Is it all in the hinge? A kryptoracemate and three of its alternative racemic polymorphs of an aminonitrile.

Four polymorphs of 2-(perfluorophenyl)-2-(phenylamino)acetonitrile have been crystallized and structurally analyzed: in addition to three racemic crystals, a rare kryptoracemate has been obtained. The central single bonds allow for conformational flexibility: the kryptoracemate as well as two of the remaining polymorphs contain several independent molecules with different conformation. In contrast to these uncommon packing modes, the fourth phase is unexceptional and crystallizes with a single molecule in the asymmetric unit. Individual crystallization batches may contain several crystal forms concomitantly.

Review of the carcinogenic potential of gasoline.

This review examines the animal, human, and mechanistic studies that precede the new studies reported in this volume. Wholly vaporized unleaded gasoline was found to produce a dose-dependent increase in renal carcinoma in male rats and an excess above background incidence of hepatocellular tumors in female mice in the high-dose group. Mechanistic studies suggest that gasoline is not mutagenic and that the probable mechanism for the male rat renal tumors involves a rat-specific protein, alpha 2u-globulin, whose binding with highly branched aliphatic compounds results in renal tubule cell death and, in turn, a proliferative sequence that increases renal tubule tumors. Human evidence generated predominantly from studies of refinery workers does not support a kidney or liver cancer risk in humans. The current epidemiologic database is inadequate to access leukemia risk from low-level benzene exposure from gasoline. Studies of gasoline-exposed workers that incorporate quantitative exposure information are needed.

Leukemia mortality by cell type in petroleum workers with potential exposure to benzene.

Workers in the petroleum industry are potentially exposed to a variety of petrochemicals, including benzene or benzene-containing liquids. Although a large number of studies of petroleum workers have been conducted to examine leukemia and other cancer risks, few existing studies have investigated cell-type-specific leukemias. One of the major reasons for the lack of cell-type-specific analysis was the small number of deaths by cell type in individual studies. In the present investigation, all cohort studies of petroleum workers in the United States and the United Kingdom were combined into a single database for cell-type-specific leukemia analysis. The majority of these workers were petroleum refinery employees, but production, pipeline, and distribution workers in the petroleum industry were also included. The combined cohort consisted of more than 208,000 petroleum workers, who contributed more than 4.6 million person-years of observation. Based on a meta-analysis of the combined data, cell-type-specific leukemia risks were expressed in terms of standardized mortality ratios (meta-SMRs). The meta-SMR for acute myeloid leukemia was 0.96. The lack of an increase of acute myeloid leukemia was attributed to the low levels of benzene exposure in the petroleum industry, particularly in comparison to benzene exposure levels in some previous studies of workers in other industries, who had been found to experience an increased risk of acute myeloid leukemia. Similarly, no increase in chronic myeloid, acute lymphocytic, or chronic lymphocytic leukemias was found in petroleum workers (meta-SMRs of 0.89, 1.16, and 0.84, respectively). Stratified meta-analyses restricted to refinery studies or to studies with at least 15 years of follow-up yielded similar results. The findings of the present investigation are consistent with those from several recent case-control studies of cell-type-specific leukemia. Patterns and levels of benzene exposure in the petroleum industry are reviewed. The results of the present epidemiologic investigation are discussed in conjunction with recent advances in leukemogenesis from other scientific disciplines.

Translocation (3;8;8)(p22 or p23;p23;q12) in a case of pleomorphic adenoma: similarity to a primary cytogenetic abnormality detected in an endometrial adenocarcinoma.

Cytogenetic findings on the recurrence of a pleomorphic adenoma of the parotid gland are herein reported. The tumor showed an abnormal chromosome #8, which was very similar to a marker chromosome recently described as the sole abnormality in an endometrial adenocarcinoma.

Laser-spectroscopic laboratory studies of atmospheric aqueous phase free radical chemistry.

