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The in vivo and in vitro susceptibility of Plasmodium falciparum to chloroquine was investigated in northern Liberia after 20 years of continuous chemosuppression and therapy with 4-aminoquinolines. In all patients studied (n = 53) parasitaemias were cleared within four days. There were no recrudescences in 16 patients followed-up for 28 days. All isolates of P. falciparum tested in vitro (n = 26) showed sensitive patterns. Schizont maturation was inhibited by a chloroquine concentration of between 0.25 and 0.75 mumol-1. In this area of Liberia no resistance to chloroquine was found in spite of extensive use of 4-aminoquinolines. This may support the view that importation of at least partially resistant strains, rather than local mutation of P. falciparum, precedes selection of resistant strains. Hence, we conclude that regular intake of chloroquine by groups at risk is justified if it is combined with regular monitoring of drug susceptibility.

Haemoglobin components in 21 Liberians with Hb S beta +-thalassaemia and four with Hb C beta +-thalassaemia were measured to classify the forms of beta +-thalassaemia present in the population. In 20 Hb S and all Hb C beta +-thalassaemics the data were consistent with the interaction of these variants with the mild type 2 (Negro) form of beta +-thalassaemia. The data available were insufficient to classify the remaining case, a young child. It was concluded that the clinically more severe type of beta +-thalassaemia giving Hb A levels of 5 to 15% in compound heterozygotes is probably uncommon in Liberia.

Serum protein variations were studied in a Liberian population living in Buchanan town. Of the alpha 1-antitrypsin genes only M1 and M3 were polymorphic. The frequencies of the haptoglobin and Gc genes were in accordance with earlier known estimates in African populations. There was, however, a relatively low frequency of Hp 0 which may be related to the low malarial parasite prevalence in this group. The transferrin C2 gene was found in a significantly lower frequency among Liberians compared to European and Asiatic populations. A new transferrin variant was observed by isoelectric focusing. This variant could not be identified with conventional starch or polyacrylamide electrophoresis.

Precipitins in nine sera from normal Liberian adults were shown to react with an alpha-globulin in goat and sheep sera. No cross-reaction was demonstrated with bovine sera. Hence these precipitins are different to others previously described. At present their significance, if any, is unknown. They are important as a possible cause of unexplained reactions in serological tests using sheep or goat serum as a source of antigen or antibody.

The influence of malaria on HbA2 levels was investigated in two groups of children aged two to nine years from the Mano tribe of northern Liberia. One group, 174 children living in a town where there is malaria control, had a parasite rate of 6.5%, only a few having palpable spleens, but 282 children living in an area of intense malaria transmission had a parasite rate of 92%. All but one child in this group had enlarged spleens. However, the difference in proportions of elevated HbA2 values within the limits for beta-thalassaemia, 8% and 10.3% respectively, was not statistically significant (0.5 greater than P greater than 0.1). It was concluded that the influence of malaria on HbA2 levels is not significant and that this parameter is valid for detecting beta-thalassaemia trait in this population. Further, iron deficiency may be a more important factor than malaria to consider when assessing the results of HbA2 estimations.

Streptococcus sanguis I gave a significantly greater percentage coverage (cell-pellicle attachment) of saliva-coated glass in the presence of sucrose than did Strep. sanguis II (p less than 0.025), and both these gave greater percentage coverages than the other species tested, between which no significant differences were noted. There was a large number of significant differences in clump size (cell-cell attachment) between species-pairs. Among the mutans streptococci, there were significant differences in the percentage coverage between Streptococcus rattus/Streptococcus mutans (p less than 0.05) and Strep. rattus/Streptococcus sobrinus (p less than 0.01), and in clump size between all species-pairs with the exception of Streptococcus cricetus or Strep. sobrinus and Strep. mutans. The rank order of species in relation to fissure caries was mutans streptococci greater than Streptococcus salivarius greater than Streptococcus milleri greater than Strep. sanguis greater than Streptococcus faecalis greater than Streptococcus mitis greater than Streptococcus lactis. There was a significant correlation between percentage coverage in vitro and fissure caries in vivo for strains of Strep. sanguis (p less than 0.05) and pooled strains of Strep. mitis and Strep. sanguis (p less than 0.01). On comparing data for adherence in the presence or the absence of sucrose, the sugar had no effect on the percentage coverage of the seven species tested, but significantly increased the clump size of the mutans streptococci (p less than 0.01) and Strep. sanguis (p less than 0.05).

