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The influence of live weight, live-weight change and diet on protein synthesis in the skin and skeletal muscle in young Merino sheep.

Wool growth is derived directly from protein synthesis in the skin of sheep, and is affected by the nutritional status of the animals. The present experiment examined both protein synthesis in the skin and muscle and wool growth in Merino lambs differing in live weight, intake and dietary protein source. The experiment was a 2(3) factorial design: twenty-four 5-month-old lambs initially weighing 33 kg (heavy) or 25 kg (light) were fed on a hay-based diet with either lupin seed or rapeseed meal as the major protein sources to maintain live weight (M) for 56 d, or were fed at 0.6 M for 28 d (period 1) followed by 28 d at 1.6 M (period 2). Fractional protein synthesis rates (FSR, % per d) in the skin and the m. longissimus dorsi on days 4 and 24 of period 1 and day 4 of period 2 were measured by means of a flooding dose of L-[ring-d5]phenylalanine, and wool growth on a skin patch over period 1 was also measured. The FSR ranged from 13.2 to 20.2% per d in the skin, higher than reported for other breeds, and 1.53-3.07% per d in the muscle. Sheep on the low intake (0.6 M) had significant reductions in FSR, protein content (g), protein synthesis (g/d) in the skin, and wool growth (g/d). The heavy lambs had similar FSR to the light lambs, but had a higher skin protein content and total protein synthesis per unit of skin area (100 cm2) and, therefore, grew more wool. The rapeseed-meal diet increased FSR and wool growth only in the light lambs over the short term. The protein deposited in wool over period 1 was 0.185 of the total protein synthesis in the skin, regardless of live weight, intake or diet, a result similar to other breeds. With the changes in dietary intake, protein synthesis in the skin and muscle responded differentially, with nutrient partitioning at sub-maintenance in favour of wool growth but at supra-maintenance, following a nutrient restriction, in favour of weight gain in young growing sheep.

Animal Nutritional Physiological Phenomena↗

Inhibition of DNA synthesis in dermal tissue of merino sheep treated with depilatory doses of mouse epidermal growth factor.

Two groups of three Merino wethers were infused intravenously with either 0.12 mg mouse epidermal growth factor (mEGF)/kg fleece-free body weight or 0.9% (w/v) NaCl over 24 h. Sheep treated with mEGF rejected food during treatment but feed intake was kept equal for both groups. Wool growth and plasma concentrations of mEGF were measured during the experiment. Pieces of skin taken from the wool-growing regions of the body were incubated with radioactive thymidine in order to measure its rate of incorporation into DNA. The skin was then divided at about the level of the sebaceous glands into sections that contained the upper dermis and epidermis (E sections) and those containing the generative wool-follicle bulbs (D sections). No mEGF was detected in the controls whereas mean levels of about 35 micrograms mEGF/1 plasma were detected during the last 4 h of infusion in the protein-treated group. After infusion, wool growth was reduced by about 20% of the mean pretreatment level in the controls and no shedding of wool fibre was evident. In the mEGF-treated sheep, on the other hand, wool growth was depressed by 75-95% of the mean pretreatment level and the fleeces were almost completely cast in all three of the animals, leaving them nude on the wool-growing regions of the body. Wool growth was restored to its pretreatment level in this group about 1 month after infusion. The D sections of skin contributed 50-60% of skin wet weight in controls throughout the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of breed and age on the voluntary intake and the micromineral status of non-pregnant sheep. II. Micromineral status.

