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PubMed1994

Detection of increased amounts of the extracellular domain of the c-erbB-2 oncoprotein in serum during pulmonary carcinogenesis in humans.

Over-expression of the c-erbB-2 oncogene-encoded p185 protein product has been implicated in the pathogenesis of a wide variety of human malignancies, including lung cancer. Over-expression of p185 can be detected immunologically by quantification of the extracellular domain of p185 (c-erbB-2 oncopeptide) in extracellular fluid in vitro and in serum in vivo. An enzyme-linked immunosorbent assay (ELISA) for the c-erbB-2 oncopeptide was used to examine banked serum samples of 11 pneumoconiosis patients who subsequently developed lung cancer and serum samples from 11 hospital controls matched for age, sex, ethnic group and smoking as well as 55 unmatched general population controls. The mean serum level for the c-erbB-2 oncopeptide in human neu units/ml in the lung cancer cases (1,756 +/- 549 HNU/ml) was statistically significantly elevated (p < 0.001) in comparison to the mean level in the matched controls (976 +/- 488 HNU/ml) or the general population controls (888 +/- 655 HNU/ml). Defining a positive elevation of the serum c-erbB-2 oncopeptide as any value more than 2 standard deviations above the mean of the matched controls, 64% (7 of 11) of the lung cancer cases were positive compared to 0% (0 of 11) matched controls and 5% (3 of 55) of the unmatched controls. In addition, 4 of the 7 c-erbB-2 oncopeptide-positive cancer cases had positive serum samples prior to the time of disease diagnosis (average = 35 months). These results suggest that serum c-erbB-2 oncopeptide may be elevated at an early stage of pulmonary carcinogenesis and that further prospective study of the utility of this biomarker is warranted.

Aged↗
PubMed1989

Genotoxicity of coal fly ash, assessed in vitro in Salmonella typhimurium and human lymphocytes, and in vivo in an occupationally exposed population.

Fly ash as a product of coal combustion is known to contain various mutagenic substances, but genotoxic properties, especially of the particular (larger-size) fly ash fraction which is electrostatically precipitated (ESP) in the energy plant, have hardly been investigated. While smaller-size fly ash particles escape through the stack during powder coal combustion, the ESP fraction is collected and used for the manufacturing, for instance according to the Lytag process, of secondary products which can serve several construction purposes. Since fly ash as well as fly ash products are generally introduced into the human environment, a study of possible genotoxic effects to human DNA is indicated. Mutagenic properties of ESP fly ash, as well as of the Lytag product, were investigated by means of the Salmonella microsome assay. The capacity to cause human chromosome damage of both ESP fly ash and Lytag dust was studied in vitro by application of the sister-chromatid exchange (SCE) test using human lymphocytes. Furthermore, effects of ESP fly ash/Lytag dust on the incidence of SCE in peripheral lymphocytes in vivo were measured in an occupationally exposed, male population, using individually matched employees from a flour-processing industry as the control population. It is demonstrated that ultrasonically treated DMSO extracts of ESP fly ash are slightly mutagenic to Salmonella tester strains TA97 and TA102. Lytag dust is effective in inducing reversions in all tester strains. Furthermore, it appeared that both compounds significantly increase the SCE frequency of human lymphocytes after incubation in vitro in comparison to non-exposed cells. Also, peripheral lymphocytes of the occupationally exposed population show a considerably higher incidence of SCE than the control population. Major disturbing factors in assessing the effects of occupational exposure to fly ash/Lytag dust on lymphocyte SCE frequency appeared to be smoking behavior and alcohol consumption. It is concluded that exposure to fly ash from powder coal combustion implies a moderate genotoxic risk to man.

Air Pollutants, Occupational↗
PubMed2003

Morphological changes of Pseudomonas pseudoalcaligenes in response to temperature selection.

