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Biomedical subjects

V Lazar

Publications and source records attributed to V Lazar.

At least 37 records · Page 2Linked to original sources

Gastroenteropancreatic neuroendocrine tumor metastases to the thyroid gland: differential diagnosis with medullary thyroid carcinoma.

Neuroendocrine tumors (NET) of the thyroid gland are rare. Apart from medullary thyroid carcinoma (MTC), metastases of gastroenteropancreatic (GEP) NET may also occur. Features of six patients (five men, one female: age range, 39-67 years) with thyroid metastases from a GEP-NET are described. Thyroid metastases were bilateral in all patients and were associated with enlarged neck lymph nodes in five. In four cases, the thyroid tumor was either the first sign of the disease (n = 2) or was an isolated site of recurrence (n = 2). The tumors were well (n = 3) or poorly differentiated (n = 3). Five tumors for which the primary site could be determined corresponded to foregut-derived tumors (3 lungs, 1 thymus and 1 pancreatic NET). One tumor demonstrated calcitonin (CT) production as shown by immunohistochemistry and elevated plasma CT levels. However, the disease history and the clinical features strongly favored a metastasizing GEP-NET. No tumoral RET proto-oncogene mutation was found in this patient. The differential diagnosis between metastatic GEP-NET and MTC is crucial because prognosis, work-up, and treatment differ greatly.

Adult↗

Expression of a novel high molecular-weight myosin light chain kinase in endothelium.

Myosin light chain phosphorylation results in cellular contraction and is a critical component of agonist-mediated endothelial cell (EC) junctional gap formation and permeability. We have shown that this reaction is catalyzed by a novel high molecular-weight Ca2+/calmodulin-dependent nonmuscle myosin light chain kinase (MLCK) isoform recently cloned in human endothelium (Am. J. Respir. Cell Mol. Biol., 1997;16:489-494). To characterize EC MLCK expression further in cultured and adult tissues, we employed immunoblotting techniques and reverse transcriptase-polymerase chain reaction to demonstrate that freshly isolated and cultured human macro- and microvascular EC express only the EC MLCK isoform (214 kD), which is distinct from smooth-muscle MLCK isoforms (130 to 150 kD). Immunocytochemical studies demonstrated the presence of the high molecular-weight MLCK isoform in adult human cardiac endothelium using anti-MLCK antibodies, which preferentially recognize the high molecular-weight EC MLCK isoform. Monitoring of MLCK expression in different cell types with antibodies generated against a unique human EC MLCK N-terminal sequence revealed a high level of expression of the 214-kD enzyme in endothelium, minimal level of expression in smooth muscle, and no expression in skeletal muscle. These data suggest that the novel 214-kD kinase, the only MLCK isoform found in endothelium, may be preferentially expressed in this nonmuscle tissue.

Animals↗

Dental expenditures by selected dentist and practice characteristics.

Total estimated dental expenditures in 1995 were approximately $47.6 billion as reported by the Bureau of Economic Analysis, or BEA. According to the Health Care Financing Administration, or HCFA, the total estimated dental expenditures in 1995 were approximately $44.7 billion. Using the reported gross billings from the annual ADA "Survey of Dental Practice," the authors estimated that the total national dental expenditures in 1995 were about $45.5 billion. As this estimate falls between the BEA- and HCFA-estimated total dental expenditures, it is one confirmation of the reliability and validity of ADA's estimates. This estimate also can be used to look at dental expenditures by selected characteristics--such as specialty, office time and number of dentists in the practice.

American Dental Association↗

Trend analysis of dental expenditures by selected dentist and practice characteristics, 1985-1995.

Using the reported gross billings from the annual ADA "Survey of Dental Practice," the authors estimated the total national dental expenditures according to various dentist characteristics for the period of 1985-1995. These selected characteristics are specialty, office time, number of dentists in the practice, sex, length of experience and U.S. region. As government agencies do not report dental expenditures by such dentist characteristics, the data presented in this article may be the first of their kind to be estimated and published.

Accounting↗

Differences in net incomes of male and female owner general practitioners.

The authors analyzed the mean net income of a cohort of male and female dentists with similar demographics and practice characteristics. The authors found that the average net income of these male dentists is higher than it is for their female counterparts. This difference is statistically significant and monetarily tangible, amounting to an annual net income balance of about $26,000 (22 percent) in favor of male dentists. If such a difference in net income persists, it could affect the profession as well as the distribution of dental school enrollments.

Adult↗

Work force trends that influence dental service capacity.