Twenty-four non-pregnant sheep, divided into four groups of six animals each, were used to test breed (Suffolk and Rambouillet) and age (mature (six years old) and yearling (16 months old) ewes) differences in micromineral status. The animals grazed alternatively two mixed pastures containing Trifolium repens latum, Lolium perenne and Pennisetum clandestinum from 07:00 to 16:30hours, and remained penned overnight. Hand-plucked forage samples, blood and wool samples were collected on Days 1 (except forage), 7 (except wool), 21, 35, 49, and 63 of the experiment and assayed for Zn, Fe, Cu, Se, and Mo. Blood and wool data were analyzed as a completely randomized design in a factorial arrangement with repeated measurements. Zinc blood levels (2.15mgkg(-1), below normal values) showed a sampling timexbreed interaction (P<0.05) with a quadratic trend (P<0.02). Iron blood levels (337.48mgkg(-1)) showed a sampling timexage interaction (P<0.05), with mature ewes having higher and more variable levels than yearlings. A sampling time effect (P<0.01) with a quadratic trend (P<0.05) dependent on the breed (P<0.01) was found in Se blood levels. Rambouillet sheep had higher (86µgkg(-1)) initial levels than Suffolk sheep (61.14µgkg(-1)) and they declined linearly, whereas Se levels in Suffolks showed a quadratic trend. Copper blood concentration (below normal values) was higher (P<0.01) in Suffolks (0.46mgkg(-1)) than in Rambouillets (0.35mgkg(-1)). Suffolk sheep had higher Zn (P<0.01) and Cu (P<0.05; below normal values) levels in wool (146.63 and 2.16mgkg(-1), respectively) than Rambouillet sheep (141.34 and 1.72mgkg(-1), respectively). No effect was found in Fe wool levels (291.22mgkg(-1)), and Se concentration in wool (204.7µgkg(-1)) only showed a sampling time effect (P<0.05) with a decreasing linear trend (P<0.01). Coefficients of variations higher than 50% were found for Zn and Se in blood and Fe and Se in wool. Molybdenum could not be detected either in blood or in wool. Rambouillet sheep, in general, showed lower and less variable micromineral levels than Suffolk sheep. Because no signs of deficiency were observed nor was the animals' productivity affected after the study, it is considered that reported normal values for Zn and Cu could be more variable than suspected, depending on breed, location, feeding practices and physiological state.

Journal Article↗

Comparison of sperm preparation methods: effect on chromatin and morphology recovery rates and their consequences on the clinical outcome after in vitro fertilization embryo transfer.

The aim of this study was to evaluate the efficacy of swim-up, PureSperm gradient centrifugation and glass-wool filtration methods for semen preparation and to assess the possible enhancement of the quality of the subpopulation of spermatozoa in terms of sperm concentration, morphology and chromatin condensation. Moreover, to determine the effect of this semen processing technique on the clinical outcome after in vitro fertilization embryo transfer (IVF-ET). A total of 180 semen samples of patients' husbands who were undergoing IVF therapy were prepared by swim-up (G1, n = 60), PureSperm gradient centrifugation (G2, n=60) or glass-wool (G3, n=60) methods. Chromatin condensation was assessed by Chromomycin (CMA3), whereas sperm morphology was evaluated according to strict criteria. In all three semen processing methods, the percentage of chromatin condensed and morphologically normal spermatozoa was higher after semen processing in comparison with native semen samples. The proportion of normal chromatin condensed spermatozoa prepared in glass-wool filtration was significantly higher than that in swim-up (G.I, p=0.02) or PureSperm (G.II, p=0.001). In addition semen processing with PureSperm yields significantly a higher percentage of morphologically normal spermatozoa than swim-up (p < 0.001) or glass-wool method (p < 0.002). However, the fertilization, implantation and pregnancy rates, in turn were similar in all semen preparation methods. In conclusion, PureSperm gradient centrifugation yields a higher percentage of morphologically normal spermatozoa than shown in traditional swim-up or glass-wool filtration. However, the percentage of chromatin condensed spermatozoa was significantly higher after semen processing via glass-wool in comparison with the other two methods. Nevertheless, there were no significant difference in the fertilization, implantation and pregnancy rates of sperm prepared by means of swim-up, PureSperm or glass-wool filtration. Therefore, glass-wool filtration should be recommended as the first choice for semen preparation for Intracytoplasmic sperm injection (ICSI) technique as the natural selection is bypassed. Whereas, swim-up and PureSperm should be used for semen processing in IVF programme.