Streptococcus sanguis 12 and a naturally occurring mutant, 12 na, were screened for their ultrastructure and adhesive properties in vitro. Negative staining showed that Strep. sanguis 12 carried three types of surface structure. The majority of cells carried long fibrils that in different batches ranged in length from 80 to 207 nm, and shorter fibrils which were 51.0 +/- 15.7 nm long. Both types of fibrils were primarily located at the poles of the cells. Occasionally cells were seen that carried fimbriae, which are structurally distinct from fibrils, and were 3-4 nm wide and less than 1.0 micron long. Strain 12 na carried no detectable surface structures. Ruthenium red staining revealed that both strains carried a loose, amorphous, extracellular polysaccharide layer attached to the cell wall. Streptococcus sanguis 12 na was 83% less adhesive than strain 12 in a saliva-coated hydroxyapatite assay, and 50% less adhesive in a buccal epithelial cell adhesion assay. In contrast, strain 12 na was more sensitive to aggregation by parotid saliva than strain 12, and both strains were equally aggregated by whole saliva. The cell surface hydrophobicity of the two strains was similar. Extraction of surface proteins by sodium lauroyl-sarcosinate followed by sodium dodecylsulphate polyacrylamide gel electrophoresis demonstrated that Strep. sanguis 12 expressed more high mol.wt proteins on its surface than strain 12 na. Using immunogold labelling, the fibrils of strain 12 labelled well with antiserum directed against the long fibrils, but so did the cell surfaces of both Strep. sanguis 12 and 12 na. High molecular weight proteins and cell surface fibrils may be associated with adhesion in this strain.

The production of inhibitory substances was sought by deferred antagonism. Streptococcus oralis, Streptococcus mitis and Streptococcus sanguis produced bactericidal concentrations of hydrogen peroxide, but no detectable bacteriocin. Actinomycetes and Neisseria pharyngis were particularly susceptible to the lethal action of hydrogen peroxide. Streptococcus milleri produced bactericidal concentrations of hydrogen peroxide and bacteriocin-like substances. S. oralis strains were inhibited by the bacteriocin-like products of strains of Streptococcus bovis, Streptococcus faecalis, Streptococcus mutans and Streptococcus salivarius. Inhibition was due neither to complete bacteriophage nor to fermentation end-products. Extracellular polysaccharides formed during growth could not protect sensitive strains from the effect of hydrogen peroxide or bacteriocin-like substances.

Controversy exists as to the appropriate methods to use in the processing of bronchoalveolar lavage (BAL) fluid for total cell numbers and cellular differential analysis. It has been shown that cell losses (primarily lymphocytes) occur by the most commonly employed methods. Therefore, we examined the total cell and differential counts obtained by several methods of cytocentrifuge preparation and by the filter preparation in 46 consecutive patients with interstitial lung disease and 29 healthy volunteers undergoing bronchoalveolar lavage. The retrieved lavage fluid was pooled, and an aliquot was used to determine the total cell count, cell viability, and the differential cell count by the filter and cytocentrifuge techniques. The remaining fluid was centrifuged (800 g for 10 min), and the cell pellet was resuspended in Hank's balanced salt solution without Ca2+ and Mg2+. An aliquot of these centrifuged and resuspended cells was used for repeat determination of the cell viability, total cell count, and cellular differential by cytocentrifuge technique. Autologous serum was added to another aliquot of these centrifuged and resuspended cells to arrive at a 10% protein solution, and the cellular differential obtained by cytocentrifuged preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Earlier studies with the random-bred Quackenbush mouse strain showed that human-type diets based on linoleic acid-enriched foodstuffs derived from ruminants fed protected polyunsaturated oils have no detrimental effects on growth, reproduction or longevity. Tumour incidence and time of onset of tumour development have now been studied in the inbred, tumour-prone mouse strain C3H, in addition to growth, reproduction and longevity. Mice were fed a polyunsaturated human diet, a conventional human diet, or mouse cubes. The results with C3H mice tended to confirm those with Quackenbush strain mice-growth rates and reproductive productivities were very similar in the two groups eating human diets. Mice on the conventional human diet tended to survive better to about 60 weeks of age than mice on the polyunsaturated diet or the cube diet, after which the mortality rates of the mice on the three diets were similar. The degree of unsaturation of the dietary fat had no significant effect on the incidence of tumours. The tumour incidence was about 40% which, taken in conjunction with the average age of onset (about 80 weeks), suggested that the NIV virus rather than the MMTV virus was responsible. It would appear that the high-fat human diets had no effect on the incidence of mammary tumours caused by this virus.

