Facilitation of the long-term store of memory with strychnine.

Female mice (C57BL/6 strain), repeatedly administered strychnine sulfate for 10 days after exposure to a six-unit maze, showed significantly improved learning when trained again. This facilitation effect was not due to overall enhancement of learning ability and could not be attributed to retrograde facilitation of consolidation processes.

Effects of Electroshock on Memory: Amnesia without Convulsions.

Mice received a single training trial on an inhibitory avoidance task and a retention trial 24 hours later. Electroshock stimulation, administered 25 seconds after the training trial, produced amnesia even if the convulsion was prevented by ether anesthesia. The amnesia produced by such shock is apparently due to the electric current and not to the convulsion.

p-wave triggered superconductivity in single-layer graphene on an electron-doped oxide superconductor.

Electron pairing in the vast majority of superconductors follows the Bardeen-Cooper-Schrieffer theory of superconductivity, which describes the condensation of electrons into pairs with antiparallel spins in a singlet state with an s-wave symmetry. Unconventional superconductivity was predicted in single-layer graphene (SLG), with the electrons pairing with a p-wave or chiral d-wave symmetry, depending on the position of the Fermi energy with respect to the Dirac point. By placing SLG on an electron-doped (non-chiral) d-wave superconductor and performing local scanning tunnelling microscopy and spectroscopy, here we show evidence for a p-wave triggered superconducting density of states in SLG. The realization of unconventional superconductivity in SLG offers an exciting new route for the development of p-wave superconductivity using two-dimensional materials with transition temperatures above 4.2 K.

Pulmonary function of haplotype-matched and mismatched allografts in dogs treated with total-body irradiation, autologous marrow transplantation, methotrexate, and donor blood.

Seven beagle recipients surviving 2-11 years after allotransplantation of a left lung were available for study of pulmonary function. Significant reductions of ventilation and perfusion to the transplanted lung were documented by radionuclide scanning. These reductions in function were well-matched, however, and allowed relatively normal gas exchange, as measured by VD/VT, arterial PO2 and shunt fraction. The vasoconstrictor response of the transplanted lung to both hypoxia and stellate ganglion stimulation was comparable to that of the native lung. An abnormal rise in graft pulmonary vascular resistance and fall in PaO2 when the normal lung was made hypoxic suggest an inability of the transplanted lung to vasodilate and recruit blood vessels normally in response to increased blood flow. The animals were sacrificed at the conclusion of the pulmonary function testing. Pathologic study of the transplanted lungs showed minimal changes of rejection in spite of the fact that these recipient animals received no immunotherapy after the second posttransplant week.

Immunohistochemical analysis of small cell tumors of the thyroid gland: an Eastern Cooperative Oncology Group study.

The majority of small cell anaplastic tumors of the thyroid gland are generally believed to be non-Hodgkin's lymphomas, including most of those formerly classified as small cell carcinomas. Using a panel of antibodies capable of detecting epithelial, neuroendocrine, and B and T cells in paraffin-embedded tissue sections, we studied 68 thyroid neoplasms in which the original diagnosis was small cell carcinoma or lymphoma. Sixty-three of the tumors were identified as lymphomas of B-cell origin on the basis of L26 reactivity used in conjunction with light chain restriction and MB2 immunostaining. Two additional tumors were classified as lymphomas of indeterminate phenotype. Immunophenotyping indicated an epithelial origin in the remaining three tumors. No cases of medullary carcinoma were detected by immunostaining. Histologic review revealed a predominance of large cell and immunoblastic lymphomas, with low-grade lymphomas of mucosa-associated lymphoid tissue histology accounting for only five cases. Our findings indicate that the majority of small cell anaplastic tumors of the thyroid are B-cell lymphomas. Although primary small cell carcinoma of the thyroid may rarely occur, this diagnosis should not be made without immunohistologic confirmation.

An improved method of cell recovery following bronchial brushing.

