The new corporate hospitals. What are they, and what is their future?
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Biomedical subjects
Publications and source records attributed to M Brown.
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Somatostatins, somatostatin-14, somatostatin-28, and desAA [D-Trp8]-somatostatin, with differential potencies, act in the brain to reverse chemical-induced hypothermia and to produce hyperthermia. Somatostatins are more potent and loger acting than prostaglandin E2 in producing hyperthermia. Hyperthermia, induced by somatostatins, is not prevented by previous treatment with the prostaglandin synthesis inhibitor indomethacin. Somtostatins given to obese ob/ob mice prevent development of lethal hypothermia and result in maintenance of euthermia. Continuous infusion of somatostatins results in desensitization to the hyperthermic effects of these peptides. Endogenous somatostatins may be involved in regulation of body temperature.
50 women with normal urinary control and 100 women with urinary incontinence wore a series of preweighed sanitary towels for 1 h. The pads were weighed again after use. Mean pad weight increase was less than 1 g/h in normal women and 12.2 g/h in women with incontinence. In each case the pad-weighing test provided information about the severity and the pattern of incontinence which was not easy to obtain either from patient interview or from clinical examination.
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Autonomic function was investigated in patients with congestive (dilated) cardiomyopathy and compared with that in controls. Heart-rate and blood-pressure were recorded during physiological and pharmacological interventions and plasma noradrenaline concentration was measured at rest and when the physiological interventions produced a peak response. The results indicate that even at an early (pre-failure) stage of the disease parasympathetic function is impaired but no significant increase in sympathetic activity occurs at this stage.
Forty-two children with various systemic malignancies in continuous remission for 1 to 3 years after the completion of chemotherapy had CT scans with normal ventricular dimensions, similar to a noncancer "control" population. Seventeen of these patients had acute lymphocytic leukemia (ALL) treated either with prophylactic cranial irradiation and intrathecal methotrexate [7] or intrathecal methotrexate alone [10] and the remaining 25 patients had soft tissue sarcomas. Sixteen other patients with sarcomatous meningitis had enlarged ventricles while on chemotherapy. Nine had ALL. Seven had soft tissue sarcomas, none of whom received any prior CNS irradiation or intrathecal chemotherapy. In this retrospective study no evidence of hydrocephalus or significant white matter hypodensity was detected in long-term survivors of childhood cancer, regardless of whether prophylactic intrathecal chemotherapy and/or cranial irradiation was given. Direct involvement of the CNS with meningeal cancer was the most important association with ventriculomegaly.
After neonatal treatment of rats with capsaicin, the spinal cord, the spinal trigeminal nucleus and spinal and trigeminal ganglia were analysed with immunohistochemistry using antisera to several peptides and 5-hydroxytryptamine. A marked decrease was observed in substance P-, cholecystokinin-, somatostatin- and VIP-like immunoreactivity present in the central branches of primary sensory neurons in the spinal cord and in substance P- and somatostatin-like immunoreactivity in sensory ganglion cells. No definite depleting effect of capsaicin could be established on 5-hydroxytryptamine and peptides, such as enkephalin and neurotensin, present in centrally originating fibres in the dorsal horn of the spinal cord. The results demonstrate that the effects of capsaicin are not confined to substance P immunoreactive primary sensory neurons. The possibility is discussed that capsaicin effects specifically functioning rather than chemically specific primary sensory neurons.
The SV40 large T antigen is a multifunctional protein presumed to represent a single translation product of the early viral genes. A wide range of biological controls including the regulation of viral DNA replication, transcription and cell transformation has been attributed to T antigen. Previous evidence has indicated that large T antigen is modified in at least two ways, N-terminal acetylation and amino acid phosphorylation. In this study, we demonstrate a novel modification of a population of SV40 T antigen molecules by poly ADP-ribosylation. The covalent linkage of this oligonucleotide side chain to large T antigen, but not small t antigen, was demonstrated in experiments in which SV40-infected cells were labeled in vivo with 32P-orthophosphate or 14C-adenosine. Treatment of this labeled T antigen with snake venom phosphodiesterase released iso-ADP-ribose or treatment with ADP-ribose glycohydrolase released ADP-ribose. A method has been developed for the in vitro ADP-ribosylation of T antigen present in an infected cell nuclear extract with radiolabeled NAD. Since this type of modification is known to affect enzyme activity, its presence on T antigen suggests a similar role in the regulation of certain biological functions under the control of this protein.