Children two to nine years old from an area of holoendemic malaria in northern Liberia had mean HbA2 and haematocrit values significantly (P less than 0.001) lower than others from a neighbouring town where malaria is hypoendemic. After regular administration of chloroquine over two years to 38 children living in a holoendemic village, their mean HbA2 rose from 2.1%, SE +/- 0.04, to 2.6%, SE +/- 0.08 (P less than 0.001) and their mean haematocrit from 0.348, SEM +/- 0.004, to 0.382, SE +/- 0.004 (P less than 0.001), values similar to those of children from the neighbouring town. In another village where chloroquine was not given regularly, mean HbA2, haematocrit and malariometric indices were little changed at the end of the two-year period. We conclude that persistent malarial parasitaemia was the main factor in the relatively low values of the village children. Although it is not clear how malaria depresses HbA, the findings were consistent with the hypothesis that chronic malaria induces iron-deficiency.

Fatty acid analyses were performed on samples of liver from 325 human infants less than 1 yr old, 275 of whom had died of sudden infant death syndrome (SIDS), and 50 of other causes (non-SIDS). Data for fatty acid composition were analyzed in relation to cause of death, age of infant, liver biotin, liver metals, and other variables by a variety of statistical methods. There were significant differences in the levels of liver fatty acids between SIDS and non-SIDS infants in the age group 1 to 6 months, notably in that the fatty acids of the SIDS infants appeared to have lower levels of dihomo-gamma-linolenic acid, which is the precursor of the "1-series" prostaglandins. Statistically significant relationships were observed between various fatty acids, and there were also significant relationships involving docosapentaenoic acid and infant age, and docosahexaenoic acid and liver iron content.

Two hundred and eighty-two children, two to nine years old, were included in a prospective three-year study in four villages with holoendemic malaria. In three villages the children received monthly doses of either chloroquine, pyrimethamine or chlorproguanil respectively for two years. In the fourth, vitamin tablets were used as placebo. Presumptive treatment with chloroquine (10 mg base kg-1) was given to all children with fever of suspected malarial origin. The two-year drug distribution was satisfactorily fulfilled to 168 children. Surveys, including physical and laboratory examinations were performed every six months, four weeks after medication. A fifth village was only visited at the start of the study and after two years. The mean crude parasite rate was initially 92%. Plasmodium falciparum was the main species. Splenomegaly was recorded in all children. In the chloroquine-treated children, the parasite rates varied between 30% and 50% during the study. By the end of the second year the spleen rate was reduced from 100% to 50%. Reported episodes of fever were reduced to half and mean haematocrit levels increased by 6% in comparison with children receiving the placebo. Total IgG concentrations were reduced from 36.7 g l-1 to 25.9 g l-1, whereas no significant decrease was observed in malarial seropositivity as measured by indirect immunofluorescence. Chlorproguanil had a weaker impact on parasitaemia with parasite rates between 50% and 90%. However, the spleen rate was reduced to 67% and there was a significant reduction of reported fever episodes. Mean haematocrits increased by 4%. Total IgG decreased from 31.8 g l-1 to 23.8 g l-1. In contrast, in the pyrimethamine group, the placebo group and the untreated group from the fifth village, the malariometric indices after two years were comparable to each other and to the initial values. During the third year only presumptive chloroquine treatment was given, and by the end of the study all malariometric indices were again comparable. From clinical observations there was no apparent impairment of protective immunity to malaria from the two years of regular distribution of the drugs. We conclude that a certain degree of malaria control could be achieved in Liberian children by the administration of monthly doses of chloroquine 10 mg base kg-1. The administration of chlorproguanil (1.5 mg kg-1) represents an alternative regimen.