Chromatin↗

Transsulfuration, protein synthesis rate and follicle mRNA in the skin of young Merino lambs in response to infusions of methionine and serine.

Methionine (Met) is usually the first limiting amino acid for sheep and supplements of Met may increase production of wool and meat. The wool response may be due to an increased supply of cysteine (Cys) from transsulfuration (TS) of Met. Met is catabolized through homocysteine to form Cys when the S from Met is transferred to serine (Ser). We hypothesized that providing additional Met would create a deficiency of Ser and that by simultaneously providing Met and Ser, TS and wool growth could be increased more than by providing Met alone. The effects of i.v. infusions of Met and Ser to young Merino lambs on TS, fractional synthesis rate (FSR) of protein in skin, follicle mRNA and wool growth were examined. Following 4 d of constant i.v. infusion of 3 g Met/d, or 10 g Ser/d or both, the isotope tracers: L-[3-(13)C]Cys, L-[ring-d5]phenylalanine (Phe) and L-[2,3,3-d3]Ser were infused over 8 h to allow for measurements of irreversible loss rate (ILR), and TS in whole body and skin. Skin biopsies were taken for measurement of FSR. Wool growth rate was measured using autoradiography. An infusion of Met significantly (P < 0.05) improved wool growth rate and increased skin FSR, Cys supply from TS and enhanced levels of follicle mRNA (from the K2.10 intermediate filament gene and three gene families encoding keratin associated proteins KAP1, KAP4 and KAP12). The extra Met lowered Ser ILR. The infusion of Ser doubled Ser ILR in the body and increased skin FSR calculated using the Cys tracer in plasma (P < 0.05). However, there were no significant (P > 0.05) changes in TS, skin FSR calculated using the Phe and Ser tracers, follicle mRNA or wool growth rate as a result of Ser infusion. While there were trends towards increased TS and FSR with Ser infusion, the overall lack of significant changes indicates a high capacity for the de novo synthesis of Ser.

Animals↗

Experience from a long-term carcinogenicity study with intraperitoneal injection of biosoluble synthetic mineral fibers.

The carcinogenic potential in the intraperitoneal cavity of three newly developed biosoluble insulation glass wool fibers (M, P, and V) and one newly developed biosoluble insulation stone wool fiber (O) was investigated and compared to that of a previously developed soluble glass fiber (B). The in vitro dissolution coefficient of the three glass wool fibers ranged from 450 to 1037 ng/cm(2) x h and was 523 ng/cm(2) x h for the stone wool fiber. The in vitro dissolution coefficient of the B fiber was 580 ng/cm(2) x h. Groups of female Wistar rats (strain Crl: Wi BR) were exposed by repeated injections to doses of 0.5, 2, and 5 x 10(9) WHO fibers, which corresponds to between 41 mg to 724 mg fiber injected. In addition, 2 groups of crocidolite were used as positive controls at doses of 0.1 x 10(9) and 1 x 10(9) WHO fibers (0.5 and 5 mg). The in vitro dissolution coefficient of crocidolite is estimated to be approximately 1 ng/cm(2) x h. The protocol of the study and the size distribution of the test samples conformed to the European Commission Protocol EUR 18748 EN, and the study was executed under Good Laboratory Practice conditions. Two of the new insulation wools, fibers M and 0, showed no statistically significant tumorigenic response even at the very high dose of 5 x 10(9) WHO fibers injected. Fibers P and V showed a small tumorigenic response in the ip cavity similar in magnitude to the B fiber, which has been declared in the German fiber regulations as a noncarcinogenic fiber. The response to the soluble insulation fibers was notably different from that of the known carcinogen crocidolite, which produced 53% tumors at a comparatively low dose of 0.1 x 10(9) WHO fibers. The incidence of mesothelioma was found to be highly correlated to the incidence of intra-abdominal nodules and masses at different sites. The incidence of abdominal nodules and masses was highly correlated to the number of animals with ascites. The incidence of chronic peritonitis with fibrotic nodules at different organs also correlated with the incidence of mesotheliomas. Differences in etiology were observed between the massive doses of the highly soluble insulation wools when injected directly into the ip cavity and the lower doses of the extremely insoluble fiber crocidolite. The variability in this reaction and the impairment of animal health put into question the value of these massive doses in evaluating the carcinogenic response of soluble insulation wools. All of the fibers tested fulfilled the exoneration criteria with respect to carcinogenicity according to the European Directive 97/69/EC ("an appropriate intra-peritoneal test has not expressed signs of excessive carcinogenicity"). The dose as defined in the EC-Protocol EUR 18748 EN was 1 x 10(9) WHO fibers with a defined geometric spectrum. The influence of fiber dimensions on the ip tumor response and the difficulty in assessing the influence of the difference in background levels between this and previous studies make direct application of the German TRGS 905 criteria difficult; however, by comparison to fiber B, which in the TRGS 905 is considered as a noncarcinogenic fiber, all of the synthetic mineral fiber types tested in this study also appear to meet the intended German criteria for exoneration.

