Cell cycle-dependent metabolism of pyrimidine deoxynucleoside triphosphates in CEM cells

We incorporated 3H-labeled thymidine, deoxycytidine, or cytidine into dNTPs and DNA of exponentially growing CEM cells. G1 and S phase cells were separated by centrifugal elutriation, and the size and specific activity of dNTP pools were determined to study the cell cycle-dependent regulation of specific dNTP synthesizing enzymes in their metabolic context. With [3H]thymidine, we confirm the earlier demonstrated S phase specificity of thymidine kinase. Incorporation of radioactivity from [5-3H]deoxycytidine into dCTP occurred almost exclusively in G1 cells. During S phase, de novo synthesis by ribonucleotide reductase was switched on, resulting in a 70-fold dilution of [3H]dCTP, confirming that ribonucleotide reductase is an S phase-specific enzyme, whereas deoxycytidine kinase is not. [5-3H]Cytidine appeared in dCTP almost to the same extent in G1 as in S phase, despite the S phase specificity of ribonucleotide reductase. During S phase, DNA replication greatly increased the turnover of dCTP, requiring a corresponding increase in ribonucleotide reductase activity. During G1, the enzyme maintained activity to provide dNTPs for DNA repair and mitochondrial DNA synthesis. The poor incorporation of isotope from deoxycytidine into DNA earlier led to the suggestion that the nucleoside is used only for DNA repair (Xu, Y-Z., Peng, H., and Plunkett, W. (1995) J. Biol. Chem. 270, 631-637). The poor phosphorylation of deoxycytidine in S phase provides a better explanation.     

Ca(2+)-ATPases in the cochlear duct

Differing levels of the Ca(2+)-ATPase enzymes that reside on the plasma membrane (PM) and on the endoplasmic reticulum (ER) were identified in individual rat cochlear tissues by the use of a semi-quantitative enzyme-linked immunosorbent assay (ELISA). Unlike other studies, a specific antibody to PM Ca(2+)-ATPase was used to detect significantly greater levels (about 2x) of PM Ca(2+)-ATPase in the stria vascularis (SV) than that in the spiral ligament (SL) and organ of Corti (OC) tissues. Similarly, levels of ER Ca(2+)-ATPase were also significantly higher in the SV than in the SL and OC tissues. The presence of ER Ca(2+)-ATPase in the tissues of the SV has not been demonstrated previously. Given the importance of Ca2+ homeostasis in the inner ear, the statistically significantly higher densities of both PM and ER Ca(2+)-ATPase measured in the SV relative to the SL and OC regions would indicate tissue-specific responses to fluctuations in systemic and local Ca2+ concentrations.     

Intracardiac thrombus trapped in a patent foramen ovale

We describe a case of impending paradoxical embolism due to a thrombus trapped in a patent foramen ovale in a 22-year-old woman. Transthoracic and transesophageal echocardiography detected the thrombus. She was operated on and discharged asymptomatic.     

Treatment of severe acute exacerbation of asthma and chronic obstructive lung disease. An interview study

A telephone survey was conducted of all the 71 Danish hospitals with the capacity to receive acutely ill medical patients. The purpose was to register treatment regimes used in acute asthma and exacerbations in chronic obstructive pulmonary disease (COPD). The house officer on duty was interviewed and questioned about the use of nebulizers, oxygen therapy, bronchodilators, steroids, theophyllins and monitoring of the patient's condition. The physician survey was supplemented by a smaller survey among emergency room nurses about nebulizing systems. The answers showed inadequate knowledge of nebulizing systems. There was a noticeable variation in the dosing of oxygen and in the dosing of bronchodilators and steroids. beta 2-agonist treatment by nebulizer differed with a factor 14 in dose. The majority of the physicians had no specific parameters for monitoring severity of disease. CONCLUSION: There is a need for improvement of the knowledge of nebulizing systems, including specific knowledge of the appropriate use of propellant gasflow and time of nebulizing for optimum performance of the used nebulizer. Divergent answers from the nurses and the physicians show the need for interdisciplinary instruction. The noticeable variation in treatment in this Danish survey displays a need for quality control in terms of concise guidelines for medical therapy in acute exacerbations of asthma and COPD and guidelines for monitoring of the response to the treatment. A suggestion for a treatment regime is proposed.     

Dental arch form in three Pacific populations: a comparison with Japanese and Australian aboriginal samples

The purpose of this study was to provide information about arch shape variations among South Pacific populations. The application of Fourier transforms, Y(phi i) = ao/2 + sigma (aicos phi i + bisin phi i) was used to separate two components of variation; size and shape. Dental arch size can be described by one coefficient (ao), while the shape can be summarized by the first three harmonics (amp1-3) in the Fourier series. The materials used in this study were dental casts of South Pacific populations (Fiji, Western Samoa and Kiribati), Australian Aboriginals and Japanese. Fijians, Western Samoans and Kiribati people have larger upper and lower dental arches than that of Japanese. These populations were separated by the arch size and first Fourier amplitudes which showed the arch depth/width ratio. The Fijian upper and lower dental arches were significantly larger than those found in other populations and was characterized by a wide posterior arch breadth. The Western Samoan and Kiribati arch shape was more similar to the Japanese arch shape than the Fijian. Distribution patterns of arch shape characteristics in these populations showed the same tendencies in the upper and lower arches.     

