A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease,seizures and cotton wool plaques,but not spastic paraparesis

Over 100 mutations in the presenilin‐1 gene (PSEN1) have been shown to result in familial early onset Alzheimer disease (EOAD), but only a relatively few give rise to plaques with an appearance like cotton wool (CWP) and/or spastic paraparesis (SP). A family with EOAD, seizures and CWP was investigated by neuropathological study and DNA sequencing of the PSEN1 gene. Aβ was identified in leptomeningeal vessels and in cerebral plaques. A single point mutation, p.L420R (g.1508T > G) that gives rise to a missense mutation in the eighth transmembrane (TM8) domain of PS1 was identified in two affected members of the family. p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family.     

De novo generation of histamine in sputum and the effect of antibiotics

We have performed experiments to test the hypothesis that bacteria may contribute to the presence of histamine in sputum. Sputum samples obtained from 7 patients with exacerbations of chronic bronchitis and 7 patients with cystic fibrosis were incubated at 37 degrees C for 72 hours. Serial sputum histamine estimations, performed by a recently-developed HPLC technique, showed large, progressive increases in both groups of samples. Both the pre-heating of samples at 100 degrees C prior to incubation and the addition of antibiotics to the incubates substantially reduced these increases. These findings strongly suggest that bacteria may contribute to sputum histamine in infective lung disease.     

Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy

We measured serum alkaline phosphatase isoenzymes and osteocalcin levels in 40 healthy women at 4-week intervals throughout uncomplicated pregnancies and 6 weeks after delivery in 17 women. Serum bone alkaline phosphatase was significantly higher in the third trimester than in early pregnancy (P less than 0.001), and this elevation was still apparent at the end of the puerperium, suggesting increased bone turnover. Serum osteocalcin was not detected (less than 0.2 micrograms/L) after the first trimester in the majority of women, and it reappeared within 48 h after delivery. The disappearance of osteocalcin after the first trimester and its rapid reappearance after delivery suggest placental clearance of this peptide. We conclude that serum osteocalcin measurements cannot be used as a marker of bone metabolism during pregnancy.     

Serum sialic acid concentration in patients with hypertriglyceridaemia showing the Frederickson's IIB phenotype.

1. Serum total sialic acid concentration, recently shown to be a cardiovascular risk factor, and also serum lipid-associated sialic acid concentration were measured in 15 patients with hypertriglyceridaemia (fasting serum triacyglycerol concentration > 2.3 mmol/l) showing a Frederickson's type IIB phenotype, 15 patients with hypercholesterolaemia showing a IIA phenotype and 15 age- and sex-matched normal control subjects. 2. Total serum sialic acid concentration was significantly raised in the hypertriglyceridaemic group (84.9 +/- 21.5 versus 64.9 +/- 20.8 mg/dl, P < 0.03, Mann-Whitney U-test) compared with the normal control group, as was serum lipid-associated sialic acid concentration (23.0 +/- 4.3 versus 12.0 +/- 3.2 mg/dl, respectively, P < 0.001, Mann-Whitney U-test). 3. Serum total sialic acid concentration was also significantly elevated in the hypertriglyceridaemic group as compared with the IIA phenotype hypercholesterolaemic group (84.9 +/- 21.5 versus 58.4 +/- 11.7 mg/dl, P < 0.03, Mann-Whitney U-test), as was serum lipid-associated sialic acid concentration (23.0 +/- 4.3 versus 14.9 +/- 4.7 mg/dl, P < 0.001, Mann-Whitney U-test). 4. We suggest that serum concentrations of both total sialic acid and lipid-associated sialic acid may be useful markers of cardiovascular risk which could, in part, be related to hypertriglyceridaemia.     

Tuberculosis of the pancreas: a case report

A 73-year-old female died of adult respiratory distress syndrome (ARDS) and multiple organ system failure (MOSF) after a routine cholecystectomy for acute cholecystitis. An autopsy revealed disseminated tuberculosis with a tuberculous abscess of the pancreas.     

Stimulation of inositol phosphate formation in cultured human retinal pigment epithelium.

