Unblocking of meiotic crossing-over between the silent mating-type cassettes of fission yeast,conditioned by the recessive,pleiotropic mutant rik1

Summary The mating-type region of Schizosaccharomyces pombe consists of three subloci: the expressed cassette at mat1, and the silent cassettes at mat2-P and mat3-M. Previous work has shown that the genetically inert spacer region of 15 kb between mat2 and mat3 is completely devoid of meiotic recombination. This crossover blockage is lifted in the recessive mutant rik1. Other properties such as mating-type switching, sporulation efficiency and spore viability are also affected in this pleiotropic mutant. Presumably the wild-type rik1 product is responsible for heterochromatinization throughout the silent domain of the mating-type region.     

Increased sympathetic tone in forearm subcutaneous tissue in primary hypothyroidism

Sympathetic reflex regulation of subcutaneous blood flow (SBF) in the forearm was studied in eight patients with primary hypothyroidism. Diastolic arterial pressure was greater than or equal to 95 mmHg in five patients. SBF was determined by local clearance of Na99mTcO4. Sympathetic vasoconstriction normally seen after lowering the forearm 40 cm below heart level was absent since SBF only decreased by 4% (+/- 7%, P greater than 0.1) during these conditions. In head-up vertical position we noticed a diminished baroreceptor response as SBF at heart level was reduced by 11% (+/- 7%, P greater than 0.1) compared to supine position. After proximal local anaesthesia SBF increased by 351% (+/- 81%, P less than 0.01) and disclosed a normal vasoconstrictor response as SBF was reduced by 53% (+/- 5%, P less than 0.01) during arm lowering. Five of the treated patients were restudied in the euthyroid state. Mean arterial pressure was reduced in mean by 20 mmHg (+/- 6 mmHg, P less than 0.02) during treatment and a significant vasoconstriction was observed both during arm lowering (SBF = -52% (+/- 6%, P less than 0.02)) and in head-up vertical position (SBF = -45% (+/- 11%, P less than 0.02)). In conclusion sympathetic vasoconstrictor activity in adipose tissue is markedly increased in primary hypothyroidism. Sympathetic tone and arterial pressure are reduced during treatment.     

Metacarpal bone measurements in renal transplant recipients, in corticosteroid-treated patients with polymyalgia rheumatica and in patients with primary hyperparathyroidism

Quantitative radiological measurements on the second left metacarpal bone were carried out in 23 patients with primary hyperparathyroidism, 22 corticosteroid-treated patients with polymyalgia rheumatica and 40 renal transplant recipients treated with prednisone and azathioprine. Women with primary hyperparathyroidism and corticosteroid-treated women showed significantly decreased mean values of metacarpal bone compared to normal controls, probably due to a higher bone resorption than formation at the endosteal surface. Bone loss was more pronounced in corticosteroid-treated women than in women with primary hyperparathyroidism, partly due to age difference. In renal transplant recipients, bone loss took place during the initial period after renal transplantation, probably due to increased endosteal bone resorption. During this period a periosteal new bone formation took place in female renal transplant recipients. The quantitative radiological measurements make it possible to determine whether bone loss is due to a higher ratio of bone resorption than of bone formation at the periosteal and/or endosteal surface.     

Leishmania interaction with human monocytes and neutrophils: modulation of the chemotactic response

Infection of host cells with Leishmania, which are obligate parasites of mononuclear phagocytes, most probably involved chemotaxis of host cells towards the parasite. We have examined the chemotactic properties of a sonicate derived from L. mexicana amazonensis promastigotes for normal human peripheral blood monocytes and neutrophils. L. m. amazonensis sonicate exhibited chemotactic activity for monocytes and neutrophils. Treatment at 65 degrees C for 30 min, enhanced the activity for neutrophils but not for monocytes, while treatment at 100 degrees C for 60 min abolished the activity. Additional studies showed that the sonicate generated chemotactic activity in serum, presumably by activating the alternative complement pathway to produce C5a, for monocytes and neutrophils. Incubation of monocytes and neutrophils with the sonicate inhibited the chemotactic activity of these cells towards various chemoattractants. When the sonicate was heat-treated the inhibitory effect was lost, except when sonicate was used as a chemoattractant. These results indicate the presence of specific receptors for factor(s) from L. m. amazonensis promastigotes on human monocytes and neutrophils.     

