Faculty Bibliography

Bromocriptine in high doses (up to 100 mg per day) was administered to 14 patients with advanced Parkinson's disease whose disorder was progressing despite optimum treatment with levodopa combined with a peripheral dopa decarboxylase inhibitor (carbidopa). In 10, bromocriptine (mean dose, 57 mg) induced a statistically significant (P less than 0.01) improvement in rigidity, tremor, bradykinesia, gait disturbance and total score. In seven patients levodopa with carbidopa was completely replaced by bromocriptine (mean dose, 70 mg), with improvement in four. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance (on-off effect) were decreased whereas orthostatic hypotension and mental changes were increased. Bromocriptine appears to be a major new agent in Parkinson's disease that is especially promising in patients no longer responding to levodopa

Peritoneoscopy was used to evaluate the liver in 35 previously untreated patients with Hodgkin disease. Four were found to have hepatic involvement. Of the 31 patients with normal peritoneoscopies, only one had liver disease demonstrated subsequently at confirmatory exploratory laparotomy. The diagnostic accuracy of peritoneoscopy was 93% for patients at high risk for hepatic disease and 97% for all patients studied. Morbidity from the procedure was minimal. There was no mortality. Peritoneoscopy is a highly accurate staging procedure that should be considered as an antecedent or as an alternative to laparotomy in patients with Hodgkin disease. Its accuracy and minimal morbidity should be considered in the critical selection process of determining which individuals should undergo laparotomy

The effects of the catecholamine neurotoxin 6-hydroxydopamine on phenylethanolamine-N-methyl transferase (PNMT) in rat brain has been investigated by biochemical and immunohistochemical analysis. 6-Hydroxydopamine was administerered either intracisternally to adult rats or systemically to newborn rats, treatments known to affect markedly central noradrenaline neurons. None of these treatments had any significant effect on the PNMT activity in the hypothalamus, pons-medulla and the spinal cord, as measured in vitro using a radiometric assay. The neonatal 6-hydroxydopamine treatment, which produced an almost complete noradrenaline denervation in the spinal cord, had no notable effect on the specific PNMT immunofluorescence localized in nerve terminals in the spinal cord. Transection of the spinal cord led to an almost complete disappearance of the PNMT activity and the specific immunofluorescence below the transection, pointing to the existence of a descending PNMT containing pathyway in the spinal cord. The present results show that the PNMT neurons are resistant to the neurotoxic action of 6-hydroxydopamine, possibly due to lack of catecholamine uptake mechanism or due to these neurons having an uptake mechanism with a low affinity for 6-OH-DA. Furthermore, the data support the view that the noradrenaline and PNMT containing neurons constitute separate neuron systems.

The localization and distribution of tyrosine hydroxylase (TH), the first enzyme in the catecholamine synthesis, in the mes- and diencephalon has been studied with the indirect immunofluorescence technique of Coons and collaborators. Principally, TH was present in neuron systems with a distribution similar to known dopamine, noradrenaline and adrenaline systems. The present data, taken together with published and some unpublished results, indicate that all parts of most central dopamine neurons, i.e. cell body, dendrites, axon and nerve terminals, appear strongly fluorescent. The adrenaline neurons also appeared strongly fluorescent, except for their axons, which only exhibited a weak fluorescence. Only cell bodies of noradrenaline neurons were strongly fluorescent, whereas the nerve terminals and axons showed a weak or moderate fluorescence intensity. The fine noradrenaline nerve terminals in some areas, such as the thalamus, were invisible or, under favourable conditions, weakly fluorescent. Therefore, in the present study we are mainly dealing with the dopamine neurons of the upper brain stem. Our results demonstrate a widespread occurrence of TH-positive neuron systems in the mes- and diencephalon. The different mesencephalic dopamine systems and their ascending projections were visualized. Numerous TH-positive cell bodies were present along the ventricle system extending from the aqueductus cerebri to the most cranial periventricular parts of the third ventricle. The caudal part of these neurons, consisting of very small cell bodies, belong to the dorsal periventricular system described by Lindvall and Bjorklund. Several TH-positive cell bodies were also observed in the inferior collicle of young animals. In the superficial layers of the inferior collicles TH positive nerve terminals were seen. At the hypothalamic level the A11 to A14 cell groups as well as some additonal cell bodies and extensive nerve terminal plexuses appeared strongly fluorescent. The differences in the intensity of the TH-related immunofluorescence between various brain regions and between various neuron systems may well reflect differences in enzyme levels between the various catacholamine systems rather than be due to the existence of different types of TH.