Abdominal Neoplasms↗

Brain HMPAO-SPECT and ocular microangiopathic syndrome in HIV-1-infected patients.

OBJECTIVE: The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome. METHODS: We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semi-quantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and, retinal cotton-wool spots were counted. CD4 count, neopterin, beta 2-microglobulin (beta 2M), haemoglobin, and age were determined as putative confounding variables. RESULTS: Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3 +/- 0.5 (mean +/- s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1 +/- 0.6 and mean cotton-wool spot count was 1.1 +/- 0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5 +/- 0.3 and mean cotton-wool spot count was 4.9 +/- 1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r = 0.72; P < 0.001) and number of cotton-wool spots (r = 0.78; P < 0.001), whereas only a slight association with staging of HIV disease was found (P = 0.052). Analysis of covariance controlling for CD4 count neopterin, beta 2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P < 0.001) and the conjunctival sludge rating (P < 0.001). CONCLUSION: There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system [corrected].

AIDS-Related Complex↗

Survival away from sheep and alternative methods of transmission of sheep lice (Bovicola ovis).

Transmission of sheep lice is thought to occur mainly by sheep to sheep contact although the possibility of other sources of infestation is often suggested. This study investigated the period of survival of Bovicola ovis after removal from sheep under varying conditions and assessed the likelihood of new infestations arising from contaminated facilities, wool caught on fences and shearers' footwear. In laboratory studies with lice held away from sheep at 4, 20, 25 and 36.5 degrees C, adults and nymphs survived longest at 25 degrees C (LT90 of 11.7 and 24.1 days for adults and large nymphs, respectively). Nymphs survived longer than adults and lice provided with raw wool survived longer than lice provided with wool that had been degreased. Nymphal lice survived for up to 29 days on unscoured wool at 36.5 degrees C, but the LT50 was less than 9 days in most experiments. In shearing sheds in winter and early spring lice survived for up to 14 and 16 days, respectively. These periods of survival are considerably longer than previously indicated for B. ovis. Most lice dropped out of wool staples attached to a fence within 1 h and only two of a total of 225 lice were still present after 24 h, suggesting that sheep are unlikely to become infested from wool caught on fences. Adult and nymphal lice readily transferred to shearers' moccasins and survived there for up to 10 days, indicating that transmission of lice on the footwear of shearers or other sheep handlers may be a cause of new infestations. Microwaving each moccasin for 5 min killed all lice and may provide a simple method of reducing the likelihood of transmission of B. ovis between properties.

Animal Husbandry↗

Subpopulations of multiparous rat lymph-node cells cytotoxic for rat tumour cells and capable of suppressing cytotoxicity in vitro.

