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Biomedical subjects

J M Hilton

Publications and source records attributed to J M Hilton.

At least 19 recordsLinked to original sources

Biologically active salmon calcitonin-like peptide is present in rat brain.

Although high densities of calcitonin (CT) receptors and potent CT-induced actions occur within the rat central nervous system, the physiological ligand for central receptors remains unidentified. This study identifies a salmon CT (sCT)-like peptide in extracts of rat brain. Aliquots of 1 M HCl brain extracts were reconstituted in 0.01 M acetic acid and assayed for sCT-like immunoreactivity using a radioimmunoassay (RIA) based on a guinea pig anti-sCT antibody (detection limit 0.1 ng). The assay was less than 0.1% cross-reactive with human CT, porcine CT, rat calcitonin gene-related peptide (CGRP)-I and human CGRP-I. Extracts of diencephalon revealed sCT-like activity (30-120 ng/g wet weight), while extracts from cortex, cerebellum and medulla oblongata did not contain detectable activity. Reverse-phase HPLC analysis demonstrated co-elution with synthetic sCT. Further, the peak material was active in 4 CT bioassay systems; (1) stimulation of cAMP production in UMR 106-06 cells and (2) T47D cells, (3) inhibition of 125I-sCT binding in UMR 106-06 cells and (4) inhibition of 125I-sCT binding in sheep brain membranes. The bioactivity of material in these assays was similar to that estimated through the RIA. The results identify, for the first time, the presence of sCT-like material in the rat brain and constitutes the first demonstration of biologically active sCT-like material from brain extracts. Salmon CT-like peptide may represent the endogenous ligand for central CT receptors.

Animals

Basophils (Bsp-1+) derive from the leukemic clone in human myeloid leukemias involving the chromosome breakpoint 9q34.

The monoclonal antibody (MoAb) Bsp-1 was used to purify basophilic cells from leukemic blood of five patients with Philadelphia chromosome (Ph') positive chronic myeloid leukemia (CML) and two patients with acute myeloid leukemia (AML) characterized by the chromosomal translocation t(6;9)(p23;q34). When cultured, Bsp-1 positive cells from all CML and AML patients showed the same clonal karyotype changes observed in diagnostic buffy coat preparations, indicating that the basophilic cells were of leukemic origin. In contrast, T lymphocytes from four of five CML patients cultured in the presence of interleukin-2 (IL-2) showed a normal karyotype and were therefore not derived from the leukemic clone. Bsp-1 staining correlated with toluidine blue-positive basophils in chronic phase CML and with toluidine blue-negative blast cells expressing an immature myeloid phenotype in blast crisis CML and AML. Chromosome in situ hybridization showed that the ABL oncogene was translocated from chromosome 9 to chromosome 22 in the CML patients but remained on chromosome 9 in the AML patients. These results indicate that the breakpoint at 9q34 in CML is 5' of ABL, whereas the breakpoint at 9q34 in AML is 3' of ABL. Field inversion gel electrophoresis showed that the 9q34 breakpoint was not within 200 kb 3' of ABL in one of the AML patients, nor was there any rearrangement of the PIM oncogene locus at 6p21.

Antibodies, Monoclonal

Hanging deaths in children.

During the 16-year period of 1972-1987, there were 11 hanging deaths in children in Western Australia. We report the circumstances and medical findings of each case.

Accidents

Unusual hanging deaths.

We describe the circumstances and medical findings of four unusual hanging deaths. In brief, the unusual features are tracheostomy, delayed death, self-mutilation combined with severe neck injury caused by lengthy drop, and homicidal hanging in a young girl.

Adult

Serum thiamin, pyridoxal, cobalamin and folate concentrations in young infants.

Blood samples were obtained from 509 apparently healthy infants between the age of 3 and 54 weeks attending for routine checks at infant health centres. Serum was assayed for thiamin, pyridoxal, cobalamin and folate. Three hundred and five infants were being breast fed and results from these were used to construct a reference range-thiamin 2-17 micrograms/l, pyridoxal 8-39 micrograms/l, cobalamin 120-800 ng/l and folate 7-47 micrograms/l (95 percentile ranges). One hundred and thirty-four infants were being fed a manufactured milk formulation and the serum concentrations of thiamin, pyridoxal and cobalamin were significantly higher than those found in breast fed infants. Thirteen infants were receiving pasteurized cow's milk. This milk was found to have more than 3 times the folate content of human breast milk yet these infants had a significantly reduced serum level of folate.

Age Factors

Pathology of the sudden infant death syndrome in Western Australia: a review of 50 cases.

Fifty cases of Sudden Infant Death Syndrome (SIDS) have been selected randomly from a group of 511 such cases studied since 1973. In addition, thiamine levels from 12,613 babies screened during the study period are also reviewed in relation to SIDS deaths. Despite exhaustive post-mortem analysis, few indications to causation are apparent. When compared with the control group, a five-fold increase in mean thiamine levels was noted in SIDS victims. However, the interpretation of thiamine screening data requires further detailed investigation. The results of this study suggest the value of adoption of a uniform basic protocol for the examination of SIDS and non-SIDS babies, along with the establishment of a central register of these deaths.

Australia

Testing sensitivity of Neisseria gonorrhoeae to spectinomycin.

