Search PubMed⌕ Search

Biomedical subjects

R Maurer

Publications and source records attributed to R Maurer.

At least 127 records · Page 7Linked to original sources

Progressive diffuse leukoencephalopathy in patients with acquired immune deficiency syndrome (AIDS).

Two adult patients with acquired immune deficiency syndrome (AIDS) presented with psycho-organic symptoms produced by an extensive cerebral and cerebellar leukoencephalopathy. Diffuse loss of myelin and axons with reactive astrocytosis and distinctive multinucleated giant cells were prominent in the deep white matter, but less so in the subcortical white matter and in compact myelinated pathways. Bilateral involvement of the centrum semiovale produced distal Wallerian degeneration of the descending pyramidal tracts, which in one patient correlated with progressive paraparesis and bladder dysfunction. Although there were morphological indications of cytomegalovirus infection and immunohistochemical evidence of papovavirus antigens, the neuropathology did not resemble that usually associated with infection by these opportunistic agents. The possibility is entertained that the progressive diffuse leukoencephalopathy (PDL) in these patients was directly related to infection with human T-cell lymphotropic virus (HTLV-III/LAV), the etiologic agent of AIDS.

Acquired Immunodeficiency Syndrome↗

[3H]205-501, a non-catechol dopaminergic agonist, labels selectively and with high affinity dopamine D2 receptors.

[3H]205-501, a noncatechol dopaminergic agonist, is presented as a ligand with high affinity (KD approximately 1 nM) and high selectivity for dopamine receptors. pKi values of dopaminergic agonists derived from competition isotherms in the [3H]205-501 binding assay correlate very well with their potency in the acetylcholine release assay, which is controlled by dopamine D2 receptors. There is however no correlation with their potency stimulating adenylate cyclase, a process controlled by dopamine D1 receptors. Thus [3H]205-501 is the first agonist ligand selective for dopamine D2 receptors.

Acetylcholine↗

Valorphin: a novel chemical structure with opioid activity.

Valorphin is a semisynthetic derivative of dihydrovaltrate with opioid analgesic activity. In vitro binding studies using brain homogenates from rat and guinea-pig indicate a preference for the mu-receptor site. Bath application to cultured cerebellar Purkinje cells inhibited the spontaneous firing, similar to the effect seen with morphine. Analgesic activity has been demonstrated in the hot plate and the tail flick test in the mouse and the Randall-Selitto test in the rat. In the rhesus monkey valorphin was self-administered, but naloxone challenge induced only mild withdrawal signs. Valorphin is a novel chemical entity, structurally not related to known opioids, which interacts preferentially with opiate mu-receptors.

Adamantane↗

Autoradiographic mapping of somatostatin receptors in the rat central nervous system and pituitary.

Somatostatin receptor-binding sites have been visualized by autoradiography in the rat central nervous system and the pituitary using the [Tyr3] derivative of the stable octapeptide somatostatin analogue SMS 201-995, code named 204-090 (sequence in text), which has been shown to label specifically high-affinity somatostatin receptors in brain homogenates. Receptors are particularly concentrated in the deeper layers of the cerebral cortex and large areas of the limbic system are rich in somatostatin receptors, in particular the hippocampus (CA1, CA2, dentate gyrus), most amygdaloid nuclei, the medial habenula and the septum. Parts of the olfactory, visual and auditory, as well as visceral and somatic sensory systems are heavily labelled, in particular the anterior olfactory nucleus and tubercle, the superior and inferior colliculi, the nucleus of the solitary tract, the substantia gelatinosa of the spinal cord and the spinal trigeminal nucleus. It is of interest that the central grey and locus coeruleus are also substantially labelled with [125I]204-090. Striatum has moderate amounts of somatostatin receptors, distributed in a patchy and heterogeneous way. Cerebellum and substantia nigra are virtually devoid of somatostatin receptors. The described receptors are likely to represent the molecular target for a variety of pharmacological actions of somatostatin in the central nervous system and they emphasize the role played by somatostatin as a neuropeptide in this organ.

