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Biomedical subjects

G G Crane

Publications and source records attributed to G G Crane.

At least 19 recordsLinked to original sources
PubMed1991

Analysis of the patterns of inheritance of splenomegaly and serum IgM levels in the Watut of Papua New Guinea.

Hyperreactive malarious splenomegaly (HMS) reflects abnormal immune responses to malarial infection. The central question is whether HMS results from unusual patterns of malarial infection or from immune incompetence in the host. Family distributions of two features of the syndrome, splenomegaly and excessively high IgM levels, have been examined in a Papau New Guinea population in which HMS is exceptionally common. Segregation analysis of spleen grade shows that a major sex-linked gene controls hyperresponsiveness to malaria. This finding is supported by additional segregation analysis, which shows that an autosomal locus cannot account for a significant proportion of variation in spleen grade, and by path analysis, which rejects a model that assumes that parents contribute equally to the child's genotype. The sex-linked gene contributing to HMS was not mediated through sex linkage of a major gene for IgM concentrations, as shown by segregation analysis. It has yet to be determined whether this pattern of inheritance also applies to HMS occurring sporadically in other less severely affected populations. The applicability of these findings to the general variability in "normal" IgM responses to malaria also remains to be established.

Adult↗
PubMed1989

HLA heterozygosity and hyperreactive malarious splenomegaly in the Upper Watut Valley of Papua New Guinea.

Hyperreactive malarious splenomegaly (HMS) represents an abnormal immune response to recurrent malarial infection. In the Upper Watut Valley of Papua New Guinea, where over 80% of adult inhabitants are known to develop the disease, human leucocyte antigen (HLA) studies have demonstrated an association between the antigen DR2 and gross splenomegaly. To test the hypothesis that the magnitude of the individual immune response to malaria is also influenced by the number of different HLA antigens present, we have studied the correlation of the level of observed heterozygosity at HLA-A, -B, -C and -DR loci with the degree of splenomegaly in adult Watut subjects. Heterozygosity per se provides additional antigens for the formation of complexes between HLA and foreign antigenic epitopes, considered crucial to mounting an immune response. Multiply heterozygous individuals were found to exhibit more intense immune responses to recurrent malarial infections than did individuals with low multiple-locus heterozygosity. On the basis of the analysis presented here, we suggest that the degree of immune response to malaria is also influenced by the level of HLA heterozygosity, although the exact mechanisms remain unclear.

Biomarkers↗
PubMed1987

Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea.

Ovalocytosis, an hereditary condition in which most erythrocytes are oval in shape, is a polymorphism that occurs in up to 20% or more of the population in Papua New Guinea and Malaysia. Due to the geographical correlation of the trait with endemic malaria, the possibility of a selective advantage in resistance to malaria has been raised. In a study of 202 individuals with greater than or equal to 50% oval red cells matched by age, sex and village of residence with controls having less than or equal to 30% oval cells, ovalocytic subjects had blood films negative for Plasmodium vivax (P = 0.009), for P. falciparum (P = 0.044), and for all species of malaria parasites (P = 0.013), more often than controls. Among individuals parasitaemic at any time there were no clear differences in density of parasitaemia. However, in children 2 to 4 years old, parasite densities of both species were lower in ovalocytic subjects than in controls (0.01 less than P less than 0.025). The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present.

Animals↗
PubMed1977

Malarial antibodies in tropical splenomegaly syndrome in Papua New Guinea.

Levels of species and class-specific malarial antibody were studied in 249 New Guineans with tropical splenomegaly syndrome (TSS) and in 87 control subjects living in the same area. Titres of IgG and IgM antibody to Plasmodium falciparum, P. vivax and P. malariae were estimated by indirect immunofluorescence. Both Ig and IgM antibody levels were higher in subjects with TSS than in controls; IgM titres were highest in those with the greatest splenic enlargement. Responses to all three species were comparable. It is concluded that there is no evidence from this study to incriminate any one species of malaria parasite in the production of tropical splenomegaly syndrome.

Adolescent↗
PubMed1977

The pathogenesis of tropical splenomegaly syndrome--the role of immune complexes.

For the last few years it has been known that high molecular weight circulating immune complexes containing IgM, other immunoglobulins and complement are usually present in TSS. Similar material to be found in the Kupffer cells of affected patients, and on the surfaces of their red cells. The recent demonstration that the immune complexes contain malarial antibody activity strengthens the belief that they also contain malarial antigen and are due to the basic immunological abnormality. As indicated in this review, further studies are required fully to confirm their role in the production of the splenomegaly, the auto-immune phenomena and the haemolysis of TSS. The balance of evidence favours a genetic rather than a purely environmental basis for development of the syndrome. Treatment is simple, inexpensive and relatively free of risk. It is feasible even in rural communities pending the advent of successful malaria eradication, the ultimate means of prevention and cure.

Anemia↗
PubMed1975

The rôle of plasma proteins in chronic expansion of plasma volume in tropical splenomegaly syndrome. III. The interrelationships of albumin, immunoglobulins and plasma volume.

The effect of alterations in serum protein levels on plasma volume in tropical splenomegaly syndrome has been investigated by determining plasma volume, serum albumin, globulin and immunoglobulin levels in 64 adult New Guineans suffering from this disease. Plasma volumes ranged from 51-2 to 129 ml./kg. Significant positive correlations were found between plasma volume and intravascular pools of albumin, IgG and IgM. Multiple regression analysis demonstrated that 70% of the variance in plasma volume in this series was attributable to increases in these three pools, IgM and IgG accounting for 42% of the total and albumin for 28%. It is probable that the unexplained 30% of plasma volume expansion arises through a splenic arterio-venous shunt effect. It is suggested that initially in tropical splenomegaly syndrome the splenic shunt and immunoglobulin overproduction combine to produce expansion of plasma volume and a fall in intravascular colloid osmotic pressure; that the latter provides the stimulus to increased albumin synthesis, and that this further aggravates the plasma volume expansion and the consequent dilutional anaemia commonly seen in this disease.

Blood Proteins↗