Evidence that the earliest generated cells of the murine cerebral cortex form a transient population in the subplate and marginal zone.

We used bromodeoxyuridine to label the earliest generated cells of the murine cerebral cortex while they were dividing, and then observed their distributions at several instances later in development. Shortly before birth, many of the labelled cells were either above the cortical plate, in the marginal zone, or below it, in the region known as the subplate in other species. These cells had disappeared by postnatal day 21.     

Measurement of diet in a large national survey: comparison of computerized and manual coding of records in household measures

A diary method using household measures was employed to obtain dietary records in a large national prospective survey and a computer program, DIDO (Diet In Data Out), was designed for direct entry of the diaries. The accuracy of this computerized coding system was examined alongside that of the manual coding used for a similar diary in a previous wave, 7 years earlier, of the same survey. Accuracy was assessed by analysis of the errors in the coded and checked records by stringent re-checking of nominal 2% random subsamples of the diet diaries coded by each method. The mean time to code and check each of the 2086 7-day records in the whole survey using DIDO was 58 minutes (SD 30) compared with reported results of 1–4 hours for manual methods. The mean error rate of computerized coding and checking with DIDO was 2.3% (SD 2.1; range 0–8.9) per diary in the subsample. Correcting these mistakes made insignificant changes to the calculated mean energy and nutrient intakes for the subsample. The percentage of individuals changing to an adjacent third of nutrient distribution after correcting unambiguous errors ranged from none (for alcohol) to 11% (for carbohydrate and calcium intake). The mean error rate on a similar subsample of diaries from the earlier survey which had been coded manually was significantly higher at 5.9% (SD 4.1; range 0–17) per diary. Emphasis is laid on the importance, in coding, of dealing with ambiguities in the subjects' records, since this can affect the accuracy and the precision of the nutrient results obtained. We conclude that the DIDO coding method has the advantages of greater accuracy, speed, consistency and efficient data handling, and affords greater data accessibility for checking, compared with manual systems.     

Phytochelatin production by marine phytoplankton at low free metal ion concentrations: laboratory studies and field data from Massachusetts Bay.

Phytochelatins are small metal-binding polypeptides synthesized by algae in response to high metal concentrations. Using a very sensitive HPLC method, we have quantified phytochelatins from phytoplankton in laboratory cultures at environmentally relevant metal concentrations and in marine field samples. Intracellular concentrations of phytochelatin, in the diatom Thalassiosira weissflogii, exhibit a distinct dose-response relation with free Cd2+ concentration in the medium--not with total Cd(2+)--and are detectable even when the free Cd2+ concentration is less than 1 pM. In Massachusetts Bay, phytochelatin levels (normalized to chlorophyll a) in the particulate fraction are similar to those measured in laboratory cultures exposed to picomolar free Cd2+ concentrations and exhibit a decreasing seaward trend. Incubations of natural samples with added Cd2+ confirmed the induction of the peptides by this metal. Ambient phytochelatin concentrations thus appear to provide a measure of the metal stress resulting from the complex mixture of trace metals and chelators in natural waters.     

Body fat in identical twins reared apart: Roles for genes and environment

We report analyses of data on body fat from a cohort of 34 separated monozygotic twin pairs (MZA) and a matched sample of 38 pairs of monozygotic twins reared together (MZT) originally studied by James Shields. The correlation for MZA pairs was. 61 and the correlation for MZT pairs was. 75. These correlations did not differ significantly, nor did correlations differ between MZA pairs subclassified as having been raised in relatively more or less similar environments. Our results suggest important roles for both genes and environment in the accumulation of body fat and support other adoption studies in suggesting that adult environments rather than rearing environments are the most important nongenetic determinants of levels of body fat in adults.Supported by National Institute of Mental Health Grant MH43409 to R.A.P. and a Grant in Aid from the Dight Institute of Human Genetics to I.I.G.     

Hypothermia differentially affects tuning curves generated by forward and by simultaneous masking.

In the gerbil maintained at euthermic (37.5 degrees C) conditions, forward masking produces a compound action potential tuning curve (CAP TC) which is less sensitive but more sharply tuned than that which is generated by simultaneous masking. These differences between forward- and simultaneously-masked CAP TCs are minimized at hypothermic (30 degrees C) conditions. The unmasking effect occurs at both temperatures, suggesting that hypothermia does not exert these changes by eliminating two-tone suppression.     

High-dose gadoteridol in MR imaging of intracranial neoplasms.

