FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

用于筛选天然产物中脲酶抑制剂的脲酶活性测试方法的建立

抑制幽门螺杆菌产生的脲酶具有治疗胃炎和消化性溃疡的作用。用酚红指示剂和Ｂｅｒｔｈｅｌｏｔ试剂在９６孔培养板上检测重组脲酶活性，其灵敏度指标酚红法每ｍｇ酶蛋白引起的每分钟吸光度变化。△Ａ为６．９，而Ｂｅｒｔｈｅｌｏｔ法每ｍｇ酶蛋白引起的每分钟吸光度比值变化△Ａ为３１３。结果表明用Ｂｅｒｔｈｅｌｏｔ试剂检测重组脲酶活性适宜在９６孔培养板上大规模筛选天然产物中的脲酶抑制剂。     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Antigen provocation to the skin, nose and lung, in children with asthma; immediate and dual hypersensitivity reactions.

Most (18/21) children with perennial asthma gave dual (immediate and late) responses to bronchial provocation with two of Dermatophagoides pteronyssinus, and either timothy grass pollen or cat fur. Most (19/21) also showed dual responses to skin prick tests, only half (11/21) gave dual responses in the nose, mainly with timothy grass pollen, and these were associated with allergic rhinitis. Only two children gave dual responses in lung, skin and nose to both antigens, and only two gave immediate reactions without late reactions in all positive tests; most showed different patterns of response according to the organ tested or the antigen used for provocation. Our results suggest that local factors may be important in determining the pattern of allergic response in a 'target' organ, and that dual responses are strongly associated with the patient's symptoms.     

Maternal smoking and cord blood immunity function.

Thymidine uptake in PHA-stimulated culture of cord blood cells from smoking mothers is greater than that from non-smoking mothers. There was no such difference when separated lymphocytes were studied; this suggests that smoking suppresses a suppressor cell. No difference was detected in haemoglobin, immunoglobulins, transferrin, cell counts, E-rosette counts and leucocyte mobility.     

An Investigation of Methods of Isolation of β2M1 Globulin (Syn.: Iota Protein, 19S γ Globulin, γ1 Macroglobulin, β2M Globulin) and its Association with Isoagglutinin Activity, together with Preliminary Observations on Other Macroglobulins of Slow Electrophoretic Mobility in Normal Human Serum

An investigation is described of methods of isolation and purification of the high molecular weight protein (here called β_2M1 globulin) which is often associated with the isoagglutinin activity of normal human serum. In the course of these experiments it was observed that ultracentrifugal concentration of this protein from serum fractions gives rise to the simultaneous concentration of two other macroglobulins (here called β_2M2 and β_2M3 globulins).

It was found that the concentration of β_2M1 globulin in normal serum is about 25–50 mg. per 100 ml. In serum from the blood of normal donors of groups A, B and O, isohaemagglutinin activity is associated with the β_2M1 globulin but probably accounts for 1 per cent or less of the total β_2M1-globulin concentration in serum. This activity may represent the so-called `natural' isohaemagglutinin.

The immunological relation is discussed of the normal β_2M1 globulin to certain other members of the `family' of immune globulins (γ globulin and β_2A globulin) and to the pathological macroglobulins occurring in Waldenström's syndrome.

Although rabbit antibody to β_2M1 globulin cross-reacts with γ globulin, suggesting that a portion of each molecule bears antigenic groupings in common, it was found that a considerable degree of β_2M1-globulin specificity could be demonstrated after absorbing antisera with purified γ globulin. Attention is also drawn to the evidence that deficiency of either β_2M1 globulin or γ globulin can occur independently, suggesting different cellular sources of origin.

The pathological macroglobulin demonstrable in Waldenström's syndrome is closely related immunologically to normal β_2M1 globulin but is often deficient in isoagglutinin activity. This immunological relation suggests the use of specific anti-β_2M1-globulin antiserum as a simple means of distinguishing macroglobulinaemia from myelomatosis or other conditions with raised levels of γ globulin.

The β_2M2 and β_2M3 globulins are only demonstrable in ultracentrifugal concentrates of normal serum. Evidence is presented to suggest that these proteins are nevertheless present as trace components of normal serum. The solubility and electrophoretic characteristics of these proteins resemble those of β_2M1 globulin, but they can be distinguished by immunological methods from β_2M1 globulin and each other. Attention is drawn to the evidence that β_2M2 and β_2M3 globulins may also be increased in the serum of some cases of macroglobulinaemia.

     

Immunological studies in patients with juvenile-onset myasthenia gravis and in their relatives

Fifty-four patients who developed myasthenia before the age of 20 had an increased incidence of autoantibodies similar to that in adult-onset myasthenics, except that there was no significant increase of striated muscle antibodies. The increase in thyroid antibodies was associated with an increase of thyroid disease.

Their 150 relatives showed a significant increase in thyroid antibodies, in thyroid disease, and a non-significant increase in the five other autoantibodies studied. There was aggregation of thyroid antibodies in some families.

Two patients and one relative were deficient for immunoglobulins (one patient and one father for IgA and one patient for IgM).

These familial immunological abnormalities, which are more marked in the families of patients with juvenile-onset myasthenia than in the families of adult-onset patients, point to fundamental genetic immunopathogenesis of the disease.

     

Prenatal asphyxia, hyperlacticaemia, hypoglycaemia, and erythroblastosis in growth retarded fetuses

The umbilical venous oxygen and carbon dioxide tensions, pH, lactate and glucose concentrations, nucleated red cell (erythroblast) count, and haemoglobin concentration were measured in 38 cases of intrauterine growth retardation in which fetal blood sampling was performed by cordocentesis. The oxygen tension was below the normal mean for gestational age in 33 cases; in 14 it was below the lower limit of the 95% confidence interval for normal pregnancies. The severity of fetal hypoxia correlated significantly with fetal hypercapnia, acidosis, hyperlacticaemia, hypoglycaemia, and erythroblastosis. These findings indicate that "birth asphyxia" is not necessarily due to the process of birth.     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.