Lymph-node cells (LNC) from multiparous pregnant rats were separated on columns prepared from nylon wool, and tested for cytotoxicity against target tumour cells. Reactivity of LNC towards hepatoma D23 and mammary carcinoma AAF57 was demonstrated in cell populations retained on the nylon wool, and not with cells eluted from the column. Although only 25% of the samples of unfractionated LNC were cytotoxic for tumour cells, retained cell fractions were cytotoxic in 11 out of 12 tests (p = less than 0.05). Similarly retained LNC were also cytotoxic for 15-day-old embryo cells but not for normal adult rat fibroblasts. Using multiparous rat serum it was shown that the reactivity of the retained LNC population could be abrogated in eight out of 11 tests (p = less than 0.05). The LNC population recovered from the nylon wool constituted 28 to 35% of the original LNC preparation, and consisted of 60-70% Ig-bearing cells together with a subpopulation of cells responding to soluble PHA. Separation of multiparous LNC on glass beads coated with rat Ig and then rabbit anti-rat Ig (in excess) also demonstrated the retained cell population to be cytotoxic against tumour cells. Approximately 17-20% of the original cell population was recovered from cells retained on the column, and consisted of an enriched Ig-bearing cell population (65-80% Ig-bearing cells) and LNC responsive to PHA. Carbonyl iron treatment of multiparous rat LNC was found to remove detectable cytotoxicity from multiparous rat LNC preparations. The cytotoxicity of multiparous rat LNC retained on nylon wool was also abolished following incubation with carbonyl iron. Definite conclusions as to the nature of the effector cell cannot be drawn from this test, since carbonyl iron treatment was found to remove not only phagocytic cells from LNC preparations but also a proportion of other cell populations including Ig-bearing lymphocytes... In addition to detecting a cytotoxic LNC population reactive towards tumour-associated embryonic antigens (retained fractions from nylon-wool column separation), a subpopulation of multiparous rat LNC was demonstrated in cell fractions eluted from the nylon wool which was shown to suppress the cytotoxicity of the retained multiparous LNC population. The exact nature of this subpopulation of LNC and the mechanism of action is at present not known.

Animals↗

Prognostic importance of retinopathy in acute leukemia.

This prospective study evaluates the relationship, between the fundus findings in leukemic retinopathy and the survival in patients with newly diagnosed acute leukemia. Fifty-four newly diagnosed consecutive patients with acute leukemia were included in this study. The patients were examined within few days of initial admission and diagnosis. Leukemic retinopathy was detected in 19 (35%) patients. The observation period ranged from 434 days to 1220 days (mean +/- SD 880 +/- 225) for those patients who survived. Despite similar chemotherapy compared to those without retinopathy (332.4 +/- 99.6 and 76 vs. 640.7 +/- 106 and 192 days respectively) although survival did not differ significantly (p = 0.073). Patients with cotton-wool spots had lower mean and median survival times than did those without such lesions (168.8 +/- 70.9 and 27 vs. 609.4 +/- 91.4 and 289 days respectively) and survival differed significantly (p = 0.04). The presence of cotton-wool spots and age > or = 40 years were the major adverse prognostic factors for survival in multivariate analysis. Cotton-wool spots had a more significant adverse prognostic effect than age > or = 40 years (hazard function coefficients: 1.0708 for cotton-wool spots vs 0.0355 for age > or = 40 years). The relative odds of dying among patients with cotton-wool spots were about 8 times higher than that for those without this feature, and about 7 times higher in patients aged > or = 40 years than that for patients aged < 20 years. Our findings suggest that the presence of leukemic retinopathy in general, and cotton-wool spots, in particular is a poor prognostic sign for survival in acute leukemia.

Adolescent↗

Autologous mixed lymphocyte reaction in human neonatal lymphocytes.

