Effects of inorganic and triethyl lead and inorganic mercury on the voltage activated calcium channel of Aplysia neurons.

Using conventional two electrode voltage clamp techniques we have studied the effects of Pb2+, triethyl lead (TEL) and Hg2+ on voltage-activated calcium channels of Aplysia neurons and found that all three metals are potent inhibitors at micromolar concentrations. However, the time course of current reduction or block and its reversibility vary when comparing Pb2+ to TEL and Hg2+. With application of Pb2+ the calcium current decreases immediately and a steady state is reached within three to seven minutes, depending upon the concentration of Pb2+ (IC50 = 61 microM). The block was easily reversed upon wash out of Pb2+ with a time course similar to that of onset. Perfusion with either TEL (5 to 50 microM) or Hg2+ (5 to 200 microM) resulted only in a small reduction of current when the substances reached the cell membrane but with clear reduction within 2 min. The decrease continued at about the same speed for the total duration of the application. Upon washing there was no recovery of the response. At the onset of washing the rate of current decline stopped for several minutes, but then the current continued to decline at a slower rate in the absence of toxicant. Our data suggest that Pb2+ acts by a direct and reversible blockade of the calcium channel. In contrast TEL and Hg2+ act slowly and irreversibly to block calcium channels at concentrations which do not greatly affect membrane potential or resistance. In spite of the slow time course these substances are probably acting directly on the calcium channel.     

PCR-SSO typing for DR4-Dw subtypes: application to unrelated bone marrow transplant donor selection

Thirty-seven DR4-positive patient-unrelated bone marrow donor pairs previously DR/DQ restriction fragment length polymorphism (RFLP) typed and tested in mixed lymphocyte culture (MLC), have been DR4-Dw subtyped retrospectively using sequence specific oligonucleotide probes. We found that DR4-Dw subtyping substantially increased the accuracy of pre-MLC matching and could potentially accelerate donor searches by avoiding unnecessary MLC tests on Dw-mismatched donors.     

Pleomorphic adenoma arising in a salivary rest in childhood.

Two children with pleomorphic adenomas developing in heterotopic salivary tissue are presented. These are unusual lesions, rarely seen in adults and not previously described in the pediatric age group.     

Olfactory primary neurons as a route of entry for toxic agents into the CNS.

Reports in the literature suggest that the primary sensory neurons of the olfactory system may provide a direct route of entry for agents into the central nervous system (CNS). To investigate whether cadmium, a heavy metal which is normally excluded from the CNS by the blood-brain barrier, can enter the CNS via the olfactory system, rats were exposed either intranasally (unilaterally) or ip to 109Cd (1 mumol Cd labeled with 1 microCi 109Cd). Rats were allowed to survive 7 days, at which point they were euthanized and the kidneys, livers, right and left forebrains, right and left olfactory bulbs, and right and left olfactory epithelia were removed. Tissues were placed in scintillation vials and radioactivity counted. In rats exposed by intranasal instillation, Cd levels were significantly elevated in the kidney, liver and ipsilateral olfactory bulb and epithelium, but not in the contralateral bulb and epithelium or forebrain areas. With the ip exposure, Cd levels were only elevated in the kidney and liver. In a second study the protocol was repeated (without ip exposure), but the olfactory bulbs and epithelium were washed in EDTA before counting. Cd was still present in the bulbs after washing, suggesting that the metal was internal and not bound to the external membrane. In the final experiment, both time course and dose effect of this phenomenon were explored. Rats were exposed either intransally to 1 mumol Cd labeled with 109Cd (1 microCi) and then sacrificed after 1, 3, 7, or 14 days or were exposed to 0.01, 0.1, or 1.0 mumol Cd labeled with 1 microCi 109Cd and sacrificed after 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dopamine D1 autoreceptor function: possible expression in developing rat prefrontal cortex and striatum.

Synthesis-modulating dopamine (DA) autoreceptor function was studied in vivo using gamma-butyrolactone (GBL) to block propagation along DA axons. DA synthesis was measured by the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) after inhibition of aromatic L-amino acid decarboxylase. GBL treatment markedly increased DOPA accumulation in both the striatum and prefrontal cortex of developing rats. The selective DA partial D1 agonist SKF-38393 inhibited this GBL-induced rise in DA synthesis in both the striatum and prefrontal cortex of 15- and 22-day-old rats, but not in adults. The effects of SKF-38393 in developing rats were mimicked by the non-catechol D1 partial agonist CY-208-243, and were blocked by the D1 antagonist SCH-23390, suggesting receptor mediation. The mixed D2/D3 agonist quinpirole attenuated DA synthesis in striatum of both two-week-old and adult rats, but failed to inhibit the GBL-induced increase in DA synthesis in the developing prefrontal cortex. These findings suggest that synthesis-modulating D1-like receptor function may emerge transiently in the developing mammalian forebrain. In the adult striatum these functions appear to be subsumed by D2-like receptors, whereas all synthesis-modulating DA receptor function in prefrontal cortex appears to be essentially lost with maturation.     

Problematic behavior of drug-dependent patients in the general hospital. A clinical and administrative approach to management

Drug-dependent patients in general hospitals behave in ways that are difficult for medical and surgical staff to manage. Common problems include drug-seeking, states of intoxication and withdrawal, poor compliance, and behavior that is disruptive or dangerous to others. The authors describe an approach to these problematic behaviors based upon early recognition, a clinical perspective, and administrative action. Institutional initiatives are needed to overcome the practical and conceptual obstacles to effective management of these patients.     

Toxicosis from and possible adaptation to Galega officinalis in sheep and the relationship to Verbesina encelioides toxicosis

Galega officinalis L (goatsrue), a plant introduced from Europe and found in abundance in northern Utah, was tested for toxicity in ewes (Ovis aries). Clinical signs of poisoning induced by doses as small as 0.8 g of dried plant/kg body weight/day included dyspnea, anoxia, and foaming nasal discharge. Pathologic signs in animals that died following overdose of the plant included severe hydrothorax, generalized lung congestion, foamy exudate in bronchioles and trachea, epicardial and endocardial petechiation, and pericardial effusion in severely affected ewes. Microscopic lesions included a severe diffuse alveolar and interlobular edema. No significant alterations in blood constituents were observed in treated animals. Ewes administered the plant on several consecutive days developed an apparent adaptation to the toxin of the plant and were thereby able subsequently to tolerate levels 5-10 times the pre-treatment lethal dose with no discernible adverse clinical or pathological effects.