Exposure to formaldehyde and cancer mortality in a cohort of workers producing resins

The mortality of 1,332 male workers employed at least 30 days in 1959-1980 in a resins-manufacturing plant was examined. Ambient measurements taken in the plant between 1974 and 1979 documented a potential for exposure to levels of formaldehyde as high as greater than 3.0 mg/m3. Vital status was ascertained for 98.6% of the cohort members, and their mortality was compared with expected deaths drawn from the national and local population rates. A statistically significant increase in lung cancer was observed, based on 18 deaths, which was not fully accounted for by possible confounding factors linked to personal habits or sociocultural characteristics. This elevated risk, however, could not be attributed specifically to exposure to formaldehyde. Mortality from digestive cancer (14 deaths observed) and hematologic neoplasms (5 deaths observed) was not substantially higher than expected. The study was limited by information bias due to incomplete work histories, by the small number of deaths from some relevant causes, and by the possibly insufficient length of the observation period. Therefore these results do not provide sufficient grounds either to link formaldehyde exposure in the plant to the increased cancer risk noted or to exclude that formaldehyde might pose such a risk to humans under certain exposure circumstances.     

Calcitonin gene-related peptide: functional role in cerebrovascular regulation.

Distribution studies disclosed that all major cerebral arteries and cortical arterioles of the cat were invested with fine varicose nerve fibers that contained calcitonin gene-related peptide (CGRP)-like immunoreactivity; the trigeminal ganglia likewise contained CGRP immunoreactivity. Sequential immunostaining with antibodies to CGRP and to substance P (SP) revealed identical distributions of these two peptides in trigeminal ganglia and cerebrovascular nerve fibers, suggesting that CGRP and SP are colocalized in these nerves. CGRP completely disappeared from ipsilateral blood vessels after unilateral section of the trigeminal nerve. Exogenous CGRP was a potent relaxant of feline middle cerebral arteries in vitro (maximum relaxation, 10.5 +/- 1.5 mN; concentration eliciting half-maximal response, 9.6 +/- 1.3 nM). Perivascular microapplication of CGRP to individual cortical arterioles of chloralose-anesthetized cats provoked dose-dependent dilatations (maximum increase in diameter, 38 +/- 5%; concentration eliciting half-maximal response, approximately equal to 3 nM). CGRP was significantly more potent than SP as a cerebrovascular dilator, both in vitro and in situ. Chronic division of the ipsilateral trigeminal nerve in cats did not modify the magnitude of arteriolar responses to perivascular microapplication of either vasoconstrictor or vasodilator agents, but the duration of vasoconstrictor responses to norepinephrine (0.1 mM) or alkaline solutions (pH 7.6) was significantly increased. The cerebrovascular trigeminal neuronal system, in which CGRP is the most potent vasoactive constituent, may participate in a reflex or local response to excessive cerebral vasoconstriction that restores normal vascular diameter.     

Localization of phospholipids in human catecholamine neurons with Baker''s acid haematein

Summary Protein bodies in catecholamine neurons of the normal human brain contain arginine-rich proteins similar to those present in the core of Lewy bodies in Parkinsonian brains. Lewy bodies are known also to contain phospholipids in their core, demonstrable with Baker's acid haematein. We used Baker's procedure on catecholamine neurons of normal brains to test whether the protein bodies also contain phospholipids. Postmortem tissues of three control individuals were used in this study. Locus coeruleus and substantia nigra were dissected out from the fresh brains and two sets of blocks were made from each area. One set was fixed in formol-calcium for the preservation of lipids, the second was fixed in Bouin's solution and treated with hot pyridine for the extraction of lipids. Finally, both sets were subjected to the same chroming and staining procedure according to Baker. In catecholamine neurons the protein bodies were stained with acid haematein, indicating the presence of phospholipids. Since this staining resisted pyridine extraction we conclude that these phospholipids are firmly bound to the basic proteins. Thus, protein bodies in healthy catecholamine neurons give the same positive reaction for phospholipids as that reported for the core of Lewy bodies in damaged neurons in Parkinsonism.     

Effect of dextran on the stability of isolated, perfused rat heart

Stability of cardiac function and myocardial intracellular ionic composition was examined in the Krebs-perfused isolated rat working heart. Hearts perfused by a conventional Krebs solution showed stable contraction for 2 h, but during this period, intracellular ionic environment (Na, K, Ca) substantially changed. Addition of dextran to the perfusate inhibited, though not completely, this time-dependent deterioration and made the heart less vulnerable to the hypoxia-reoxygenation.     

A preliminary study of radioimmunoimaging by 131I-COC183B2 monoclonal antibody in patients with epithelial ovarian cancer.