Human neonatal mononuclear cells were examined to determine their ability to participate in an autologous mixed lymphocyte reaction (AMLR). Stimulator cells were isolated by plastic adherence and nylon wool adherence. The nylon wool-nonadherent cells were used as responder cells. In 10 of 10 neonatal samples and 6 of 7 adult samples, a significant AMLR was present when plastic-adherent cells were used as stimulators. Neonatal blood showed a mean increase in proliferation of 7.6 (3.6-14.9), while adult cultures showed a mean stimulation index of 11.8 (1.0-39.0). When nylon wool-adherent cells were used as stimulator cells, only 2 of 7 neonatal blood samples and 1 of 5 adult blood samples showed a significant AMLR. When recombinant interleukin 2 (IL-2) was added to AMLR cultures of plastic-adherent cells and nylon wool-nonadherent cells, a mean augmentation of 12.0 was seen in the neonatal AMLR, while the adult cultures were augmented by a mean response of 4.1. Addition of IL-2 to nylon wool-nonadherent cells alone produced a 5.9-fold increase in adult cells, while neonatal cells showed an 85.8-fold mean increase in proliferation. The results suggest that autoreactive T cells are present in neonatal blood and that these cells can be activated by plastic-adherent autologous cells. However, neonatal and adult nylon wool-adherent cells do not consistently activate autoreactive T cells.

Female↗

A retrospective analysis of contact allergy to lanolin.

BACKGROUND: Lanolin is often stated to be an important sensitizer but some of the available literature is based on the analysis of high-risk patients. OBJECTIVES: To analyse the frequency of contact allergy to lanolin (wool alcohols) in a central London teaching hospital patch-test population. METHODS: Review of 24,449 patients recorded on our database during 1982--96 who were tested with a standard series containing 30% wool alcohols. RESULTS: The mean annual rate of sensitivity to this allergen was 1.7%. The wool alcohols-allergic group contained a higher proportion of females (P < 0.05), and the mean age of both males and females (48.4 and 49.2 years) was higher than that of non-wool alcohols-allergic patients (41.4 and 35.9 years; P < 0.0005). There was no difference in atopic eczema status between these groups. The highest prevalence of allergy to wool alcohols was among patients with lower leg dermatitis (6.0%; 95% confidence interval, CI 4.46--7.54), followed by those with anogenital dermatitis (3.23%; 95% CI 1.81--4.65). There was an unexplained decline in the rate of positive patch tests to Amerchol L-101. However, some patients who reacted to this were negative with wool alcohols, so it may be a useful additional test reagent. The mean rates of allergy to Eucerin (0.65% per annum) and 50% hydrogenated lanolin in petrolatum (1% per annum) were low, and we no longer use these as test reagents. CONCLUSIONS: This study illustrates that lanolin sensitization has remained at a relatively low and constant rate even in a high-risk population (i.e. patients with recent or active eczema).

Adolescent↗

A synthetic vitreous fiber (SVF) occupational exposure database: implementing the SVF Health and Safety Partnership Program.

The Health and Safety Partnership Program is a voluntary workplace safety program for workers involved in the manufacture, fabrication, installation, and removal of glass wool and mineral wool products. This article describes one element of this Partnership Program, the development of an occupational exposure database that characterizes exposures by fiber type, industry sector, product type, and job description. Approximately 6000 exposure samples are included in the database, most of which were collected over the past decade, making it the most extensive and recent exposure data set on record for glass wool and mineral wool. The development of this database, as well as the initial results for exposure measurements segmented by product type and/or job description, are described. The current database shows that most applications and uses of glass wool and mineral wool involve exposures below the voluntary 1 f/cc permissible exposure limit, although some specific product types and job descriptions involve average exposures approaching the 1 f/cc limit.

Databases, Factual↗

Cancer mortality among man-made vitreous fiber production workers.

