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Biomedical subjects

C Wolf

Publications and source records attributed to C Wolf.

At least 109 records · Page 6Linked to original sources
PubMed1997

Cholesterol biosynthesis inhibited by BM15.766 induces holoprosencephaly in the rat.

To confirm that blocking 7-dehydrocholesterol delta 7 reductase (7DHC reductase), as observed in Smith-Lemli-Opitz syndrome (SLOS), induces craniofacial defects, we tested BM15.766, which blocks 7DHC reductase but is chemically unrelated to the holoprosencephaly-inducing teratogen AY9944. Rats were given BM15.766 either in methylcellulose from days (D) 1 through D11 (3 treated groups: protocol A) or in olive oil from D4 through D7 (300 mg/kg/d: protocol B). The sera were sampled on D0, D3, and D5 or D6, D10, D14, and D21 to measure cholesterol and dehydrocholesterols in all groups and steroid hormones in protocol B. D21 fetuses showed the holoprosencephaly spectrum of malformations and the treated dams low cholesterol and accumulation of 7DHC, 8DHC, and trienols, as in SLOS-affected children. In the 3 dosage groups the malformations were dose-related and enzymatic cholesterol decreased to a plateau. The DHC reached 25-44% of the total sterols in the dams. In protocol B, one-third of the BM15.766-treated fetuses presented facial malformations and almost two-thirds pituitary agenesis. On D10, cholesterol reached a minimum and the DHC a maximum while estradiol 17 beta and progesterone were lowered, the latter decreasing in correlation with cholesterolemia. A sterol profile similar to that previously observed after AY9944 associated with a similarly high incidence of pituitary agenesis confirmed that time-limited inhibition of 7DHC reductase induces holoprosencephaly and that pituitary agenesis is the minor form of holoprosencephaly.

Animals↗
PubMed1997

In utero exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters reproductive development of female Long Evans hooded rat offspring.

Prenatal administration of a single dose of 1 microg TCDD/kg induces malformations of the external genitalia and subfertility in female offspring (L. E. Gray, Jr., and J. S. Ostby (1995) Toxicol. Appl. Pharmacol. 133, 285-294). A cross-fostering study indicated that in utero but not lactational TCDD exposure (1 microg TCDD/kg on gestational Day 15) induces cleft phallus, vaginal thread formation, and reduced ovarian weight. TCDD treatment on the 15th day of pregnancy at 0, 0.05, 0.20, or 0.80 microg TCDD/kg delayed vaginal opening at 0.80 microg/kg in the progeny. A persistent vaginal thread was displayed by 27% of the progeny at 0.20 and 92% at 0.80 microg TCDD/kg. These effects did not appear to result from abnormal ovarian function during prepubertal development; neither serum estradiol levels nor ovarian estradiol production were reduced in 21- or 28-day-old progeny of dams exposed to 1 microg TCDD/kg. In addition, partial to complete clefting of the phallus was displayed in TCDD-treated rats (10% at 0.20 and 60% at 0.80 microg TCDD/kg) and these dosage levels also increased the length of the urethral slit, increased distance from the urethral opening to the tip of the phallus, and decreased distance from the urethral opening to the vaginal orifice. Although fertility rates were normal, time-to-pregnancy was delayed by treatment with 0.80 microg TCDD/kg. When necropsied at 20 months of age, females from the TCDD-dose groups displayed histopathological alterations of the reproductive tract. In summary, administration of TCDD at dosage levels of 0.2, 0.8, and 1.0 microg/kg produces morphological reproductive alterations in female rat offspring as a consequence of in utero exposure.

Abnormalities, Drug-Induced↗
PubMed1997

Potential impact of altitude on lung function.

OBJECT: The effect of altitude on lung function was evaluated in 21 healthy volunteers at 171 m and at 1580 m above sea level. METHOD: Results were obtained using an open spirometry system. DESIGN: The parameters analyzed were forced vital capacity (FVC), forced expiration volume after 1 s (FEV1), relative 1-s capacity (FEV1/FVC), mean expiratory flows at 75%, 50% and 25% of FVC (MEF75, MEF50, MEF25), and maximal expiratory flow (peak flow, PEF). RESULTS: MEF75 and MEF50 revealed a positive correlation with altitude, with mean rises of 15% and 11%, respectively. The difference was statistically significant for MEF75 (P = 0.0009) and MEF50 (P = 0.0001), whereas the other parameters revealed no significant difference. CONCLUSION: Altitude could be a variable influencing spirometric measurements.

Adult↗
PubMed1997

Pulmonary function and symptoms of welders.