Nitrate radical (NO(3)) reactions with benzene (R-1), toluene (R-2), p-xylene (R-3), p-cresol (R-4) and mesitylene (R-5) have been studied by laser photolysis/long path laser absorption (LP-LPLA) in aqueous solution. Rate constants of k(1)=(4.0+/-0.6). 10(8), k(2)=(1.2+/-0.3). 10(9), k(3)=(1.6+/-0.1). 10(9), k(4)= (8.4+/-2.3). 10(8) and k(5)=(1.3+/-0.3). 10(9) lmol(-1)s(-1) were obtained at T=298 K. In addition, reaction rate coefficients for SO(-)(5)+Fe(2+)-->prod. (R-6) and SO(-)(5)+Mn(2+)-->prod. (R-7) of k(6)=(4.3+/-2.4). 10(7) lmol(-1)s(-1) and k(7)=(4.6+/-1.0). 10(6) lmol(-1)s(-1) (T=298 K, I-->0) have been obtained by the application of laser photolysis/UV-VIS broadband diode array spectroscopy. A new laser photolysis/UV-long path laser absorption experiment has been applied to study the reaction of the Cl(-)(2) radical anion with dissolved sulfur(IV). For the reactions Cl(-)(2)+HSO(-)(3)-->2Cl(-)+H(+)+SO(-)(3) (R-8) and Cl(-)(2)+SO(2-)(3)-->2Cl(-)+SO(-)(3) (R-9) rate coefficients of k(8)=(1.7+/-0.2). 10(8) lmol(-1)s(-1) (T=298 K, I-->0) and of k(9)=(6.2+/-0.3). 10(7) lmol(-1)s(-1) (T=279 K, I-->0) were obtained.

Non-Hodgkin's lymphoma and exposure to benzene in a multinational cohort of more than 308,000 petroleum workers, 1937 to 1996.

Petroleum workers are exposed to benzene or benzene-containing petroleum products. As such, studies of these workers provide an opportunity for investigating the relationship between benzene and non-Hodgkin's lymphoma (NHL). However, few cohort studies of petroleum workers report results of NHL separately. One reason is that NHL is usually grouped with other lymphopoietic cancers in the analysis. Another reason is the relatively small number of NHL cases in some studies. To determine the risk of NHL in petroleum workers, we identified 26 cohorts of petroleum workers in the United States, the United Kingdom, Canada, Australia, Italy, and Finland. Authors of the original studies were contacted, and data on the number of observed deaths and person-years of observation were requested. Data from these studies were reviewed individually as well as combined in a pooled analysis (meta-analysis). In particular, results for individual cohorts, most of which had never been reported before, were presented. The combined multinational cohort consisted of more than 308,000 petroleum workers (6.6 million person-years), and the observation period covered an interval of 60 years from 1937 to 1996. A total of 506 NHL deaths were observed, compared with 561.68 expected. The standardized mortality ratio was 0.90 and the 95% confidence interval was 0.82 to 0.98. Analyses were performed by type of facility and industrial process. Stratum-specific standardized mortality ratios (95% confidence intervals) were 0.96 (0.86 to 1.07) for US refinery workers, 1.12 (0.90 to 1.37) for non-US refinery workers, 0.64 (0.50 to 0.82) for product (gasoline) distribution workers, and 0.68 (0.47 to 0.95) for crude oil workers. When individual cohorts were stratified by length of observation, no pattern was detected. In general, exposure levels before 1950 were much higher than thereafter. However, analysis of workers by hire date (< 1950, > or = 1950) revealed no difference in NHL mortality. Furthermore, none of the individual studies showed significant exposure-response relations. In summary, results from individual studies, as well as from the pooled analysis, indicated that petroleum workers were not at an increased risk of NHL as a result of their exposure to benzene or other benzene-containing petroleum products in their work environment. This conclusion was supported by cohort studies of workers in other industries who were exposed to benzene as well as by population-based case-control studies of NHL and occupational exposures.

A case-control study of lung cancer among refinery workers.

