Learning and memory deficits in rats following exposure to 3,3'-iminodipropionitrile

Rats were examined using a learning and memory test battery 4 weeks following exposure to 3,3'-iminodipropionitrile (IDPN). Initial testing revealed deficits in olfactory discrimination and passive avoidance (PA) conditioning. In order to dissociate learning and performance effects, additional tests were conducted. First, to rule out the possibility that IDPN reduced the aversiveness of foot shock, rats were tested in a simple shock sensitivity paradigm. The results indicated no change in shock sensitivity produced by IDPN. Second, to determine if the hyperactivity produced by IDPN was responsible for deficits in conditioning, several additional tests were conducted including (a) repeated-trials active avoidance (AA) and PA conditioning, (b) a PA study which included both a 1- and 24-hr training-testing interval, and (c) long-delay flavor-aversion conditioning. Rats treated with IDPN required more conditioning trials to reach criterion on both AA and PA procedures suggesting that they were capable of performing the required response but acquired those responses at a much slower rate. The deficits in PA conditioning were similar at both the 1- and 24-hr training-testing interval. Finally, the effects of IDPN on flavor-aversion conditioning depended on the delay separating flavor intake and lithium administration during conditioning. Rats treated with IDPN demonstrated robust flavor aversions when trained with a 30-min but not with a 6-hr delay. In summary, the neurotoxic profile of effects produced by IDPN must be expanded to include a prominent cognitive component characterized by protracted deficits in learning and memory capacity. The present experiment illustrates how chemically induced disruption of learning and memory produced by IDPN can be experimentally dissociated from associate neurological symptoms using a simple, routine battery of neurobehavioral tests.     

Is progression in postencephalitic parkinson's disease late and age-related?

Summary Follow-up data are presented of ten patients with autopsy-proven postencephalitic Parkinson's syndrome (PEP) (mean age at death: 56.0 years) with regard to motor and psychic deterioration over a period of institutional observation between 3 and 30 years. Four patients showed deterioration of their Hoehn-Yahr score of at least one grade. These patients did not differ statistically with respect to age of occurrence of lethargic encephalitis, interval to PEP, age at start of PEP, duration of survival with PEP, and age at death. Motor deterioration in these patients seems to be attributed more to inherent disease progression, rather than to an age-related process. Clinical and pathological evidence for this conclusion is presented.     

Age and simple reaction time: decade differences for 5,325 subjects

In a booth at a public exhibition entitled "Medicines for Man," 5,325 men, women, and children carried out a 1-minute test of simple reaction time (RT) with 1 to 10 second randomized variable preparatory interval (PI). They recorded their ages by decade. Average RT over the last eight (of ten) trials increased progressively from the 20s up to age 60 and over, and downward to the teens and under 10s. The single fastest RT in each test varied much less with age, only the 20s being clearly faster than the rest, with the under 10s slower. Within-subject variability of RT was increased only in the under 10s and over 60s. Ability to sustain attention during the longer PIs may underlie the gross average RT differences with age, and possibly some more basic neural property the superiority of the 20s in fastest RT.     

Morphology of temperate bacteriophage SfV and characterisation of the DNA packaging and capsid genes: the structural genes evolved from two different phage families

The entire genome of SfV, a temperate serotype-converting bacteriophage of Shigella flexneri, has recently been sequenced (Allison, G.E., Angeles, D., Tran-Dinh, N., Verma, N.K. 2002, J. Bacteriol. 184, 1974-1987). Based on the sequence analysis, we further characterised the SfV virion structure and morphogenesis. Electron microscopy indicated that SfV belongs to the Myoviridae morphology family. Analysis of the proteins encoded by orf1, orf2, and orf3 revealed that they were homologous to small and large terminase subunits, and portal proteins, respectively; the protein encoded by orf5 showed homology to capsid proteins. Western immunoblot of the phage with anti-SfV sera revealed two antigenic proteins, and the N-terminal amino acid sequence of the 32-kDa protein corresponded to amino acids 116 to 125 of the ORF5 protein, suggesting that the capsid may be processed. Functional analysis of orf4 showed that it encodes the phage capsid protease. The proteins encoded by orfs1, 2, 3, 4, and 5 are homologous to similar proteins in the Siphoviridae phage family of both gram-positive and gram-negative origin. The capsid and morphogenesis genes are upstream and adjacent to the genes encoding Myoviridae (Mu-like) tail proteins. The organisation of the structural genes of SfV is therefore unique as the head and tail genes originate from different morphology groups.     

Production of delayed hypersensitivity by antigen associated with peritoneal exudate cells and the effect of pretreatment with Freund's complete adjuvant

The immunogenicity of antigens associated with peritoneal exudate cells was compared with the immunogenicity of free antigens for the induction of delayed hypersensitivity. Oil induced peritoneal exudate cells were incubated with antigens labelled with radioactive iodine, washed and injected intraperitoneally into recipient guinea-pigs. Comparable amounts of free antigens were also injected. All sixteen inbred guinea-pigs given human or bovine gamma-globulin associated with peritoneal exudate cells gave positive reactions (greater than 5 mm) while the eighteen guinea-pigs given free antigens failed to show a reaction. Similar results were obtained with serum albumins in inbred guinea-pigs. The increased immunogenicity of antigens associated with peritoneal exudate cells was also seen in outbred guinea-pigs.

Pretreatment with Freund's complete adjuvant did not depress the immunogenicity of antigens associated with peritoneal exudate cells and actually increased the induration of the 24-hour reaction to picrylated human serum albumin and human serum albumin associated with peritoneal exudate cells.

     

Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes.

Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.