OBJECTIVE: As the findings on changes in pulmonary function of welders have been inconsistent, this study aimed to analyze respiratory symptoms and pulmonary function among welders and controls with particular emphasis on small airways dysfunction. METHODS: Cross-sectional analysis, using spirometry and a standardized questionnaire, was used to evaluate 521 participants, 166 of whom (64 welders and 102 controls) were evaluated for pulmonary symptoms, occupational inhalative exposures, leisure time activities, and anamnestic data. RESULTS: The welders reported more pulmonary symptoms than the controls. They exhibited a decreased mean expiratory flow (MEF) at 25% and 50% of vital capacity (MEF25, MEF50) while the other parameters tested (forced vital capacity, forced expiratory volume in 1 s) were unchanged compared with the controls. Multivariate regression analysis revealed that smoking explained the observed variance; only in MEF25 the duration of welding exposure had a significant influence on this parameter. CONCLUSIONS: The significantly reduced flow values among the welders compared with the controls indicates the presence of small airways disease. Differences in smoking habits accounted for more than double the differences in MEF25 than did chronic welding fume exposure, confirming the role of the former as the main risk factor leading to the decline in lung function. Longitudinal studies are needed to evaluate the long-term effects of chronic welding fume exposure, in particular with a view to identifying especially susceptible workers.

Adult↗
PubMed1997

Acquired dyschromatopsia in combined exposure to solvents and alcohol.

HYPOTHESIS: Does occupational exposure to solvents in combination with alcohol intake give rise to acquired color vision defects? METHOD: A total of 138 individuals exposed to solvents (toluene, xylene, trichloroethylene, tetrachloroethylene) were examined using Lanthony's D-15 test and compared with 100 nonexposed controls. The extent of color vision loss was quantitatively assessed based on Bowman's color confusion index (CCI). A cumulative exposure index was calculated from the hours of exposure per day and the years of exposure. In 30 persons who were exposed to trichloroethylene and tetrachloroethylene, urinary trichloroacetic acid was assessed as a parameter of exposure. Alcohol intake was calculated as based on interviews of patients in grams of ethyl alcohol per week. RESULTS: Individuals who consumed more than 250 g alcohol/week and were simultaneously exposed to solvents showed a significantly elevated CCI (P = 0.0044). No significant correlation emerged between trichloroacetic acid excretion in the urine or the cumulative exposure index and the CCI. CONCLUSION: The combination of alcohol intake and occupational exposure to solvents discloses the risk of acquired subclinical color vision defects.

Adult↗
PubMed1997

Online detection of REM sleep based on the comprehensive evaluation of short adjacent EEG segments by artificial neural networks.

1. For scientific and clinical requirements the present objective is a robust automatic online algorithm to detect rapid eye movement (REM) sleep from single channel sleep EEG data without using EMG or EOG information. 2. For data preprocessing 20 seconds time periods of the continuous EEG activity are digitally filtered in 7 frequency bands. Then the RMS values of these filtered signals are calculated along segments of 2.5 seconds. The resulting matrix of RMS values is representing information on the power of the signal localized in time and frequency and serves as input to an artificial neural network. A pooled set of EEG data together with the corresponding manual evaluation of the recordings was used in the training process. 3. Afterwards more than 90% of the time periods not belonging to the training set could be correctly labeled into REM and nonREM periods. In comparison to an older algorithm based on RMS values calculated along segments of 20 seconds, the error rate could be reduced by 20%.

Adult↗
PubMed1997

Laboratory markers of veno-occlusive disease in the course of bone marrow and subsequent liver transplantation.

Plasminogen activator inhibitor 1 (PAI-1) and amino-propeptide of type III procollagen (PIIINP) have been described as markers of hepatic veno-occlusive disease (VOD) after bone marrow transplantation (BMT). We determined these parameters in two patients undergoing BMT and subsequent liver transplantation due to VOD. Previously normal PAI-1 levels (maximum 30.0 ng/ml in patient 1, 23.7 ng/ml in patient 2) were elevated for the first time in both patients at the time of clinically diagnosed VOD on days 40 and 20, respectively (patient 1: 317.5 ng/ml; patient 2: 317.2 ng/ml). Levels remained elevated until liver transplantation was performed on days 79 and 41, respectively. Baseline levels (day -8) of aminopropeptide of type III collagen (patient 1: 4.44 microg/l; patient 2: 8.1 microg/l) peaked at the time of BMT in both patients (155.0 microg/l and 108.3 microg/l). After an intermittent decrease at the time of discharge on day 32, a second elevation was observed in patient 1 when she was readmitted and presented with typical signs of VOD on day 40. In patient 2, PIIINP levels remained high until VOD was diagnosed (day 20) and liver transplantation was performed. After liver transplantation, PAI-1 levels normalized in both patients and PIIINP levels declined. Both patients died due to infectious complications and multiorgan failure on days 141 and 101, respectively. Whereas the early rise of PIIINP did not correlate with the clinical onset of VOD, the results emphasise the relevance of PAI-1 for diagnosing VOD.