This case-control study examined the relationship between lung cancer and the work histories of male employees at a large Texas refinery. The study included 112 lung cancer deaths observed between 1946 and 1987 and 490 matched controls. Employment histories were obtained from personnel records, and smoking information was available from medical records. Both stratification methods and conditional logistic regression were used in data analyses. Overall employment in four general job categories (administrative, engineering/laboratory, process, maintenance/mechanical) was not associated with lung cancer mortality. Results by hire period (< 1940, 1940+) showed that workers hired into process jobs before 1940 had a nonsignificantly elevated odds ratio (OR) of 1.71 (95% confidence interval [CI] = 0.85-3.45) compared with nonprocess workers hired before 1940. Among process workers hired before 1940, there was a significant trend toward increasing OR with increasing duration of employment in process jobs, and the association with lung cancer was strongest among smokers in the highest duration category of 30+ years (OR = 2.98, 95% CI = 1.07-8.31). Latency analyses of process workers hired before 1940 indicated that their lung cancer risk had peaked between 30 and 50 years since first employment. Definitive statements about causal factors are limited because results among process workers were based on small numbers of subjects in some exposure categories, and there was no information on specific workplace exposures. The OR for maintenance/mechanical jobs after adjustment for smoking was 1.00 (95% CI = 0.55-1.82). Furthermore, there was no pattern in relation to duration of employment in maintenance/mechanical jobs. The results from this study do not support the hypothesis that work in maintenance/mechanical jobs increases lung cancer risk. On the basis of analyses in this study, it is unlikely that asbestos exposure contributed to excess lung cancer mortality. Additional analyses were conducted for specific maintenance jobs with potential exposure to asbestos and by duration in jobs with occasional or routine asbestos exposure. No significant increase in lung cancer was found in any subgroup. Furthermore, there was no significant trend toward lung cancer risk in relation to duration of employment in jobs with asbestos exposure.

An updated mortality study of workers at a petroleum refinery in Beaumont, Texas, 1945 to 1996.

The present investigation represents an update of a previous cohort mortality study of 7543 workers who were employed at a petroleum refinery in Beaumont, Texas, for at least 1 year between 1945 and 1996. The updated study covered an observation period of 51 years, from 1946 to 1996, with a total of 208,627 person-years of observation. A total of 3020 (40.0%) cohort members were known to have died. The mortality data were analyzed in terms of cause-specific standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs). The overall mortality of the cohort was significantly lower than expected when compared with that of the general US population (SMR, 95.7; 95% CI, 92.3 to 99.2). Overall cancer mortality was also lower than expected (SMR, 85.8; 95% CI, 79.4 to 92.5). For specific cancer sites, significant mortality deficits were observed for the following: buccal cavity and pharynx, esophagus, large intestine, rectum, larynx, lung, and bladder and other urinary organs. No significant increase was reported for any site-specific cancer. A non-significant increase in acute myeloid leukemia was observed among male employees (SMR, 147.2; 95% CI, 76.1 to 257.2). Detailed analyses indicated that the excess was restricted to workers hired before 1950. No increase was detected for other leukemia cell-types, non-Hodgkin's lymphoma, or multiple myeloma. For non-malignant diseases, the majority of SMRs were below 100, and no significant increase was observed for any cause. In particular, significant mortality deficits were reported for ischemic heart disease (SMR, 91.0; 95% CI, 85.4 to 96.9), non-malignant respiratory disease (SMR, 61.5; 95% CI, 52.2 to 72.0), pulmonary fibrosis (SMR, 51.0; 95% CI, 22.0 to 100.4), cirrhosis of the liver (SMR, 47.2; 95% CI, 30.6 to 69.7), and accidents (SMR, 81.7; 95% CI, 66.3 to 99.6). Separate analyses of male workers by job classification (process and maintenance) were conducted. Mortality from acute myeloid leukemia was elevated among employees in maintenance jobs (8 observed deaths vs 4.31 expected; SMR, 185.5; 95% CI, 80.1 to 365.6). However, no upward trend by length of service was found. A detailed analysis indicated that the acute myeloid leukemia mortality excess was limited to maintenance workers who were hired before 1950. No other significant excess was detected for any cause among maintenance or process workers. These findings from the present study were discussed in conjunction with results from previous investigations of employees at the Beaumont refinery and with results from other refinery studies. Potential limitations of the study were also discussed.

Updated mortality study of workers at a petroleum refinery in Torrance, California, 1959 to 1997.

