Amazonian palm Oenocarpus bataua ("patawa"): chemical and biological antioxidant activity--phytochemical composition.

In French Guiana, "diversity" within the Palm family is obvious since more than 75 species have been identified. Oenocarpus bataua Mart., called "patawa" is well known for its culinary uses whereas literature on its phytochemical composition and biological properties remains poor. This work deals with determining the antioxidant activity of this palm fruit and its polyphenol composition; Euterpe oleracea (açai) used as a reference. It turned out that patawa had a stronger antioxidant activity than açai in TEAC and FRAP tests. A similar activity was observed by DPPH assay whereas in ORAC and KRL tests, that açai showed an antioxidant activity respectively 2.6 and 1.5 fold higher than patawa. Polyphenolic composition, determined by UPLC/MS(n), would imply the presence of anthocyanins, condensed tannins, stilbenes and phenolic acids, well known for their biological activities. These results present patawa fruit as a new amazonian resource for cosmetics, food and pharmaceuticals purposes.

Value and payment for oncology in the United States.

Rather than focus on reducing prices for innovative biopharmaceuticals, insurers in the United States are changing methods of payment for oncologists in order to moderate the growth in cancer drug expenditures. The desire is for a better pattern of utilization and expenditures without adversely affecting incentives for research and development. After an overview of the contemporary discussions of price and value, this paper describes three initiatives to influence the selection and management of oncology drugs. This includes initiatives to reduce the profit margins earned by oncologists as part of the purchasing of office-infused biopharmaceuticals; "episode-of-care" payments that bundle into a single fee the reimbursement for care management and specialty drugs; and payment methods that case rates for physician care management activities with cost-based reimbursement for the oncology drugs.

Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry.

The EMAPII (endothelial monocyte-activating polypeptide II) domain is a tRNA-binding domain associated with several aminoacyl-tRNA synthetases, which becomes an independent domain with inflammatory cytokine activity upon apoptotic cleavage from the p43 component of the multisynthetase complex. It comprises a domain that is highly homologous to bacterial tRNA-binding proteins (Trbp), followed by an extra domain without homology to known proteins. Trbps, which may represent ancient tRNA chaperones, form dimers and bind one tRNA per dimer. In contrast, EMAPII domains are monomers. Here we report the crystal structure at 1.14 Angstroms of human EMAPII. The structure reveals that the Trbp-like domain, which forms an oligonucleotide-binding (OB) fold, is related by degenerate 2-fold symmetry to the extra-domain. The pseudo-axis coincides with the dyad axis of bacterial TtCsaA, a Trbp whose structure was solved recently. The interdomain interface in EMAPII mimics the intersubunit interface in TtCsaA, and may thus generate a novel OB-fold-based tRNA-binding site. The low sequence homology between the extra domain of EMAPII and either its own OB fold or that of Trbps suggests that dimer mimicry originated from convergent evolution rather than gene duplication.

Oral pemphigus vulgaris: a review of the literature and a report on the management of 12 cases.

Twelve cases of oral pemphigus vulgaris are described to illustrate the long-term behavior of the disease and the treatment challenges it presents to the oral medicine practitioner. In addition, we review the literature on oral pemphigus vulgaris with respect to clinical history, signs and symptoms, management, and treatment outcome. Pemphigus vulgaris is a chronic vesiculobullous disease with a potentially fatal outcome. Mortality from pemphigus vulgaris before the development of effective therapies was as high as 90%. Today, with treatment, it is closer to 10%. Involvement of the oral mucosa is common and in most cases precede skin lesions; in our patients, the oral lesions preceded the development of extraoral disease in 75% of cases. Pemphigus vulgaris was more frequent among women (9:3), and there was a tendency for the severity and frequency of disease to decrease with time.

Cadherin-6, a cell adhesion molecule specifically expressed in the proximal renal tubule and renal cell carcinoma.