Acute Disease↗
PubMed1997

Psychosocial predictors of long-term success of in-patient pulmonary rehabilitation of patients with COPD.

Studies of the long-term outcome of pulmonary rehabilitation have measured quality of life (QOL) mainly as disease-specific functional impairment, but long-term effects on overall satisfaction with health or life have not yet been adequately evaluated. Furthermore, the influence of personality traits on the long-term outcome of pulmonary rehabilitation have not so far been examined. The following questions were studied: 1) What are the short- and long-term effects of a rehabilitation programme on lung function (forced expiratory volume in one second as percentage of predicted (FEV1 % pred)), on satisfaction with life (defined as quality of life), and on health satisfaction (HS)? 2) Are there physical or psychosocial predictors for the success of pulmonary therapy? In this prospective clinical study, baseline data (FEV1 % pred, arterial oxygen tension (Pa,O2), QOL, HS, dyspnoea, coping scales) were studied at entry (t1); follow-up on discharge (t2); and 1 yr after hospitalization (t3) in 54 consecutive patients (mean age 64 yrs) with chronic obstructive pulmonary disease (COPD). Complete data were obtained at follow-up on 32 subjects. FEV1 % pred improved from 42% (t1) to 52% (t2) (p<0.001) but dropped to 46% at t3 (t1-t3: p<0.05). QOL improved significantly during hospitalization but dropped to initial levels 1 yr after discharge. A significant increase in health satisfaction during hospitalization was maintained at follow-up. Improvements in lung function were greater in patients with higher QOL scores on entry; subjects with the greatest tendency to use wishful thinking as a coping strategy had less improvement. In conclusion, the effects of pulmonary rehabilitation on lung function and health satisfaction are positive and enduring. Quality of life and coping have an effect on the long-term outcome of pulmonary rehabilitation, probably as expressions of patients' personality traits.

Adaptation, Psychological↗
PubMed1997

Work-related low back injuries caused by unusual circumstances.

Expanding the knowledge of issues that surround work-related injuries allows for the development of more successful work accident prevention policies, treatment and rehabilitation protocols, and education programs. Specifically, clinical observation indicated that many patients did not perceive or report the circumstances of the injury as being part of their regular duties. The objective of this study was to investigate whether unusual activities or circumstances at work played any significant role in the rehabilitation of patients with disabling low back pain. Four hundred thirty-seven patients with severe disabling pain due to work-related injuries and surgery as an option for treatment were studied. The circumstances at the time of the accident were investigated, including demographic data, type of job held at the time of injury, rapport with supervisor, recent cutbacks in job force, and number of highly related injuries. Thirty-three percent of workers were injured while performing their ordinary job duties, with lifting implicated as the most common cause of injury (66%) followed by pushing/pulling (13%). In most patients (67%), the injury occurred under unusual circumstances or activities not normally described in the worker's job routine. This finding has not been previously addressed and implies that physical therapists can improve patient confidence about rehabilitation and returning to work by educating the patients about these circumstances.

Accidents, Occupational↗
PubMed1997

Normal and inhibited cholesterol synthesis in the cultured rat embryo.

The Smith-Lemli-Opitz syndrome-affected fetus presents a deficiency in delta7-dehydrocholesterol reductase, the last enzymatic step in the cholesterol biosynthesis pathway. Development of the abnormal human fetus takes place in a normal environment as the heterozygous mother's cholesterolemia remains normal. An animal model for this disease has been obtained from the offspring of pregnant rats treated with "distal" inhibitors of delta7-dehydrocholesterol reductase, AY-9944 or BM15766. In the animal model, embryonic development occurs in a disturbed environment characterized by hypocholesterolemia and accumulation of delta7-dehydrocholesterol and delta8-dehydrocholesterol in the maternal serum. The purpose of the present study was to assess, in cultured rat embryos at early developmental stages, the relative contributions of exogenous and de novo synthesized cholesterol in the total embryonic cholesterol, according to the conditions of normal and altered de novo biosynthesis. Cultured rat embryos are able to synthesize cholesterol as shown by 13C-incorporation into cholesterol from 13C-labeled precursors added to the culture medium. De novo cholesterol biosynthesis is altered by addition to the culture medium of AY-9944 which inhibits the delta7-dehydrocholesterol reductase and the delta8-delta7-sterol isomerase as suggested by the emergence of characteristic aberrant sterols in the embryonic tissues. Cholesterol-rich serum used for embryo culture alters the pattern in a way that confirms that the rat embryos are able to import exogenous cholesterol which down-regulates de novo cholesterol biosynthesis. Exogenous cholesterol substitutes for the deficit in a manner efficient enough to prevent the embryonic abnormalities induced by AY-9944.