The updated cohort consisted of 3328 workers who were employed at the Mobil (now ExxonMobil) Torrance, California, refinery for at least 1 year between 1959 and 1997. The vital status of the cohort was determined through a variety of sources, including company employment or retirement records, the Social Security Administration's Death Master File, and the National Death Index. The updated study covered an observation period of 38 years from 1960 to 1997, with a total of 60,612 person-years of observation. A total of 705 (21.2%) cohort members were identified as having died. Mortality data were analyzed in terms of cause-specific standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs), with expected deaths based on US national cause-, gender-, race-, year-, and age-specific mortality rates. The overall mortality of the cohort was significantly lower than expected when compared with the US general population (SMR, 81.9; 95% CI, 76.0 to 88.2). Overall cancer mortality was also lower than expected (SMR, 79.8; 95% CI, 67.9 to 93.1). For specific cancer sites, significant mortality deficits were observed for cancer of the digestive system (SMR, 70.9; 95% CI, 49.4 to 98.6) and cancer of the respiratory system (SMR, 74.1; 95% CI, 55.5 to 97.0). No significant increase was reported for any site-specific cancer. For nonmalignant diseases, no significant increase was observed for any cause. In particular, significant mortality deficits were reported for ischemic heart disease (SMR, 87.7; 95% CI, 77.2 to 99.3), chronic endocardial disease and other myocardial insufficiencies (SMR, 8.3; 95% CI, 0.2 to 46.0), all other heart disease (SMR, 64.2; 95% CI, 43.0 to 92.2), and influenza and pneumonia (SMR, 59.2; 95% CI, 33.1 to 97.6). Detailed analysis by length of employment did not reveal any significant mortality excess or upward trend. Analyses of male employees by job classification (process and maintenance) were conducted. Among maintenance workers, mortality from cirrhosis of the liver (SMR, 190.1; 95% CI, 101.2 to 325.1) and suicide (SMR, 208.6; 95% CI, 111.1 to 356.7) were significantly elevated. However, these mortality excesses did not seem to be related to employment at the refinery. No other causes of death showed significant increase among maintenance workers. A similar separate analysis was conducted for process workers, and no significant excess was detected for any cause. The findings from the present study are discussed in conjunction with results from previous investigations of employees at the Torrance refinery and with results from other refinery studies. Potential limitations of the study are also discussed.

A framework for addressing health issues in or near a manufacturing facility.

Clustering of health events in or around industrial facilities sometimes leads to worker and community concerns that plant management or local health professionals must address. We provide an eight-step process to deal with these concerns systematically. We emphasize the use of good scientific practices with managerial oversight for effective worker and community communication. This process is directed to plant management and the local health professional and emphasizes the practical aspects of the investigation.

Cytokeratin pattern of clinically intact and pathologically changed oral mucosa.

The various cytokeratin polypeptides in oral epithelia are expressed in dependence on site and formation of a stratum corneum. Certain cytokeratins occur permanently and others occasionally. In fibrous hyperplasia and Lichen ruber planus, patterns of cytokeratins did not deviate significantly from normal. In some but not all cases of squamous cell carcinoma and leukoplakia studied, marked aberrations of pattern were characterized by (i) appearance of cytokeratin No. 19, (ii) somewhat more frequent occurrence of cytokeratins Nos. 8 and 18, (iii) proteolytic modifications of cytokeratins, and (iv) partial loss of a few site-specific cytokeratins. The aberrations may be taken as additional diagnostic criteria for differentiation between non-aggressive and potentially aggressive leukoplakic lesion, even if they are not correlated with the conventional histological grading of dysplasia.

[Hyperplasiogenic polyps and stomach carcinoma risk--experiences following 1074 polypectomies and follow-up studies]. / Hyperplasiogene Polypen und Magenkarzinomrisiko--Erfahrungen nach 1074 Polypektomien und Follow-up-Studien.

In 731 hyperplasiogenic polyps which have been removed by endoscopical polypectomy there were ten polyps with an early cancer and eight polyps with severe dysplasias (borderline lesions) as well as one polyp, in which an advanced carcinoma had developed. This is to date the greatest series of hyperplasiogenic polyps with malignant transformation. In addition, in nine patients with hyperplasiogenic polyps carcinomas could be discovered, i.e. a rate for malignancy of 3.8%. It seems that stomachs with multiple polyps are particularly endangered. The recurrence rate on follow-up examinations covering a period of up to eight years was 36.1%.

Asymmetric Synthesis of Novel Ferrocenyl Ligands with Planar and Central Chirality.

A stereogenic center at the position beta to the metallocene backbone is present in ferrocenyl ligands 2, which are interesting for asymmetric catalysis. These planar-chiral compounds are accessible for the first time by a highly diastereoselective and enantioselective synthesis (de=93-97 %; ee>/=96 %) from the ferrocenyl ketones 1. A variety of donor groups (E(1)=Ph(2)P small middle dotBH(3), SMe, SiPr; E(2)=SMe, STol, SePh, Ph(2)P small middle dotBH(3), iPr(2)P small middle dotBH(3)) can be introduced as electrophiles. Tol=tolyl=CH(3)C(6)H(4).

