Water-Quality Trends in the Nation's Rivers.

Water-quality records from two nationwide sampling networks now permit nationally consistent analysis of long-term water-quality trends at more than 300 locations on major U.S. rivers. Observed trends in 24 measures of water quality for the period from 1974 to 1981 provide new insight into changes in stream quality that occurred during a time of major changes in both terrestrial and atmospheric influences on surface waters. Particularly noteworthy are widespread decreases in fecal bacteria and lead concentrations and widespread increases in nitrate, chloride, arsenic, and cadmium concentrations. Recorded increases in municipal waste treatment, use of salt on highways, and nitrogen fertilizer application, along with decreases in leaded gasoline consumption and regionally variable trends in coal production and combustion during the period appear to be reflected in water-quality changes.

Direct antitumor effect of high-molecular-weight levan on Lewis lung carcinoma cells in mice.

The polysaccharide levan exerted a direct effect on Lewis lung carcinoma cells in vitro. Tumor cells incubated with levan showed a pronounced decrease in oncogenic properties when inoculated sc in the syngeneic hosts (C57BL mice), although the viability of cells as determined by the trypan blue exclusion test was not diminished. The effect of pretreatment of inoculated mice with levan. Radiolabel incorporation into DNA, RNA, and protein was not affected in cells incubated with levan, but transport properties were selectively altered: Thymidine, uridine, and leucine transport was enhanced, whereas deoxyglucose transport was unchanged. The results indicated that levan exerted a direct antitumor effect on Lewis lung carcinoma cells in vitro.

Effects of route and schedule of administration of high-molecular levan on the growth of AKR lymphoma.

The route and schedule of treatment with high-molecular levan markedly influences its inhibitory effect on the growth of transplanted AKR lymphoma. Injections of levan into the site of the primary tumor were more effective in inhibiting tumor growth and preventing tumor-associated weight loss and mortality than were i.p. injections. Local levan injections inhibited metastatic spread only in mice treated from Days 0 and 2. Levan i.p. was more effective in inhibiting metastases in animals started on treatment 7 to 13 days after tumor inoculation than in animals in which levanization was started earlier. Local injection of levan before inoculation of tumor enhanced tumor growth and shortened life-span in comparison to nonlevanized animals. In mice treated with levan for a short period only, the inhibitory effect on tumor growth slowly vanished within 2 weeks. Some animals treated for 5 to 8 months remained completely free of tumor. The results indicate that the effect of levan on tumor development is mainly topical and depends on the concentration of the polysaccharide in the site. The tumor growth period from 0 to 5 days appears to differ from the following period in the reaction to levan treatment. The nature of this difference is not clear, but possible explanations are discussed.

Effects of high-molecular levan on the growth and spread of lymphoma in AKR mice.

Levan was shown to inhibit lymphoma development in AKR mice. Growth of tumor was inhibited at the site of injection and in metastases. Levan caused a decrease in the incidence of tumors, and it reduced pleomorphism, mitoses, and invasiveness of tumors in comparison to nonlevanized mice. Evidence of tumor cell destruction was observed in levanized mice. The effect of levan on tumor development was dose dependent.

Effects of chlorocyclizine on pulmonary lipid metabolism in rats.

Pulmonary lipidosis was induced in rats by including 0.36 and 0.54% chlorocyclizine in their diet. Chemical analyses of the lung tissue revealed a very marked increase in phosphatidylcholine concentration. Phosphatidylglycerol and phosphatidylinositol concentrations were also markedly increased. An increase in the phosphatidylcholine content was also observed in lavage fluid and macrophages. Microscopic examination of the cell fraction showed that almost all the cells of the lavage fluid were macrophages and that histochemically demonstrable acid esterase activity was mostly inversely related to storage of lipids in the cells. Sonication of macrophages isolated from normal or chlorocyclizine-treated rats yielded a soluble acid phospholipase (pH optimum, 4.0) and a neutral (pH optimum, 8.2) membrane-bound, CaCl2-dependent enzyme. An inhibitory effect of chlorocyclizine in vitro on the activity of the soluble phospholipase was shown.

A histochemical principle bearing on correctness of diagnosis in storage diseases.