Twelve patients with a high suspicion of brain metastases by previous clinical or radiologic examinations were studied in a phase III investigation with magnetic resonance (MR) imaging at 1.5 T after a bolus intravenous injection of 0.1 mmol/kg gadoteridol followed at 30 minutes by a second bolus injection of 0.2 mmol/kg gadoteridol. All lesions were best demonstrated (showed greatest enhancement) at the 0.3-mmol/kg (cumulative) dose, with image analysis confirming signal intensity enhancement in the majority of cases after the second gadoteridol injection. More lesions were detected with the 0.3-mmol/kg dose than with the 0.1-mmol/kg dose, and more lesions were detected with the 0.1-mmol/kg dose than on precontrast images. In this limited clinical trial, high-dose gadoteridol injection (0.3-mmol/kg cumulative dose) provided improved lesion detection on MR images specifically in intracranial metastatic disease.     

Induction of calcium-independent nitric oxide synthase by allergen challenge in sensitized rat lung in vivo.

There is some evidence that nitric oxide synthase (NOS) is induced in the lungs of patients with allergic asthma, but the mechanism of this is not understood. The aim of the present study was to investigate whether the levels of NOS in rat lung could be altered by exposure of the animals to aerosols of allergen (ovalbumin). Brown-Norway rats were actively sensitized to ovalbumin, raising a mixed IgE/IgG antibody response. The levels of total and calcium-independent NOS in lung tissue homogenates were elevated at 6 h and 24 h after allergen exposure in sensitized rats but not in unsensitized rats. The induction was not due to contaminating lipopolysaccharide in the challenge solution. The allergen-induced increase in calcium-independent lung NOS was inhibited by pretreatment of the animals with the corticosteroid betamethasone (3 mg kg-1 i.p., 1 h prior to and 6 h after allergen). These results show that allergen challenge induces calcium-independent NOS in the lungs of sensitized rats, a process inhibited by an anti-inflammatory corticosteroid.     

In vitro platelet aggregability studies: lack of evidence for platelet hyperactivity in systemic sclerosis.

Systemic sclerosis is characterised by vascular endothelial damage. Platelets adhering to the exposed subendothelium may contribute to the inflammatory changes found in the vessel wall. Increased in vitro platelet aggregability in systemic sclerosis has been reported. In vitro platelet aggregation of platelet rich plasma obtained from patients with systemic sclerosis (CREST (calcinosis, Raynaud's phenomenon oesophageal dysmotility, sclerodactyly, telangiectasia) variant) and from controls matched for age and sex was compared. Collagen, ADP, and platelet activating factor were used as aggregating agents. The actions of a platelet activating factor antagonist, BN52063, were also examined. Each agonist caused dose dependent platelet aggregation; there was no difference in either rate of primary aggregation or maximum percentage aggregation between platelets derived from patients with systemic sclerosis and from the control group (analysis of variance). BN52063 was shown to be a dose dependent, competitive antagonist of platelet aggregation induced by platelet activating factor; there was no difference in its action on platelets derived from patients with systemic sclerosis or controls. These results do not support the hypothesis that platelets from patients with systemic sclerosis are hyperactive and may explain the disappointing results obtained with antiplatelet drugs in systemic sclerosis.     

Assessment of clinical renal preservation by phosphorus-31 magnetic resonance spectroscopy

To evaluate the role of magnetic resonance spectroscopy (MRS) and to develop surface coils for assessing cadaveric renal viability during hypothermic storage, we used the monophosphate/inorganic phosphate ratio (MP/Pi) to monitor phosphorous metabolites in intact kidneys during various renal preservation maneuvers. Eighteen canine kidneys and 16 cadaveric kidneys were studied as follows: Group 1 (N = 4) in situ kidneys were monitored by implanted MRS coils; Group 1 (N = 4) ex vivo kidneys were immediately attached to vascular cannulas and monitored by MRS surface coils during normothermic perfusion; Group 3 (N = 4) kidneys were removed, cold-flushed and, after 24 hours of 4C storage, monitored by MRS surface coils before and during four hours of reperfusion via vascular cannulas; Group 4 (N = 6) kidneys were removed, cold-flushed and monitored by surface coils during cold storage up to 72 hours. In addition, 16 cadaveric kidneys were studied while in sterile cold-storage containers. Postoperative renal function was followed in recipient patients. The MP/Pi ratios in Group 1 kidneys correlated with the ability to regenerate adenosine triphosphate (ATP). Groups 2 and 3 showed similar regeneration of ATP and MP/Pi after postischemic reperfusion, and the signal-to-noise ratios of the surface coils were better than those in the implanted coils in Group 1. Surface-coil monitoring in Group 4 kidneys showed predictable decay rates of MP/Pi during one to 72 hours of cold storage; in contrast, simultaneous cortical medullary microcirculation studies with 99mTc-macroaggregated albumin were inconclusive. Human cadaveric kidneys with high MP levels were associated with excellent renal function after transplantation, while those with low MP (less than or equal to 0.50) were associated with nonviability. We conclude that MRS is a practical and safe diagnostic modality for clinical transplantation.