Cadherins are a family of calcium-dependent, cell-cell adhesion molecules that play an important morphoregulatory role in a wide variety of tissues. Alterations in cadherin function have been implicated in tumor progression in a number of adenocarcinomas. Despite the increasing number of new cadherins identified, little is known about cadherins in normal renal tissue and renal carcinomas. A novel cadherin transcript, cadherin-6, was recently described to be present in renal cancer cell lines and fetal kidney, but no data on protein expression nor tissue localization has been reported. In this study, we demonstrate that the expression of cadherin-6 is restricted to the proximal tubule epithelium. This finding is critical because these cells give rise to the majority of neoplasms of this organ. Furthermore we demonstrate typical cadherin features of cadherin-6, including cytoplasmic binding to alpha- and beta-catenin. We present data of cadherin-6 expression in a series of 32 primary renal cell cancers. Cadherin-6 expression tended to vary with histology in these samples. Whereas the majority of renal cell cancers with histology-associated poor prognosis (i.e., high grade clear cell carcinomas and sarcomatoid renal tumors) show aberrant expression of cadherin-6, in tumors with a favorable prognosis (i.e., low grade clear cell carcinomas and papillary cancers), normal cadherin-6 expression was predominant. Overall, these findings demonstrate specific expression of cadherin-6 in the proximal renal tubules in normal human kidney and suggest that alterations of cadherin-6 expression are associated with progression of renal cell carcinoma.

The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyte-activating polypeptide II cytokine.

p43 is one of the three auxiliary components invariably associated with nine aminoacyl-tRNA synthetases as a multienzyme complex ubiquitous to all eukaryotic cells from flies to humans. The cDNA encoding the hamster protein was isolated by using mixed oligonucleotides deduced from peptide sequences. The 359-amino acid protein is the hamster homologue of the recently reported murine and human EMAP II cytokine implicated in a variety of inflammatory disorders. The sequence of several proEMAP II proteins suggests that the p43 component of the complex is the precursor of the active mature cytokine after cleavage at a conserved Asp residue. The COOH-terminal moiety of p43 is also homologous to polypeptide domains found in bacterial methionyl- or phenylalanyl-tRNA synthetases and in the yeast Arc1p/G4p1 protein that associates with yeast methionyl-tRNA synthetase. Our results implicate the COOH-terminal moiety of p43 as a RNA binding domain. In the native state, as a component of the multisynthetase complex, p43 may be required for tRNA channeling and, after proteolytic processing occurring in tumor cells, would acquire inflammatory properties possibly related to apoptosis. The release of a truncated p43 from the complex could be involved in mediation of the signaling of tumor cells and stimulation of an acute inflammatory response.

Decline in hospital utilization and cost inflation under managed care in California.

OBJECTIVE: To measure the impact of health maintenance organizations (HMOs) on hospital capacity, utilization, and expenditures between 1983 and 1993. DESIGN: Multivariate regression analysis. SETTING: Private nonprofit and for-profit hospitals in California with 25 or more beds. PATIENTS: Patient discharge abstract data were used to measure growth of HMO penetration of local hospital markets. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Hospital closures, changes in bed capacity, changes in acute care admissions and length of stay, psychiatric inpatient days, subacute inpatient days, inpatient and outpatient surgical procedures, ambulatory patient visits, and hospital expenditures. RESULTS: Between 1983 and 1993 hospital expenditures grew 44% less rapidly in markets with high HMO penetration than in markets with low HMO penetration. Of this, 28% was due to reductions in the volume and mix of services, 6% was due to reductions in bed capacity, and 10% was due to changes in the intensity of services provided. Health maintenance organizations accelerated the substitution of outpatient for inpatient surgery, the shift from acute to subacute inpatient days, and the reduction of psychiatric hospitalization. CONCLUSION: Managed care is shifting the acute hospital from the center toward the periphery of the health care system.

Pericytosis and edema generation: a unique clinicopathological variant of meningioma.

OBJECTIVE: We report a group of eight patients with a distinctive histological variant of meningioma that is associated with severe peritumoral edema. The clinical presentation, radiographic findings, and histology of this type of tumor may lead to misdiagnosis as an aggressive or malignant process. METHODS: We reviewed the histology from patients who had removal of meningiomas performed in our institution between 1978 and 1992. Tumors having abnormal proliferation of cells in the intramural vascular spaces were selected for study; case histories and radiographs were reviewed. Tumor material was subjected to special stains, immunocytochemical examination, and election microscopy. RESULTS: Several lesions were misread radiographically as being malignant. Patients underwent craniotomy with complete excision of the tumor. All lesions were small (< or = 3 cm), and no brain invasion, unusual tumor vascularity, or dural sinus involvement was noted in any case. Histologically, the meningioma pattern in each case was meningothelial and benign in appearance. The immunocytochemical and electron microscopic features of the unusual cells in the blood vessel walls are most consistent with their being of pericytic origin. All patients have remained asymptomatic and without evidence of tumor recurrence with follow-up from 3 to 12 years. CONCLUSION: These tumors showed proliferation of pericytes in blood vessel walls and represent a new subtype of meningothelial meningioma. The apparently benign nature of these lesions necessitates their recognition. Characteristic findings of pericytic proliferation associated with edema generation have led us to descriptively term this the PEG variant of meningioma.

