Eye position effects on visual, memory, and saccade-related activity in areas LIP and 7a of macaque

We studied the effect of eye position on the light-sensitive, memory, and saccade-related activities of neurons of the lateral intraparietal area and area 7a in the posterior parietal cortex of rhesus monkeys. A majority of the cells showed significant effects of eye position, for each of the 3 types of response. The direction tuning of the light-sensitive, memory and saccade responses did not change with eye position but the magnitude of the response did. Since previous work showed a similar effect for the light-sensitive response of area 7a neurons (Andersen and Mountcastle, 1983; Andersen et al., 1985b), the present results indicate that this modulating effect of eye position may be a general one, as it is found in 3 types of responses in 2 cortical areas. Gain fields were mapped by measuring the effect of eye position on the magnitude of the response at 9 different eye positions for each neuron. The gain fields were usually planar or largely planar for all 3 types of response in both areas, indicating that the magnitude of the response usually varies linearly with both horizontal and vertical eye position. A similar observation was made previously for the gain fields of the light-sensitive response of area 7a neurons (Andersen et al., 1985b). Although gain fields sloped in all directions for the population of cells, the gain field slopes of the light-sensitive, memory and saccade responses for individual cells were usually similar. It is proposed that these eye position effects play an important role in making coordinate transformations for visually guided movement.     

A comparison of monocyte oxidative responses in leprosy patients and healthy subjects as influenced by mycobacterial lipid pretreatment

Superoxide anion (O2-) release by monocytes from leprosy patients in a paired study was lower than that released by monocytes from healthy controls. Pretreatment of healthy control monocytes with phenolic glycolipid-I (PGL-I) of Mycobacterium leprae resulted in the release of less O2- than released by buffer-treated cells or cells pretreated with structurally similar lipids. However, pretreatment of patient monocytes with PGL-I did not affect the O2- generation, perhaps because the cells already had a lower capacity to produce O2-. Upon further examination of the data from the patient population, monocytes from lepromatous patients released significantly less O2- than cells from normal controls, while tuberculoid patient cells released O2- in amounts similar to that generated by cells from normal controls. In addition, monocytes from patients with a high bacterial index had a lower capacity to generate O2- when compared to cells from healthy individuals.     

Familial benign hypercalcaemia: hypercalciuria and hypocalciuria in affected members of a small kindred

Familial benign hypercalcaemia has also been termed familial hypocalciuric hypercalcaemia because a major feature of this condition has been a relative hypocalciuria in relation to the hypercalcaemia, such that the calcium to creatinine clearance ratio is less than 0.016. The following is a report of a small kindred of patients with familial benign hypercalcaemia in which two of the affected members have frank hypercalciuria.     

An on-site test battery to evaluate giant slalom skiing performance

The purpose of this study was to determine if an on-site test battery would distinguish among three levels of giant slalom skiing ability. The test battery consisted of a 20-m shuttle run test, Wingate 60s cycling test, hexagonal obstacle test, high box test, double leg jumping test and vertical jump test. These tests were selected since previous studies have identified aerobic endurance, anaerobic endurance, power and agility as important components for Alpine skiers. Both construct validity and criterion related validity of the test battery were examined using data from 11 club skiers, 14 divisional level skiers, and 9 provincial level skiers. To establish construct validity, univariate F tests examined differences among the three levels of skiers. Significant (P less than 0.05) differences were found between the club skiers and the better skiers (divisional and provincial level) for the following test variables: peak power, mean power, and post-exercise lactate for a 60s Wingate cycle ergometer test, high box test, hexagonal obstacle test, double leg jumping test, and shuttle run test. Criterion related validity was established since there were significant correlations between giant slalom performance time and the hexagonal obstacle test (r = 0.82), high box test (r = -0.80), and double leg jumping (r = -0.86). These data illustrate that an on-site test battery can be used to distinguish among giant slalom Alpine skiers.     

Possible evidence of invasiveness ofHelicobacter (Campylobacter)pylori

Gastric/duodenal biopsy material from 52 patients was examined immunohistochemically forHelicobacter (Campylobacter) pylori. Specimens from 34 of the patients harbouredHelicobacter pylori along the mucosal surface and 13 of these featured, in addition, immunopositive material within the lamina propria. The remaining 18 biopsies were non-reactive. This observation suggests thatHelicobacter pylori can penetrate the epithelium and its basement membrane, resulting in the production of specific systemic antibodies.     

Pharmacological characterisation of a new oral GH secretagogue, NN703.