Although the total number of active private dentists increased by 21.7 percent between 1982 and 1995, the number of active private part-time dentists increased by 104 percent, while the number of active private full-time dentists increased by 8 percent. Thus, the total number of hours active private dentists spent in the office has not increased to the same extent as the number of active private dentists. During the same period, however, the average number of hours spent treating patients increased, indicating that dentists are becoming more efficient in directing their office hours toward clinical dentistry. The distribution of active private part-and full-time dentists and the actual number of hours they spent in the dental office and spent treating patients provide a more complete picture of the capacity of the dental care delivery system than only looking at the increase in the total number of dentists.

Dental Care↗

Net income, gross billings and practice expenses of independent dentists.

One way to measure the vitality of a profession is to look at the trend in its practitioners' real incomes. During the 10-year period 1986 through 1995, the average real net income of all independent dentists rose 30.7 percent, or 2.7 percent annually, after being adjusted for inflation using 1995 U.S. dollars. The national per capita personal income (base = 1995) increased 10.1 percent during this same period, or about 1.0 percent annually [corrected]. Using real per capita income as a benchmark, the authors found that the purchasing power of dentists as a group has increased more rapidly than the purchasing power of the overall U.S. population.

Fees, Dental↗

Solo general practitioners and specialists.

A solo practitioner is the sole owner of and the only dentist in a dental practice and also is the most common type of dental practitioner in the United States. The authors provide a brief look at solo general practitioners' and specialists' characteristics, including employment status, number of employees, time spent in the office, number of patient visits per week, gross billings, net income and practice expenses.

Accounting↗

Dental procedure fees 1975 through 1995: how much have they changed?

A shift toward diagnostic and preventive dentistry in the last two decades is evident from the change in the number of dental procedures performed, as well as the change in the percentage of time spent performing different types of procedures. During the period 1975 through 1995, the average nominal fees for selected dental procedures increased. Once inflation was taken into account, however, the increase in the average real fees charged was more modest.

Adult↗

p53 status does not predict initial clinical response to bacillus Calmette-Guerin intravesical therapy in T1 bladder tumors.

PURPOSE: In superficial urothelial tumors of the bladder, p53 status is currently the most informative pretreatment parameter to define a population at higher risk for invasive carcinoma. Also, in T1 tumors, occurrence of muscular invasion is often related to an early relapse following BCG therapy. With the knowledge of biological parameters able to identify the group of initial BCG therapy non-responders, it would be possible to offer earlier treatment to the patients who need a more aggressive mode of therapy. The aim of this work was to study the predictive value of the p53 tumor status on the early BCG therapy response. MATERIALS AND METHODS: The population included a selected group of 43 patients presenting T1 bladder tumors with no carcinoma in situ (Tis), treated by transurethral resection (TUR) followed by intravesical BCG therapy. Clinical outcome was analyzed in relation to usual clinical and histopathological parameters, and pretreatment p53 tumor status was assayed by an immunohistochemical technique using DO7 monoclonal antibody. For 16 specimens, p53 gene was investigated using a Single Strand Conformation Polymorphism (SSCP) analysis and sequence determination. RESULTS: p53 anomalies were strongly correlated to smoking behavior (p = 0.003) and tumoral grade (p = 0.025). Univariate analysis revealed an absence of correlation between p53 immunostaining and initial, one and two years response-rate to BCG therapy. However, longterm followup revealed a trend between positive staining and disease progression. The p53 molecular study validated the use of DO7 immunostaining in detection of p53 anomalies. CONCLUSIONS: In T1 bladder tumors, pretreatment p53 determination was not useful to define a group of early BCG non-responders. Thus, p53 status and immunological response induced by BCG endovesical therapy are two independent events.

Adult↗

Prognostic value of chorionic gonadotropin beta gene transcripts in human breast carcinoma.

The beta subunit of human chorionic gonadotropin is potentially encoded by six genes, which can be categorized into two types based on a sequence change at codon 117: GCC for the type I and GAC for the type II genes. We previously showed that, whereas type I genes were exclusively expressed in normal breast tissues, expression of type II genes was associated with malignant transformation (Bellet, D., et al. Cancer Res., 57: 516-523, 1997). We designed a simple and robust test (the CG117 assay) that measures the percentage of type II over both types of chorionic gonadotropin beta mRNAs. Normal breast tissues consistently had a negative CG117 index, whereas cancer breast tissues showed indexes ranging from 0 to 100%. The prognostic significance of the CG117 index was investigated in a series of 99 unilateral invasive primary breast cancer patients with known long-term outcome (median follow-up, 9 years). The CG117 index was positive in 48 (48.5%) of the 99 tumor mRNA samples. The index was not significantly associated with standard prognostic parameters, including clinical and macroscopic tumor size, histopathological grade, and lymph node status or steroid receptor status. Patients with a positive CG117 index in primary tumor mRNA had significantly shorter metastasis-free survival (P = 0.014) and overall survival (P = 0.038) after surgery, compared to patients with a negative index. The prognostic significance of the CG117 index persisted in Cox multivariate regression analysis, both for metastasis-free survival (P = 0.008) and overall survival (P = 0.016), together with lymph node status (P = 0.027 and P = 0.009, respectively). These findings indicate that the CG117 index may contribute to the identification of high-risk breast cancer patients.

