Keratinocyte cytogenetics in 10 patients with pigmentary mosaicism: identification of one case of trisomy 20 mosaicism confined to keratinocytes.

BACKGROUND: Hypomelanosis of Ito and linear and whorled hypermelanosis are pigmentary disorders that follow Blaschko's lines and are associated with cytogenetic mosaicism. However, mosaicism cannot always be shown using conventional karyotyping of blood lymphocytes or skin fibroblasts. This may be because these cell lines originate from mesoderm, whereas Blaschko's lines are an ectodermal phenomenon. OBJECTIVES: To investigate the diagnostic value of keratinocyte cytogenetics in patients with pigmentary mosaicism (PM). METHODS: We undertook a prospective study of 10 patients with clinically suspected PM. Previous karyotyping of blood, and in some cases skin fibroblasts, was normal in all cases. Keratinocytes and fibroblasts were cultured from skin biopsies taken from light and dark skin, and examined for cytogenetic abnormalities. RESULTS: In 9 of 10 cases both keratinocyte and fibroblast cytogenetic analyses were normal. The remaining patient showed trisomy 20 mosaicism confined to keratinocytes from hypopigmented skin. Fluorescent in situ hybridization using a probe for 20q confirmed trisomy 20 mosaicism in keratinocytes but not fibroblasts, with higher signal expression in hypopigmented compared with normal skin. CONCLUSIONS: In patients with clinically suspected PM but normal blood cytogenetics, keratinocytes may be more sensitive than skin fibroblasts in identifying cytogenetic mosaicism in selected patients. However, the additional diagnostic yield appears to be insufficient to justify routine keratinocyte cytogenetic investigation. Our findings indirectly support the hypothesis that Blaschko's lines delineate the embryonal migration paths taken by ectodermal cells including keratinocytes and melanocytes.

Comparison of the acute pharmacodynamic responses after single doses of ephedrine or sibutramine in healthy, overweight volunteers.

OBJECTIVE: With an increase in the incidence of obesity, tremendous effort has been devoted to the development of weight loss agents and the prospective surrogate markers of both a product's efficacy and safety. The objective of the present study was to compare the pharmacodynamic responses of ephedrine and sibutramine using surrogate markers of weight loss potential and potential adverse events. DESIGN AND SUBJECTS: The study was designed as a 5-way, randomized, double-blinded, placebo-controlled trial with 3 single doses of ephedrine sulfate (0.25, 0.5 and 1 mg x kg(-1)) followed by an open-labeled sibutramine (10 mg) treatment. Healthy, mildly overweight (BMI = 25) subjects were administered the respective treatment and pharmacokinetic and pharmacodynamic measurements (body surface temperature, resting metabolic rate, blood pressure, heart rate, glucose, glycerol, nonesterified fatty acids, triglycerides) were obtained for 8 hours post dose and for an additional 4 measurements during the sibutramine treatment period. RESULTS: Sibutramine treatment significantly increased resting metabolic rate compared to the placebo condition. Ephedrine significantly increased heart rate, systolic blood pressure and glucose but did not significantly affect other measurements. CONCLUSION: Both sibutramine and ephedrine have been shown to have weight loss potential, however, they elicit different metabolic and biochemical responses after a single dose. The nontherapeutic responses from these types of compounds may serve as a screening tool for the development of agents in the treatment of obesity.

A review of keratinocyte delivery to the wound bed.

Over the last 20 years, confluent sheets of cultured epithelial autograft have been used for patients with major burns. Problems with the lack of "take" and long-term durability, as well as the time delay to produce such grafts, have led to the development of delivery systems to transfer keratinocytes to the wound bed. This review article describes the problems of using cultured epithelial autograft and the advantages of using preconfluent keratinocytes. Despite the numerous delivery systems that have been reported, most studies are limited to animal wound bed models. There are a few small clinical studies that have demonstrated enhanced healing using mainly subjective methods. There is a need for controlled, randomized clinical trials to prove the efficacy of keratinocyte delivery systems. Proposals for the use of this technology are made.

