Biomedical subjects
Publications and source records attributed to K Flynn.
Undifferentiated carcinoma of the parotid gland contains clonal Epstein-Barr virus episomes without ladder arrays of restriction enzyme fragments representing virion DNA. Analysis of Epstein-Barr virus transcription in situ in parotid carcinoma specimens revealed that the EBER RNAs, latent membrane protein mRNA, and the BamHI-A rightward reading frame, BARF0, are expressed in the malignant epithelial cells.
The glue genes of Drosophila melanogaster comprise a family of genes expressed at high levels in the salivary glands of late third instar larvae in response to the insect hormone ecdysone. We present evidence that, in contrast to the other glue genes, Sgs-4 is turned on throughout Drosophila development and is not expressed exclusively in the larval salivary glands. Larvae transformed with an Sgs-4/Adh (alcohol dehydrogenase) hybrid gene exhibit Sgs-4-directed Adh expression in the larval proventriculus as well as in the salivary glands as early as the first instar. Sgs-4-specific RNA can be detected at very low levels during all stages of development. During late third instar, levels of Sgs-4 RNA in the salivary glands increase several-thousand-fold, thereby accounting for the large amounts of Sgs-4 protein present in the glue produced by the salivary glands. This pattern of expression is unique to the Sgs-4 gene. While expression of several of the other glue genes can be detected in embryos and early larvae, they appear to be expressed neither throughout development nor in the larval proventriculus. Appearance of the glue gene RNAs in mid third instar salivary glands is noncoordinate, even for the chromosomally clustered genes Sgs-3, Sgs-7, and Sgs-8.
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Because hydroxyzine hydrochloride is frequently used to tranquilize patients, who are receiving narcotic analgesics for pain relief, its effect alone and in combination with meperidine on arterial blood gases and ventilation in patients at rest was evaluated in 65 healthy volunteers, who gave informed consent. Hydroxyzine hydrochloride, 1.5 mg/kg IV given over 30 seconds, caused no decrease but rather a significant (P less than .001) increase in PaO2 and no increase in PaCO2 and/or pH at 5, 10, 20, 30, and 60 minutes (N = 29; mean age = 47.0 years). Meperidine, 1.5 mg/kg IV given over 30 seconds, caused a significant (P less than .01) reduction in PaO2 at 5 minutes indicating ventilatory depression but no increase in PaCO2 and/or pH (N = 19; mean age = 32.4 years). The combination of the same doses of hydroxyzine with meperidine IV caused a significantly greater decrease in PaO2 only at 10 minutes but a greater increase in PaCO2 and pH at all times for 60 minutes than did meperidine alone (N = 17; mean age = 39.5 years), which indicates greater ventilatory depression with the combination than with hydroxyzine alone. However, PaO2, PaCO2 and pH remained within the awake normal ranges for PaO2, PaCO2, and pH for the age group of volunteers even at 10 minutes after IV injection of the drug combination when most of the volunteers were asleep. In conclusion, hydroxyzine even when given IV in excess of the maximum IM therapeutic doses caused no changes in PaO2, PaCO2 or pH, which would indicate clinically important ventilatory depression.(ABSTRACT TRUNCATED AT 250 WORDS)
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Since methotrimeprazine proved to be both an effective tranquilizer and analgesic, its effect in a tranquilizing dose of 0.15 mg/kg on the arterial blood gases was determined in human volunteers. Because of the known potentiating effect of some phenothiazines on the narcotic-analgesic induced respiratory depression and analgesia, the effect of methotrimeprazine on the meperidine-induced respiratory depression was also studied. Before, and at five minute intervals after the administration of the test drugs, PaO2, PaCO2 and pH were determined by a Radiometer Copenhagen Blood Gas Analyzer (Radiometer Copenhagen, 72 Endruvej, Denmark) through a Riley-needle. Continuous ECG lead II tracings were taken during the experiment. No significant decrease in PaO2 or increase in PaCO2 (P less than 0.01) was observed in 6 healthy volunteers (mean age = 25 yrs) after 0.15 mg/kg i.v. methotrimeprazine. In 19 volunteers (mean age = 32 yrs), the intravenous infusion of 1.5 mg/kg meperidine caused significant decrease in PaO2 and increase in PaCO2 five minutes after its administration. The combined administration of both drugs to 6 volunteers (mean age = 23 yr) caused initially the same decrease in PaO2 as after meperidine alone with subsequent increase in PaO2 over normal levels, however, the PaCO2 significantly increased both as compared to baseline values and as compared with meperidine alone. The pH reductions after the combination of both drugs were greater than after meperidine alone, which in combination with the PaCO2 values confirms the potentiation of meperidine-induced respiratory depression by methotrimeprazine. The results indicate the methotrimeprazine alone causes no significant respiratory depression, but it potentiates the respiratory depression caused by meperidine.