Adaptation to novel environments usually entails morphological changes. The cell morphology of six experimental populations of Pseudomonas pseudoalcaligenes and their common ancestor were examined with scanning electron microscopy (SEM). The six experimental populations were propagated under different temperatures for 10 months: three of them cultured at constant normal temperature (35 degrees C) forming the control group, and the other three cultured at incremental higher temperatures (from 41 degrees to 47 degrees C) as the HT group. SEM showed the deformed and elongated cells in the 6-h cultures of both ancestral and control populations at 45 degrees C, indicating that 45 degrees C is stressful for the ancestral and the control populations. In contrast, the HT populations retained normal cell shape in the 6-h cultures at both 35 degrees C and 45 degrees C. The mean cell volumes of control and HT populations increased 29% and 34%, respectively, relative to the ancestor at their respective thermal regimens, suggestion that the culturing conditions might favor larger cells.

Adaptation, Physiological↗
PubMed1981

Response of a human tumour cell line to chronic potassium dichromate exposure.

Cultures of the human cell line NHIK 3025 were exposed over an 18-month period to 0.5 mumol/1 potassium dichromate (K2Cr2O7) containing 1 mumol/1 hexavalent chromium. The chronically exposed cells increased their tolerance to K2Cr2O7 in comparison to control populations. The doubling time of the chronically exposed cell populations increased even in the absence of K2Cr2O7, but they did not change their morphology (light level), nor contain as many giant cells as newly exposed control populations. Cells returned to control medium for 6 months after 12-months exposure to K2Cr2O7 showed a gradual but incomplete reversal of these effects. The results are compared with those obtained from cells of non-tumour origin.

Cell Line↗
PubMed2000

[Roaming through methodology. XVIII. Selection of control groups].

The selection of a valid control group is important in case control studies and has therefore generated a fair amount of discussion in the epidemiologic literature. The proposal of the study usually determines the type of control group that should be selected. It is possible to select population controls, hospital controls, friends or relatives of patients or a variant of these. Each method has specific advantages and disadvantages. Random-digit dialing can be used to select population controls by telephone. This method is a valuable alternative when no registry exists.

Case-Control Studies↗
PubMed2001

A major marker for normal tension glaucoma: association with polymorphisms in the OPA1 gene.

Normal tension glaucoma (NTG) is a major form of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. OPA1, the gene responsible for autosomal dominant optic atrophy represents an excellent candidate gene for NTG, as the clinical phenotypes are similar and OPA1 is expressed in the retina and optic nerve. Eighty-three well-characterized NTG patients were screened for mutations in OPA1 by heteroduplex analysis and bi-directional sequencing. Sequences found to be altered in NTG subjects were examined for variations in 100 population controls. A second cohort of 80 NTG patients and 86 population controls was subsequently screened to determine whether the initial findings could be replicated. A single nucleotide polymorphism (SNP) on intervening sequence (IVS) 8 (IVS8 + 4 C/T) was found to be strongly associated with the occurrence of NTG in both cohorts (chi(2)=7.97, P=0.005 in the first cohort, chi(2)=9.93, P=0.002 in the second cohort; odds ratio 3.1 (95% CI: 1.8-5.6). A second SNP (IVS8 + 32 T/C) appeared to be associated with disease in the first cohort (chi(2)=4.71, P=0.030), but this finding could not be replicated in the second cohort. In the combined cohort, the compound at-risk genotype IVS8 + 4 C/T, + 32 T/C was strongly associated with the occurrence of NTG (chi(2)=22.04, P=0.00001 after correcting for testing four genotypes). These results indicate that polymorphisms in the OPA1 gene are associated with NTG and may be a marker for the disease.

Base Sequence↗
PubMed1989

Clinical management of the fetus with markedly diminished umbilical artery end-diastolic flow.