The correlation of CA15.3 and TPS with tumor course in patients with metastatic breast cancer

Courts routinely award coverage for TMJ disorders under medical plans, despite exclusionary language and evidence that the insured failed to disclose preexisting treatment as required by the plan and neglected to attempt more conservative treatment first. Such decisions adversely affect both the health carrier and the plan participants. Various states have enacted legislation mandating coverage of TMJ; however, TMJ issues still exist and will remain a frequent topic for litigation until the judiciary recognizes that validating contract language ultimately benefits insureds as consumers and reinforces the integrity of the industry as a whole.     

Molecular analysis of the PDS gene in Pendred syndrome

Pendred syndrome is an autosomal recessive disorder characterized by the association between sensorineural hearing loss and thyroid swelling or goitre and is likely to be the most common form of syndromic deafness. Within the thyroid gland of affected individuals, iodide is incompletely organified with variable effects upon thyroid hormone biosynthesis, whilst the molecular basis of the hearing loss is unknown. The PDS gene has been identified by positional cloning of chromosome 7q31, within the Pendred syndrome critical linkage interval and encodes for a putative ion transporter called pendrin. We have investigated a cohort of 56 kindreds, all with features suggestive of a diagnosis of Pendred syndrome. Molecular analysis of the PDS gene identified 47 of the 60 (78%) mutant alleles in 31 families (includes three homozygous consanguineous kindreds and one extended family segregating three mutant alleles). Moreover, four recurrent mutations accounted for 35 (74%) of PDS disease chromosomes detected and haplotype analysis would favour common founders rather than mutational hotspots within the PDS gene. Whilst these findings demonstrate molecular heterogeneity for PDS mutations associated with Pendred syndrome, this study would support the use of molecular analysis of the PDS gene in the assessment of families with congenital hearing loss.     

Psychopathology among offspring of parents with substance abuse and/or anxiety disorders: a high-risk study

Fas (CD95) and Fas ligand (FasL) play major roles in staphylococcal enterotoxin B (SEB)-induced peripheral deletion of Vbeta8+ T cells. We found that peripheral deletion was defective in radiation chimeras with non-functional tissue FasL, regardless of the FasL status of the bone marrow-derived cells. SEB induced a dramatic upregulation of FasL expression and function in nonlymphoid cells of liver and small intestine. This effect was resistant to inhibition by cyclosporin A, which also failed to inhibit peripheral deletion. In SCID animals nonlymphoid tissues did not express FasL in response to SEB unless transplanted lymphocytes were present. Thus, some immune responses induce FasL in nonlymphoid tissues, which in turn kills activated lymphocytes, leading to peripheral T cell deletion.     

Expression pattern of CD2 locus control region containing retroviral vectors in hemopoietic cells in vitro and in vivo

OBJECTIVE: To determine whether individual surgeon experience is associated with improved short-term clinical and economic outcomes for patients with benign and malignant thyroid disease who underwent thyroid procedures in Maryland between 1991 and 1996. SUMMARY BACKGROUND DATA: There is a prevailing belief that surgeon experience affects patient outcomes in endocrine surgery, but there is a paucity of objective evidence outside of clinical series published by experienced surgeons that supports this view. METHODS: A cross-sectional analysis of all patients who underwent thyroidectomy in Maryland between 1991 and 1996 was conducted using a computerized statewide hospital discharge data base. Surgeons were categorized by volume of thyroidectomies over the 6-year study period: A (1 to 9 cases), B (10 to 29 cases), C (30 to 100 cases), and D (>100 cases). Multivariate regression was used to assess the relation between surgeon caseload and in-hospital complications, length of stay, and total hospital charges, adjusting for case mix and hospital volume. RESULTS: The highest-volume surgeons (group D) performed the greatest proportion of total thyroidectomies among the 5860 discharges, and they were more likely to operate on patients with cancer. After adjusting for case mix and hospital volume, highest-volume surgeons had the shortest length of stay (1.4 days vs. 1.7 days for groups B and C and 1.9 days for group A) and the lowest complication rate (5.1 % vs. 6.1% for groups B and C and 8.6% for group A). Length of stay and complications were more determined by surgeon experience than hospital volume, which had no consistent association with outcomes. CONCLUSIONS: Individual surgeon experience is significantly associated with complication rates and length of stay for thyroidectomy.