Distal dorsal forearm flap

Reinstatement and spontaneous recovery of previously extinguished nicotine-taking behavior were examined in rats. Male subjects were trained to self-administer nicotine (30 microg/kg per infusion, IV; one 60-min session per day for 3 weeks). Extinction sessions were then given for 5-10 days during which saline was substituted for nicotine. Subsequently, in the first set of tests for nicotine seeking, the reinstatement of lever presses that previously delivered nicotine was examined after priming injections of saline and nicotine (75, 150 and 300 microg/kg, SC; and 30 and 60 microg/kg, IV). In the second set of tests for nicotine-seeking, rats were tested after an additional 21-day drug-free period during which they were not exposed to the self-administration chambers (a test for the spontaneous recovery of drug seeking), and after priming injections of nicotine (150 and 300 microg/kg, SC). Reinstatement of extinguished food-reinforced behavior after exposure to nicotine was also determined. Priming injections of nicotine reinstated nicotine seeking regardless of the route of administration. In addition, previously extinguished nicotine seeking recovered spontaneously after a 21-day period during which rats were not exposed to the drug-taking environment. Nicotine also reinstated extinguished food-reinforced behavior in rats with a history of nicotine self-administration, but not in drug-naive rats. The present results extend previous work with opioid and stimulant drugs on reinstatement of drug seeking by the self-administered drug. It also appears that, as with other positive reinforcers, the mere passage of time is a sufficient condition for the spontaneous recovery of extinguished nicotine seeking.     

Head trauma

Progress in research includes studies concerning the pathophysiology and outcome of pediatric head injury, the pathology of the hippocampus in fatal injury, and the use of multivariate statistics to predict outcome in survivors. Recent research has confirmed and extended findings regarding the differential effects of closed head injury, depending on the age of the individual. These studies indicate that the consequences of head injury are more severe in older adults and in children younger than 2 years. Neuroimaging findings include evidence for delayed brain injury as a major cause of mortality and disability. Functional brain imaging provides evidence for cerebral dysfunction that is not appreciated by structural brain imaging techniques and may have a stronger relationship to neurobehavioral sequelae. The neurobehavioral sequelae frequently implicate frontal dysfunction, even in the absence of structural findings on computed tomography or magnetic resonance imaging. Studies of mild head injury have expanded our knowledge concerning the pathogenesis of postconcussional symptoms, including a preinjury vulnerability based on recent life events. Persistent postconcussional symptoms after mild head injury are frequently associated with emotional disturbance of clinical proportions.     

Role of glutathione, glutathione S-transferases and multidrug resistance-related proteins in cisplatin sensitivity of head and neck cancer cell lines

Spontaneous proliferative liver lesions were found in 15 (13 males and 2 females) of 244 (122 of each sex) transgenic (Tg) mice carrying the human prototype c-H-ras gene (rasH2). The liver lesions included 3 foci of cellular alteration, 1 hepatocellular adenoma, 5 hepatocellular carcinomas, and 4 hepatic hemangiosarcomas in the males and 1 focus of cellular alteration and 1 hepatocellular carcinoma in the females. The mutation patterns of the human and endogenous mouse c-H-ras codon 61 in these proliferative liver lesions were analyzed by DNA amplification using polymerase chain reaction, single-strand conformation polymorphism (PCR-SSCP), and oligonucleotide dot blot hybridization. The hepatocellular carcinomas in 4 males and 1 female contained a point mutation in the mouse c-H-ras gene: 3, 1, and 1 carcinomas had a CAA to AAA transversion at the first base of codon 61, a CAA to CTA transversions, and a CAA to CGA transition at the second base of codon 61, respectively. No point mutations in the human c-H-ras transgene were detected in any hepatocellular carcinoma. All 4 hepatic hemangiosarcomas had a CAG to CTG transversion at codon 61 of the human c-H-ras gene, but no point mutations were detected in codon 61 of the mouse c-H-ras gene. No mutations in human or mouse c-H-ras codon 61 were detected in altered cell foci or hepatocellular adenoma. These results indicate that spontaneous liver tumors in rasH2 Tg mice contain different mutation patterns depending on the histologic type or cell origin of the tumors (i.e., hepatocellular carcinomas or hepatic hemangiosacomas). The absence of similar mutations in foci of cellular alteration and the hepatocellular adenoma suggests that the occurrence of codon 61 point mutations is a late event in the progression of hepatocellular neoplasia in rasH2 Tg mice.     