The in vivo response of Plasmodium falciparum to standard treatment with sulphadoxine/pyrimethamine was studied in 19 hospital patients from Yekepa town with hypoendemic malaria and in 28 children, two to nine years old, living in a village with holoendemic malaria. In vitro tests were performed on eight isolates. In the hospital patients all parasites cleared with mean clearance time of 2.2 (range one to three) days and no recrudescence occurred during a 28-day follow-up period. In the village children, despite a high sporozoite inoculation rate, recurrent parasitaemias were only recorded after 28 days, suggesting a rather long-lasting prophylactic effect against reinfection by the drug combination. In vitro, inhibition of parasite multiplication was achieved by 3 X 10(-7) M sulphadoxine and 3.8 X 10(-9) M pyrimethamine.

A population survey in northern Liberia showed an average incidence of 9 percent of beta-thalassaemia trait. There was considerable tribal variation, the highest rates being mainly found in tribes having a low incidence of Hb S. A single example of deltabeta-thalassaemia trait was also found; the incidence of delta-chain variants was 1.8 percent. The effect of malaria on Hb A2 levels was investigated but appeared to be negligible. The problems of beta-thalassaemia and Hb S occurring in the same population are discussed. It is considered that, although made on a local sample, the results of this survey indicate a high incidence of beta-thalassaemia trait elsewhere in Liberia and that this is a suitable are for investigations of linkage at beta- and delta-chain loci. No conclusion is at present possible from the data on the presence of alpha-thalassaemia although 10 percent of neonates were found to have increased levels of Hb Barts.

In a study of the impact of malaria prophylaxis upon the physical working capacity of Liberian industrial workers, two groups of men, one with and the other without malaria prophylaxis, were compared over a period of one year. At the beginning and at the end of the study, the haemoglobin concentration, haematocrit, blood volume and physical performance--measured by bicycle ergometry and expressed as work load at heart rate 170--were compared. No significant differences were found, either within or between the two groups. Routinely distributed malaria prophylaxis thus seems to be of little importance with respect to working capacity in this type of community, where malaria is meso-endemic.

The efficacy of different doses of chloroquine in suppressing patent parasitaemia was investigated in 326 children two to 12 years old, living in six villages with holoendemic malaria. The children were given single doses (2, 3, 5-7 or 9-12 mg base kg-1) or a standard treatment over three days (25 mg base kg-1). Parasite prevalences were recorded after one, two, three, four, six and eight weeks. Complete clearance of Plasmodium falciparum trophozoites (TC) by day 7 was achieved by a dosage of 9-12 mg kg-1. By probit analysis of log dose response, 50% clearance (TC50) was established at about 1.5 mg kg-1, whereas a TC95 required 5.5 mg kg-1. The reappearance of patent parasitaemia was dependent on the dose of chloroquine given and on malaria transmission. After the standard dose treatment, only one re-infection in 56 children appeared within 21 days despite high sporozoite inoculation rates in the area. The dosage of 9-12 mg kg-1 yielded a hundredfold reduction of mean parasite density in the children if calculated over a four-week period. It may represent a suitable monthly regimen in a malaria control scheme in a holoendemic area with high P. falciparum sensitivity to chloroquine.