Animals↗

Synthesis and pharmacological evaluation of cis-2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo[5,4-c]pyridine: a structural analogue of the GABA agonist THIP.

The pharmacological activities of the GABA agonist muscimol (1) and its dihydro analogue (2) have been shown to be almost identical. The closely related 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, 3), although biologically less active than muscimol, was selected for clinical trials. We report the synthesis of the so far elusive cis-2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo[5,4-c]pyridine (cis-DH-THIP, cis-4), which--surprisingly--is devoid of any GABAergic activity.

Animals↗

Luteinizing hormone beta-subunit mRNA amounts increase during the preovulatory surge of luteinizing hormone in the ewe: the highest levels are observed at the completion of the peak.

Amounts of mRNA for luteinizing hormone (LH) beta-subunit were assessed during selected times in the normal estrous cycle of sheep. These times spanned the luteal phase through the preovulatory LH surge, and included groups designated as: (i) day 12 of the cycle (day 12); (ii) 24 hr before the onset of the expected behavioral estrus (E - 24); and (iii) 5, 15, and 25 hr after the onset of behavioral estrus (E + 5, E + 15 and E + 25). These groups were characterized by criteria such as serum and pituitary LH concentrations, serum progesterone, and ovarian morphology. Specific LH beta-subunit mRNA was evaluated by Northern transfers, using a specific bovine LH beta cDNA probe. Slopes were determined using a linear regression analysis and then expressed as fold stimulation relative to the values for the day 12 group. The results indicate that LH beta mRNA amounts increase after day 12, reaching a value of approximately 12-fold by E + 25. When correlated with serum and pituitary LH amounts, it is observed that the amounts of beta mRNA increase in a fashion parallel to serum and pituitary LH concentrations through the time E + 5. After this time, LH beta mRNA amounts continue to increase despite a dramatic fall in both serum and pituitary LH. These results suggest that LH beta mRNA amounts are regulated during the LH preovulatory surge.

Animals↗

Magnetic resonance imaging of the hip.

Magnetic resonance imaging of the musculoskeletal system in general and the hip in particular offers many exciting opportunities for innovative and revolutionary diagnostic avenues, the full potential of which awaits further investigative and clinical experience.

Bone Marrow Diseases↗

[Vascular sinus transformation of the lymph nodes. Morphological and immunohistochemical analysis of 6 cases].

Vascular sinus transformation (VST) of lymph nodes is characterized by the intrasinusoidal proliferation of endothelial cells forming a system of anastomosed channels filled with blood, and by an intrasinusoidal fibrous reaction. By analysis of six cases, the authors recall the histological criteria of this rare lesion and discuss its differential diagnosis. The endothelial nature of the proliferating cells is demonstrated by the presence of factor VIII related antigen. VST is usually observed in association with a thrombosis of lymph node veins. On the basis of their observations the authors suggest that a venous congestion only, accompanied by lymph congestion of lymph flow may induce a VST.

Adult↗

Primary aldosteronism due to adrenal carcinomas.

In the present study two patients with aldosterone-producing adrenal carcinomas are reported. The clinical features were characterized by hypertension and severe hypokalemia with muscular weakness, flaccid paralysis of arms and legs, diarrhea and polyuria. In both cases excessively high plasma aldosterone levels and suppressed plasma renin activity were found. In contrast to most other cases with aldosterone-secreting tumours plasma cortisol, urinary free cortisol excretion, 17-hydroxy- and 17-ketosteroids were in the normal range. There was no clinical evidence of oversecretion of sex hormones. After adrenalectomy blood pressure and serum potassium normalized and the clinical symptoms disappeared. Plasma aldosterone and urinary aldosterone secretion returned to normal, while plasma renin activity remained low. Three and a half and 6 months later primary aldosteronism and the associated clinical symptoms reappeared due to hormonally active metastases. After introducing the antitumour drug o,p'-DDD in patient 1 aldosterone secretion normalized and the clinical status of the patient markedly improved. However, 10 months after diagnosis the patient died due to a haemorrhage from a liver metastasis. In patient 2 tumour-invaded regional lymph nodes were surgically removed with only minor changes in the hormone pattern.