Lung reduction surgery in chronic obstructive lung disease

In the 1960s the promise of the Brantigan lung reduction surgery was shattered when it was shown that the improvement in airway conductance drifted back towards the preoperative value over a period of 12 to 18 months. Since then there has been a marked improvement in our understanding of emphysema, its pathology, and techniques for obtaining images of the lung. In addition, reliable automated cardiopulmonary and physiologic testing, advances in critical care medicine, and new pharmacologic agents have improved patient care. Surgical techniques now allow better control of air leaks and access to anatomic regions not previously accessible. The combination of all of the above makes lung reduction surgery worth re-examining as a palliative procedure for severely symptomatic patients. Clearly, it is not a panacea but can in some cases produce dramatic improvements in symptomatology and quality of life. This article presents the available data describing potential mechanisms of improvement and clinical outcomes following lung reduction surgery. It also outlines areas that need further work, such as patient selection and surgical techniques.     

Toxicity of an antitumor ribonuclease to Purkinje neurons

Purkinje cell toxicity is one of the characteristic features of the Gordon phenomenon, a syndrome manifested by ataxia, muscular rigidity, paralysis, and tremor that may lead to death (Gordon, 1933). Two members of the RNase superfamily found in humans, EDN (eosinophil-derived neurotoxin) and ECP (eosinophil cationic protein), cause the Gordon phenomenon when injected intraventricularly into guinea pigs or rabbits. We have found that another member of the RNase superfamily, an antitumor protein called onconase, isolated from Rana pipiens oocytes and early embryos, will also cause the Gordon phenomenon when injected into the cerebrospinal fluid of guinea pigs at a dose similar to that of EDN (LD50, 3-4 micrograms). Neurologic abnormalities of onconase-treated animals were indistinguishable from those of EDN-treated animals, and histology showed dramatic Purkinje cell loss in the brains of onconase-treated animals. The neurotoxic activity of onconase correlates with ribonuclease activity. Onconase modified by iodoacetic acid to eliminate 70% and 98% of the ribonuclease activity of the native enzyme displays a similar decrease in ability to cause the Gordon phenomenon. In contrast, the homologous bovine pancreatic RNase A injected intraventricularly at a dose 5000 times greater than the LD50 dose of EDN or onconase is not toxic and does not cause the Gordon phenomenon. A comparison of the RNase activities of EDN, onconase, and bovine pancreatic RNase A using three pancreatic RNA substrates demonstrates that onconase is orders of magnitude less active enzymatically than EDN and RNase A. Thus, another member of the RNase superfamily in addition to EDN and ECP can cause the Gordon phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)     

A PET study of the neural systems of stuttering

The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking.     

The protein structure code: what is its present status?

Current methods of prediction of protein conformation are reviewed and the algorithms on which they rely are presented. For non-homologous proteins and after cross-validation the reported methods exhibit a probability index, i.e. the per cent of correctly predicted residues per predicted residues, of 63-65% with a standard deviation of the order of 7% for three conformational states--helix, beta-strand and coil. This present limitation in the accuracy of predictions that use only the information of the local sequence can be related essentially to the effect of long-range interactions specific for each protein family. The methods based on sequence similarity can improve the accuracy of prediction by expressing explicitly the homology of the protein to be predicted with proteins in the database. In these circumstances the probability index can reach 87% with a standard deviation of 6.6%. This property can be used for modeling homologous proteins by aiding in amino acid sequence alignments. The prediction of the tertiary structure of a protein is still limited to the case of modeling a structure based on the known three-dimensional structure of a homologous protein.