Stimulus specific adaptation in excited but not in inhibited cells in inferotemporal cortex of Macaque

Many cells in inferotemporal cortex respond more actively to a novel presentation than to a subsequent re-presentation of the same image, exhibiting stimulus specific adaptation (SSA). Previously, analysis of this adaptation was limited to visually excited cells, excluding visually inhibited cells. In the present experiment we studied 654 cells in four macaques performing visual tasks. Strong SSA (P < 0.0001) was observed in those cells which were excited by visual stimuli. This adaptation was also seen in the subset of such cells which, though excited by visual stimuli, failed to show visual specificity in their responses. Interestingly, no SSA (P > 0.1) was observed in the group of cells inhibited by visual stimuli. Furthermore, most inhibited cells failed to show visual specificity. This lack of visual specificity and SSA suggest that the visually inhibited cells have a limited role in the detailed information processing of visual perception and memory activated by the tasks used in the present experiments.     

Intestinal Absorption of Inorganic Mercury in Rat

Abstract: ²⁰³Hg-Mercuric chloride was administered intragastrically to female rats. The absorption rate evaluated for a broad range of doses was found constant for low and medium range, and higher for high doses. Mercury was determined in internal organs and intestines. The time-course of intestinal mercury indicated that a deposit formed initially in the mucosa was further absorbed into the circulation. No indication was found of a protection mechanism based on exfoliation of the mucosal deposits of metal.     

Pain perception in major depression depends on pain modality

One frequently described feature of depression is an increased vulnerability to pain complaints, and chronic pain is frequently accompanied by symptoms of depression. In contrast to this, a decreased sensitivity to experimental pain has been described in major depression. The physiological basis of this phenomenon is yet elusive. We investigated 30 patients suffering from a major depressive disorder and matched controls. Pain testing (threshold and tolerance) was performed on both sides of the body and included assessment of thermal, electrical and ischemic pain. While confirming hypoalgesia to heat and electrical pain in comparison to controls, we found hyperalgesia to ischemic muscle pain. Furthermore, thermal pain tolerance and electrical pain tolerance were significantly increased on the right hand side confirming previous results of a lateralized perception of pain in depression. Our main finding suggests that painful stimuli are processed differentially depending on the localization of pain induction in depression. This knowledge may enable us to understand and ultimately treat pain complaints more appropriately in depressed patients.     

The Bcl-2/Bax ratio of lymphocytes from human systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease. It has recently been suggested that a failure of apoptosis wherein autoreactive lymphocytes continue to survive is a major factor in the pathogenesis of SLE. Fas antigen is increased on peripheral blood lymphocytes from human SLE patients while Bcl-2 protein, which inhibits apoptosis, is highly expressed in peripheral T lymphocytes of SLE patients. The Bcl-2 family includes homologs that are believed to be related to regulation of apoptosis. Of these, Bax is capable of forming heterodimers with Bcl-2, thereby counteracting the action of Bcl-2. The present study examines the ratio of Bcl-2 to Bax in relation to the activity of SLE, with implications relating to the survival or death of lymphocytes. The ratio of Bcl-2 to Bax in active SLE was significantly higher than in inactive SLE and in normal controls. Although the exact role of apoptosis in SLE is still unclear, a high ratio of Bcl-2 to Bax in active SLE patients might support the survival of autoreactive cells.     

Effect of glucagon on gastric and pancreatic secretion and peptic ulcer formation in cats

In conscious cats with gastric and pancreatic fistulas, glucagon caused a dose-related inhibition of pentagastrin and meal-induced gastric secretion but did not block histamine-induced secretion. From the dose response curves to pentagastrin alone and in combination with glucagon, Michaelis-Menten analysis was typical of noncompetitive inhibition. Glucagon resulted in the inhibition of pancreatic bicarbonate and protein outputs evoked by exogenous secretion, duodenal acidification, or peptone meal. Glucagon prevented the formation of pentagastrin- but not histamine-induced peptic ulcers in cats. The antiulcer action of glucagon can be attributed mainly to its inhibitory effect on gastric acid and pepsin secretion.     