A concentration of 16 mg/l spectinomycin incorporated in agar gave the best discrimination between Neisseria gonorrhoeae sensitive and resistant to spectinomycin. This method was compared with spectinomycin sensitivity testing with 25 micrograms or 100 micrograms discs. Both methods agreed fully for 197 spectinomycin sensitive and three spectinomycin resistant gonococci. The agar incorporation "breakpoint" concentration technique failed to detect a small spectinomycin resistant population in a fourth isolate, which was detected by disc testing. It may be possible to predict the emergence of spectinomycin resistance among strains of N gonorrhoeae.

Microbial Sensitivity Tests

Sudden infant death syndrome caused by poliomyelitis.

Most seemingly well infants who die suddenly and unexpectedly have no adequate cause of death found on thorough postmortem examination. Respiratory and enteric viruses are often present, especially in the upper respiratory tract, but the infective process seems, of itself, insufficient to cause death. In the remainder of the cases, a variety of lesions will be discovered, including viral myocarditis, bronchiolitis, and sepsis. We report a case of sudden and unexpected death in a 5-week-old male infant due to acute anterior poliomyelitis. This case illustrates the importance of a thorough postmortem examination, including histologic studies of the brain stem and spinal cord in cases of sudden infant death syndrome.

Humans

Type I hyperlipoproteinemia presenting as sudden death in infancy.

A routine post-mortem investigating sudden death in an eight week old male infant revealed gross Type I hyperlipoproteinemia (triglyceride concentration 825 mmol/L). Death was attributed to generalized cerebral anoxia. Study of the family revealed the parents were first cousins both of whom had depressed postheparin lipolytic activity, as did five out of seven of the remainder of the family members tested. This family is a notable example of deficiency of extrahepatic lipoprotein lipase.

Brain Ischemia

High serum thiamine and the sudden infant death syndrome.

Serum thiamine concentrations in 233 infants dying from the sudden infant death syndrome were compared with those found in 46 infants dying from other explicable causes. The levels in the sudden infant death group ranged from 22- greater than 500 micrograms/1 (mean 144.3 micrograms/1) and in the controls less than 1.0-95 micrograms/1 (mean 26.5 micrograms/1). The difference was highly significant (p less than 0.001). Only 13 (5.6%) of the sudden infant death group had a serum thiamine concentrations below 50 micrograms/1 whereas four (8.7%) of the control infants had a level above 50 micrograms/1. Thiamine was measured in nine samples of human breast milk and was present in concentrations ranging from 55-366 micrograms/1 (mean 178 micrograms/1); manufactured milk based formulae contained up to 2160 micrograms/1. Absorption of thiamine in man is rate limited but it appears that in infants dying from the sudden death syndrome the vitamin may be freely absorbed leading to very high serum levels.

Animals

Sudden death in infancy syndrome in Western Australia.

The objects of the Western Australian investigation into the sudden death in infancy syndrome are stated. Evidence is presented which suggests that these children are subject to an asphyxial mode of dying. It is postulated that anaphylaxis, due to hypersensitivity to the house dust mite, and possibly other allergens, is implicated, with the respiratory system as the target organ. A family counselling service is described.

Asphyxia

IgE antibodies to Dermatophagoides pteronyssinus (Housedust mite), Aspergillus fumigatus, and beta-lactoglobulin in sudden infant death syndrome.

The prevalence of serum IgE antibodies to Dermatophagoides pteronyssinus (house-dust mite), Aspergillus fumigatus, and bovine beta-lactoglobulin was significantly greater in cases of sudden infancy death (S.I.D.) than in a control group of infants of the same age range. This difference was most pronounced with D. pteronyssinus antibodies, which suggests that hypersensitivity to house-dust mite may be a factor in the aetiology of S.I.D. in Western Australia. Both the S.I.D. and control infants had similar serum concentrations of immunoglobulins G, M, and E but IgA levels were significantly higher in the control group.

Allergens

RAST studies : IgE antibodies to Dermatogoides pteronyssinus (house dust mite), Aspergillus fumigatus and beta-lactoglobulin in sudden death in infancy syndrome (SDIS).

The incidence of 2.5 SDIS cases per 1,000 live births found in Western Australia is in agreement with figures reported for other centres. While the age range of SDIS victims extended from two weeks to 15 months, 57 per cent of deaths occurred in children of two to four months of age. Boys outnumbered girls 1.6:1. Environmental factors are implicated in that the majority of deaths occurred in a biphasic distribution - autumn and late winter months. No significant differences were observed in total IgE levels in serum from SDIS victims, post mortem children who died in trauma of known aetiology and live control children of the same age range. Serum IgE antibodies to D.pteronyssinus were found in 37% of SDIS victims compared with 7% of matched controls (post mortem plus live groups). IgE antibodies to beta-lactoglobulin, the major allergen of cow's milk, appeared with twice the frequency in SDIS vs. control group but both groups showed a similar incidence of antibodies to the allergens of Aspergillus fumigatus. The prevalence of IgE antibodies to D.pteronyssinus in SDIS victims who died in the late winter -- early spring period was double that found in the group who died in the autumn period. Sixtyfour percent of the SDIS victims had antibodies to two or more of the three allergens tested while the control sera were positive to only one allergen. These results support the hypothesis that anaphylaxis induced by immediate hypersensitivity to D.pteronyssinus in particular may be one of the causative factors in SDIS in Western Australia.

Allergens