Electrophysiological properties of calcitonin-secreting cells derived from human medullary thyroid carcinoma

Primary cultures of human medullary thyroid carcinoma tissue were prepared from lymph node metastases in two patients. The parenchymal, cultured cells displayed positive immunocytochemical staining for CT, and the cells also released the hormone into the culture medium. The membrane potential and resistance of the CT-producing cells were 50.1 +/- 8.9 mV and 634 +/- 154 M omega (mean +/- SD, n = 46). TTX sensitive action potentials with maximum rate of rise up to 51 V s-1 were evoked by current injection in Na+-containing solution, whereas TTX insensitive action potentials with maximum rate of rise up to 9 V s-1 were generated in Na+-free solution. These action potentials were reversibly blocked by D-600. We conclude that the action potentials of the human MTC cells have both a Na+ and a Ca2+ component. Ejection of CA2+-free solution close to the cells caused membrane hyperpolarization associated with decreased membrane resistance. The reversal potential of this response was -66.2 +/- 10.9 mV (n = 10), indicating that a permeability increase to Cl- and/or K+ may be involved. We suggest that elevated plasma Ca2+ concentration in vivo may cause increased excitability due to membrane depolarization and resistance increase, thus leading to enhanced Ca2+ influx and hormone secretion.     

Trifluoperazine stimulated sodium transport through the apical surface of isolated frog skin

When added to the apical solution of isolated frog skin, the calmodulin antagonist trifluoperazine (TFP)* stimulated the short-circuit current (SCC) in a dose-dependent manner. The increase in SCC was due to an enhanced active transepithelial Na transport. After addition of TFP (15 microM) the intracellular voltage depolarized, showing that TFP acts by increasing the sodium (Na) permeability of the apical membrane. The TFP-induced increase in SCC was not accompanied by an increase in prostaglandin E2 release from the skins as observed by basolateral addition of TFP. When the apical Na concentration in fast-flow experiments was changed from 0 to 50 mM, the SCC increased promptly and then reclined. The presence of TFP in the apical solution abolished this recline. The apparent inhibition constant for amiloride changed in the presence of TFP from 1.42 +/- 0.12 microM to 0.38 +/- 0.05 microM (n = II) and TFP abolished the inhibition of SCC caused by high apical Na concentrations. These observations indicate that TFP acts by abolishing the Na self-inhibition of the Na channels. Calmidazolium and chlorpromazine stimulated the SCC to the same degree and in the same concentration range as TFP, suggesting that the effect of TFP was not mediated by the Ca2+-calmodulin complex.     

The effect of drugs on the acquisition of stimulus control in a conditioned suppression procedure

Rats were trained to press a lever under a variable-interval (VI) schedule of water reinforcement. After stable responding had developed, a 4.5-KHz tone (CS) was conditioned classically to a 2.5-mA electric shock (US) in groups of animals which had been given various psychoactive drugs or saline. Twenty-four hours later, a stimulus generalization test was conducted in the absence of drug; during this session, tones that varied in frequency around 4.5 KHz were presented while the animals were responding under the VI schedule. In animals conditioned under saline, all tones (non-differentially) suppressed responding which, however, recovered gradually over time. This suppressive effect was eliminated by lysergic acid diethylamide (LSD; 0.2 and 0.32 mg/kg), cocaine (20 mg/kg), diazepam (2.5 mg/kg), lisuride (0.08 mg/kg), mescaline (20 mg/kg) and 5-methoxy-N,N-dimethyltryptamine (4 mg/kg), and was attenuated by amphetamine (4 mg/kg), pentobarbital (15 mg/kg) and morphine (4 mg/kg). Atropine (10 mg/kg), scopolamine (1 mg/kg), clonazepam (0.5 mg/kg), and chlorpromazine (4 mg/kg) did not alter the suppressive effect of the tone. The serotonin antagonist BC-105 (6 mg/kg) reversed the effect of 0.2 mg/kg of LSD. These results suggest (1) that drug-induced stimuli may overshadow other (e.g., external) stimuli during classical conditioning and, (2) that drugs might affect behavior by altering processes (stimulus control or others) that do not simultaneously involve response or motor control.     

A comparison between two emergency cricothyroidotomy instruments

As part of a training programme for younger doctors, two commercially available, emergency cricothyroidotomy sets were evaluated. Prior to the surgical procedure, half of the doctors in each group received an audiovisual lesson. In a simulated but realistic emergency situation, involving autopsy material, cricothyroidotomy was performed utilizing either the "Nutrake" or the "Gentofte" system. The audiovisual lesson increased the speed and the success rate of the doctors performing this procedure as well as strengthening their confidence. Both systems allowed positive pressure ventilation. The participating doctors achieved a higher success rate at a faster speed with the "Nutrake" set.     

Aortobifemoral bypass with autogenous saphenous vein in treatment of paninfected aortic bifurcation graft

An alternative method is presented in which aortobifemoral bypass with autogenous great saphenous vein is implanted after excision of previously inserted synthetic aortobifemoral grafts because of prosthetic "paninfection." The procedure was followed in five patients; one death occurred and the remaining four patients recovered completely from graft infection. Only in one case did saphenous vein thrombosis occur. These results are encouraging considering the high mortality rates following the previously available methods of management.