Seven strains of Streptococcus oralis were found to possess surface structures. Four strains possessed long fimbriae which ranged in length from 266-366 nm, while the remaining three strains possessed shorter peritrichously distributed fibrils which ranged in length from 80-197 nm. The fibrillar strains were morphologically similar to strains of Streptococcus sanguis I and II and Streptococcus mitis. No strain of S. oralis produced tufts of fibrils like certain strains of S. sanguis I. Strains of Streptococcus milleri produced peritrichously distributed fimbriae which were morphologically dissimilar to the fimbriae produced by S. oralis strains. S. oralis strains were moderately to highly hydrophobic, but hydrophobicity could not be related to adhesion parameters or type or length or density of surface structures. Furthermore, there appeared to be no correlation between type of surface structures and adhesion parameters. Two of the three fibrillar strains of S. oralis and the peritrichously fibrillar strains of S. sanguis, together with one strain of S. milleri, were able to co-aggregate with actinomycetes.

The epidemiology of malaria was studied in a West African mining town (Yekepa) and three surrounding zones defined as Close, Middle and Far areas. Malariometric parameters were investigated in children two to nine years of age at the end of the rainy season. In Yekepa, vector control measures and intense suppression of malaria with drugs had created an almost hypoendemic situation with a spleen rate of 11%. In Close area, vector control was applied to some extent and malaria drugs were frequently used for treatment; the spleen rate was 40%. In Middle area, a mobile clinic provided sporadic malaria treatment to small children, but the clinic did not reach out to Far area. The spleen rates were 95 and 99%, respectively. Three species of Plasmodium were found in all areas. The prevalences in Far area were P. falciparum 82%, P. malariae 39% and P. ovale 9%. The crude parasite rates increased from 13% in Yekepa to 92% in Far area, whereas haematocrit levels decreased from 37.6 to 35.2, respectively. Plasmodium falciparum seropositivity, as measured by indirect immunofluorescence, was 74% in Yekepa and 99% in Middle and Far areas. Total IgG concentrations ranged from 18 g1(-1) in Yekepa to 33 g1(-1) in Far area. Three main anopheline species were found in the zones outside Yekepa. Their relative frequencies in Far area were Anopheles funestus 45%, A. hancocki 37%, and A. gambiae 18%. The local inoculation rates gradually increased outwards from Yekepa from less than 0.01 to 0.17 inoculations per man and night at the beginning of the dry season.(ABSTRACT TRUNCATED AT 250 WORDS)

Cats, anesthetized with sodium pentobarbital, were cannulated to measure pulmonary, systemic, and left atrial pressures and pulmonary ventilation, compliance, and resistance. Intracranial pressure was elevated to 30 mm Hg by injecting silicone oil into the extradural space. After an average time of 56 minutes, pulmonary systolic and diastolic pressures more than doubled, systemic systolic pressure sometimes rose and sometimes fell, and diastolic pressure rose 5%. Left atrial pressure never exceeded 8 cm of saline. Pulmonary compliance decreased by one-half, but airway resistance was unchanged. Pulmonary edema was estimated from histological sections. The pulmonary hypertension may be the result of a sympathetic discharge confined to the lung, since no remarkable changes in heart rate or systemic blood pressure occurred. The decrease in pulmonary compliance followed the rise in pulmonary arterial pressure, and is interpreted as the result of interstitial edema. There was no evidence that left heart failure or elevated left atrial pressure caused the pulmonary edema.

Psychophysical procedures were used to investigate the effects observed by humans when two odorants were presented simultaneously through the same nostril (physical mixture) or separate nostrils (dichorhinic mixture). The odor pairs were (+)-limonene and alpha-pinene, (+)-limonene and propionic acid, alpha-pinene and propionic acid. With both types of mixtures subjects indicated the acid had no effect on the perception of the other odorants. In contrast, limonene suppressed perception of the acid and pinene in physical and dichorhinic mixtures, pinene suppressed limonene in both types of mixtures but only suppressed the acid in physical mixtures. The magnitude of suppression with dichorhinic mixtures never exceeded that seen in physical mixtures, whilst suppression with physical mixtures was often significantly greater than in dichorhinic mixtures. The absence of suppression in dichorhinic mixtures in almost one-third of instances when suppression occurred with physical mixtures suggests that different mechanisms are involved in the perception of the two types of mixtures. A hypothesis that accounts for non-reciprocal suppression with both types of mixtures is proposed.