A principle is proposed which may help pathologists avoid errors in diagnosis of storage diseases. Tissues from patients in whom a tentative diagnosis of a metabolic disorder has been made often store a number of metabolites in the cells. The presence of these metabolites can occur in single-enzyme or activator defects as a result of the following causes: (a) deposition of metabolites situated near the main substrate of the defective enzyme in the catabolic path, and compounds which were changed after they were deposited; (b) presence of multiple substrates for this enzyme; (c) co-deposition of molecules bound to the main substrates; (d) existence of multiple substrates for a single defective activator molecule. In contrast to these causes, variability in processes not associated with a single-enzyme or activator deficiency may be due to the following: (e) inhibition of multiple hydrolases by drugs or metabolites; (f) localization of substrates and hydrolases in different compartments; (g) multiple enzyme deficiencies; (h) concentration of metabolites beyond the catabolic capacity of cells. According to the proposed principle, diagnosis of storage disease resulting from a single enzyme deficiency can be negated if a wide-range histochemical test shows that the main substrate of a deficient enzyme is not present in some primary storage cells. The validity of the principle and possible pitfalls are discussed.

Histochemical study of the blue autofluorescence of collagen in oral irritation fibroma: effects of age of patients and of the duration of lesions.

The intensity of the autofluorescence of collagen was measured in 27 irritation fibromata of the buccal mucosa and 13 of the lip. The intensity of fluorescence correlated positively with the duration of the lesion. The fluorescence intensity also increased with the patients' age. The present observations show that in irritation fibromata of buccal and lip mucosae, the intensity of blue autofluorescence of the collagen increases with duration of the lesions and with the age of patients.

Encephalopathy with astrocytic residual bodies. Report of a case and review of the literature.

Biopsy and autopsy findings in a girl who died at 7 1/2 months after having suffered from progressive axial hypotonia, myoclonus, EEG changes and retarded psychomotor development. Inclusions consisting of lamellar profiles, situated in membrane-bound cytosomes were found mainly in astrocytes, but also in neurones and in axons of peripheral nerves. Lipofuscin bodies were also increased in number. The patient belongs in the same category as cases studied by Towfighi et al. (1975) and Martin et al. (1977). Etiology and pathogenesis of this syndrome remain unknown. It is suggested, however, that the pathological changes observed might have been caused by the administration soon after birth of anti-epileptic drugs (diphenylhydantoin, clonazepam and nitrazepam).

Pathological changes in organs of rats chronically exposed to hypoxia. Development of pulmonary lipidosis.

Rats were exposed to chronic normobaric hypoxia of progressively increasing severity; down to 8% or 7% oxygen concentrations. In addition to loss of weight, pathology revealed congestion, haemorrhages, hypertrophy of the heart involving mainly the right ventricle, thickening of arteries, ischaemic changes in the myocardium and extramedullary haematopoiesis in the spleen. Changes not described up until now were: 1) sheets of foam cells in the pulmonary alveoli; 2) foamy and solid storing cells in the spleen; 3) mucoid changes in the atrioventricular valve leaflets; 4) hyperplasia of the juxtaglomerular apparatus; 5) atrophy of the adrenal glomerulosa and hyperplasia of medulla; 6) atrophy of the perifollicular B-cell zone in the spleen; and 7) lipid pigment deposition in various organs. The findings indicate that severe chronic hypoxia induces a significant pulmonary lipidosis similar to that caused by amphiphilic cationic drugs, presumably by inhibiting hydrolytic enzyme activities. The observations are of importance in human hypoxic conditions and open the possibility of their rational treatment.

Development and verification of a schistosomiasis transmission model.

Development of a model to predict the impact of water resource projects on transmission of schistosomiasis is described and verified with data from 54 villages in Khuzestan Province, Iran. Changes in disease prevalence following construction of an irrigation project are related to the linear extent of snail habitats and size of the infected human population. The model is used to compare the costs and effectiveness of alternative disease control measures. Results indicate that a combined controls program is most cost-effective but further work is needed to determine the optimal combination of controls.

Workplace contact investigations in the United States.

SETTING: Five state tuberculosis (TB) control programs in the United States. OBJECTIVES: To determine the prevalence of and treatment for latent TB infection (LTBI) among contacts of active TB cases identified in the workplace, and to describe TB control program policies for the initiation and conduct of workplace investigations. DESIGN: Retrospective review of health department records for all culture-positive pulmonary tuberculosis cases aged > or = 15 years reported in 1996, and their contacts. RESULTS: There were 349 cases of active TB, of whom 134 (38%) were employed. Workplace contact investigations were conducted for 42 cases, resulting in the identification of 724 contacts. The rate of LTBI was 29% overall, varying by worksite from a low of 16% to a high of 51%. LTBI estimates were higher for fully-screened contacts of smear-positive rather than of smear-negative index cases. However, fully-screened contacts of index patients with cavitary disease had lower LTBI estimates than those of index patients without cavitation. Treatment for LTBI was initiated in 45% of infected contacts. The five programs had somewhat variable policies regarding workplace contact investigations. Data on HIV co-infection and place of birth of contacts were largely missing. CONCLUSION: Factors contributing to LTBI among workplace contacts may include the presence of persons with pre-existing LTBI or a positive skin test as a result of BCG vaccination, clinical characteristics of the index case, and workplace environmental characteristics conducive to transmission. Standard guidelines for workplace investigations, written workplace investigation policies, and standard data collection practices are needed to better apportion the causes of observed infection rates in the workplace.