Cytologic examination of bronchial brush specimens is effective in diagnosing bronchogenic carcinoma. A major problem is loss of cells and cellular detail associated with the direct smear technique (DST). A more recent method, the Saccomanno brush wash (SBW), uses a narrow-mouthed vial to scrape cells off the brush directly into fixative. We sampled 12 directly visualized airway tumors using standard brush technique. The same brush was then agitated in a SBW vial, which was centrifuged, the cell pellet being smeared over a predetermined area of a slide. Designated areas of each slide were counted and total malignant cells per slide extrapolated. DST slides had significantly fewer cells than SBW slides, and cellular detail was better with SBW in seven cases, DST in one case, and equal in four cases. SBW appears preferable for handling of bronchial brush specimens.

Bronchopulmonary bacillary angiomatosis.

A man with prior AIDS developed acute febrile interstitial pneumonitis, hilar and paratracheal adenopathy, and bronchial polyps. The polyps were histologically typical for bacillary angiomatosis and complete symptomatic and radiographic response to oral clarithromycin was seen. The clinical presentation of bacillary angiomatosis includes pulmonary disease and in particular bronchial polyps; clarithromycin is an effective oral antibiotic.

Reinterpretation of the literature indicates differential sensitivities of long-sleep and short-sleep mice are not specific to alcohol.

This paper reviews the findings and conclusions of the literature pertinent to the Long-Sleep and Short-Sleep selectively-bred lines of mice and challenges the widely-held notion that the selective breeding program was successful in separating alleles for specific sensitivities to just alcohol. Rather, it is argued that these lines of mice were selected for differing activity of a more general process. Recent evidence, as well as reevaluated previous evidence, indicates that Long-Sleep mice are more sensitive to the soporific effects of three major classes of CNS depressants (alcohols, barbiturates, and benzodiazepines), as well as many other anesthesia-inducing compounds (adenosine, chloral hydrate, trichloroethanol, paraldehyde, nitrous oxide, enflurane, and isoflurane). Further, much evidence also supports the conclusion that most of these hypnotic-depressants and anesthetics could exert their soporific influence by a potentiation of GABA activity. The other characteristic of interest in this regard is susceptibility to convulsions. Short-Sleep mice have significantly lower thresholds to both flurothyl-induced and bicuculline-induced convulsions, as well as being more likely to suffer from paroxysms during ethanol withdrawal.

Evidence that the selectively bred long- and short-sleep mouse lines display common narcotic reactions to many depressants.

This report challenges the notion that the long-sleep and short-sleep selectively bred mouse lines display unique narcotic reactions to alcohols. First, we found that the specific ethanol sensitivity hypothesis is not supported by the relevant literature. Second, we found that much of the ambiguity with respect to this hypothesis concerns just pentobarbital. Consequently, the major intent of this paper was to further explore what effect pentobarbital had on these two mouse lines. Additionally, we examined the effects of barbital and ethanol. Our results for each of these compounds clearly indicate that when these mouse lines can be differentiated by particular doses the long-sleep animals always displayed greater narcotic reactions. In this inquiry only one sex was employed, and testing was always initiated at the same time of day. It is our contention that many of the equivocal findings that have been reported concerning pentobarbital are due to combining data from both sexes, circadian rhythmicity, and similar procedural variables.

Maturational changes related to dopamine in the effects of d-amphetamine, cocaine, nicotine, and strychnine on seizure susceptibility.

The effects of four neural excitants (damphetamine, cocaine, nicotine, and strychnine) on myoclonic and clonic seizure susceptibility were investigated in two age groups (30 and 120 days) of short-sleep mice. Amphetamine and cocaine decreased susceptibility to myoclonus in young mice and increased susceptibility in mature mice. These effects were attenuated by pretreatment with haloperidol, indicating mediation by a dopaminergic system. Amphetamine did not alter clonic susceptibility in either age group of mice, whereas cocaine affected clonic susceptibility and myoclonus. These effects were not attenuated by haloperidol, indicating mediation by systems other than dopamine. Nicotine decreased susceptibility to myoclonus and increased susceptibility to clonus, whereas strychnine increased susceptibility to both types of seizure. Haloperidol, however, failed to alter any of these effects. These results are consistent with our previous work which suggests that a dopaminergic mechanism in these mice undergoes marked developmental changes between 30 and 120 days of age.