Adrenal Cortex Neoplasms↗

[What does computer tomography and abdominal ultrasound studies accomplish in the staging of Hodgkin's disease?].

In a prospective series of 25 patients with early-stage Hodgkin's disease, abdominal assessment by computer tomogram and ultrasound was controlled by staging laparotomy. It was found that the probability of Hodgkin's disease increased with increasing diameter of the abdominal lymph nodes. 42% of the nodes between 16-20 mm in diameter had evidence of disease. Overall accuracy and specificity for the assessment of abdominal lymph nodes by CT and US was around 90%. Sensitivity was much lower than in other series, probably due to the fact that our patient sample was relatively small and consisted of patients in earlier stages with small lymph nodes. Assessment of lymph nodes by US is more, and assessment by CT less, dependent on individual factors. It is concluded that neither CT or US can replace staging laparotomy if precise information about abdominal lymph nodes is needed. Assessment of the spleen by CT and US is usually unreliable and needs histologic confirmation.

Adult↗

Pitrazepin, a novel GABAA antagonist.

Pitrazepin is a potent new GABA antagonist which differs from bicuculline in its chemical structure and its interaction with both [3H]muscimol and [3H]flunitrazepam binding sites, whereby the potency of pitrazepin in displacing [3H]muscimol exceeds that of bicuculline by at least a factor of 10. In physiological experiments, blockade of synaptically released GABA by pitrazepin was shown to reduce inhibitory postsynaptic potentials and resulted in the onset of bursting activity which persisted for hours following drug application. The effect of pitrazepin was not tissue specific since it induced a bursting discharge pattern in cultures derived from hippocampus and hypothalamus. Bursting activity was abolished by GABA, baclofen and pentobarbital, but only weakly reduced by midazolam. Pitrazepin also antagonized the action of exogenous GABA, but failed to influence the action of baclofen, an effect which was associated with a decreased membrane input resistance and which was blocked by barium. These results indicate that pitrazepin selectively interacts with the putative GABAA site, thereby antagonizing the chloride-dependent GABA response.

Animals↗

Kaposi's sarcoma and malignant lymphoma in AIDS.

A 48-year-old homosexual with contacts in different countries, including Haiti, presented with multiple pigmented or bluish nodules on both lower legs and upper arms. He had a history of secondary syphilis, hepatitis B and herpes zoster ophthalmicus. Biopsies of the skin tumors revealed a typical Kaposi's sarcoma of low grade malignancy. The endothelial origin of the tumor was indicated by the presence of specific endothelial organelles (Weibel-Palade bodies) in the cytoplasma of the tumor cells. Erythrocyte phagocytosis was found in tumor cells within and without the vascular channels. Laboratory tests were compatible with the clinical diagnosis of an acquired immune deficiency syndrome (AIDS) with a helper: suppressor T-lymphocyte ratio of 0.28 and a cutaneous anergy. In the course of the illness tumors of the stomach and duodenum were detected. Histology showed a malignant non-Hodgkin lymphoma of high grade malignancy. Within weeks the patient died in a cachectic state. Autopsy revealed a Kaposi's sarcoma of the skin with metastases in the stomach and a wide-spread malignant lymphoma in the gastrointestinal tract, in several visceral organs and in many lymph nodes.

Acquired Immunodeficiency Syndrome↗

Undifferentiated thyroid tumors of diffuse small cell type. Histological and immunohistochemical evidence for their lymphomatous nature.