Mechanism of the inhibitory effect of levan on experimental tumors.

The mechanism of the antitumoral effect of levan was studied in the C57BL mice-Lewis lung carcinoma system. Modulation of host immune response and a direct inhibitory effect on tumor cells were found. Local treatment was more effective when begun early. It reduced tumor incidence without affecting the size of developing tumors. Systemic treatment was more effective when started late, inhibiting equally the tumor size in all mice. Macrophages are involved in local, lymphocytes possibly in systemic, inhibition. A direct effect on tumor cells was suggested by a decrease in oncogenicity, following preincubation with levan. Levan augments the antitumoral effect of cyclophosphamide in vivo and in vitro.

Animal models for tumor progression (short review).

During recent years the number of studies concerning tumor progression has increased considerably, with the important breakthrough in the study of neoplastic development being the selection of variants of malignancy. Some of the models used for the selection of these variants and the assays for malignancy by which they are tested are, however, quite remote from the natural process of tumor progression. Various models are herein discussed with their advantages and drawbacks evaluated. The validity of the models for the testing of antitumoral drugs at various stages of tumor progression are also discussed.

Opposite effects on tumor growth depending on dose of an immunomodulatory polysaccharide with or without cyclophosphamide.

Opposite effects on the growth of the F10 variant of B16 melanoma--inhibitory and stimulatory--were found with varying doses of the polysaccharide levan. Low (0.1 and 1 mg) daily doses inhibited, while high (5 and 10 mg) doses enhanced tumor growth. In combined cyclophosphamide-levan treatment, these opposite effects were more pronounced.

The tissue reaction to implanted foreign bodies in levan-treated mice.

The effect of local administration of levan on the reaction to foreign bodies was studied in the subcutaneous tissues of mice implanted with sterile cotton wool pellets or Melenex plastic coverslips. Treatment with levan reduced leucocytic invasion of the implanted pellets as well as the vasoproliferative response of the surrounding tissue. Reduction in the thickness of the capsule surrounding the implant in levan-treated mice provided further evidence for the latter. Assessment of cells attached onto implanted coverslips showed that levan treatment diminished the number of macrophages attaching to the plastic and significantly reduced the number of nuclei within the multinucleate giant cells formed at the site of implantation. This reduction indicates that levan also exerts an inhibitory action on fusion between macrophages.

Can pseudomonas infection in experimental animals mimic Kawasaki's disease?

Experiments aimed at producing a model of Kawasaki's disease by injecting animals intraperitoneally with Pseudomonas bacilli are described. Injection of large numbers of bacilli into mice caused rapidly fatal sepsis. With appropriate numbers of organisms, some mice died within 3 days, most remained healthy, while in some an inapparent chronic disease developed. Positive blood cultures were occasionally obtained 4-17 weeks after the slow infection. An alcohol-precipitable polysaccharide, which could be measured by Roe's procedure for levan, was found in 20% of the experimentally infected mice. We suggest that this substance was partly responsible for the course of the infection. Severe vasculitis with little acute inflammatory reaction and carditis with coronary aneurysms were often obtained by injecting mice and guinea-pigs with supraliminal doses of bacilli at the same time as their immune system was impaired by treatment with either nitrogen-mustard or cyclophosphamide. We suggest that pseudomonas infection in immunologically deficient animals may mimic Kawasaki's disease and that a similar mechanism may operate in the natural form of the disease in children.

Lipid pigments and aging.

It is a short survey of lipid pigment formation in which the role of free radicals in the peroxidation of lipids is particularly stressed. The chemical structure of lipopigments and the role of the chemical moiety in histochemical reactions is shortly overviewed. A new aspect of age in the formation of lipopigments is brought to light. Finally the role of hypoxaemia and no-reflow phenomenon influencing the pigment formation is discussed.