Intracisternal injection of octapeptide analogs of somatostatin (SS), Cys-Phe-Phe-D-Trp-Lys-Thr-Phe-Cys (des-AA1,2,4,5,12,13-[D-Trp8]SS (ODT8-SS)) and Cys-Phe-Phe-D-Trp-Lys-Thr-Phe-D-Cys, increased the volume and the acid output of gastric secretion in rats. ODT8-SS given intravenously did not affect basal gastric secretion. The gastrosecretory effect of ODT8-SS, administered intracisternally is dose-dependent (0.01-1 micrograms), long acting, reversible, specific, and abolished by vagotomy, or systemic injection of atropine or SS. SS (5-10 micrograms) or [D-Trp8]SS (1 microgram) had no effect on gastric secretion when given intracisternally. These results demonstrate that some octapeptide SS analogs, unlike SS or other SS analogs, have the capability to act in the brain to induce a vagal dependent stimulation of gastric secretion.
Brain alteration of catecholaminergic, serotoninergic, dopaminergic, gabaergic and cholinergic pathways by intracisternal injection of agonists, antagonists or specific neurotoxic drugs did not significantly affect gastric acid secretion in 2 hr pylorus-ligated rats. In contrast, several neuropeptides were found to be very potent in influencing gastric secretion when administered intracisternally but not when given intravenously. Bombesin-like peptides, opioid peptides and arginine vasopressin acted within the brain to inhibit gastric acid secretion through yet unknown neurohumoral pathways, whereas TRH and some somatostatin analogs elicited brain stimulation of gastric acid output through vagal-dependent mechanisms. These observations have led to the concept that some specific neuropeptides may be important chemical messengers involved in physiologic brain processes regulating gastric acid secretion, and appear as new chemical probes to further investigate the brain-gut relationship.
Twenty-six peptides, analogs of bombesin (BNa) and gastrin releasing peptide (GRP), have been synthesized by the solid phase method. The synthetic peptides were purified by ion exchange and partition chromatography and shown to be homogenous under various conditions on RP-HPLC. They were further characterized by TLC, amino acid analysis and optical rotation. These peptides have been administered IC to rats and their effects on thermoregulation and glucoregulation have been compared to those of the two natural peptides: frog skin bombesin (BNa) and GRP. Their structure activity relationship is also discussed. The minimum essential residues required for full potency of bombesin-like effects is represented by an acetylated C-terminal 8-peptide fragment, where in position 7 of this peptide an L-amino acid such as alanine, histidine or glutamine, or the D-glutamine residue can be introduced. Modification of the tryptophan [8] and histidine [12] residues by alanine abolished the biological potency of those peptides. Analogs with a free N-terminus were found to express little, but significant, activity, thus indicating that blocked N-terminus is necessary for maximal response. [Ac-Ala7, DAla11]-bombesin (7--14) and [Ac-DGln7 DAla11]-bombesin (7--14) were found to be more potent than bombesin, whereas [Ac-DAla7, DAla11]-bombesin or [Ac-DAla7, DAla11] bombesin N-methylamide were found to have 10 and 1% of bombesin potency, respectively.
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Nuclear dacryocystography is simple, relatively harmless method of evaluating patients suspected of having abnormalities of the nasolacrimal drainage system. A group of normal saline containing approximately 100 muCi of 99mTc-pertechnetate is placed on the conjunctiva near the lateral canthus, and serial scintigrams are obtained as the pertechnetate flows along the tear strips, through the nasolacrimal drainage system, into the nasal fossa. By using a pinhole collimator with a very small aperture (1mm), the canaliculi, the nasolacrimal sac, and the nasolacrimal duct are readily visualized. When flow is impaired, the site of obstruction can often be identified. Contrast dacryocystography provides similar information but requires the injection of contrast material directly into a canaliculus. Nuclear dacryocystography provides good functional assessment of nasolacrimal drainage but has serious shortcomings in defining pathologic anatomy. Contrast dacryocystography outlines the anatomy well but often misses minor obstructions. The two studies are complementary and together provide an effective means of evaluating the nasolacrimal drainage system.
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Immunoglobulin (IgG) and the F(ab')2 fragment of IgG were prepared from serum of a rabbit immunized with purified calf thymus DNA polymerase alpha (deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7). An indirect immunofluorescent method based on these reagents was used to detect the intracellular localization of DNA polymerase alpha in primary fetal bovine fibroblasts. The results show that the bulk of DNA polymerase alpha is located in the perinuclear region of the cytoplasm. Immunofluorescent staining of cytoplast and Ficoll-Paque gradient-purified karyoplast fragments resulting from cytochalasin enucleation show the presence of DNA polymerase alpha in cytoplasts and the virtual absence of the enzyme in the nucleus of the karyoplast itself. The implication of this unusual intracellular location for DNA polymerase alpha is discussed.
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