Family members of patients with sporadic medullary thyroid carcinoma must be screened for hereditary disease.

BACKGROUND: Medullary thyroid carcinoma (MTC), a tumor arising from calcitonin-secreting C cells, appears in either a sporadic nonfamilial or a hereditary form as a component of a multiple endocrine neoplasia syndrome or familial non-multiple endocrine neoplasia MTC. Screening kindred of a patient with familial MTC to detect MTC in the early curable state is standard practice. Opinions conflict about whether it is necessary to screen relatives of patients with apparently nonfamilial MTC to exclude hereditary disease or whether the clinicopathologic features can differentiate between the two forms. METHODS: Clinically well kindred of a patient with MTC that was histopathologically characteristic of the sporadic type were screened for hereditary disease by measurement of plasma levels of basal and stimulated calcitonin. RESULTS: Three of four immediate relatives tested positive for excessive calcitonin secretion and underwent thyroidectomy. All had C-cell hyperplasia, the premalignant phase of MTC. CONCLUSIONS: The patient with apparently sporadic (nonfamilial) MTC was clearly an index case of familial disease. We conclude that clinical presentation and histopathologic examination are not adequate to reliably exclude hereditary MTC. Until genetic markers are readily available to distinguish between sporadic and familial forms, biochemical screening should be done in primary relatives of all patients with newly detected MTC.

Intracellular lipid droplets in functioning transitional parathyroid oxyphil adenomas. A caveat.

Histochemical demonstration of intracellular lipid droplets on frozen section has been used to distinguish normal parathyroid tissue from that of adenoma and chief cell hyperplasia. Differentiation is based on the observation that the cells of adenoma and chief-cell hyperplasia largely lack intracellular lipid, which is present in the suppressed chief cells of normal glands in patients with adenoma. We present two functional transitional oxyphil adenomas that contained abundant intracellular lipid. Failure to recognize that transitional oxyphilic adenomas may contain focal accumulation of intracellular lipid droplets could lead to confusion in histologic interpretation.

Scrotal lymphangioma.

Congenital malformations of the intrascrotal lymphatic system may form cystic masses. A case of a lymphangioma arising in Colles fascia is presented. This rare clinical entity should be included in the differential diagnosis of cystic lesions of the external male genitalia. Total surgical excision is the treatment of choice.

Coping and seizure susceptibility: control over shock protects against bicuculline-induced seizures.

Rats were either given 80 escapable shocks, yoked inescapable shocks, restraint or given no treatment. Two hours later all subjects received i.p. injection of bicuculline (4, 6 or 8 mg/kg) and were immediately tested for latency to initial myoclonic jerk and clonus. The latency to clonic convulsion was dramatically affected by prior shock treatment, and the direction of this change depended upon the escapability/inescapability of the shock. Subjects that were given escapable shock showed a delay of onset to seizure, while subjects inescapably shocked demonstrated a decreased latency to clonus in comparison to restrained and naive controls. It was also demonstrated that if the subjects were tested immediately following a stress experience, both the 80 escapable and inescapable shock condition protected against bicuculline-induced seizures in comparison to the control condition. Finally Experiment 2 confirmed a previous finding that less stress, i.e., 20 inescapable shocks, protects against seizures when the animals are challenged with bicuculline either immediately or 2 h later. Our suggestion is that control over stress may facilitate GABAergic transmission, and this may be the mechanism whereby coping protects against the behavioral and physiological disruption produced by exposure to a stressor.

Patterns of convulsive susceptibility in the long-sleep and short-sleep selected mouse lines.