Several hormones, neurotransmitters, and neuropeptides were screened for the ability to stimulate inositol phosphate formation in cultured human retinal epithelial (RPE) cells. Carbachol, vasopressin and thrombin were found to be effective. Treatment of RPE cells with all three agents produced increases in inositol monophosphate, inositol bisphosphate and inositol trisphosphate in the presence of 10 mM LiCl. Carbachol stimulated a 4-fold increase in the total of inositol phosphates at 1 mM. Studies with cholinergic antagonists showed a rank order of 4 DAMP greater than QNX greater than pirenzepine greater than methoctramine, suggesting the presence of M3 muscarinic receptors. Vasopressin gave a 2.5-fold stimulation at 10 microM. Agonists of vasopressin were also tested and gave differential responses. Studies using a V1 agonist (PIOVP) and a V2 agonist (DAVP) showed DAVP matching the level of stimulation elicited by vasopressin whereas treatment with PIOVP only reached 50% of the vasopressin response. These data suggested the presence of V2 receptors in the RPE cells. Several proteases were tested for their ability to stimulate RPE inositol phosphates. Thrombin caused a 7-fold increase in inositol phosphate formation at 1 U/ml, whereas trypsin and plasmin elicited smaller responses (approximately 2-fold). The thrombin effect was blocked by the thrombin-specific inhibitor, hirudin, but not by other protease inhibitors. Several mediators of inflammation such as bradykinin, histamine and serotonin were also tested, and they were ineffective in stimulating inositol phosphate turnover in the RPE cells.     

GABA-induced inactivation of functionally characterized sites in cat visual cortex (area 18): effects on orientation tuning.

Microiontophoresis of the inhibitory transmitter GABA was used to reversibly inactivate small sites of defined orientation specificity at a horizontal distance of some 600 microns from single cells recorded in area 18 of cat visual cortex, and the effects on orientation tuning were studied. The receptive fields of cells at the recording and inactivation sites overlapped extensively. During the inactivation of sites where the orientation preference differed by 45 degrees or more from that of a recorded cell ("cross-orientation" sites), 65% of 54 cells tested showed significant broadening of orientation tuning, with a mean increase in tuning width (measured at half the maximum response) of 93%, and an almost fourfold increase in the relative response to the orientation orthogonal to the optimum, compared with the response to the optimum; four cells essentially lost their orientation tuning. Broadening of tuning reflected an increase in response to nonoptimal orientations and was reversible upon termination of GABA application. The effects on orientation tuning typically peaked within 10-15 min of the onset of GABA iontophoresis with 50-100 nA ejecting currents, and could not be replicated by inactivating sites where the orientation preference was similar to that of a recorded cell; when the orientation preference at the inactivation sites was within 22.5 degrees of that of a recorded cell ("iso-orientation" sites), only 3 of 22 cells showed significant broadening of tuning, and in these cases, the effects were relatively weak (mean increase in tuning width of 39% and a negligible change in the relative response to the orientation orthogonal to the optimum). The effect of inactivating "iso-orientation" sites consisted primarily in an increase in response magnitude. The difference in the magnitude of the effects on orientation tuning elicited by inactivating "cross-orientation" and "iso-orientation" sites was highly statistically significant. Additionally, inactivation of "cross-orientation" or "iso-orientation" sites elicited differential effects on orientation tuning in 10 of the 13 cells in which direct comparisons were made. It is argued that the observed broadening of tuning was due to the loss of a "cross-orientation" inhibitory input, which normally sharpens orientation tuning by suppressing responses to nonoptimal orientations.     

Ecological memory assessment in normal aging. A preliminary report on an Italian population

Forty-eight healthy volunteers were administered a computerized battery of "ecological" memory tests simulating real life everyday tasks and actions such as recalling people's names or telephone numbers. The group was dichotomized according to recent criteria proposed by a NIMH study group. Younger individuals (below 50 years of age) always showed better performances than those over 50. Although the learning curves were significantly lower for the older subgroup, the forgetting rate did not differ, suggesting that most of the memory complaints of the elderly might be attributable to the initial encoding phase of the memorizing activity rather than to a retrieval problem. It seems that easy distractability and inefficient strategic elaboration of incoming information are also, at least in part, responsible for the memory problems associated with normal aging. This article reports preliminary findings of a normative and representative Italian population sample.