Immunologic studies of Epstein-Barr virus (EBV) have implicated EBV in undifferentiated and partially differentiated, non-keratinizing nasopharyngeal carcinoma (NPC). Patients with the well-differentiated, keratinizing form of NPC have EBV serologic patterns similar to those of control populations. In addition, viral DNA has not been detected in the differentiated tumors using viral cRNA probes to DNA immobilized on filters. In this study we have tested for EBV DNA using recombinant DNA probes to Southern blots of DNA from 33 NPC specimens. The 24 undifferentiated and 4 partially differentiated specimens generally contained a relatively high number of EBV genome equivalents, while the 5 well-differentiated NPC all contained detectable EBV, but at low copy number. The viral DNA from one of the well-differentiated specimens was cloned into a cosmid vector. Five recombinant clones representing the fused viral termini were obtained, indicating the presence of episomal, intracellular DNA in the tumor. These findings indicate that all histologic subsets of NPC contain EBV DNA.
A cis acting regulatory region has previously been identified 300-500 bp upstream of the Drosophila glue protein gene, Sgs-4. The functional capabilities of this region have now been examined by fusing it to the Drosophila Adh gene and determining the pattern of expression from the fused construct after transformation. The results show that the Sgs-4 sequences between -150 and -568 are able to direct Adh expression in late third-instar salivary glands, the appropriate tissue and timing for Sgs-4 expression. In addition, the Sgs-4 sequence elevates Adh expression in the anterior midgut and fat body, despite the fact that Sgs-4 is not normally expressed there. All three regulatory activities, tissue specificity, timing and enhancement, show the positional flexibility of enhancer elements. In addition, the Sgs-4 and Adh regulatory elements combine to direct expression in novel spatial/temporal combinations in which neither would normally be expressed.
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The linear virion form of Epstein-Barr virus (EBV) DNA has variable numbers of direct tandem 500 bp repeats at each terminus. The terminal restriction endonuclease fragments and the fused terminal fragments in the intracellular episomal form are heterogeneous in size, and vary by increments of 500 bp. The structure of the termini of EBV in carcinomas of the nasopharynx and the parotid gland was compared with the EBV termini in monoclonal and polyclonal tissues or cell lines. A single band representing the EBV joined termini was detected in each of the carcinomas and in the monoclonal lymphoid proliferations. Polyclonal cell lines contained multiple forms of the joined termini. The detection of a homogeneous episomal population suggests that EBV-associated epithelial malignancies are clonal expansions of a single EBV-infected progenitor cell.
T-cell and B-cell lymphocyte subpopulations, monocytes, granulocytes, and immunoglobulin receptors were measured with monoclonal antibodies and flow cytometric techniques in the peripheral blood of 266 patients with posterior uveal melanoma before therapy. Statistically significant differences were found in T-helper/inducer (OKT4), T-suppressor/cytotoxic (OKT8), and B-lymphocyte populations between patients with uveal melanoma and age-matched controls.
A 63-year-old man had epithelioid sarcoma. Light microscopy showed the tumor to resemble granuloma annulare. Enzymatic histocytochemical and ultrastructural studies demonstrated the tumor's histiocytic features. Literature review of epithelioid sarcoma and granuloma annulare showed them to have a similar anatomic distribution.
Flow cytometric DNA analysis was used to compare nuclear DNA content of carcinogen-induced F-344 rat tracheal epithelial cell lines as they progressed from non-tumorigenic (preneoplastic) to tumorigenic (neoplastic) populations in vitro. Normal tracheal cell populations were used as diploid reference cells. All of the tracheal epithelial cell lines established from carcinogen-treated tracheas showed increases in nuclear DNA content as compared to normal cell populations. For five cell lines, measurements were made during the preneoplastic state as well as after conversion to the neoplastic state. Four of the five cell lines showed a major shift in DNA content as the culture progressed from preneoplastic to neoplastic populations. However, there was no consistent change in DNA content as cultures progressed to neoplastic populations in vitro. Two cell lines showed shifts to higher levels as the cultures became tumorigenic, while two showed shifts to lower levels. Additionally two cell lines (3F3 and 165D) had DNA distribution profiles indicative of mixed cell populations during the neoplastic phase. Cloning experiments of cell line 3F3 confirmed that those cells having a model DNA value the same as that of their preneoplastic progenitor populations were non-tumorigenic. Evidence that such shifts in DNA content correlate with comparable changes in chromosome number was presented for the 3F3 cell line. These studies demonstrate that the transition from preneoplastic tracheal epithelial cells to neoplastic population is often associated with a change in DNA content, and would suggest that the malignant cell type emerges as a new cell type from preneoplastic progenitor populations.
We measured the serum concentrations of moxalactam in 10 children receiving antibiotic prophylaxis for surgery and in 18 children treated for documented or suspected infections. Moxalactam was administered intravenously at a dose of 50 mg/kg every 8 h. After the first dose in 28 patients, mean moxalactam concentrations 5 min, 30 min, 2 h, and 8 h after infusion were 257, 177, 82.2, and 17.5 micrograms/ml, respectively. The mean half-life (T 1/2) was 2.44 h (range: 0.55 to 7.96 h). The mean distribution volume (VD) was 0.30 liters per kg. No significant accumulation was observed with multiple doses. Prophylactic and therapeutic groups had similar serum levels, T 1/2, and VD. The five infants less than 1 year of age had a lower mean 30-min level (P less than 0.01), larger VD (P less than 0.001) and longer T 1/2 (P less than 0.025) than the children older than 1 year. A dose of 50 mg/kg produced 30-min levels in excess of 64 microgram/ml in all patients studied, but 8-h trough levels were below the minimal inhibitory concentrations breakpoint of 17 mg/ml in 32% of patients.
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