This study was conducted to evaluate prospectively a management protocol for fetuses with a markedly abnormal umbilical artery velocity waveform. The study population consisted of fetuses whose systolic/diastolic ratio was greater than 2 SD above the mean for gestational age. The matched control population consisted of fetuses with similar gestational ages, indications for testing, and estimated fetal weights with normal systolic/diastolic ratios. Abnormal Doppler results were used only to determine the frequency of fetal testing. Biophysical profile testing was performed semiweekly on all patients. Patients with absent or reversed end-diastolic flow were admitted for daily testing. The following criteria were used as indications for delivery: (1) worsening maternal condition, (2) oligohydramnios, (3) intrauterine growth retardation with lung maturity, and (4) biophysical profile score less than or equal to 4. Fifty-one patients (7%) had abnormal Doppler blood flow velocity studies. When the study population was compared with the control population at the time of delivery, there were no differences in umbilical artery pH, Apgar score, or incidence of intrauterine growth retardation. However, study patients were delivered at a significantly lower gestational age and lower birth weight and experienced a higher likelihood of neonatal intensive care unit admission. When study patients with documented end-diastolic flow were compared with study patients with no end-diastolic flow, there were no differences in umbilical artery pH, Apgar score, or incidence of intrauterine growth retardation. However, fetuses with no end-diastolic flow had a significantly shorter test-to-delivery interval, lower gestational age, lower birth weight, and more neonatal intensive care unit admissions. There were no perinatal deaths among the study patients. The range of systolic/diastolic ratios for the five patients who failed to follow our protocol for intensive maternal-fetal surveillance was 4.3 to infinity; all experienced fetal death within 18 days. These results suggest that immediate delivery of the fetus with diminished end-diastolic flow may not be mandatory. The combined use of fetal biophysical testing and commonly used criteria for delivery results in acceptable fetal outcome and prolongation of gestational age.

Blood Flow Velocity↗
PubMed1992

In situ hybridization histochemistry in the human hypothalamus.

We have seen that mRNA for several neuropeptides can be visualized at the microscopic level in human post-mortem brain tissues using in situ hybridization histochemistry and oligonucleotides as probes. The specificity of the hybridization signal detected in each case is supported by several criteria such as Northern blot analysis, use of at least two oligonucleotides complementary to different regions of the same target mRNA, cohybridization of labeled and excess unlabeled oligonucleotide probes, and melting curve analysis of the formed hybrids. Furthermore, factors such as age, post-mortem delay or gender did not show a significant effect in the levels of hybridization in the control population studied. Hybridization signals comparable to those found in the control population were obtained in frozen tissues, stored for up to 6 years before analysis. The results obtained for the different neuropeptides examined are, in general, in good agreement with the available information on their distribution and cellular localization as determined by radioimmunoassay or immunohistochemistry. The use of in situ hybridization histochemistry has clearly revealed the location of neurons synthesizing these neuropeptides, adding important information to that provided by radioimmunoassay or immunohistochemistry. A typical example is the identification of peptide synthesizing neuronal cell bodies by immunohistochemistry. This requires, in some cases, the use of treatments such as colchicine, obviously impossible with human brain tissues. The abundance of mRNA could be further related to transcriptional activity and, when compared with peptide levels, can provide some clues on peptide turnover rates. Thus in the hypothalamus, the paraventricular and supraoptic nuclei were found to contain cells expressing arginine-vasopressin and oxytocin mRNAs. Their distribution was in good agreement with that determined by immunohistochemistry (Dierickx and Vandesande, 1977). We have also found that these nuclei contain transcripts for neuropeptide genes such as preproenkephalin A, neuropeptide Y and somatostatin, in agreement with previously reported immunohistochemical data (Agid and Javoy-Agid, 1985; Emson et al., 1986). In the basal ganglia, numerous cells heterogeneously distributed throughout the caudate and putamen nuclei were found to contain preproenkephalin A mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Basal Ganglia↗
PubMed2002

Skewed X-chromosome inactivation is associated with trisomy in women ascertained on the basis of recurrent spontaneous abortion or chromosomally abnormal pregnancies.

