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Biomedical subjects

J P McMillan

Publications and source records attributed to J P McMillan.

7 recordsLinked to original sources

LINE-1: a human transposable element.

Among the 10(5) LINE-1 sequences (L1Hs) in the human genome are one or more 6-kb segments that are active retrotransposons. Expression of these retrotransposons appears to be favored in cells of germ line origin, as well as in some other tumor cells of epithelial origin. In such cells, the product of the first L1Hs open reading frame (ORF), a protein called p40, is detectable; p40 has no apparent similarity to gag proteins, but contains a leucine zipper region which may be responsible for the occurrence of p40 multimers. Transcription of L1Hs initiates at residue 1 although the transcriptional regulatory regions are downstream in the first 670 bp of the 5' untranslated region; deletion of a YY1-binding site in the first 20 bp reduces transcription by fivefold. Translation of the second ORF, which encodes reverse transcriptase, is independent of the translation of the frame encoding p40.

Amino Acid Sequence↗

Translation of the human LINE-1 element, L1Hs.

Full-length RNA transcribed from the human LINE-1 (L1) element L1 Homo sapiens (L1Hs) has a 900-nt, G+C-rich, 5'-untranslated region (UTR). The 5' UTR is followed by two long open reading frames, ORF1 and ORF2, which are separated from each other by an inter-ORF region of 33 nt that includes two or three in-frame stop codons. We examine here the mechanism(s) by which the translation of L1Hs ORF1 and ORF2 is initiated. A stable hairpin structure (delta G = -74.8 kcal/mol), inserted at nt 661 of the 5' UTR, caused a 3- to 8-fold decrease in the in vitro and in vivo translation of either a lacZ reporter gene for ORF1 or the ORF1 polypeptide product, p40, but translation of a lacZ reporter gene in ORF2 was increased. The results are compatible with a model for ORF1 translation initiation in which the majority of ribosomes scan from a point 5' of nt 661 but suggest that ORF2 is not translated by attached ribosomes that reinitiate after the termination of ORF1 translation. Our data are compatible with a model whereby the translation of L1Hs ORF2 is initiated internally.

Animals↗

Nucleotide sequence of the histone gene cluster in the coral Acropora formosa (Cnidaria; Scleractinia): features of histone gene structure and organization are common to diploblastic and triploblastic metazoans.

We report the nucleotide sequence of the core histone gene cluster from the Cnidarian Acropora formosa. This is the first histone gene cluster to be sequenced from a diploblastic organism and the predicted amino acid sequences most resemble those of sea urchin equivalents. Each of the Cnidarian histone genes has two conserved regions 3' of the coding sequences and these closely resemble those of the metazoan alpha-class histone genes. In A. formosa the core histone genes are arranged as opposed (H3/H4 and H2A/H2B) pairs, a pattern common to the nondeuterostome metazoa, and tandem repetition is the predominant pattern of organization in the Cnidarian. With the recent identification of several classes of homeobox genes in Cnidarians these features clearly align the Cnidaria with triploblastic metazoans, supporting a monophyletic origin of the metazoa.

Amino Acid Sequence↗

The mouse ciguatoxin bioassay: a dose-response curve and symptomatology analysis.

Chromatographically purified ciguatoxin from toxic blackfin snapper (Lutjanus buccanella) obtained from an impounded catch in the U.S. Virgin Islands was used together with a refined mouse bioassay to construct a dose-response curve. The LD50 was calculated to be 87 mg/kg and the range of ciguatoxin doses between 0% and 100% lethality was narrow (62.5-112.5 mg/kg). Symptoms appeared in a rather stereotypic pattern with the most frequent being lowered rectal temperature and reduced locomotor activity and reflexes. Diarrhea and cyanosis were common. Breathing difficulties and convulsions occurred more often at higher doses. Approximately one-half of the animals which succumbed to ciguatoxin showed convulsions at some time, often just prior to death. The mouse bioassay described permits a reproducible and moderately sensitive detection of ciguatoxicity and would, if uniformly adopted, facilitate a comparison among future reports on ciguatera research.

Animals↗

Preliminary immunologic studies of ciguatera poisoning.

Preliminary immunologic studies of ciguatera poisoning were performed with serum samples from patients and extracts from both toxic and nontoxic fish. Counterimmunoelectrophoresis disclosed precipitin lines with toxic fish extracts and effectively discriminated between samples established as toxic or nontoxic on the basis of human toxic reactions and by an in vivo mouse bioassay. However, it is not currently possible to conclude that affected individuals had specific antibody to ciguatoxin, since putative immune and nonimmune serum samples gave equally clear precipitin reactions with toxic extracts.

Animals↗

Melatonin: effects on the circadian locomotor rhythm of sparrows.

The continuous administration of low levels of melatonin via intraperitoneally placed Silastic capsules either (i) shortened the free-running period of activity or (ii) induced continuous activity in house sparrows (Passer domesticus) maintained in constant darkness. After the melatonin-filled capsules were removed, the period of the circadian rhythm of activity lengthened in rhythmic birds and normal rhythmicity was restored in continuously active birds. The results suggest that melatonin is involved in the physiological control of circadian rhythmicity in sparrows.

Animals↗