A new interstitial deletion of chromosome No. 4 del(4) (q22::q25)

A female child is described with multiple anomalies including epicanthus, frontal bossing, short sternum, polydactyly, cleft of the larynx, renal cysts, and unusual dermatoglyphics. She died aged 3 months and was found to have a unique de novo deletion of chromosome No. 4 (q22-q25). This case is compared with other long arm deletions of 4q and reference made to assignment of genetic markers to chromosome No. 4.     

Identification of mycobacteria by high-performance liquid chromatography.

Mycolic acids extracted from saponified mycobacterial cells were examined as p-bromophenacyl esters by high-performance liquid chromatography (HPLC). Standard HPLC patterns were developed for species of Mycobacterium by examination of strains from culture collections and other well-characterized isolates. Relative retention times of peaks and peak height comparisons were used to develop a differentiation scheme that was 98% accurate for the species examined. A rapid, cost-effective HPLC method which offers an alternative approach to the identification of mycobacteria is described.     

Regional central serotonin-2 receptor binding and phosphoinositide turnover in rats with 5,7-dihydroxytryptamine lesions

"Denervation supersensitivity" of serotonin (5-HT) receptors has been proposed to explain the behavioral supersensitivity to 5-hydroxytryptophan (5-HTP) which develops after lesions of indoleamine neurons with 5,7-dihydroxytryptamine (5,7-DHT). To examine the possible role of receptor recognition sites and second messenger activity in supersensitivity, we measured regional 5-HT2 receptor ligand binding and 5-HT-stimulated phosphoinositide turnover in adult rats with 5,7-DHT lesions made by intracisternal injection and their saline-treated controls. In [3H]ketanserin binding studies of fresh brain tissue two weeks after 5,7-DHT injection, there were no significant changes in frontal cortex, brainstem, or spinal cord in Bmax, Kd, or nH of 5-HT2 receptors, 5,7-DHT lesions did not affect basal levels of [3H]inositol phosphate (IP) accumulation but significantly increased 5-HT-stimulated [3H]IP accumulation in the brainstem (+27%) and cortex (+23%). Because brainstem rather than cortex is involved in 5-HTP-evoked myoclonus, increased 5-HT-stimulated phosphoinositide hydrolysis in brainstem following 5,7-DHT lesions in the rat may be relevant to serotonergic behavioral supersensitivity.     

Clinical and genetic features of variegate porphyria in a Chinese patient

Acute porphyria is rare in orientals. We describe a Chinese woman with recurrent generalised tonic-clonic seizures and abdominal pain. Genomic DNA studies identified a heterozygous base substitution from guanine to adenine at nucleotide position 503, resulting in substitution of arginine by histidine at position 168 of the protein (R168H). This genetic abnormality is similar to the mutation reported in Caucasians with variegate porphyria. To the best of our knowledge, this is the first report in the English literature a Chinese patient with variegate porphyria with an identifiable mutation. A brief review of porphyria is presented.     

Measuring patient benefit from botulinum toxin in the treatment of dystonia. Feasibility of cost-utility analysis

The dystonias are a group of movement disorders arising from CNS dysfunction and characterised by involuntary and prolonged spasms of muscle contraction. Recently there has been increasing demand for treatment with botulinum toxin (BT), a relatively expensive neurological paralytic agent. As there has been no systematic assessment of patient benefit from BT, this study was undertaken to develop and test a methodology for assessing the cost utility of BT therapy for patients with dystonias. A generic health status instrument, the EuroQOL, was completed at regular intervals over at least 6 months by 130 patients with a current diagnosis of dystonia. A general population tariff was used to calculate quality-adjusted life-year (QALY) gains from BT treatment, and relevant cost data were obtained from patients and medical records. The cost-per-QALY estimates ranged considerably, depending on the type of dystonia, the duration of BT treatment, type of health-related quality-of-life (HR-QOL) tariff used and baseline characteristics of participants. The study findings reflect the general clinical impression of BT: that it can benefit patients with dystonia, but the benefit may be small compared with many treatments for other diseases. The nature of the disease and its cyclical treatment caused practical difficulties in recruiting participants, administering questionnaires and in estimating QALY gains.     

Neocuproine,a selective Cu(I) chelator,and the relaxation of rat vascular smooth muscle by S-nitrosothiols

1. A study has been made of the effect of neocuproine, a specific Cu(I) chelator, on vasodilator responses of rat isolated perfused tail artery to two nitrosothiols: S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and S-nitroso-glutathione (GSNO).
2. Bolus injections (10 μl) of SNAP or GSNO (10⁻⁷–10⁻³ M) were delivered into the lumen of perfused vessels pre-contracted with sufficient phenylephrine (1–7 μM) to develop pressures of 100–120 mmHg. Two kinds of experiment were made: SNAP and GSNO were either (a) pre-mixed with neocuproine (10⁻⁴ M) and then injected into arteries; or (b) vessels were continuously perfused with neocuproine (10⁻⁵ M) and then injected with either pure SNAP or GSNO.
3. In each case, neocuproine significantly attenuated vasodilator responses to both nitrosothiols, although the nature of the inhibitory effect differed in the two types of experiment. We conclude that the ability of exogenous nitrosothiols to relax vascular smooth muscle in our ex vivo model is dependent upon a Cu(I) catalyzed process. Evidence is presented which suggests that a similar Cu(I)-dependent mechanism is responsible for the release of NO from endogenous nitrosothiols and that this process may assist in maintaining vasodilator tone in vivo.

     

Detection of k-ras mutation in normal and malignant colonic tissues by an enriched PCR method

ras oncogene mutations appear in over 50% of colon tumors in humans. Studies in animal systems have revealed that ras mutations are also present in preneoplastic lesions, suggesting the possibility of early detection of ras mutation in morphologically normal colon tissues for diagnostic purposes. An Enriched PCR, developed by us, eliminates most of the normal ras alleles prior to amplification; subsequent analysis via RFLP enables the detection of one mutant allele within 10(4) normal alleles. Using the Enriched PCR, we have determined the frequency of mutant ras alleles in normal mucosae and in adenomatous polyps of patients with or without adenocarcinoma. Of the 42 patients who had colon tumors, 15 were found to harbor K-ras oncogene mutation (35%). In two of the 14 cases with mutant K-ras in the tumor tissue we were able to identify mutations in tissues that had been obtained from a site at considerable distance from the tumor (13%); Analysis of 7 adenomas identified one as a carrier of the mutant ras allele (14%). Of 11 normal colonic mucosa obtained from patients without neoplasia, one specimen contained K-ras mutation. Thus, mutated alleles of K-ras may be present, at low frequency, throughout the 'normal appearing' tissue. Cells of normal appearance that harbor such mutation, have the potential to undergo further changes and to develop into the transformed phenotype. Overall, our findings suggest that mutant ras alleles can be detected in preneoplastic mucosa that is morphologically normal, and in adenomas, suggesting the occurrence of an initiation event, and possibly enabling the identification of patients who may be at high risk for developing malignant tumors.