An increase in extremely skewed X-chromosome inactivation (XCI) (> or = 90%) among women who experienced recurrent spontaneous abortion (RSA) has been previously reported. To further delineate the etiology of this association, we have evaluated XCI status in 207 women who experience RSA. A significant excess of trisomic losses was observed among the women who had RSA with skewed XCI versus those without skewed XCI (P=.02). There was also a significant excess of boys among live births in this group (P=.04), which is contrary to expectations if the cause of skewed XCI was only that these women carried X-linked lethal mutations. To confirm the association between skewed XCI and the risk of trisomy, an independent group of 53 women, ascertained on the basis of a prenatal diagnosis of trisomy mosaicism, were investigated. Only cases for which the trisomy was shown to be of maternal meiotic origin were included. The results show a significantly higher level of extreme skewing (> or = 90%) in women whose pregnancies involved placental trisomy mosaicism (17%) than in either of two separate control populations (n=102 and 99) (P=.02 compared with total control subjects). An additional 11 cases were ascertained on the basis of one or more trisomic-pregnancy losses. When all women in the present study with a trisomic pregnancy (n=103) were considered together, skewed XCI was identified in 18%, as compared with 7% in all controls (n=201) (P=.005). This difference was more pronounced when a cutoff of extreme skewing of 95% was used (10% vs. 1.5% skewed; P=.002). Maternal age was not associated with skewing in either the patient or control populations and therefore cannot account for the association with trisomy. Previous studies have shown that a reduced ovarian reserve is associated with increased risk of trisomic pregnancies. We hypothesize that the association between skewed XCI and trisomic pregnancies is produced by a common mechanism that underlies both and that involves a reduction of the size of the follicular pool.

Abortion, Habitual↗
PubMed1995

Coronary sinus morphology in patients with atrioventricular junctional reentry tachycardia and other supraventricular tachyarrhythmias.

BACKGROUND: Coronary sinus access by electrode catheters is easier in patients with atrioventricular junctional reentry tachycardia (AVJRT) than in patients with other supraventricular tachyarrhythmias. The reason for this has not been addressed. METHODS AND RESULTS: The size and shape of the proximal coronary sinus were measured in 15 patients with AVJRT and 14 control subjects after angiographic visualization. Coronary sinus dimensions, morphology, and angle of origin from the right atrium were measured. The proximal coronary sinus in patients with AVJRT was larger than in the control population. The mean ostium diameter was 12.2 +/- 2 mm compared with control dimensions of 8.5 +/- 1.5 mm, P = .00001. At a distance of 5 mm from the ostium, the coronary sinus measured 10.2 +/- 1.8 mm compared with 8.1 +/- 1.9 mm, P = .007. The dilatation persisted 10 mm into the coronary sinus, with a measurement of 9 +/- 1.4 mm compared with 7.6 +/- 2 mm, P = .04. In 73% of AVJRT patients, the proximal coronary sinus had the appearance of a wind sock. This morphology was seen only in 7% of control patients, in whom the coronary sinus was tubular (in 93%). There was considerable interindividual variability in the angle of origin. CONCLUSIONS: The proximal coronary sinus in patients with AVJRT was significantly different from a control population. The ostium was 44% larger and remained more dilated to at least 10 mm from the ostium. The appearance was like a wind sock in AVJRT patients and tubular in the control patients. These findings may have important implications for arrhythmia pathogenesis in such patients.

Adolescent↗
PubMed2000

Evolution of reduced pre-adult viability and larval growth rate in laboratory populations of Drosophila melanogaster selected for shorter development time.

Four large (n > 1000) populations of Drosophila melanogaster, derived from control populations maintained on a 3 week discrete generation cycle, were subjected to selection for fast development and early reproduction. Egg to eclosion survivorship and development time and dry weight at eclosion were monitored every 10 generations. Over 70 generations of selection, development time in the selected populations decreased by approximately 36 h relative to controls, a 20% decline. The difference in male and female development time was also reduced in the selected populations. Flies from the selected populations were increasingly lighter at eclosion than controls, with the reduction in dry weight at eclosion over 70 generations of selection being approximately 45% in males and 39% in females. Larval growth rate (dry weight at eclosion/development time) was also reduced in the selected lines over 70 generations, relative to controls, by approximately 32% in males and 24% in females. However, part of this relative reduction was due to an increase in growth rate of the controls populations, presumably an expression of adaptation to conditions in our laboratory. After 50 generations of selection had elapsed, a considerable and increasing pre-adult viability cost to faster development became apparent, with viability in the selected populations being about 22% less than that of controls at generation 70 of selection.

Adaptation, Physiological↗
PubMed2005

Occupational exposures and mycosis fungoides. A European multicentre case-control study (Europe).