Monoclonal antibody 131I-COC183B2, developed in our laboratory and proved to fit for human treatment was injected intraperitoneally or subcutaneously in 13 patients. In 8 cases with i.p. injection the disease corresponded with the image, i.e. 3 primary ovarian epithelial cancers showed positive images, 1 ovarian Krukenberg tumor was negative and the other 4 negative images included 1 uterine myoma and 3 ovarian teratomas. In the subcutaneous injection group, 4 cases had ovarian carcinoma, surgery and chemotherapy. Two negative images corresponded with the clinical status-in good health, another negative case had metastatic left supraclavicular lymph node due to ovarian mucinous adenocarcinoma. The last negative image in this group was a case of benign ovarian teratoma which was proved after surgery. The 1 positive case was waiting to be proved by a scheduled third operation. The computer scintigram calculation of T/NT was 5.35 to 13.7. The results suggest that this monoclonal antibody can be used for radioimmunoimaging for the localization of ovarian carcinoma, which is not only helpful for clinical staging and differential diagnosis but is also a good follow-up method.

     

Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin-induced extracorporeal LDL precipitation (HELP)

Heparin-induced Extracorporeal LDL-Precipitation (HELP) is an effective procedure for the elimination of both plasma LDL and fibrinogen. In 10 adult patients with severe type II hyperlipoproteinemia, a single HELP treatment of 3 1 plasma led to an acute decrease in the average plasma viscosity (PV) from 1.30 to 1.1 mPas. At the same time, an even more marked decrease in the mean erythrocyte aggregation rate from a pathological value of 7.9% to a value of 3.7% (normal range less than 5%) was observed. Long-term studies on five patients demonstrated a lasting improvement in these two haemorheological variables. The acute rheological changes were also accompanied by an improvement in polarographically determined muscle oxygen tension. Mean oxygen tension values measured in both the m.biceps brachii and the m.tibialis anterior in five patients before and after a single HELP treatment increased from 30 +/- 4 to 37 +/- 7 mmHg and from 27 +/- 2 to 31 +/- 3 mmHg respectively. These results may provide an explanation for the rapid improvement in patients' clinical symptoms such as angina pectoris and in stress electrocardiogram which have been observed during HELP therapy.     

Isolation and characterization of a distinct immunoregulatory isoform of alpha-fetoprotein produced by the normal fetus

In this report, we examine the functional significance of the molecular microheterogeneity of alpha-fetoprotein (AFP). In doing so, we have taken the direct approach of purifying the naturally occurring isomeric forms of fetal-derived AFP using a preparative anion exchange column linked to an automated fast protein liquid chromatography (FPLC) system followed by parallel testing of each isolated molecular variant for in vitro immunoregulatory activity. The data obtained demonstrate the presence of seven distinct variants of AFP as defined by their retention volumes on FPLC elution profiles, by their pIs on analytical IEF gels, and by Western blot analysis. Molecular mass determination by SDS-PAGE showed each isomer to be equivalent in size to 69,000-dalton native unfractionated AFP molecules. All the immunosuppressive activity of AFP was localized to a single variant representing only 6% of the total composition of native AFP. The immunoregulating isomer termed AFP-1 was the least acidic of the seven isolated variants with a pI of 5.1 and displayed a sialic acid content of 1 mol/mol of protein. The inhibitory activity of AFP-1 could be readily measured on T cell-dependent antibody synthesis, Con A-induced stimulation of Lyt-1+23- thymocyte DNA synthesis, and lymphokine-activated NK cell activity. All other isomers were without effect in these test systems. The immunosuppressive AFP-1 isomer also displayed the strongest growth-promoting influence on cultured bone marrow lymphocytes. There was no correlation between functional activity and degree of expression of sialic acid residues on the AFP molecules. These findings demonstrate that the immunoregulating function of AFP is confined to a distinct and relatively small subpopulation of native AFP molecules and should therefore contribute to the resolution of outstanding questions regarding the structure/function relationship of this onco-fetal glycoprotein.     

Study of peripheral blood thrombocytes in smokers

Total circulating platelet count and thrombocytogram were examined in 60 tobacco smokers and in 30 nonsmoking normal subjects aged 23-32. The smokers were divided into two subgroups, 30 subjects in each: Group 1 included those with a history of smoking under 5 years and Group 2 those smoking for 5 years and Group 2 those smoking for 6-10 years. The platelet count was found increased in Group 1 smokers at the expense of old, atypical, and involutional forms. In Group 2 smokers the total platelet count and the counts of their differentiation forms were reduced. This evidences the effect of tobacco smoking on circulating platelets, this effect depending on the length of tobacco smoke inhalation.