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Biomedical subjects

A Jacobson

Publications and source records attributed to A Jacobson.

At least 73 records · Page 4Linked to original sources

LCH-I: a randomized trial of etoposide vs. vinblastine in disseminated Langerhans cell histiocytosis. The Histiocyte Society.

An international randomized trial in Langerhans cell histiocytosis (LCH) has been initiated by the Histiocyte Society. This report reviews the rationale, design, and progress of LCH-I, which compares etoposide (VP-16) and vinblastine in the treatment of disseminated LCH. Data on the risk of etoposide-associated (therapy-induced) malignancy, in the setting of histiocytosis, are reviewed. The available evidence leads to the recommendation that the study of etoposide in LCH should be continued.

Drug Administration Schedule↗

Air-rotor stripping and enamel demineralization in vitro.

This investigation sought to evaluate the effects of air-rotor stripping on the susceptibility of human enamel to demineralization using an in vitro caries model. Crowns of extracted premolar teeth were abraded (0.5 mm) on one proximal surface by air-rotor stripping. The teeth were placed in a demineralizing gel and removed at various intervals up to 336 hours. Lesion depth and mineral content on the abraded and intact surfaces was measured with contact microradiography and computerized image analysis (double window technique). For each time interval measured, lesion depth was greater (p < 0.05) on the abraded surfaces and mineral density was significantly less (p < 0.05). In a second experiment, the effect of fluoride supplements (dentifrice or topical gel) were examined on abraded and intact enamel surfaces that were exposed to the acid gel for 192 hours. The data showed that fluoride treatments significantly reduced lesion penetration on intact and abraded surfaces compared with a no fluoride group. Lesion depth on the abraded, fluoride treated surfaces was significantly greater (p < 0.05) than on the intact untreated surfaces. No significant differences (p < 0.05) were apparent between the fluoride treatment groups with respect to lesion depth and mineral density within the lesion. These results suggest that air-rotor stripping significantly increases the susceptibility of proximal enamel surfaces to demineralization. As a result, the clinician should use caution in the application of this technique until the long-term effects on caries susceptibility have been determined.

Acidulated Phosphate Fluoride↗

The quantification of soft tissue cervicomental changes after mandibular advancement surgery.

Surgical mandibular advancement results in many soft tissue changes. The purpose of this study was to quantify the changes seen in the cervicomental angle and the lip-chin-throat angles in response to mandibular advancement, as well as hyoid bone positional changes. As a result of statistical analysis of hyoid bone and soft tissue linear and angular changes, prediction models are presented as to the soft tissue response to mandibular advancement in the cervicomental region.

Adaptation, Physiological↗

Argon beam coagulation rescue to correct bleeding during pelviscopy.

A new technique of unipolar laparoscopic coagulation is particularly useful for the treatment of pelvic or abdominal bleeding during laparoscopic procedures. Blood present at the coagulation site is blown clear with a stream of argon gas prior to tissue coagulation. Of particular importance is the virtual absence of smoke, and because the procedure involves a nontouch technique, eschar is not removed inadvertently. The speed of tissue coagulation is faster than that of conventional bipolar and unipolar techniques.

Argon↗

Outpatient laparoscopic-assisted vaginal hysterectomy.

STUDY OBJECTIVE: To compare laparoscopic-assisted hysterectomy (LAVH) with conventional abdominal hysterectomy. DESIGN: First 50 consecutive LAVH procedures. SETTING: An outpatient facility at a major medical center (35 procedures) and a nonhospital free-standing surgicenter (15). PATIENTS: Sequential sample of 50 women requiring hysterectomy. INTERVENTIONS: LAVH in 46 women, converted to open laparotomy in 4. MEASUREMENTS AND MAIN RESULTS: Outpatient LAVH was performed successfully in the majority of women. Most patients had significant uterine enlargement, pelvic adhesions, or endometriosis. Only six required replacement of autologous blood postoperatively. Other complications were cystotomy and postoperative pelvic hematoma in one patient each. CONCLUSIONS: LAVH can be performed safely in free-standing surgicenters. It offers several advantages to patients, and is considered cost effective by third-party payers.

Abdomen↗

AIDS, HIV infection, and illicit drug use within inner-city families and social networks.

OBJECTIVES: Drug use is commonly depicted and treated as an individual problem. This study describes the extent of drug use, human immunodeficiency virus (HIV) infection, and acquired immunodeficiency syndrome (AIDS) among drug users' sexual partners and family and household members in order to broaden considerations of risk. METHODS: Social network charts and structured interviews were administered to 126 women (predominantly African American and Latino) enrolled in methadone treatment. The charts elicited the prevalence of drug use and HIV infection among subjects' family and household members. RESULTS: Drug use and HIV/AIDS permeated subjects' sexual, familial, and household relationships. More than half of the women who resided with a sexual partner reported that their partners currently used drugs. Almost one third of the subjects' siblings were drug users. Of the 715 total siblings (all subjects plus their siblings), 69 (9.7%) were known to be HIV positive or to have an AIDS diagnosis. CONCLUSIONS: The sexual, familial, and household expressions of drug use underscore the notion that drug use and attendant risks, including but not limited to HIV infection, might be usefully viewed and treated as an inter- and intracommunity problem rather than as an exclusively individual one.

Acquired Immunodeficiency Syndrome↗

Stabilization and ribosome association of unspliced pre-mRNAs in a yeast upf1- mutant.