OBJECTIVES: Mycosis Fungoides (MF) is a rare disease with an occurrence indicating that occupational exposures may play a role. To estimate the association between MF and occupational exposures as measured by means of an job-exposure matrix (JEM). METHODS: A European multicenter case-control study was conducted from 1995 to 1997 and included seven rare cancers, one of which was MF. Patients between 35 and 69 years of age, diagnosed with MF (n=140), were recruited and the diagnoses were checked by a reference pathologist who classified 83 cases as definite, 35 cases as possible and 22 cases as not accepted. Among the 118 accepted cases, 104 cases were interviewed, of which 76 were definite cases. We selected population controls and colon cancer controls to serve all seven case groups. Altogether 833 colon cancer controls and 2071 population controls were interviewed. Based on the reported occupational experiences, a team of industrial hygiene specialists identified five potential exposures and developed an JEM. This JEM was used to estimate the odds ratios (OR) for MF as a function of these exposures. The JEM included aromatic and/or halogenated hydrocarbons (AAHs), chrome (VI) and its salts, electromagnetic radiations, silica and pesticides. RESULTS: Exposures to AHHs (OR 6.3, C.I 2.4-16.7 for male) were associated with a high MF risk. CONCLUSIONS: The study supports the hypothesis that some MFs have an occupational etiology but only a small fraction of exposed workers are apparently susceptible since the disease is so rare.

Adult↗
PubMedDate not supplied

Wegener's granulomatosis: role of environmental exposures.

OBJECTIVE: The etiology of Wegener's granulomatosis (WG) remains unknown. The predominant involvement of the airways and the presence of neutrophilic alveolitis at disease onset have led us to postulate that an inhaled agent may trigger the onset of WG. This study is designed to analyze differences in self-reported environmental exposures between patients with WG and various control populations. METHODS: We conducted a standard interviewer-administered questionnaire case controlled survey of 101 patients with WG, 54 healthy controls, 24 patients with sarcoidosis or idiopathic pulmonary fibrosis, and 45 patients with various inflammatory rheumatologic diseases. We assessed environmental exposures for one year prior to the onset of symptoms or prior to the interview date for healthy controls. RESULTS: Seasonal differences in the onset of WG were not apparent. More than 75% of the patients in all groups noted remarkable environmental exposure to inhaled substances (fumes or particulate matter), within one year prior to disease onset for WG and other diseases or prior to the interview date for healthy controls. Differences between WG and control groups were apparent in several categories of exposure. Statistically significant differences occurred in regard to a vocational exposure to fumes or particulate materials (WG > healthy controls and rheumatic disease controls), residential exposure to particulate materials from construction (WG > pulmonary disease controls) and occupational exposure to pesticides (WG > healthy, pulmonary and rheumatic disease controls). CONCLUSION: This study confirms the absence of seasonal differences in the onset of WG. It also demonstrates high rates of self-reported environmental exposures to inhaled substances in WG and all control populations. It is possible that more significant differences in the quality, quantity and intensity of exposure to inhaled potential precipitants of WG had occurred between groups, but were not detected by our survey. Alternatively, the absence of substantial differences in patients with WG and controls may reflect the more important role of host susceptibility factors.

Adolescent↗
PubMed2006

Lack of evidence of hypervolemia in children with insulin-dependent diabetes mellitus.

Hypervolemia is considered to play a major role in the pathogenesis of diabetic vasculo- and nephropathy. The aim of our study is to determine whether children and adolescents with insulin-dependent diabetes mellitus (IDDM) experience alterations in blood volume (BV) before onset of apparent nephropathy. BV (calculated as the sum of measured plasma volume (PV) and red cell volume (RCV)) was determined in 31 children (9-16 yr) with a mean duration of IDDM of 6.6 yr and without microalbuminuria. Due to dependence of these values on age, size and sex, all data were normalised for body size parameters. While no statistical difference for BV normalised for lean body mass (LBM) (86.98+/-9.5 ml/kg) was found in diabetic children compared with our control population (84.91+/-12.08 ml/kg), a difference could be shown when normalised for body surface area (BSA) (diabetic children 2.37+/-0.3 L/m(2); control population 2.15+/-0.38 L/m(2), p=0.002). Increased BV is only present when normalising for BSA and not for the theoretical superior LBM-index. Because the study population exhibited a poor glycemic control (HbA1c 10.2+/-2.4 %), an influence of glucosuria-induced polyuria on BV cannot be excluded. Taking into account these limitations our data do not confirm the presence of hypervolemia before onset of diabetic nephropathy.

