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Biomedical subjects

G Curtis

Publications and source records attributed to G Curtis.

14 recordsLinked to original sources

A reinvestigation of thirty three fragile(X) families using probe StB12.3.

We have reinvestigated 33 fragile X families using probe StB12.3. In 31 families the affected individual showed an insert while in 2 families no insert was detected. The insert fell into two size categories: small (less than 0.5 kb); and large (greater than 0.6 kb) accompanied by methylation of an EagI site. All individuals of either sex having a small insert were fra(X) negative and intellectually normal, while all males having a large insert were fra(X) positive and intellectually impaired. Females having a large insert were either fra(X) positive or negative and either intellectually normal or impaired. No new mutation was found. All daughters of males with a small insert had a small insert; females with a large insert produced males and females who had a large insert, while females with a small insert had offspring with either a large or a small insert. However, females with a small insert tended to fall into one of two categories: either they had only children with a small insert or only children with a large insert, there being only one exception to this rule. We found four unexpected small inserts, two in unrelated spouses and two in female carriers who proved to be compound heterozygotes, indicating that they had inherited an insert from both their parents. These observations suggest that individuals with a small insert must be not uncommon in the general population.

DNA Probes

Earliest Homo.

The origin of our own genus, Homo, has been tentatively correlated with worldwide climatic cooling documented at about 2.4 Myr (million years). It has also been conjectured that members of Homo made the first stone tools, currently dated at 2.6-2.4 Myr. But fossil specimens clearly attributable to Homo before about 1.9 Myr have been lacking. In 1967 a fossil hominoid temporal bone (KNM-BC1) from the Chemeron Formation of Kenya was described as family Hominidae gen. et sp. indet. Although a surface find, its provenance within site JM85 (BPRP site K002) was established and a stratigraphic section provided indicating the specimen's position. This evidence has been affirmed but the exact age of the fossil was never determined, and the absence of suitable comparative hominid material has precluded a more definitive taxonomic assignment. Here we present 40Ar/39Ar age determinations on material from the hominid site indicating an age of 2.4 Myr. In addition, comparative studies allow us to assign KNM-BC1 to the genus Homo, making it the earliest securely known fossil of our own genus found so far.

Animals

A family with X-linked deafness showing linkage to the proximal Xq region of the X chromosome.

Linkage analysis has been carried out in a family with severe congenital sensorineural deafness with a structural abnormality of the inner ear. Recombinations show the gene responsible for deafness in this family to lie between the loci DXS255 (Xp11.22) and DXS94 (Xq22). Close linkage was found to locus DXS159 (cpX289) in Xq12, with a LOD score of 3.155 and 0 recombination. This location is consistent with other linkage studies of X-linked deafness.

Chromosome Mapping

Incubation of 3,4-benzo(s)pyrene with serum fractions: effect on tumor production.

The effect on tumor formation in Swiss mice of incubation of 3,4-Benzo(a)pyrene [B(a)P]either with saline or saline containing serum, gamma-globulin or albumin (form mouse or rabbit) was investigated. A high incidence of sarcomas (80--100%) was obtained in Swiss mice by B(A)P incubated in vitro with rabbit serum, rabbit gamma-globulin, mouse serum, mouse gamma-globulin, and saline. A lower incidence (60--65%) was obtained with B(a)P incubated with mouse serum, mouse albumin, and rabbit albumin. The data suggest that binding of B(a)P to protein, particularly to albumin, significantly decreases the biological activity of B(a)P.

Animals

Benzo[alpha]pyrene antibody inhibition of benzo[alpha]pyrene-induced mutageneis.

An antibody to benzo[alpha]pyrene (BP) was prepared. The isolated antibody showed a specificity for BP and a low reactivity with another carcinogenic hydrocarbon, 7,12-dimethylbenz[alpha]anthracene (DMBA). The BP-antibody inhibited the in vitro cytotoxic and mutagenic activity of BP in both a rat embryo fibroblast- and a rat lung cell-mediated mutagenesis system. A possible correlation of these in vitro findings to the in vivo carcinogenesis situation is discussed.

9,10-Dimethyl-1,2-benzanthracene

"Flooding in vivo" during the circadian phase of minimal cortisol secretion: anxiety and therapeutic success without adrenal cortical activation.

Seven patients with maximally severe phobias for physical objects were treated by "flooding in vivo", i.e. live confrontation with the feared object. Each reported to the laboratory for 3 hr on five separate occasions, all in the early evening during the circadian phase of minimal adrenal cortical activity. At 20-min intervals during each session, blood was taken for cortisol assay, and anxiety was self-rated on a scale of 0 to 100. Treatment was carried out during the 2nd hr of the third and fourth sessions. The remaining time provided control observations. By behavioral and subjective criteria, the treatment hours produced very intense anxiety. However, they failed to evaluate plasma cortisol levels. The remission of the phobias was 100%. Anxiety, even when intense and dramatic, does not necessarily activate the adrenal cortex, and an adrenal "stress" response is not necessary for the therapeutic effect.

Adrenal Cortex

Two families with Xq27.3 fragility, no detectable insert in the FMR-1 gene, mild mental impairment, and absence of the Martin-Bell phenotype.

In 2 families, propositi were investigated because of mild developmental delay and, in one case, behavior disorders. Seven males in the 2 families were found to have a fragile site at Xq27.3 but the usual insert in the FMR-1 gene was absent. The affected males had mild, or in some cases, no clear intellectual impairment and did not have the Martin-Bell phenotype. Carrier females in one family tended to show a high level of cytogenetic expression of the fragile site but were clinically normal. It is not yet clear whether these families have unusual mutations in the FMR-1 gene or whether their fragile sites are different, but cytogenetically indistinguishable from, that associated with inserts in the FMR-1 gene.

Adolescent