Adaptation, Physiological↗
PubMed1997

[Cholesterol and development].

The teratogenic action of distal inhibitors of cholesterol synthesis has been known for some time. The induced malformations are of a particular type: they include holoprosencephalies. Recently these observations have solicited increased interest due to: 1/ the discovery in 1993 of a similar form of inhibition of cholesterol synthesis which is responsible for a human malformation syndrome, Smith-Lemli-Opitz; 2/ the demonstration of the involvement of the Sonic Hedgehog gene in normal development of prosencephalon and the description of the mode of action of the protein Shh: autoprocessing followed by "cholesterolisation".

Animals↗
PubMed1996

High levels of stromelysin-3 correlate with poor prognosis in patients with breast carcinoma.

Stromelysin 3 (ST3) is a matrix metalloprotease (MMP) expressed in fibroblast-like cells of most human invasive carcinomas. In this investigation, ST3 was measured by semiquantitative immunohistochemistry in 111 primary breast cancers. ST3 levels showed no correlation with tumor size, axillary-node status or tumor grade (Scarff-Bloom-Richardson system; SBR) but were significantly associated with higher nuclear grade (modified SBR). In addition, ST3 levels were significantly higher in ductal than in lobular cancers. Patients with high scores of ST3 staining had a shorter disease-free interval and shorter overall survival than patients with low scores. ST3 is thus one of the first MMPs to correlate with patient outcome in breast cancer. These findings are consistent with earlier clinical and experimental observations suggesting that ST3 contributes to breast-cancer progression.

Biomarkers, Tumor↗
PubMed1996

[Multiple chemical sensitivity (MCS)--the so-called chemical multiple hypersensitivity].

Multiple chemical sensitivity syndrome (MCS) is believed to be a multiple organ disease caused by low-level exposure to chemical substances. It is characterized by central-nervous, gastrointestinal and irritative mucocutaneous symptoms. This phenomenon is not recognized in traditional medicine, opponents of the theory of a separate disease attributing all symptoms to psychopathological processes. Since this phenomenon is becoming increasingly prevalent in Western countries, appropriate strategies for its study need to be developed.

Diagnosis, Differential↗
PubMed1996

Inhibition of 7-dehydrocholesterol reductase by the teratogen AY9944: a rat model for Smith-Lemli-Opitz syndrome.

Our aim is to verify the validity of a rat model proposed for Smith-Lemli-Opitz (SLO) syndrome, a developmental disorder characterized by a defect in 7-dehydrocholesterol-delta 7 (7DHC)-reductase and by facial dysmorphism close to the holoprosencephaly caused by the teratogen AY9944. We investigated the sterol profile in rats treated with AY9944 blocking 7DHC-reductase. AY9944 was given orally to rats on gestation day 3 (D3). The sera were sampled for kinetic data on D3, D6, D9, D12, and D21. Cholesterol was measured in parallel by the routine enzymatic method and by the gas chromatography/mass spectrometry (GC-MS) procedure used in SLO diagnosis. In addition to sterols, we dosed steroid hormones punctually on D4 and on D10, and examined D21 fetuses in other animals. The enzymatic method was not specific for cholesterol, and measured 70% pure 7DHC added to a normal serum. On D21, 77% live fetuses showed pituitary agenesis. Cholesterol was rapidly reduced by more than 50% on D6 involving an accumulation of 7DHC, 8DHC, and trienols, as identified in SLO-affected children. The most abundant 7DHC reached a maximum from D9 to D12, equaling cholesterol on D9 (11 mg/dl). On D10, the magnitudes of hypocholesterolemic and of 7DHC accumulation were found to be dose-dependent. Progesterone was reduced as early as 24 hr after treatment and dropped to 40% of the levels in the controls on D10, correlating to the decrease in cholesterolemia. This rat model reproduces the same biochemical perturbations as seen in SLO, strongly suggesting that aberrant sterols (7DHC, 8DHC, or nortrienol) may contribute to the developmental defects.

Animals↗