Adolescent↗
PubMed2005

Mycobacterium tuberculosis transmission among high school students in Greece.

BACKGROUND: The aim of this study was to investigate the requirements and practical steps for screening of Mycobacterium tuberculosis (MTB) transmission among high school student populations in two regional high schools of central Greece. Case-matched control populations from other regional schools were included. METHODS: Case study of two indexed cases, 61 close contacts, 212 casual contacts and 369 controls were investigated. Detailed questionnaires, tuberculin-skin test (PPD test), chest radiography, medical evaluation and DNA fingerprinting of sputum isolates were used. RESULTS: In case A, three (1.97%) of 152 close and casual contacts developed tuberculosis, and a further 25 (16.4%) were classified as infected. In contrast, none of the 121 close or casual contacts investigated for Case B developed tuberculosis or were classified as infected. None of the control populations contained infected individuals. Contacts of case A had a much higher risk (3.08 < RR = 22.29 < 161.69, P < 0.001) of being infected than contacts of case B. Two different strains of MTB were found responsible for these outbreaks. CONCLUSION: There was a considerable difference in the infectivity of the two cases presumably due to environmental and clinical factors, although two different MTB strains were responsible. It is proposed that the extent of case investigation should be individualized with particular emphasis placed among close contacts.

Adolescent↗
PubMed2000

Specific HLA in pulmonary MAC infection in a Japanese population.

Patients with pulmonary Mycobacterium avium complex (MAC) infection occasionally have neither past histories of pulmonary diseases nor underlying immunodeficiency conditions. Therefore, we hypothesized that MAC may be linked with a disease-susceptibility gene and determined human leukocyte-associated antigens (HLA) in patients with pulmonary MAC infection. HLA phenotypes were tested in 59 patients with pulmonary MAC infection, and diagnosed according to the criteria of the American Thoracic Society. Data of a Japanese population reported at the Tenth Japan HLA Workshop were used as a control. HLA-A33 (28.8% versus 12.5%, p = 5 x 10(-)(4)) and HLA-DR6 (50.8% versus 20.2%, p = 5 x 10(-)(8)) antigen frequencies in patients with MAC were significantly increased compared with those of the control population. Frequency of a haplotype A33-B44-DR6 in the MAC patients was also significantly increased compared with those of the control population (23.7% versus 4.2%; p = 3 x 10(-)(9)). These data suggest that development of pulmonary MAC infection is associated with specific HLA in a Japanese population.

Adult↗
PubMed2000

Inguinal hernia in patients with Ewing sarcoma: a clue to etiology.

BACKGROUND: Various congenital anomalies have been associated with childhood cancer, but as yet no anomaly has been consistently found with Ewing sarcoma (ES). Recently a large case-control study of ES patients reported a greater number of hernias in both cases and their sibling controls than in population controls. Most of these hernias were inguinal. Because these anomalies were also reported previously in two case series, we looked for inguinal hernias in a different population of ES patients. PROCEDURE: We abstracted medical records for 306 pathologically confirmed ES/primitive neuroectodermal tumor (PNET) patients seen at NIH between 1960 and 1992. Epidemiological data on demographics and medical conditions were analyzed. The frequency of anomalies was compared to expected rates to calculate relative risk and confidence intervals. RESULTS: Anomalies were present in 67 (22%) cases. A particular anomaly, inguinal hernia, was reported for 13 (5%) NIH cases. Compared to population estimates for white children, the relative risk of inguinal hernia among white NIH cases was 13.3 (95% CI 3.60-34.1) for females and 6.67 (95% CI 2.67-13.7) for males. CONCLUSIONS: The findings of inguinal hernias in some patients with ES suggest that a disruption in normal embryological development occurred. This may provide an important clue to the etiology of ES. We hypothesize that these hernias may relate to an in utero exposure or indicate an underlying genetic disorder. Future studies should carefully evaluate ES families for genetic disease and explore environmental factors. Med. Pediatr. Oncol. 34:195-199, 2000. Published 2000 Wiley-Liss, Inc.

Adolescent↗