It has been hypothesized that the Long-Sleep and Short-Sleep mouse lines were bidirectionally selected for high and low brain excitability, and further, that these differences are mediated by the benzodiazepine/gamma-aminobutyric acid (GABA) receptor-chloride channel complex. Hence, mice from both lines were administered seven convulsants (bicuculline, pentylenetetrazol, 3-carbomethoxy-beta-carboline, picrotoxin, caffeine, flurothyl and strychnine) and myoclonic and clonic seizure latencies recorded. Supporting the original hypothesis, the results show that the two lines were differentiated by all of the convulsants and that in response to the drugs, three distinct convulsive patterns were found. Nevertheless, a simple genetic model accounting for these results was not evident. To further clarify these susceptibility patterns, a convulsant representing each of these patterns (bicuculline, pentylenetetrazol or caffeine) was administered in conjunction with the anticonvulsant-barbiturate phenobarbital or the benzodiazepine antagonist Ro 15-1788. Irrespective of the convulsant given, phenobarbital attenuated both myoclonus and clonus subsequent to all convulsants, while Ro 15-1788 had a more discrete anticonvulsant profile.

The medial amygdaloid nucleus modifies social behavior in male rats.

Electrical stimulation of the medial amygdaloid nucleus (AME) produces a behavioral state in male rats that resembles the postejaculatory interval, but electrical recording from cells in the AME shows that they become active earlier in sexual behavior, around the time that the male first appears to become aware of estrus in the female. In an attempt to resolve which feature of sexual behavior was mediated by the AME, we stimulated the structure bilaterally in freely behaving males using voltage levels too low to produce the postejaculatory interval. We found that electrical activation of this kind facilitated sexual behavior when it would not otherwise occur (i.e., in the presence of a nonestrous female). However, the stimuli suppressed sexual behavior when it would normally occur (i.e., in the presence of a nonestrous female). We discuss alternative interpretations of the results in the context of a general model for the central organization of sexual behavior in males.

Peptide YY ameliorates cerulein-induced pancreatic injury in the rat.

Peptide YY (PYY), a known inhibitor of both pancreatic secretion and the release of cholecystokinin (CCK), may play a role in the pathophysiology of acute pancreatitis (AP). Supramaximal stimulation of the pancreas with CCK, or its analogue cerulein, induces edematous AP. We previously documented significant decreases in plasma PYY in sodium taurocholate-induced AP in the anesthetized pig, with exogenous PYY suppressing plasma amylase activity. We hypothesized that PYY may ameliorate cerulein-induced pancreatic injury in a conscious animal model. Thirty-two male Sprague-Dawley rats underwent chronic cannulation of the jugular vein and carotid artery for drug infusion and blood sampling. The animals were allowed to recover from anesthesia for a minimum of 16 hours, after which they were randomized to one of four (n = 8) treatment groups (cerulein 10 micrograms/kg/h, PYY 400 pmol/kg/h, cerulein+PYY, and control-saline 2 mL/kg/h). All treatments were administered by intravenous infusion over the first 6 hours of the experiment. Blood samples were taken prior to infusion and at 1, 3, 6, 9, and 24 hours into the study; the rats were then killed and the pancreata removed for weighing and histologic examination. All pancreatic specimens were graded in a blinded fashion for vacuolization, edema, inflammation, and necrosis. The mean basal plasma amylase level for all animals was 1,171 +/- 100 U/L and was not significantly different between groups. Infusion of cerulein resulted in significant increases in plasma amylase levels at 3, 6, 9, and 24 hours (4,827 +/- 1,022 U/L at 24 hours). In the group receiving both cerulein and PYY, the hyperamylasemia was attenuated with a return to basal values at 24 hours (1,206 +/- 103 U/L). There was significant pancreatic weight gain (1.99 +/- 0.07 g versus 1.03 +/- 0.07 g) and a worsened histologic picture in cerulein-treated animals compared with control animals (worsened edema, necrosis, and vacuolization). The addition of PYY to cerulein resulted in significantly lower pancreatic weight (1.27 +/- 0.11 g) than in the non-PYY-treated rats receiving cerulein. Pancreatic weight was not significantly different in this group compared with the control group. In addition, pancreatic histologic findings were significantly improved in those rats receiving PYY (decreased vacuolization and necrosis). Amylase levels, pancreatic weight, and morphologic findings were not significantly changed compared with basal values in the control or PYY alone treated groups. e conclude that as an inhibitor of pancreatic exocrine secretion, PYY ameliorates cerulein-induced pancreatic injury in the conscious rat.