We have updated the follow-up of cancer mortality for a cohort study of man-made vitreous fiber production workers from Denmark, Finland, Norway, Sweden, United Kingdom, Germany, and Italy, from 1982 to 1990. In the mortality analysis, 22,002 production workers contributed 489,551 person-years, during which there were 4,521 deaths. Workers with less than 1 year of employment had an increased mortality [standardized mortality ratio (SMR) = 1.45; 95% confidence interval (CI) = 1.37-1.53]. Workers with 1 year or more of employment, contributing 65% of person-years, had an SMR of 1.05 (95% CI = 1.02-1.09). The SMR for lung cancer was 1.34 (95% CI = 1.08-1.63, 97 deaths) among rock/slag wool workers and 1.27 (95% CI = 1.07-1.50, 140 deaths) among glass wool workers. In the latter group, no increase was present when local mortality rates were used. Among rock/slag wool workers, the risk of lung cancer increased with time-since-first-employment and duration of employment. The trend in lung cancer mortality according to technologic phase at first employment was less marked than in the previous follow-up. We obtained similar results from a Poisson regression analysis limited to rock/slag wool workers. Five deaths from pleural mesothelioma were reported, which may not represent an excess. There was no apparent excess for other categories of neoplasm. Tobacco smoking and other factors linked to social class, as well as exposures in other industries, appear unlikely to explain the whole increase in lung cancer mortality among rock/slag wool workers. Limited data on other agents do not indicate an important role of asbestos, slag, or bitumen. These results are not sufficient to conclude that the increased lung cancer risk is the result of exposure to rock/slag wool; however, insofar as respirable fibers were an important component of the ambient pollution of the working environment, they may have contributed to the increased risk.

Aged↗

Are fetal cells in maternal blood mainly B lymphocytes?

In 10 blood samples from mothers who were studied after the delivery of a male infant and who had Y-body-containing cells in their circulations (mean value, 0.06%) the proportions of surface-Ig- and Y-body-positive lymphocytes were determined after passage through nylon wool. In each case one part of the sample was treated with pronase before the nylon wool incubation and the other was not. Passage through nylon wool of maternal lymphocytes not treated with pronase resulted in a drastic decrease of fetal cells, since only 1 Y-body-containing cell was found in 1 of the 10 maternal blood samples studied, as compared with 28 Y bodies in the 10 samples not passed through nylon wool. In lymphocytes pretreated with pronase, 7 fetal cells were recovered after passage through nylon wool, although only in 5 of the 10 samples. Thus most fetal cells in maternal blood adhere to nylon wool, as do B lymphocytes, but this adherence is to some extent affected by pronase incubation.

B-Lymphocytes↗

Retinal complications and plasma C5a levels during interferon alpha therapy for chronic hepatitis C.

OBJECTIVE: The pathogenesis of retinal complications, such as retinal hemorrhage and cotton-wool spots formation, during interferon (IFN) therapy is unclear. We studied the relationship between the presence of retinal complications and levels of plasma-activated complement 5 (C5a), a known potent intravascular aggregator of granulocytes, during IFN-alpha therapy. METHODS: Forty-five patients with chronic hepatitis C but without diabetes mellitus and hypertension were studied. IFN-alpha was used 10 MU per day for 2 wk and 3 times weekly for an additional 22 wk. In 25 patients with IFN therapy, the optic fundi were examined before therapy began, every 4 wk thereafter, and whenever patients complained of visual symptoms. C5a levels were measured before, and during the 4th, 8th, 12th, and 24th wk, and at any time that a retinal complication was discovered. Twenty patients served as IFN-untreated controls. They had six optic fundi examinations, each 4 wk apart. C5a levels were measured three times, 4 wk apart, in 10 controls. RESULTS: No retinal hemorrhage or cotton-wool spots were detected before IFN-alpha therapy or in any of the controls. However, retinal hemorrhage occurred in six patients (24%) during IFN-alpha therapy. Five of six episodes occurred within the first 8 wk. Only three patients with retinal hemorrhage had visual symptoms. Cotton-wool spots developed in four patients with retinal hemorrhage. Retinal hemorrhage and cotton-wool spots resolved gradually despite continuous administration of IFN-alpha. Before IFN therapy and in controls, all C5a levels were <7 ng/ml. When retinal hemorrhage occurred, C5a was significantly increased (27.3+/-15.6 ng/ml,p < 0.01) relative to levels from the same patients before and after the hemorrhage (5.7+/-1.1 ng/ml), and also relative to levels in IFN-a-treated patients without retinal hemorrhage (5.7+/-1.1 ng/ml) and compared with levels in IFN-untreated controls (5.4+/-0.7 ng/ml). CONCLUSIONS: Retinal hemorrhage or cotton-wool spots often occur during IFN-alpha therapy for chronic hepatitis C. This study suggests that a high C5a level may be an important step in the pathogenesis of retinal capillary infarction, hemorrhage, and cotton-wool spots formation.