NN703 is a novel orally active GH secretagogue (GHS) derived from ipamorelin. NN703 stimulates GH release from rat pituitary cells in a dose-dependent manner with a potency and efficacy similar to that of GHRP-6. The effect is inhibited by known GHS antagonists, but not by a GH-releasing hormone antagonist. Binding of (35)S-MK677 to the human type 1A GHS receptor (GHS-R 1A) stably expressed on BHK cells was inhibited by GHRP-6 and MK677 as expected. NN703 was also able to inhibit the binding of (35)S-MK677. However, the observed K(i) value was lower than expected, as based on the observed potencies regarding GH release from rat pituitary cells. Similarly, the effect of NN703 on the GHS-R 1A-induced inositol phosphate turnover in these cells showed a lower potency, when compared with GHRP-6 and MK677, than that observed in rat pituitary cells. The effect of i.v. administration of NN703 on GH and cortisol release was studied in swine. The potency and efficacy of NN703 on GH release were determined to be 155+/-23 nmol/kg and 91+/-7 ng GH/ml plasma respectively. A 50% increase of cortisol, compared with basal levels, was observed for all the tested doses of NN703, but no dose-dependency was shown. The effect of NN703 on GH release after i. v. and oral dosing in beagle dogs was studied. NN703 dose-dependently increased the GH release after oral administration. At the highest dose (20 micromol/kg), a 35-fold increase in peak GH concentration was observed (49.5+/-17.8 ng/ml, mean+/-s.e.m.). After a single i.v. dose of 1 micromol/kg the peak GH plasma concentration was elevated to 38.5+/-19.6 ng/ml (mean+/-s.e.m.) approximately 30 min after dosing and returned to basal level after 360 min. The oral bioavailability was 30%. The plasma half-life of NN703 was 4.1+/-0.4 h. A long-term biological effect of NN703 was demonstrated in a rat study, where the body weight gain was measured during a 14-day once daily oral challenge with 100 micromol/kg. The body weight gain was significantly increased after 14 days as compared with a vehicle-treated group. In summary, we here describe an orally active and GH specific secretagogue, NN703. This compound acts through a similar mechanism as GHRP-6, but has a different receptor pharmacology. NN703 induced GH release in both swine and dogs after i.v. and/or p.o. administration, had a high degree of GH specificity in swine and significantly increased the body weight gain in rats.     

'Melanoma? It can't be melanoma!' A subset of melanomas that defies clinical recognition.

We diagnosed histologically 178 cases of malignant melanoma in 1990. Thirteen cases were recorded in which the diagnosis of malignant melanoma was not considered by the clinician prior to biopsy or, in retrospect, following pathologic diagnosis. Eight of the 13 lesions were amelanotic. The majority were deeply invasive at the time of biopsy, implying poor prognosis. Despite improvements in early detection of malignant melanoma, a significant subcategory of melanomas escapes clinical diagnosis.     

Pharmacokinetics of intravenous, intrathecal and epidural morphine and fentanyl in the goat

Intrathecal and epidural catheters and an intravenous cannula were inserted in 10 goats. After administration of either morphine 4 mg, intravenously, 1 mg intrathecally or 4 and 8 mg epidurally, or fentanyl 0.1 mg intravenously, 0.05 mg intrathecally or 0.1 and 0.2 mg epidurally, venous blood and CSF were sampled at 2, 5, 10, 15, 30 min and 1, 2, 4, 6, 8 and 24 h. The concentrations of the drugs were measured by radioimmunoassay. After administration of intravenous morphine the plasma concentration-time curve fitted a 3-compartment model (body clearance = 84 +/- 23 ml/min/kg, mean +/- s.d., N = 5), while after fentanyl the plasma concentration-time curve was best described by a 2-compartment model (body clearance = 3.9-5.8 ml/min/kg, N = 3]. After intrathecal injection the elimination rates of the opioids from CSF were 0.3 to 2.0 and 0.6 to 2.4 ml/h/kg for morphine and fentanyl, respectively (N = 3). The time to reach maximum CSF concentration after epidural administration was 0.22 +/- 0.14 h for morphine (N = 6) and 0.22 +/- 0.13 h for fentanyl (N = 8). In the same goat the CSF availability was 2.3 and 11.3% for morphine and 0.8 and 3.3% for fentanyl following epidural administration of the low and high doses, respectively. After epidural administration, morphine and fentanyl are absorbed into CSF at the same rate but the relative amount of drug absorbed may be higher for morphine than fentanyl. Bulk flow is supposed to be the principal mechanism of opioid elimination from CSF.