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Biomedical subjects

S I Miller

Publications and source records attributed to S I Miller.

At least 91 records · Page 5Linked to original sources
PubMed1989

Limb defects in gray short-tailed opossums (Monodelphis domestica) following postnatal injection with ethanol or saline.

Because the hindlimbs of marsupials at birth are in an embryonic stage of development, this group can prove useful for studies of limb teratology. In this study, injection of neonatal gray opossums with 2 mg ethanol (ETOH) or saline (SAL) in the right or left hindquarter resulted in defects of the associated limb in 44% of ETOH animals and 16% of SAL animals. Affected SAL animals showed gait abnormalities, foot clubbing, and moderately reduced limb size. Affected ETOH animals showed these abnormalities as well as fused digits, missing digits, and, in one case, a partially missing limb. Thus, while injection itself may have resulted in altered limb development, local infusion of alcohol had a further teratogenic effect on such development.

Animals↗
PubMed1989

A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence.

We have determined that Salmonella typhimurium strains with mutations in the positive regulatory locus phoP are markedly attenuated in virulence for BALB/c mice. The DNA sequence for the phoP locus indicates that it is composed of two genes present in an operon, termed phoP and phoQ. The deduced amino acid sequence of the phoP and phoQ gene products are highly similar to other members of bacterial two-component transcriptional regulators that respond to environmental stimuli. S. typhimurium strains with transposon insertions that create transcriptional and translational gene fusions that require phoP and phoQ for expression have been isolated and have different chromosomal locations, indicating that this system is a regulon. One of these fusion strains, containing a mutation in a gene termed pagC, has a virulence defect. Other strains, including those containing mutations in the phoN gene, encoding an acid phosphatase, have wild-type virulence. Strains with pagC, phoP, or phoQ mutations have decreased survival in cultured mouse macrophages. When used as live vaccines in mice, strains with phoP or phoQ mutations afford partial protection to subsequent challenge by wild-type S. typhimurium.

Amino Acid Sequence↗
PubMed1989

Bacteremia with Streptococcus bovis and Streptococcus salivarius: clinical correlates of more accurate identification of isolates.

Two biotypes of Streptococcus bovis can be identified by laboratory testing and can be distinguished from the phenotypically similar organism Streptococcus salivarius. We assessed the clinical relevance of careful identification of these organisms in 68 patients with streptococcal bacteremia caused by these similar species. S. bovis was more likely to be clinically significant when isolated from blood (89%) than was S. salivarius (23%). There was a striking association between S. bovis I bacteremia and underlying endocarditis (94%) compared with that of S. bovis II bacteremia (18%). Bacteremia with S. bovis I was also highly correlated with an underlying colonic neoplasm (71% of patients overall, 100% of those with thorough colonic examinations) compared with bacteremia due to S. bovis II or S. salivarius (17% overall, 25% of patients with thorough colonic examinations). We conclude that careful identification of streptococcal bacteremic isolates as S. bovis biotype I provides clinically important information and should be more widely applied.

Adolescent↗
PubMed1988

trans splicing in Leishmania enriettii and identification of ribonucleoprotein complexes containing the spliced leader and U2 equivalent RNAs.

The 5' ends of Leishmania mRNAs contain an identical 35-nucleotide sequence termed the spliced leader (SL) or 5' mini-exon. The SL sequence is at the 5' end of an 85-nucleotide primary transcript that contains a consensus eucaryotic 5' intron-exon splice junction immediately 3' to the SL. The SL is added to protein-coding genes immediately 3' to a consensus eucaryotic 3' intron-exon splice junction. Our previous work demonstrated possible intermediates in discontinuous mRNA processing that contain the 50 nucleotides of the SL primary transcript 3' to the SL, the SL intron sequence (SLIS). These RNAs have a 5' terminus at the splice junction of the SL and the SLIS. We examined a Leishmania nuclear extract for these RNAs in ribonucleoprotein (RNP) particles. Density centrifugation analysis showed that the SL RNA is predominantly in RNP complexes at 60S, while the SLIS-containing RNAs are in complexes at 40S. We also demonstrated that the SLIS can be released from polyadenylated RNA by incubation with a HeLa cell extract containing debranching enzymatic activity. These data suggested that Leishmania enriettii mRNAs are assembled by bimolecular or trans splicing as has been recently demonstrated for Trypanosoma brucei. Furthermore, we determined the partial sequence of the Leishmania U2 equivalent RNA and demonstrated that it cosediments with the SL RNA at 60S in a nuclear extract. These RNP particles may be analogous to so-called spliceosomes that have been demonstrated in other systems.

Animals↗
PubMed1986

Cloning and characterization of a Leishmania gene encoding a RNA spliced leader sequence.

Recent studies on leishmania enriettii tubulin mRNAs revealed a 35 nucleotide addition to their 5' end. The gene that codes for this 35 nucleotide leader sequence has now been cloned and sequenced. In the Leishmania genome, the spliced leader gene exists as a tandem repeat of 438 bases. There are approximately 150 copies of this gene comprising 0.1% of the parasite genome. This gene codes for a 85 nucleotide transcript that contains the spliced leader at its 5' end. The 35 nucleotide sequence and the regions immediately 5' and 3' to it are highly conserved across trypanosomatids. We have detected a RNA molecule that is a putative by-product of the processing reaction in which the 35 nucleotide spliced leader has been transferred to mRNA. We suggest that this molecule is the remnant of the spliced leader transcript after removal of the 35 nucleotide spliced leader.

Animals↗
PubMed1986

Chromosome location of four genes in Leishmania.