Intraosseous glomus tumor of the spine. Case report and review of the literature.

The authors report a case of glomus tumor originating within the lumbar spine. Glomus tumors of intraosseous origin are rare, with the only case reported in the spine arising in the sacrum. The patient presented with the solitary complaint of radiating back pain that resolved postoperatively. The histopathological and radiographic findings are reviewed. To the authors' knowledge, this represents the first case report of a glomus tumor of the spine originating above the sacrum.

An uncertain role for p53 gene alterations in human prostate cancers.

Inactivation of the p53 gene has been implicated in prostate cancer progression. To determine the role of p53 inactivation in the progression of clinical prostatic carcinomas, we assessed 67 tumors derived from patients with clinically localized disease for chromosome 17p and p53 gene allelic loss, p53 gene mutations using single-strand conformational polymorphism and direct sequencing, and p53 protein expression using immunohistochemical staining. Of 55 informative tumors, 10 demonstrated loss of 17p or the p53 gene; however, only a single tumor had a mutation in its remaining p53 allele. Significant p53 overexpression was observed in 2 of 38 tumors, and 9 others had faint staining of a few nuclei ( < 1%). p53 overexpression occurred in no informative tumor with allelic loss or mutation. In a 1-7-year follow-up, positive immunohistochemical staining did not confer an increased risk of recurrence (risk of recurrence, 0.86, P = 0.78), whereas allelic loss of chromosome 17p appeared to be highly correlated with recurrence (risk of recurrence, 3.7, P = 0.003). In an unrelated group of 42 patients with metastatic prostate cancer, p53 overexpression was found in 26 tumors (62%), and 15(36%) had high grade staining. Neither the presence nor the degree of expression correlated with time to progression or time to death. This series suggests that p53 gene inactivation is rare in primary prostatic tumors, not essential to the development of prostate cancer metastases, and of limited use as a prognostic marker in patients with primary or metastatic disease. Another gene or genes on chromosome 17p may be involved in prostate cancer progression.

Indomethacin and epinephrine effects on outflow facility and cyclic adenosine monophosphate formation in monkeys.

PURPOSE: To investigate the effect of indomethacin inhibition of prostanoid production on the epinephrine-stimulated increase in outflow facility and cyclic adenosine monophosphate (cAMP) production in the anterior segment of the monkey eye. METHODS: Topical indomethacin was given 1 hour before the intracameral administration of epinephrine to living cynomolgus monkeys. Outflow facility was measured for 45 to 60 minutes, beginning 3 hours after epinephrine administration, by two-level constant pressure perfusion of the anterior chamber. Cyclic adenosine monophosphate formation was measured in cell membranes isolated from rhesus monkey ciliary muscle, ciliary processes, trabecular meshwork, and iris in the presence of forskolin, indomethacin, epinephrine, or indomethacin and epinephrine combined. RESULTS: Three hours after the intracameral administration of 5.5 micrograms epinephrine, facility increased by approximately 40%, a putatively maximal response, at which time the intracameral epinephrine concentration was approximately 15 microM. Pretreatment with topical indomethacin produced a dose-dependent inhibition of epinephrine's facility-increasing effect; the maximum inhibition of 50% to 70% occurred at an indomethacin dose of 50 to 125 micrograms. Doubling the indomethacin dose (250 micrograms) produced no further inhibition, whereas a fivefold larger epinephrine dose (27.5 micrograms) did not overcome the inhibition. Forskolin and epinephrine both stimulated cAMP production in vitro, whereas [indomethacin] > or = 10(-4) M partially inhibited both basal and epinephrine-stimulated cAMP production in all four tissues. CONCLUSIONS: Approximately half of the epinephrine-induced facility increase is inhibited by indomethacin, but it is unclear whether the indomethacin-inhibitable fraction is mediated by epinephrine-stimulated prostanoid production or release.