A histological review of 72 undifferentiated thyroid tumors was performed in order to discover small cell anaplastic carcinomas and Non-Hodgkin lymphomas. Cases suspected to be lymphoma were examined for the presence of Ig and keratin and lectins with a PAP-procedure. Among the 72 cases, 68 (94,5%) were anaplastic carcinomas of various types. Four cases (5,5%) were diffuse small cell tumors, which had previously been regarded as anaplastic carcinomas. All four could be identified as Non-Hodgkin lymphomas by histology, immunohistochemistry, repeat biopsy or autopsy. The findings suggest that the majority of small cell anaplastic thyroid tumors are lymphomas and that true anaplastic small cell carcinoma of the thyroid must be extremely rare. Its diagnosis requires electronmicroscopy and/or immunohistochemistry to demonstrate the epithelial nature of tumor cells.

Adenocarcinoma↗

Opioid binding sites of the kappa-type in guinea-pig cerebellum.

(-)-[3H]Bremazocine interacts almost equally well with the mu-, delta- and kappa-types of opioid binding sites. In homogenates of guinea-pig cerebellum, it was bound with high affinity (KD = 0.046 nM) and the maximum binding capacity was 7.04 pmol/g wet wt of tissue. When the mu- and delta-binding of (-)-[3H]bremazocine was prevented with unlabelled ligands, a KD of 0.034 nM and a capacity of 5.94 pmol/g tissue was found for the kappa-binding site, which therefore comprised 84% of the opioid binding sites in the cerebellum. Autoradiographic analysis showed that the binding of (-)-[3H]bremazocine was relatively low in lobules IX and X and that it was predominantly located in the molecular and to a lesser extent in the granular layers. The addition of unlabelled mu- and delta-ligands did not alter the distribution. Thus, the guinea-pig cerebellum contains opioid binding sites of which almost all are of the kappa-type and is therefore an ideal tissue for the isolation of kappa-receptors and for the investigation of their biochemical and pharmacological properties.

Animals↗

Functional interchangeability of DNA replication genes in Salmonella typhimurium and Escherichia coli demonstrated by a general complementation procedure.

Twenty-four genes from Salmonella typhimurium that affect DNA replication were isolated from a lambda-Salmonella genomic library by lysogenic complementation of temperature-sensitive mutants of Salmonella or E. coli, using a new plaque complementation assay. The complementing lambda clones, which make red plaques in this assay, and noncomplementing mutant derivatives, which make uncolored plaques, were used to further characterize the temperature-sensitive Salmonella mutants and to establish the functional similarity of E. coli and Salmonella DNA replication genes. For 17 of 18 E. coli mutants representing distinct loci, a Salmonella gene that complemented the mutant was found. This result indicates that single Salmonella replication proteins are able to function in otherwise all E. coli replication complexes and suggests that the detailed properties of Salmonella and E. coli replication proteins are very similar. The other seven Salmonella genes that were cloned were unrelated functionally to any E. coli genes examined. --As an aid to the derivation of chromosomal mutations affecting some of the cloned genes, a general method was developed for placing a transposon in the Salmonella chromosome in a segment corresponding to cloned DNA. Chromosomal mutations were derived in Salmonella affecting a gene (dnaA) that was cloned by complementation of an E. coli mutant by using the transposon-encoded drug resistance as a selectable marker in local mutagenesis.

Alleles↗

Genetic analysis of DNA replication in bacteria: dnaB mutations that suppress dnaC mutations and dnaQ mutations that suppress dnaE mutations in Salmonella typhimurium.

We have isolated and characterized extragenic suppressors of mutations in two different target genes that affect DNA replication in Salmonella typhimurium. Both the target and the suppressor genes are functional homologues of known replication genes of E. coli that were identified in intergeneric complementation tests. Our results point to interactions in vivo involving the dnaB and dnaC proteins in one case and the dnaQ and dnaE proteins in the other case. The suppressor mutations, which were isolated as derivatives of lambda-Salmonella in vitro recombinants, were detected by an adaptation of the red plaque complementation assay. This method was applicable even when the locus of suppressor mutations was not chosen in advance.

Alleles↗