Sedative-hypnotic anomalies related to dose of pentobarbital in long-sleep and short-sleep selectively-bred mice.

Hypnotic effects following administration of three doses of pentobarbital were evaluated in mice selectively-bred for differential hypnotic sensitivity to ethanol. Although the ethanol-sensitive Long-Sleep (LS) line displays greater sedation to a wide variety of CNS depressants (alcohols, barbiturates, benzodiazepines, general anesthetics), when compared to the ethanol-insensitive Short-Sleep (SS) line, the response pattern to pentobarbital remains equivocal. Thus, to clarify the effect of pentobarbital, certain variables (dose, sex, circadian rhythmicity) believed to be important in the expression of sleep time were evaluated. For all doses examined "sex" and "time of day tested" impacted on sleep time. With these provisos, 40 mg/kg consistently induced shorter sleep time in SS mice. The 60 mg/kg dose either failed to distinguish these two lines, or induced greater sleep times in the SS mice. The 80 mg/kg dose tended to have the same effect as the 60 mg/kg dose, but to a greater degree. Overall, it appears that for each line the dose response curve for pentobarbital is sigmoidal, but that the slope of the curve for the middle range of doses is greater for the SS line. Since pentobarbital has a unique effect on these lines of mice that is dissimilar to those reported for other barbiturates, the implication is that an additional factor, that is unimportant for other barbiturates, is essential for pentobarbital-induced hypnosis. Factors that could be responsible for this effect include differential metabolism of Gabaergic receptor dynamics.

d-Amphetamine: disruptive effects on the long-term store of memory and proactive facilitatory effects on learning in inbred mice.

Male, C57BL/6J mice were given two daily trials on an appetitively-motivated successive brightness discrimination maze problem; they then received daily intraperitoneal injections of saline or d-amphetamine for 5 days. When trained again in the maze, mice in all d-amphetamine groups tended to display impaired retention: retention was significantly impaired in the 2.0 mg/kg group. Naive mice were treated exactly as were the pretrained mice except that they received no initial maze training prior to drug treatments. Mice in all naive d-amphetamine groups tended to display enhanced acquisition of the maze problem: acquisition was significantly enhanced in the 1.0 mg/kg groups. These results could not be explained as effects of d-amphetamine on attentional, motivational or other performance factors.

Differential convulsive susceptibility of high-activity and low-activity selected mice in response to GABA antagonists.

Lines of mice selectively-bred for High and Low-Activity in an open-field maze were tested for seizure susceptibility to three analeptics: flurothyl, pentylenetetrazol and bicuculline. The major finding was that two replicate High-Activity lines were more susceptible to myoclonic convulsions but less susceptible to clonic convulsions than their respective replicate Low-Activity lines. The major exception to this finding was that the High and Low-Activity lines did not differ for bicuculline-induced clonus although females tended to conform to the general pattern. These results are interesting because they demonstrate that diametrically opposite susceptibility to myoclonus and clonus is not an isolated phenomenon. Similar seizure susceptibility patterns and activity differences have also been reported for the Long-Sleep and Short-Sleep selectively-bred mouse lines. Further, since the progenitor population of the High-Activity and Low-Activity lines were developed from strains that were also part of the progenitor population of the Long-Sleep and Short-Sleep lines, it is hypothesized that some of the same alleles underwent selection in both selective-breeding programs.