Can postmenopausal hormone replacement improve plasma lipids in women with diabetes? The Atherosclerosis Risk in Communities Study Investigators.

OBJECTIVE: to evaluate the association of postmenopausal hormone replacement with plasma lipids in diabetic women. RESEARCH DESIGN AND METHODS: Cross-sectional data from a multiracial population study were used to evaluate the relationship of hormone replacement status with plasma lipids in diabetic (n = 694) versus nondiabetic (n = 5,321) postmenopausal women. RESULTS: Although diabetic women who currently used hormone replacement had higher adjusted mean HDL cholesterol levels than those who did not (56.9 vs. 53.6 mg/dl), they had proportionately lower hormone-related increases in HDL, HDL2, and HDL3 cholesterol than did nondiabetic women (HDL cholesterol 64.9 [current users] vs. 55.7 mg/dl [those who never used hormones]). There was a trend toward greater triglyceride values with hormone replacement in diabetic women (156.6 [current users] vs. 125.4 mg/dl [those who never used hormones]) than in nondiabetic women (143.3 [current users] vs. 123.7 mg/dl [those who never used hormones]). LDL cholesterol and apolipoprotein B levels were lower and apolipoprotein A-I levels were higher with hormone replacement, to a similar degree in diabetic and nondiabetic women. CONCLUSIONS: Diabetic women appear to have a blunted response to the HDL-raising effects of estrogen and an exaggerated hypertriglyceridemic response. This may result in attenuated cardioprotection from postmenopausal hormone replacement therapy and potentially an increased risk of acute pancreatitis from hypertriglyceridemia. The risks and benefits of postmenopausal hormone replacement need to be carefully weighed in diabetic women.

Chromosome 5 suppresses tumorigenicity of PC3 prostate cancer cells: correlation with re-expression of alpha-catenin and restoration of E-cadherin function.

Considerable evidence now exists to support an important role for the E-cadherin-mediated cell-cell adhesion pathway as a suppressor of the invasive phenotype in adenocarcinoma cells. Previous studies have found that this pathway is frequently aberrant in prostate cancers, particularly those that are likely to metastasize. In this study, we report on the effects of re-establishment of this pathway in a prostate cancer cell line, PC-3, in which this adhesion system is dysfunctional by virtue of a deletion of the gene that codes for alpha-catenin, an E-cadherin-associated protein necessary for normal E-cadherin function. Re-expression of alpha-catenin was accomplished either by transfection of PC-3 cells with a copy of the alpha-catenin cDNA under the control of a heterologous promoter or by microcell-mediated transfer of chromosome 5, which contains the alpha-catenin gene and its normal regulatory elements. In both cases, re-expression of alpha-catenin is associated with a similar, dramatic alteration in cell morphology, whereby extensive cell-cell contact is observed. In the case of transfection of the cDNA, this expression is only transient, because the transfected cells either cease to proliferate or, more commonly, revert to the parental phenotype with concomitant cessation of alpha-catenin expression. In contrast, cells containing one or more copies of microcell-transferred chromosome 5 express alpha-catenin in a stable manner and continue to proliferate. Upon injection into nude mice, these latter cells are no longer tumorigenic, or form only slowly growing tumors with greatly extended doubling times when compared to the parental PC-3 cells. During passage in culture, clones that contain only one transferred copy of chromosome 5 reproducibly revert to the parental phenotype. This reversion is associated with loss of the chromosome 5 region containing the alpha-catenin gene and consequent loss of alpha-catenin expression, as well as re-emergence of tumorigenicity. Transfer of chromosome 5 into prostate cancer cells that are E-cadherin negative does not result in either morphological transformation or suppression of tumorigenicity, suggesting that these effects of alpha-catenin expression are dependent upon concomitant expression of E-cadherin. These data demonstrate the tumor suppressive ability of chromosome 5 in the PC-3 prostate cancer cells and suggest that re-expression of alpha-catenin with resultant restoration of E-cadherin function plays a critical role in this process.

Interleukin-2 transfected prostate cancer cells generate a local antitumor effect in vivo.