Items for developing revised classification criteria in systemic sclerosis: Results of a consensus exercise

Objective

Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated. Our objective was to select a set of items potentially useful for the classification of SSc using consensus procedures, including the Delphi and nominal group techniques (NGT).

Methods

Items were identified through 2 independent consensus exercises performed by the Scleroderma Clinical Trials Consortium and the European League Against Rheumatism Scleroderma Trials and Research Group. The first‐round items from both exercises were collated and redundancies were removed, leaving 168 items. A 3‐round Delphi exercise was performed using a 1–9 scale (where 1 = completely inappropriate and 9 = completely appropriate) and a consensus meeting using NGT was conducted. During the last Delphi round, the items were ranked on a 1–10 scale.

Results

In round 1, 106 experts rated the 168 items. Those with a median score of <4 were removed, resulting in a list of 102 items. In round 2, the items were again rated for appropriateness and subjected to a consensus meeting using NGT by European and North American SSc experts (n = 16), resulting in 23 items. In round 3, SSc experts (n = 26) then individually scored each of the 23 items in a last Delphi round using an appropriateness score ( 1 - 9 ) and ranking their 10 most appropriate items for the classification of SSc. Presence of skin thickening, SSc‐specific autoantibodies, abnormal nailfold capillary pattern, and Raynaud's phenomenon ranked highest in the final list that also included items indicating internal organ involvement.

Conclusion

The Delphi exercise and NGT resulted in a set of 23 items for the classification of SSc that will be assessed for their discriminative properties in a prospective study.     

Effect of diversion and replacement of bile on pancreatic secretion

Pancreatic bicarbonate and protein outputs have been studies under basal conditions and in response to a variety of endogenous and exogenous stimuli in conscious dogs with biliary and pancreatic fistulas and with bile diverted and then replaced into the intestine. Infusion of bile into the duodenum and jejunum but not the ileum caused a marked increase in pancreatic protein secretion, and to a lesser degree in bicarbonate output, only in tests performed under basal conditions. Pancreatic dose-response curves to intravenous secretin and caerulein, to intraduodenal hydrochloric acid and amino acids, or to feeding liver meal were not significantly altered by the diversion and subsequent replacement of bile into the duodenum. It is suggested that the release of cholecystokinin or neuroreflex stimulation of pancreas by the bile in the intestine may explain the bile stimulation of pancreatic secretion observed.     

Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism

OBJECTIVES: Multisystem pseudohypoaldosteronism (PHA) is a rare autosomal recessive aldosterone unresponsiveness syndrome that results from mutations in the genes encoding epithelial sodium channel (ENaC) subunits alpha, beta and gamma. In this study we examined three PHA patients to identify mutations responsible for PHA with different clinical presentations. PATIENTS: All three patients presented uniformly with symptoms of severe salt-loss during the first week of life and were hospitalized for up to a year. Beyond infancy, one of the patients showed mild renal salt loss and had no lower respiratory tract infections until 8 years of age, while the other patients continue with a severe course. RESULTS: We sequenced the complete coding regions and intron-exon junctions of the genes encoding alpha, beta and gamma subunits of ENaC for all patients. The results revealed that the mild case represents a novel compound heterozygote including a missense (Gly327Cys) mutation in the alphaENaC gene. Sequences of relatives over three generations confirmed that the missense mutation co-segregates with PHA. This mutation was not found in 60 control subjects. The other patients with severe PHA had two homozygous mutations, a novel deletion mutation in exon 8 of the alphaENaC gene and a splice site mutation in intron 12 of the betaENaC gene. Most of the PHA-causing mutations appear in the alphaENaC gene located on chromosome 12 rather than in the beta and gammaENaC genes located tandemly on chromosome 16. However, the frequency of sequence variants in patients and control subjects showed no difference between genes. CONCLUSIONS: Severe PHA cases are associated with mutations leading to absence of normal-length alpha, beta or gammaENaC, while a mild case has been found to be associated with a missense mutation in alphaENaC. The predominance of PHA-causing mutations in the alphaENaC gene may be related to the function of this subunit.