Postexercise and positional variation in mechanical properties of the radius in young horses.

The metacarpal of the horse is severely loaded during vigorous exercise. Metacarpal specimens have a greater impact strength in young horses that have been exercised than in those that have only been walked. We did not find a corresponding difference in the radius of the same horses. We show that cranial (anterior) cortical bone from the radius, which is loaded in tension during locomotion, has a greater Young's modulus, and tensile and bending strength, than bone from the caudal (posterior) cortex, which is loaded in compression. Caudal bone is, however, stronger in compression. The differences can be explained by differences in the histological structure developed by the 2 cortices and are presumably adaptive. This work confirms the work of others. Furthermore, we demonstrate that the impact energy absorption of cranial bone is nearly twice as great as that of caudal bone. The caudal cortex has apparently paid a heavy price in its reduction in resistance to accidental impact loading for being stronger than the cranial cortex in compressive loading.

The relative abundance of dopamine D4 receptor mRNA in post mortem brains of schizophrenics and controls.

An increase in dopamine D4 receptors has recently been reported in post mortem brain samples from schizophrenics. We have attempted to complement this finding by assessing the levels of the specific messenger RNA (mRNA) for the D4 receptor, using the technique of quantitative RNA-PCR. No significant differences in the levels of expression of mRNA for the D4 receptor were found in the brains from schizophrenics compared to controls. The relationship between D4 receptors and schizophrenia, therefore, remains unclear.

Allelic variations in apolipoprotein E and prion protein genotype related to plaque formation and age of onset in sporadic Creutzfeldt-Jakob disease.

Prion gene sequence is thought to affect the phenotypic expression of prion disease and the E2 variant of apolipoprotein E (Apo E) can be neuroprotective in dementia. We determined codon 129 of the prion gene and the Apo E variants in Creutzfeldt-Jakob disease (CJD) using PCR and restriction digest. We found a significant correlation between valine at codon 129 of the prion protein gene and the presence of plaque in CJD and a later age of onset in CJD cases possessing the Apo E2 allele. This study provides further evidence that sequence variations in the prion gene can modify disease pathology and the neuroprotection afforded by Apo E2 is not confined to Alzheimer's disease.

The abundance of mRNA for dopamine D2 receptor isoforms in brain tissue from controls and schizophrenics.

The possibility that schizophrenia is associated with a differential expression, in the brain, of the short and long isoforms of the dopamine D2 receptor has been investigated by assessing the abundance of mRNA for each of the isoforms. Using a quantitative RNA-PCR technique, increased mRNA for both isoforms of the D2 receptor were observed in some brain regions, with no differential distribution between the isoforms in the schizophrenics compared to controls.

Fast and reliable QRS alignment technique for high-frequency analysis of signal-averaged ECG.

The process of QRS alignment as required in signal-averaged ECG can impose serious limitations on the spectral range of the signal output. This effect depends basically on the particular alignment technique being used and on the level and type of noise present in the recorded ECG. In clinical studies where a wide-band (1000 Hz) ECG averager is required, the conventional QRS alignment technique, based on maximum coherence matching (MCM) with a template beat, may not perform consistently well. An alternative QRS alignment technique based on the accurate detection of a single fiducial point (SFP) in the bandpass filtered (3-30 Hz) QRS complex was developed. Using computer simulation methods, a comparative assessment of the frequency bandwidths (3 dB points) offered by both MCM and SFP techniques as a function of noise level (15-100 muRMS) and type (EMG and 50 Hz interference), was carried out. The results of the comparative assessment indicated a better performance by the SFP technique in all cases of noise. Hence, the SFP technique would perform more reliably for high-frequency analysis of a noisy ECG, especially when 50 Hz interference is high. Furthermore, SFP is considerably faster than MCM (about four times) when implemented digitally, and its analogue realisation is feasible. The SFP technique is suitable for late-potential analysis in the signal-averaged ECG.