Adult↗

Localization of group IIc low molecular weight phospholipase A2 mRNA to meiotic cells in the mouse.

We use in situ hybridization to demonstrate that the testicular expression of a novel, mouse, low molecular weight phospholipase A2 (PLA2 Group IIc) mRNA is specific to cells undergoing meiosis. A complete cDNA (1421 bp) encoding the mouse Pla2g2c gene was generated with reverse transcription-PCR (RT-PCR) and 5' and 3' RACE (rapid amplification of cDNA ends) RT-PCR, and its nucleotide sequence was determined. Northern blots of RNA from different tissues revealed a single 1.6 kb transcript only in testis. In situ hybridization indicated that this mouse gene is transcribed mainly in pachytene spermatocytes, secondary spermatocytes, and round spermatids. Expression of the gene is seen in all stages of the seminiferous epithelium, especially in stages VI-VII.

Amino Acid Sequence↗

Malignant transformation of nontrophoblastic cells is associated with the expression of chorionic gonadotropin beta genes normally transcribed in trophoblastic cells.

The beta subunit of human chorionic gonadotropin (hCGbeta) is encoded by four nonallelic CGbeta genes. An assay was developed for distinguishing type I CGbeta allelic genes beta7 and beta6, which possess a GCC codon corresponding to an alanine at position 117 of hCGbeta, from type II CGbeta genes beta8, beta5, and beta3 and its allele beta9, which possess a GAC codon corresponding to an aspartic acid at the same position. In normal trophoblast, hCGbeta is encoded by type II CGbeta genes, whereas normal nontrophoblastic tissues of differing histological origin (breast, prostate, skeletal muscle, bladder, adrenal glands, thyroid, colon, and uterus) express only type I CGbeta genes. We studied the expression of CGbeta genes in 86 tumor specimens collected from patients with breast, bladder, prostate, and thyroid cancer and found that up to 61% of these nontrophoblastic tumors expressed type II CGbeta genes. Experiments performed on tumor tissues and their normal counterparts confirmed that the malignant transformation of nontrophoblastic cells is associated with the expression of type II CGbeta genes. These findings provide the basis for a simple test (the CG117 assay) that may be useful for the diagnosis of the most frequent malignancies.

Cell Line↗

Myosin light chain kinase in endothelium: molecular cloning and regulation.

The phosphorylation of myosin light chains by myosin light chain kinase (MLCK) is a key event in agonist-mediated endothelial cell gap formation and vascular permeability. We now report the cloning and expression of a nonmuscle MLCK isoform in cultured endothelium. Screening of a human endothelial cell cDNA library identified a 7.7 kb cDNA with substantial (> 95%) homology to the coding region of the rabbit and bovine smooth muscle (SM) MLCK (amino acid #923-1913) as well as with the reported avian nonmuscle MLCK (65-70% homology). Sequence analysis also identified, however, a 5' stretch of novel sequence (amino acids #1-922) which is not contained in the open reading frame of mammalian SM MLCK, and is only 58% homologous to the avian fibroblast MLCK sequence. Immunoprecipitation with NH2-specific antisera revealed a 214 kD high molecular weight MLCK in bovine and human endothelium which exhibits MLC phosphorylation properties. Amino acid sequence analysis revealed endothelial MLCK consensus sequences for a variety of protein kinases including highly conserved potential phosphorylation sites for cAMP-dependent protein kinase A (PKA) in the CaM-binding region. Augmentation of intracellular cAMP levels markedly enhanced MLCK phosphorylation (2.5-fold increase) and reduced kinase activity in MLCK immunoprecipitates (4-fold decrease). These data suggest potentially novel mechanisms of endothelial cell contraction and barrier regulation.

Amino Acid Sequence↗

To solo or not to solo.

An analyst from the ADA Survey Center provides a brief overview of the differences and similarities of solo and nonsolo (group) practices, based on data gathered from the 1995 Survey of Dental Practice.

Adult↗