxytricini was determined as (2S,3S,5S,7Z,10Z)-5-[(S)-2-formamido-4-methylpentanoyloxy ]-2-hexyl-3- hydroxy-7,10-hexadecadienoic lactone by spectroscopic and chemical methods. Structurally lipstatin is closely related to the known esterase inhibitor esterastin. It contains a N-formyl-L-leucine side chain instead of the N-acetyl-L-asparagine in esterastin.

Chemical Phenomena↗

Somatostatin binding sites in human leptomeninx.

Specific binding sites for somatostatin (SRIF) have been visualized in the human leptomeninx by means of autoradiographical techniques using the stable SRIF octapeptide analog 125I-204-090 as radioligand. The binding sites are specific for SRIF since only biologically active SRIF analogs compete with the radioligand. The density of the binding sites is comparable to that of the adjacent cortical structure. The presence of SRIF binding sites in the human leptomeninx, together with the recent demonstration of SRIF binding sites in human meningiomas, strongly suggest that this peptide may play a role in the physiology of the leptomeninx.

Arachnoid↗

Somatostatin receptors in rat hippocampus: localization to intrinsic neurons.

The effect of neurotoxic chemical and electrolytical lesions on somatostatin (SS) receptor binding in the septo-hippocampal afferents, pyramidal and granule cells of the rat hippocampus was examined by autoradiography using the stable SS analogue 125I-204-090 as radioligand. Electrolytical lesions of the septum did not result in modification of SS binding in the hippocampus. In contrast, both granule cell lesion with colchicine and pyramidal or pyramidal and granule cell lesions with increasing kainic acid doses did result in a specific decrease of binding in the dentate gyrus and hippocampus (CA1 and CA3). These results suggest that SS receptors in the hippocampus are probably associated with elements from intrinsic neurons.

Animals↗

Distribution and coregulation of three peptide receptors in adrenals.

Receptors sites for angiotensin II and atrial natriuretic factor were concentrated in the zone glomerulosa of the adrenal cortex in the rat, mouse, hamster, rhesus monkey, guinea-pig and the cow. Angiotensin Ii receptor sites were also accumulated in adrenal medullary tissue of the rat, mouse and the hamster. With exception of the cow the zonae fasciculata and reticulata of the adrenal cortex were not labelled with the angiotensin II ligand, but showed a moderate density of atrial natriuretic factor receptor sites in all species except the rhesus monkey. In comparison, somatostatin receptors were even more heterogeneously distributed in all species mentioned above. In the rat, the increased growth of zona glomerulosa cells found after three weeks of sodium deprivation was accompanied by a similar increase in number of receptor sites for angiotensin II, atrial natriuretic factor and somatostatin. This shows that all three peptide receptors are regulated simultaneously by a single metabolic disturbance, suggesting that they might be localized on the same cell type in the adrenal cortex.

Adrenal Glands↗

Opioid binding sites in the nigrostriatal system of the guinea pig are not located on nigral dopaminergic neurons.

Unilateral 6-hydroxydopamine injection into the compact zone of the guinea pig substantia nigra was used to destroy nigral dopamine neurons. The glyoxylic acid method for monoamine fluorescence was employed to ascertain the loss of dopaminergic fibers in the striatum and substantia nigra. It could be shown that there was no change in the number of [3H](-)-bremazocine binding sites in the substantia nigra or the striatum on the lesioned side of these guinea pigs.

Animals↗