Chromosome-sized DNA molecules from Leishmania isolates (L. mexicana amazonensis, L. mexicana mexicana, L. chagasi, L. major, L. donovani, and L. braziliensis) were separated by orthogonal field alternation gel electrophoresis. The chromosome locations of four genes were mapped. The alpha-tubulin and rRNA genes each mapped to a single chromosome size class. The beta-tubulin and the 5'-spliced-leader-sequence genes were found on more than one chromosome size class and showed variation of hybridization profiles across species.

Animals↗
PubMed1986

Transcriptional mapping of Leishmania enrietti tubulin mRNAs.

We have mapped the mRNAs for alpha- and beta-tubulins of Leishmania enriettii promastigotes and amastigotes and have demonstrated that each RNA contains a 35 nucleotide sequence on its 5' end which is not encoded contiguously with the rest of the message. Sequencing of the 5' end of the alpha- and beta-tubulin mRNAs revealed that this 35 nucleotide leader sequence is identical in both messages and that it is homologous to the spliced leader found on the 5' end of mRNAs in the related parasite Trypanosoma brucei. Additionally, we have sequenced regions of the alpha- and beta-tubulin genomic clones upstream from the mRNA encoding regions and have shown that the leader sequence is not encoded within these regions of DNA. Hence, Leishmania tubulin mRNAs may be synthesized by a discontinuous transcription process that links together the transcription products of two separate gene families, as suggested previously by others for the assembly of T. brucei mRNAs. Homologies between the Leishmania alpha- and beta-tubulin genes themselves and between these genes and the T. brucei alpha- and beta-tubulin genes have revealed sequences which may be important in synthesis or processing of Leishmania tubulin mRNAs.

Animals↗
PubMed1986

Significant determinants of susceptibility to alcohol teratogenicity.

Typically, the rate of abusive drinking during pregnancy considerably exceeds the rates of fetal alcohol syndrome (FAS) and alcohol-related birth defects, suggesting that other factors may modify the impact of alcohol on the developing organism. Data in the literature supporting this susceptibility hypothesis are sparse. In this paper, two studies in different samples, using different analytic strategies to examine susceptibility to different adverse outcomes are presented. Among 176 pregnancies in which lowered birth weight for gestational age was detected as an effect attributable to frequent beer drinking, 27 infants weighted less than 2,700 grams and 149 weighed more. Using discriminant analysis to contrast these groups, lowered birth weight for gestational age was associated with black race and lower maternal weight and weight gain. The effects of these factors were additive with that of persistent alcohol exposure; no interactions were detected, but pregnancies with risks in addition to alcohol were more likely to yield growth-retarded infants. In a second study, pregnancies resulting in 25 FAS cases were contrasted with 50 controls. A four-factor model accounted for nearly two-thirds of the explainable variance in the occurrence of FAS. Adjusted for frequency of maternal drinking, chronic alcohol problems and parity, there was a sevenfold increase in risk for FAS among black infants. The findings from both studies are consistent with the susceptibility hypothesis and have potentially important implications for public health and clinical approaches to prevention, as well as for future research.

Abnormalities, Drug-Induced↗
PubMed1986

Psychiatrists and the treatment of addictions: perceptions and practices.

4,657 out of a total APA membership of 28,000 expressed a particular interest in alcoholism and substance abuse. 1,705 of these responded to a questionnaire studying their attitudes and practices. Most of these do part-time work in the field with 9.9% being subspecialists. Self-report responses indicated that psychiatrists have incorporated a disease concept, abstinence orientation, utilized AA, education, supportive therapy, and a range of other modalities, think of addictions as treatable psychiatric disorders, and very infrequently use maintenance minor tranquilizers. Most became interested because of community need. However, 41.4% had a training experience including 36.1% who had a rotation on a substance abuse service. Psychiatrists are becoming aware that substance use disorders are an important component of psychiatry, and they are growing more assertive about their role in it.

Alcoholism↗
PubMed1983

Exposure of dog thyroid slices to acetylcholine induces refractoriness to its subsequent stimulation of glucose oxidation.

An initial incubation of dog thyroid slices with 0.1 or 1 microM acetylcholine (ACH) for at least 2 h decreases its subsequent stimulation of [1-14C]glucose oxidation. Refractoriness persists for as long as 6 h in the absence of ACH. While new protein synthesis is essential for recovery, it is not necessary for its induction. Refractoriness is prevented when 25 microM tropicamide, an atropine-like drug, is present from the beginning of the initial incubation, but not when it is added after 2 h of incubation of slices with ACH, indicating that at this time ACH is no longer necessary for refractoriness. During refractoriness induced by ACH, stimulation of glucose oxidation by thyroid-stimulating hormone, prostaglandin E1, dibutyryl cyclic AMP, and cholera toxin, but not menadiol, is also significantly diminished. Incubation of thyroid slices with ACH does not modify its stimulation of iodide organification or 32Pi incorporation into phospholipids. These results suggest that the desensitization is not due to changes in the ACH receptor but rather to intracellular metabolic effects. This phenomenon may be important in the regulation of cholinergic effects on the thyroid.

Acetylcholine↗
PubMed1983

Interaction of alcohol and zinc in fetal dysmorphogenesis.

The interaction of low doses of alcohol and marginal zinc deficiency during gestation was studied in pregnant mice and their fetuses. The combination of the two agents at subteratogenic doses was related to increased external and internal defects. Pregnant mice fed a diet containing 10 micrograms/g zinc were orally dosed with 2.0 micrograms/g of 50% ethanol for 18 days of pregnancy. Fetuses from these dams presented with more fetal defects than fetuses from control dams. Analysis of maternal livers showed a significant effect of alcohol on liver magnesium and zinc. Changes in fetal heart zinc levels were the only significant tissue effect of alcohol in the fetus.

Abnormalities, Drug-Induced↗