Terpenols as substituents for the diastereoselective formation of enantiomerically pure triple lithium-bridged helicate type-coordination compounds.

The terpenols l(-)-borneol, (1S2S3S5R)-3-pinanol, (-)-menthol, and (-)-myrtenol are easily available chiral alcohols for the preparation of enantiomerically pure catechol esters -H2. Those ligands are used for the hierarchical assembly of triple lithium-bridged dinuclear titanium(iv) triscatecholate helicates Li[Li3()6Ti2]. In solution, the dimeric species are in a solvent dependent equilibrium with the monomer Li2[()3Ti]. The equilibrium is studied by (1)H NMR. CD spectroscopy indicates that the configuration at the complex units of the enantiomerically pure dimeric α-chiral derivatives Li[Li3()6Ti2] is opposite to the configuration of the monomers Li2[()3Ti]. For the γ-chiral complex Li2[()3Ti] only a de of 25% is observed and in this case no interpretation of the mechanism of stereocontrol is possible.

[Necrotizing sialometaplasia--a specific differential diagnosis of an ulcer of the hard palate]. / Die nekrotisierende Sialometaplasie--die besondere Differenzialdiagnose einer Neubildung in der Mundhöhle.

BACKGROUND: Ulcers of the hard palate are mostly caused by malignancies. In addition, rare diseases should be included in the differential diagnosis. Beside specific inflammations (lues, tuberculosis) necrotizing sialometaplasia belongs to these uncommon medical conditions. PATIENTS: A 51-year-old male was admitted to the hospital with an algetic ulcer of the hard palate. Malignancy was ruled out by pathohistological examination. Inflammation or infection was excluded by serological examination. A second biopsy was investigated by the pathologist suspecting necrotizing sialometaplasia and confirmed the suspicion. By applying local treatment and systemic antibiosis against bacterial superinfection the ulcer finally healed. CONCLUSIONS: Necrotizing sialometaplasia is a rare medical condition generated by local circulatory disorder. 128 cases were published so far. Typical patients are males aged 50 and above. Characteristics of this ulcer are a high rate of spontaneous healing and lacking malignancy. After excluding a malignant tumor this rare disease has to be considered when diagnosing an ulcer of the hard palate.

[Histological classification of oral leukoplakia by a classification number]. / Histologische Klassifizierung der oralen Leukoplakien durch eine Kennzahl.

From 1969 to 1980 the authors examined 587 histological specimens of oral leukoplakia obtained from 424 patients. The histological findings were assessed in classification numbers qualitatively and quantitatively characterizing the subepithelial inflammation, epithelial hyperplasia, keratosis, the grade of epithelial dysplasia an the degree of infiltration when carcinoma had already developed. From this histological classification a classification number resulted which allows conclusions on the prognosis of the leukoplakia under study. Besides the grade of dysplasia also the features of the subepithelial inflammation are important for the prognostic assessment of leukoplakia. The classification numbers are suitable for data processing. In the grading system reported, the most important morphological findings are represented with qualitative and quantitative objectiveness. The classification number leads to more reliable comparison and evaluation of the results obtained by different research groups.

Cell proliferation in chorionic villi at different gestational ages, as analyzed by premature chromosome condensation.

The technique of premature chromosome condensation (PCC) was adapted to human first-trimester chorionic villi cells to analyze the cell-cycle kinetics of interphase chromatin. Uncultured cells of the cytotrophoblast (CT) and the mesenchymal core (MC) were obtained by a two-step digestion. PCC was induced by fusion of the chorionic interphase cells with mitotic Chinese hamster ovary or HeLa cells. Cells showing PCC in G1 (classes 1-6), S, and G2 were found. To analyze further the proliferation stages of chorionic G1 interphases, the proliferation potential index (PPI) of 34 placentae recovered between the 8th and 12th week of gestation was determined. The mean PPI found in the CT and MC cells ranged from 18% to 73%, values similar to those described for intensely proliferating tissues. The highest mean PPI value (73%) was observed in CT cells from placentae recovered at the 9th week of gestation, indicating a high specific proliferative activity of CT cells at this developmental stage.