The effects of changes in serum osmolality on the volume flow of fluid into the cerebral ventricles and on brain water content was examined in cats with kaolin-induced hydrocephalus. Slopes of the regression lines relating volume flow and serum osmolality for both normal and hydrocephalic cats are the same. The constant difference in flow rates between the two lines, 7 mul per minute, is probably due to impaired choroid plexuow rates between the two lines, 7 mul per minute, is probably due to impaired choroid plexus function of the hydrocephalic cats. The osmotic pressure gradient that causes the flow of fluid is therefore probably between blood and brain. Under these conditions changes in brain water content of hydrocephalic cats were smaller than in normals and can be related to the edema present in this disorder. Despite the inflammatory response to kaolin, the blood-brain barrier remains intact. From the calculated filtration coefficient, it can be inferred that the flow of water from serum through brain and into cerebrospinal fluid is limited by the resistance of fluid flow through the brain.

The mechanisms of steroid and peptide hormone action in human breast cancer are poorly understood. We have previously characterized a cell line of human breast cancer in long-term tissue culture that possesses various steroid hormone receptors and responses, providing a model for the study of steroid hormone action. The present studies describe a human breast cancer in vitro that responds to physiologie concentrations of insulin with an increased rate of macromolecular synthesis and growth. Thymidine and uridine incorporation in cells in serum-free medium are stimulated by 10(-11) M insulin and are maximal with 10(-8) M. Leucine incorporation is stimulated by 5 X 10(-11) M insulin and is maximal with 10(-9) M. Significant stimulation of uridine and leucine incorporation is evident by 3 hr and maximal by 10 hr. A 10-hr lag period exists for insulin stimulation of thymidine incorporation, which is maximal form 14 to 24 hr. The effect of 10(-8) M insulin on macromolecular synthesis is accompanied by a 69% increase above controls in the number of cells after 24 hr. The effect on macromolecular synthesis is observed in glucose-free medium. Insulin's effect on protein synthesis is not blocked by inhibition of RNA synthesis with actinomycin D. Glucocorticoids partially inhibit the action of insulin in these cells. This system provides a model for studying insulin action, and suggests that some human breast cancer may show growth regulation by insulin

The mesencephalic nucleus of the trigeminal nerve (mes V) in the brain of the skate (Raja oscellata) was studied by electron microscopy. Mes V neurons are large (40-80 mum diameter) and are located in the periventricular grey matter. Their perikaryal cytoplasm is rich in Golgi apparatus, small mitochondria, rough endoplasmic reticulum, polysomes and bundles of neurofilaments. A striking feature is the presence of masses of glycogen granules, at times surrounded by membrane wrappings and lysosomal bodies. Two types of conventional synaptic contacts were made onto mes V perikarya and dendrites. One had round, agranular vesicles and usually also contained dense-cored vesicles, the other had flattened, pleomorphic, agranular vesicles and usually lacked dense-cored vesicles. Additional membrane complexes consisting of a region of gap junction flanked by sites of desmosomal attachment were observed to link neighbouring mes V neurons. Somato-somatic, dendro-somatic, axo-somatic, and dendro-dendritic junctions were noted. Except for the somato-somatic union, one or more chemical synapses were located close to the sites of gap junctions.