Nonsense-mediated mRNA decay, the accelerated turnover of mRNAs transcribed from genes containing early nonsense mutations, is dependent on the product of the UPF1 gene in yeast. Mutations that inactivate UPF1 lead to the selective stabilization of mRNAs containing early nonsense mutations but have no effect on the half-lives of almost all other mRNAs. Since the transcripts of nonsense alleles are not typical cellular constituents, we sought to identify those RNAs that comprise normal substrates of the nonsense-mediated mRNA decay pathway. Many yeast pre-mRNAs contain early in-frame nonsense codons and we consider it possible that a role of this pathway is to accelerate the degradation of pre-mRNAs present in the cytoplasm. Consistent with this hypothesis, we find that, in a strain lacking UPF1 function, the CYH2, RP51B, and MER2 pre-mRNAs are stabilized 2- to 5-fold and are associated with ribosomes. We conclude that a major source of early nonsense codon-containing cytoplasmic transcripts in yeast is pre-mRNAs and that the UPF1 protein may be part of a cellular system that ensures that potentially deleterious nonsense fragments of polypeptides do not accumulate.

Gene Expression Regulation, Fungal↗

Improvement of pregnancy rates with oocyte donation in older recipients with the addition of progesterone vaginal suppositories.

Pregnancy rates and implantation rates with oocyte donation in recipients 40 years of age and older were significantly lower than those obtained in recipients under the age of 40. This difference was eliminated when P vaginal suppositories were added to the luteal regimen in older recipients. Our experience suggests that uterine aging may play a role in the successful initiation of a pregnancy, but this may be overcome with the preparation of the uterus with P vaginal suppositories.

Adult↗

mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor.

Nonsense mutations in a gene can accelerate the decay rate of the mRNA transcribed from that gene, a phenomenon we describe as nonsense-mediated mRNA decay. Using amber (UAG) mutants of the yeast PGK1 gene as a model system, we find that nonsense-mediated mRNA decay is position dependent, that is, nonsense mutations within the initial two-thirds of the PGK1-coding region accelerate the decay rate of the PGK1 transcript < or = 12-fold, whereas nonsense mutations within the carboxy-terminal third of the coding region have no effect on mRNA decay. Moreover, we find that this position effect reflects (1) a requirement for sequences 3' to the nonsense mutation that may be necessary for translational reinitiation or pausing, and (2) the presence of an additional sequence that, when translated, inactivates the nonsense-mediated mRNA decay pathway. This stabilizing element is positioned within the coding region such that it constitutes the boundary between nonsense mutations that do or do not affect mRNA decay. Rapid decay of PGK1 nonsense-containing transcripts is also dependent on the status of the UPF1 gene. Regardless of the position of an amber codon in the PGK1 gene, deletion of the UPF1 gene restores wild-type decay rates to nonsense-containing PGK1 transcripts.

Base Sequence↗

Analysis of chimeric mRNAs derived from the STE3 mRNA identifies multiple regions within yeast mRNAs that modulate mRNA decay.

In the yeast Saccharomyces cerevisiae unstable mRNAs decay 10-20 fold more rapidly than stable mRNAs. In order to examine the basis for the differences in decay rate of the unstable STE3 mRNA and the stable PGK1 and ACT1 mRNAs we have constructed and measured the decay rates of numerous chimeric mRNAs. These experiments indicate that multiple regions within yeast mRNAs are involved in modulating mRNA decay rates. Our results suggest that at least two regions within the STE3 mRNA are involved in stimulating rapid decay. One region is located within the coding region and requires sequences between codons 13 and 179. In addition, the STE3 3' UT can also function to stimulate decay. Surprisingly, the STE3 3' UT is not sufficient to accelerate the turnover of the stable PGK1 transcript unless portions of the PGK1 coding region are first deleted. These results not only identify sequences that function within yeast to stimulate mRNA turnover but also have important implications for an understanding of the basis of differences in eukaryotic mRNA decay rates.

Base Sequence↗

A coding region segment is necessary, but not sufficient for rapid decay of the HIS3 mRNA in yeast.

In Saccharomyces cerevisiae, the HIS3 (encoding imidazoleglycerolphosphate dehydratase) mRNA is unstable (t1/2 = 7 min), whereas the ACT1 (encoding actin) mRNA is more stable (t1/2 = 30 min). To define determinants responsible for rapid mRNA decay, hybrid genes comprised of various regions of these two mRNAs were constructed, transformed into yeast on centromere-containing vectors, and the half-lives of the resultant chimeric mRNAs were measured. To examine whether the 3'-untranslated region (3'-UTR) of HIS3 can confer instability to the ACT1 mRNA, DNA encoding the 3'-UTR of ACT1 was replaced with the corresponding region of HIS3. The hybrid mRNA containing the HIS3 3'-UTR decayed at a rate similar to the endogenous ACT1 mRNA. The mRNA containing the HIS3 5'-UTR and most of the HIS3 coding region fused to an ACT1 3'-fragment was unstable, indicating that HIS3 instability determinants are located within the HIS3 5'-UTR or coding sequence. Deleting 411 nucleotides (nt) from the coding region of either HIS3 or the 5'-HIS3-ACT1-3' chimeric gene resulted in a three- to fourfold stabilization of the respective mRNAs. However, insertion of this 411-nt fragment in-frame into the entire ACT1 gene had no destabilizing effect on the resultant hybrid mRNA. We conclude that the instability determinants of HIS3 mRNA are complex, involving a coding region segment and, possibly, the 5'-UTR.

Actins↗