In an effort to stimulate host-mediated antitumor response against prostate cancer in an animal model, highly malignant Dunning MAT-LyLu rat prostate carcinoma cells were transfected with the interleukin-2 (IL-2) cDNA, resulting in their ability to secrete large amounts of biologically active IL-2. Although parental cells form lethal tumors when injected subcutaneously into syngeneic hosts at doses of > or = 5,000, injections of IL-2 secreting cells initially formed tumors and regressed completely in each of over 200 animals at all doses tested (10(4)-8 x 10(7) cells). Mixtures of parental and IL-2 transfected cells were similarly rejected, demonstrating the non-cell autonomous nature of the response. Histological analysis of regressing tumors revealed a vigorous, predominantly lymphocytic and macrophage infiltrate at day 2 and marked tumor necrosis by day 6. Immunohistochemical staining of infiltrating lymphocytes at this latter time point demonstrated numerous T cells bearing either CD4 or CD8 surface markers, suggesting these cells as possibly mediating the tumor rejection. The ability of athymic mice to reject the IL-2 secreting tumor cells, however, suggests a non-T-cell-mediated mechanism. Although splenic natural killer (NK) activity is increased following injection of IL2 secreting tumor cells, this activity appears to be unnecessary for tumor elimination since syngeneic animals injected with asialo-GM1 antiserum to decrease NK activity also rejected IL-2 transfected cells, albeit slightly less effectively than untreated animals. Immunization of animals with subcutaneous injections of IL-2 transfected cells protected animals against a subsequent challenge of 10(4) wild-type cells 1 to 2 weeks later in 19 of 51 cases; however, immunization did not confer protection against larger doses of parental tumor. These studies indicate that high local concentrations of IL-2 stimulate the elimination of large local burdens of prostate cancer in this model system, and this elimination results in a weak, but detectable systemic immune response against wild-type prostate cancer cells.

Chronic pelvic pain.

Chronic pelvic pain is a complex problem with a long history of attempts to elucidate the cause and to design effective therapies. This review is structured around recent articles in the field which contribute to our understanding, support certain therapeutic approaches, or describe a specific case. The pain aspects of endometriosis are included for their contribution to our understanding of pain and the difficulty encountered in managing these patients.

A comparison of serum and vaginal dialysate concentration of 13,14-dihydro-15-keto-PGF2 alpha in women undergoing 1st trimester therapeutic abortions.

13,14-Dihydro-15-keto-PGF2 alpha(PGFM) levels in serum and vaginal secretion, before, one hour, and 24 hours post abortion were measured in 13 women from 8 to 12 weeks pregnant. The mean metabolite levels in the blood were 61.2 pg/ml pre-termination, 73.1 pg/ml and 121.4 pg/ml one hour and 24 hours post-termination. The vaginal dialysate means were 136.7 pg/ml, 425.7 pg/ml, and 211.7 pg/ml respectively.

PIP: 13, 14-Dihydro-15-keto prostaglandin F2alpha (PGFM) levels in serum and vaginal secretion before and hour and 24 hours after abortion were measured in 13 women from 8 to 12 weeks pregnant. Patients coming to the Department of Gynecology and Obstetrics at the Johns Hopkins Hospital, Baltimore, United States, were recruited at the time they applied for a first trimester therapeutic abortion (TAB). Prior to the procedure, a blood sample was drawn and a semi-permeable tampon was inserted into the vagina for about 2 hours while the patient waited for her surgery. Upon completion of dilation and suction curettage, a new tampon was placed in the vagina and remain in place for about 2 hours. A blood sample was taken when the tampon was removed. The anesthesia included local 1% lidocaine with IV sedation and 20 units pitocin given during and after the procedure. PGFM was measured by radioimmunoassay. The mean metabolite levels in the blood were 61.2 pg/ml pre-termination. 73.1 pg/ml and 121.4 pg/ml 1 hour and 24 hours post-termination, respectively. The vaginal dialysate means were 136.7 pg/ml, 425.7 pg/ml, and 211.7 pg/ml, respectively. A MANOVA was performed using SPSS/PC+ to determine the significance of changes in vaginal fluid and plasma PGFM levels over time. P-values were 0.0001 for both the dialysate and for plasma. T-test analysis demonstrated significant differences between baseline dialysate levels and levels just after TAB (p 0.0001, two tailed) and between levels just after TAB and 24 hours later (p 0.0001). A similar analysis of plasma demonstrated a significant rise in PGFM levels from baseline to 24 hours later (p 0.0001) and from just after TAB to 24 hours later

Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer.

