Cytoplasmic loop of beta-adrenergic receptors: synaptic and intracellular localization and relation to catecholaminergic neurons in the nuclei of the solitary tracts

Pharmacological studies suggest that beta-adrenergic receptors (beta AR) in the medial nuclei of the solitary tracts (m-NTS) facilitate presynaptic release of catecholamines and also function at postsynaptic sites. We have localized the antigenic sites for a monoclonal antibody against a peptide corresponding to amino acids 226-239 of beta AR in the m-NTS of rat brain. By light microscopy, immunoperoxidase labeling for this antibody was detected in somata and proximal processes of many small cells that were distributed throughout the rostrocaudal extent of the m-NTS. Electron microscopy confirmed the cytoplasmic localization of beta AR in perikarya and proximal dendrites of neurons. Immunoreactivity occurred as discrete patches associated with cytoplasmic surfaces of plasma membrane and with irregularly-shaped saccules with clear lumen in the immediate vicinity. Select regions of nuclear envelopes, mitochondrial membranes, and rough endoplasmic reticulum were also immunoreactive along their cytoplasmic surfaces. In contrast, the Golgi apparatus was labeled, but infrequently. Immunoreactivity was also detected at numerous post- and occasional presynaptic membrane specializations of select axodendritic junctions. Dual labeling for the beta AR-antibody by the immunoperoxidase method and for a rabbit antiserum against the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), by the immunoautoradiographic method within the same sections, further established the precise cellular relations between beta AR and catecholaminergic neurons. Immunoreactivity for beta AR was detected in numerous perikarya and proximal dendrites that did not show detectable levels of TH. However, a few cells were dually labeled for both antigens, as seen by both light and electron microscopy. The TH-labeled terminals formed synapses at junctions both with and without beta AR-like immunoreactivity. These results from the single and dual labeling studies: (1) confirm biochemical predictions that amino acids 226-239 of beta AR protein reside intracellularly; (2) provide the first ultrastructural evidence for beta AR localization within both pre- and postsynaptic membrane specializations of a subset of catecholaminergic synapses; and (3) suggest select intracellular sites that may be involved with synthesis and/or internalization and degradation of the receptor protein.     

Stimulation of Alpha-Adrenoceptors Facilitates the Release of Growth Hormone-Releasing Hormone from Rat Hypothalamus in vitro

While extensive evidence suggests that adrenoceptors play an important role in the control of growth hormone in the rat, there are few studies involving the direct measurement of growth hormone-releasing hormone (GHRH). We have therefore developed a radioimmunoassay for rat GHRH, and used it to investigate the modulation of GHRH release by noradrenaline from incubated rat hypothalamus in vitro. The GHRH radioimmunoassay had no significant cross-reactivity with other hypothalamic or GHRH-related peptides, and was sensitive to 4 pg/tube; intra- and interassay coefficients of variation were 6% and 12% respectively. Single incubated rat hypothalami produced a stable and readily measurable output of GHRH in successive 20 min incubations after an initial 60 min preincubation; the release of GHRH was increased in the presence of 56 mM KCI, but did not respond to KCI-depolarization when calcium was excluded from the medium. Stimulated GHRH release was identical to synthetic rat GHRH(1–43) on high-performance liquid chromatography and Sephadex G-75 chromatography.
Noradrenaline stimulated GHRH secretion in a dose-dependent manner in the concentration range 10⁻¹⁰— 10⁻⁶M, with a plateau in response at 10⁻⁷M. Stimulation with noradrenaline 10⁻⁷M was blocked by idazoxan 10⁻⁵M and attenuated by thymoxamine 10⁻⁵M, but was unaffected by timolol 10⁻⁵M. Both the α₂-adrenoceptor agonist guanfacine, and the α₁-adrenoceptor agonist methoxamine, specifically stimulated GHRH secretion.
It is concluded that noradrenaline stimulates the release of GHRH at both α₁ and α₂-adrenoceptors.     

Divided attention, as measured by dichotic speech performance, in dementia of the Alzheimer type

To determine if impaired dichotic performance in patients with dementia of the Alzheimer type is due to the inability to divide attention or the inability to perceive degraded auditory stimuli, we measured performance on tasks of both dichotic and degraded monotic speech materials. We also examined whether perception of degraded speech stimuli presented monaurally is related to abnormalities of temporal lobe anatomy and physiology, as we have shown for dichotic performance. Although the patients were impaired on both dichotic and monotic tests, significantly greater impairment was seen on the dichotic test. Our earlier finding of a significant relation between dichotic performance and measures of anterior temporal lobe atrophy and reduced glucose metabolism was replicated, but no significant relation was found between monotic tests and measures to temporal lobe integrity. We conclude that the inability to divide attention, rather than abnormal processing of degraded stimuli per se, is reflected in poor dichotic performance in patients with dementia of the Alzheimer type, and that dichotic performance, unlike degraded monotic perception, depends directly on the integrity of temporal cortex in these patients.     

Depression and attempted suicide: a comparative study

The Levine-Pilowsky depression questionnaire was used to compare the qualitative and quantitative characteristics of depression in 176 patients admitted to a general hospital following a suicide attempt and 65 psychiatric inpatients with a diagnosis of major affective disorder. The study showed that despite significant age and sex differences there was a striking similarity between the groups on all measures of depression. Diagnostic and therapeutic implications of these findings are discussed, and further research directions are suggested.     

Carcinoma-associated dermatomyositis responding to plasmapheresis

We report a case of severe carcinoma-associated dermatomyositis which, having shown no response to conventional treatment, improved markedly within 48 h of plasmapheresis. We believe that this is the first time that dermatomyositis associated with an advanced carcinoma has been reported to respond in this way. Dermatomyositis can prove extremely difficult to treat and sometimes fails to respond even to very high doses of steroids and immunosuppressants. There is currently only a single report of the use of plasmapheresis in adult dermatomyositis. We therefore wish to support the findings of Dau and draw attention to the value of this therapeutic option in refractory dermatomyositis.     

Experience in treating psoriasis patients with the preparation Ditrastic

The results of clinical trials of ditrastic, an agent manufactured by Orion, Finland, are analyzed. The drug contains 1.5 or 3% of ditranol. Of the 59 patients treated with this drug complete resolution of clinical eruptions was achieved in 43, the condition of 10 patients considerably improved, a partial effect was observed in 4, and no effect in 2 patients. Therefore ditrastic has proved to be a highly effective agent for the treatment of psoriasis, convenient for outpatient therapy.     

Manifesto of space medicine: the next dermatologic frontier

As the fields of astronomy, cosmology, and space travel move rapidly forward, so must space medicine. The manned space program and medical knowledge and support have developed in tandem. Dermatology will play a fundamental role in survival during space flight. This paper reviews past, present, and future accomplishments of the space program as they relate to medicine and characterizes some of dermatology's multiple roles in the future. It further explores the immunologic alterations noted during space flight and the attendant implications for health and well-being both in flight and on return to Earth, or to an Earthlike environment.