Adult↗

Hydrogen peroxide release and hydroxyl radical formation in mixtures containing mineral fibres and human neutrophils.

The ability of different mineral fibres (rock wool, glass wool, ceramic fibres, chrysotile A, chrysotile B, amosite, crocidolite, antophyllite, erionite, and wollastonite) to stimulate hydrogen peroxide (H2O2) and hydroxyl radical (OH.) formation in mixtures containing human polymorphonuclear leucocytes (PMNLs) was investigated. In the presence of azide, all the fibres caused considerable H2O2 formation, and about twice as much H2O2 was found in mixtures with the natural fibres (asbestos, erionite, and wollastonite) than in mixtures with the manmade fibres (rock wool, glass wool, and ceramic fibres). In the presence of externally added iron, all the fibres were found to generate OH. and the natural fibres caused about three times more OH. formation than the manmade fibres. In the absence of external iron, there was less OH. formation; however, amosite, crocidolite, antophyllite, erionite, and wollastonite still generated considerable amounts of OH., also under circumstances in which only small amounts of OH. were produced in mixtures with the manmade fibres. These findings indicate that natural fibres generate more H2O2 and OH. than manmade fibres when incubated with PMNLs in the presence of external iron. They also suggest that the natural fibres, amosite, crocidolite, antophyllite, erionite, and wollastonite may act catalytically in the dissociation of H2O2 to OH. in the absence of external iron, whereas manmade fibres such as rock wool, glass wool, and ceramic fibres, do not seem to be able to generate OH. in the absence of external iron.

Asbestos↗

Studies of cell subpopulations mediating mitogen hyporesponsiveness in patients with Hodgkin's disease.

Hodgkin's disease (HD) is associated with a deficit in T-cell immunity characterized by skin test anergy and decreased lymphocyte responses to phytohemagglutinin (PHA). To investigate this mitogen hyporesponsiveness in HD, we separated peripheral blood mononuclear cells on Ficoll-Hypaque gradients and determined their response to various suboptimal concentrations of PHA. As was expected, patients with HD demonstrated marked mitogen hyporesponsiveness relative to normal controls; however, if the cell suspensions were first passed through glass wool columns to remove adherent cells, the PHA responsiveness of the hyporesponsive HD cells was markedly increased. In contrast, the responsiveness of normal controls was decreased so that the responses of nonadherent normal and HD cells were statistically indistinguishable. Evidently, a glass wool-adherent suppressor cell had been removed from patients with HD, while a glass wool-adherent cell which enhanced mitogenic responses had been removed from normal controls during column passage. Previous to column depletion, patients with HD had decreased proportions of E-rosettes and increased proportions of cells with surface alpha-fetoprotein; however, the proportion of these cells was not changed after column passage. Significant changes with column depletion of glass wool-adherent cells in HD were recorded in the proportions of monocytes (13.2 vs 5.8%) and lymphocytes with C-3 receptors (12.6 vs. 7.8%). The only significant change in normal controls was a decrease in the proportion of monocytes (10 vs. 1.7%). To determine if glass-adherent cells would have a suppressor effect, HD-adherent cells were added in progressively increasing numbers to mononuclear cell suspensions depleted of glass wool-adherent cells. PHA responsiveness returned toward predepletion levels. In summary, patients with HD possess a glass wool-adherent suppressor cell which is responsible at least in part for in vitro mitogen hyporesponsiveness.

Hodgkin Disease↗