Fragile X expression in thymidine-prototrophic and auxotrophic human-mouse somatic cell hybrids under low and high thymidylate stress conditions

Expression of the fragile X site fra(X)(q27.3) was studied in thymidine-prototrophic and auxotrophic human-mouse somatic cell hybrids. In these cells, low thymidylate stress, achieved by 5-fluoro-2'-deoxyuridine (FdU) treatment and by limiting the exogenous supply of thymidine (dT), induced fragile X expression. High thymidylate stress, produced by supplying excess amounts of dT, was also effective in inducing fragile X expression, even in a hybrid clone that retained a fragile X chromosome as the only human chromosome; addition of deoxycytidine (dC) completely abolished this effect. In contrast, 5-bromo-2'-deoxyuridine (BrdU) did not induce fragile X expression. Cell-cycle analysis of BrdU-deprived thymidine-auxotrophic hybrid cells indicated that one round of DNA replication under thymidylate stress conditions is sufficient for fragile X expression. Our results suggest that the expression is an intrinsic property of the fragile site itself, which is believed to be composed of replicon clusters with pyrimidine-rich DNA sequence(s).     

What's new in cerebral palsy

Among new researches bearing on cerebral palsy are the growth of brain cells in tissue cultures for experimentation; the use of polysaccharides to prevent the formation of a glial barrier to nerve growth after injury; observation of changes in reactions of neurons at various stages of development; the finding of hypernatremia and hyperchloremia in lesions of the frontal lobe and the thalamus; stimulation of cerebral blood flow by injection of sodium bicarbonate and retardation with ammonium chloride; and studies of serial sections of brains of palsied children who died. Study of development in the early months of life has made possible the detection of significant abnormalities in behavior early in life. Loss of hearing may be tested in very young children by measuring minute variations in electrical resistance of the skin upon auditory stimulation of the sympathetic nervous system. Conditions which have been described as having been confused with cerebral palsy are dislocation of a cervical vertebra, hereditary spastic paraplegia, transverse myelopathy, injury to the spinal cord or cauda equina by anomalous growths of the spine, and also encephalitis and meningitis. Sedation has proved a valuable adjunct to electroencephalographic study of cerebral palsy. Better criteria for abnormality in the young child should be determined and the application of them more clearly standardized. Simple exercises are useful for early training of palsied children to stimulate development. "Crossed laterality"-the dominant eye being contralateral to the preferred hand-has been counteracted by special training with great success in eliminating emotional and behavior problems and accelerating development.Recent studies indicate that only 50 per cent of cerebral palsy patients have normal or better intelligence. Subluxation of the hip joint, a common deformity associated with cerebral palsy, can sometimes be corrected by operation if detected at an early stage. Radical ablation of epileptogenic foci in the cortex is also being done in young patients if drug control of seizures fails. Frontal topectomy, cingulate gyrectomy or prefrontal labotomy may be advisable in cases in which proper response to drug therapy is not obtained. Improvement in behavior as well as control of seizures may follow the use of Benzedrine,(R) Dexedrine,(R) Dilantin(R) sodium, Mebaral(R) and phenobarbital. Alcohol, paraldehyde and chloral hydrate have been effective as relaxants.     

The small hospital's role in poliomyelitis

Medical skills should be developed by the staffs of smaller hospitals for the differential study of patients with symptoms resembling those of poliomyelitis in order to provide the rudiments of care for the occasional patient with mild poliomyelitis, to recognize the indications which point to the necessity of superior technical assistance, and to decide when it is appropriate to move patients to better equipped centers. The impetuous acquisition of mechanical aids for the treatment of special problems will be effective in small communities only to the extent that this equipment is kept serviceable and is operated by persons of sufficient skill. Epidemic situations in a small community can be met only by mobilization of facilities under adequate direction and by integration of care with that provided by larger treatment centers.     

The physical mapping of bacteriophage T5 transfer tRNAs.

Transfer RNAs, isolated from Escherichia coli F cells infected with T5 bacteriophage, were charged with radioactive amino acids and used in RNA-DNA hybridization studies to detect and locate T5 tRNA cistrons in the T5 DNA chromosome. Hybridization of 14 3H-aminoacyl-tRNA species, including purified T5 [35S]Met-tRNAm and [35S]Met-tRNAf, to the separated strands of T5+ DNA indicates that most, if not all, of the T5 tRNAs are transcribed from the continuous heavy strand of T5 DNA. Heteroduplex mapping of eight mutant T5 DNA deletions has enabled us to locate and determine the size of these deleted segments. By correlating this information with the presence and absence of specific tDNA sequences in these mutants, as determined by tRNA-DNA hybridization, we were able to define the physical limits of four tDNA-containing loci along the T5 DNA molecule. A physical map for 15 tRNA species examined indicates that the structural genes for these tRNAs are clustered within a segment length of T5 DNA that represents approximately 11.2% of the total wild type T5 DNA. The existence of the deletion mutants indicates that T5 tRNAs are dispensable for T5 replication under the growth conditions and for the host employed.