The four species, each represented by two strains, all produced high levels of fissure caries in the upper and lower jaws of gnotobiotic Fisher rats. Streptococcus rattus strains and Streptococcus mutans NCTC 10832 gave low levels of approximal caries, whereas Streptococcus cricetus, Streptococcus sobrinus and Strep. mutans NCTC 10449 gave high levels. The only strains to produce buccal surface lesions were Strep. sobrinus and Strep. cricetus. All strains were able to form dense plaque in the central fissure of the second molar. Strep. cricetus, Strep. rattus and Strep. sobrinus strains were capable of producing smooth-surface plaque. This difference in plaque-forming ability did not correlate precisely with differences in cariogenicity, and such differences occurred between strains of the same species.

Agglutinins reacting with normal and tanned sheep erythrocytes were the probable cause of false positive reactions given by 51 of 214 Liberian sera when using a commercial passive-haemagglutination test for hepatitis-B surface antigen. Absorption showed these agglutinins to be identical to those described earlier in Nigerian sera. Rheumatoid factor and anti-sheep-serum antibodies although present in 12 and five per cent respectively of all sera were not responsible for any false positive reactions. The practical conclusion is that such tests, based on sheep erythrocytes are unsuitable for screening this population.

Thirty-two strains of Streptococcus spp., of known cariogenicity in the gnotobiotic WAG/RIJ rat, were tested for their in vitro adhesion properties. Computerized image analysis measured percentage coverage by, and clump size of, cells adhering to saliva-coated glass. An analysis of variance revealed significant differences for percentage coverage for the majority of species-pairs. There were fewer significant differences for mean clump size between species-pairs. Within the Strep. mutans group there was a highly-significant difference between Strep. mutans/Strep. cricetus (p less than 0.01) with respect to mean clump size. There was a significant correlation between cariogenicity and percentage coverage (p = 0.05) but not clump size (p = 0.359) for pooled strains of Strep. mitis and Strep. sanguis combined.

For seven years, chlorproguanil (1.0 to 2.0 mg kg-1) was administered monthly to the children below 15 years of age in a village with holoendemic malaria. Malariometric indices were recorded every six months. Susceptibility in vivo was monitored by the clearance of Plasmodium falciparum parasitaemia after drug intake. Three parasite species were found initially: P. falciparum (52%), P. malariae (8%) and P. ovale (4%). The parasites found during the study were mainly P. falciparum, and parasite rates ranged from 37 to 87% at the different surveys one month after respective drug intake. A fifty-fold decrease of mean parasite density was generally observed seven days after drug intake. Splenomegaly was initially recorded in all two to nine year old children, with a mean size of 2.64 according to Hackett's index. From 18 months onwards as the mean spleen index was 1.15 in the same age group. Chlorproguanil may represent an important alternative drug to groups at risk in malaria control schemes.

The size and distribution of mitral cells in the olfactory bulbs of rats were determined using a computer-assisted morphometric technique. Rats were reared from 2 weeks of age for 10 weeks in an animal colony, or in cages through which a stream of deodorized air or cyclohexanone vapor passed. Statistical analyses indicated that each treatment produced a different distribution of cell sizes in the coronal but not along the rostrocaudal plane of the bulb. The mean size of mitral cells in rats reared in deodorized air was substantially smaller than that of normal rats, and the mean length of their mitral cell layer in the coronal plane was less than in the other groups. Overall, these findings indicate that mitral cells which were of normal size in rats exposed to cyclohexanone had been stimulated by this odor. Cells which had not been stimulated by an odor in either of the experimental groups were smaller than normal and were degenerating or underdeveloped. The results also suggest that there are bands of mitral cells aligned along the rostrocaudal axis of the olfactory bulb which are responsive to specific odors and other evidence is presented which supports this view. The functional significance of exposure effects and their implications for the spatial coding of odor quality are discussed.