Allelic loss studies have been instrumental in identifying tumor suppressor gene loci in a variety of cancers. In this study we analyzed prostate cancer specimens from 52 patients for allelic loss using 8 polymorphic probes for the short arm of chromosome 8. Overall, 32 of 51 (63%) informative tumors showed loss of at least one locus on chromosome 8p. The most frequently deleted region is observed at chromosome 8p22-8p21.2. Loss of one allele is identified in 14 of 23 (61%) tumors at D8S163, in 15 of 32 (47%) tumors at lipoprotein lipase, and in 20 of 29 (69%) tumors at MSR, all on 8p22. Loss of one allele is identified in 16 of 27 (59%) tumors at D8S220 at 8p21.3-8p21.2. In addition to frequent loss of one allele at the MSR locus, one metastatic prostate cancer sample demonstrated homozygous deletion of MSR sequences. Loci telomeric and centromeric to this region are largely retained. A chromosome 8p deletion map is constructed and defines the smallest region of overlap to a 14-cM interval at 8p22 between D8S163 and lipoprotein lipase, flanking the MSR locus. Evidence of chromosome 8q multiplication at locus D8S39 was detected in 5 of 32 (16%) tumors, all of which demonstrated loss with at least one probe on chromosome 8p. This study extends the previous finding of frequent loss of chromosome 8p in prostate cancer by defining a common region of loss of heterozygosity at 8p22 and a homozygous deletion of the MSR locus contained within this region. This is the first homozygous deletion identified in the genome of a human prostate cancer and the highest rate of loss yet reported on chromosome 8p in cancer. These results strongly suggest the presence of a tumor suppressor gene in this region which is frequently inactivated in prostate cancer.

DNA methylation of the fragile X locus in somatic and germ cells during fetal development: relevance to the fragile X syndrome and X inactivation.

To obtain insights into mechanisms responsible for methylation of CpG islands on the inactive X chromosome of normal females, we examined methylation of the fragile X (FraX) locus in a variety of tissues from normal fetuses and adults, and from males with the FraX syndrome. We identified 20 CCGG sites (MspI-HpaII sites M1-M20) within a 12-kb BglII fragment that includes the CpG island. Sites M3-M18, within the 1.2-kb CpG island are unmethylated on the active X in normal males and females at all ages and in all tissues studied. In contrast, these sites are at least partially methylated on the inactive X chromosome in a variety of tissues from normal females by six weeks from conception. The exceptional tissues are chorionic villi and gonads, which are significantly undermethylated. In addition, fetal germ cells are unmethylated at site M3, which is methylated on the inactive X in other tissues; thus, the methylation imprint of the inactive X has been erased. Methylation of the locus on the fragile X chromosome is similar to that of the normal inactive X but is more extensive and less heterogeneous. This suggests that the expansion of the island and the greater number of CpGs that result from amplification of the CGG repeat enhance the methylatibility of the island. Additional studies show that the chromatin of the CpG island is nuclease hypersensitive on the active X but insensitive on both inactive and FraX.

The role of threshold limit values in U.S. air pollution policy.

This paper analyzes the role of threshold limit values (TLVs) in national air pollution policy during the 1980s, a period in which the Environmental Protection Agency (EPA) sought to delegate to individual states the authority to evaluate and regulate airborne toxic substances. We focus on 20 carcinogens and 11 substances with non-genotoxic health effects that were regulated by local air toxics programs using TLVs. Data from EPA's National Air Toxics Information Clearinghouse indicate that maximum TLV-based Ambient Air Level guidelines (AALs) frequently exceed minimum TLV-based AALs by a factor of greater than 1,000. Cancer potency data from EPA's Integrated Risk Information System suggest significant risks remain at TLV-based AALs. Cancer risks at the median TLV-based AAL exceed 1,000 cases per million exposed persons for cadmium (1,040), nickel and its compounds (1,420), propylene oxide (1,550), coke oven emissions (1,860), benzene (2,500), arsenic and its compounds (7,300), N-nitrosodimethylamine (21,000), asbestos (21,500), and ethylene dibromide (55,000). We also summarize published studies that report non-genotoxic health effects in workers exposed at levels near the TLV for 11 substances whose AALs were based on TLVs. Contrary to the assumption frequently made by state air toxics program, TLVs cannot be taken to represent no observed effect levels (NOELs) for regulatory purposes.