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D Sinclair

Publications and source records attributed to D Sinclair.

At least 19 recordsLinked to original sources
PubMed1992

Effect of calcitonin on the alcohol drinking of rats.

Previous work has shown that calcitonin inhibits eating by rats and that it affects several neurotransmitter systems suspected to play a role in alcohol consumption. The present study was an initial test of whether calcitonin does affect voluntary alcohol consumption by male Wistar rats with prolonged alcohol experience. Calcitonin (20 IU/kg) or saline was injected subcutaneously on 10 consecutive days when the rats (n = 20) had continual access to 10% (v/v) ethanol solution, and to food and water. Using a cross-over design, the effects of 40 IU/kg calcitonin vs. saline were then examined in a second 10-day treatment period. Similar patterns of effects were obtained with both calcitonin doses, but the patterns differed with alcohol, food, and water intake. Alcohol drinking showed biphasic changes with both doses, producing highly significant Treatment x Day interactions (p < 1E-10 and p = 6E-7): it was significantly reduced on the first day of calcitonin treatment and significantly increased on the last few days. Food intake was reduced on all calcitonin days although most markedly on the first. Water drinking was not altered on the first calcitonin day, but was greatly increased on the second, then gradually returned toward the baseline. In a second experiment, the animals were switched to 1 hr of alcohol access per day, and calcitonin (20 IU/kg) was administered periodically to one group 4 hr before the alcohol access. Alcohol drinking was significantly reduced in all cases when the calcitonin injection was preceded by at least 1 day without calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1992

Newborn screening for sickle cell and other hemoglobinopathies: a Canadian pilot study.

We estimated incidence of HbS disease in Quebec. It is approximately 9 cases per 100,000 births (equivalent to the incidence of the hyperphenylalanemias). Accordingly, we performed a voluntary pilot study in 9 self-identified ethnic groups; 3528 families were counselled about the relevance of newborn screening for hemoglobinopathies; and 2779 cord blood samples were collected (participation rate, 78.7%) and analyzed for Hemoglobin S and other hemoglobin variants by cellulose acetate electrophoresis. There were 95 (3.42%) positive tests on the initial (cord blood) samples, of which only 40 could be confirmed because of low participation in follow-up. We identified 8 false-positive tests; 7 had been classified initially as alpha-thalassemia trait and one as HbC heterozygosity on the first test. The relative frequency of hemoglobinopathy genes (confirmed) was: 52.5% HbS; 22.5% alpha-thalassemia; 22.5% other mutation; all but one patient with sickle cell disease were heterozygotes; the majority (71%) of HbS genes were accounted for by the 7% of screened newborns who were Black; a further 24% of the HbS genes were accounted for by 7% with Central American ancestry. Record linkage of the findings in heterozygotes for use later in life is an unsolved problem. Seventy five first-degree relatives of the 48 probands were screened in follow-up studies (64% of parents participated); 5 couples at risk for having a future child with a hemoglobinopathy were identified. Attitudes toward follow-up varied among the ethnic groups. The single family with an affected newborn (sickle cell anemia) was counselled effectively; the infant received penicillin prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Sickle Cell↗
PubMed1991

Quantifying serum antibody class and subclass responses by enzyme immunoassay in humidifier-related disease.

Antibody activity in the major classes and IgG subclasses against antigens in factory humidifier water was quantified by enzyme immunoassay (EIA) in 88 subjects who were exposed at work to the output from these contaminated humidifiers. Those with work-related symptoms had significantly higher mean titres than those who were symptom free, although values overlapped. The individuals with the highest IgG antibody titres also had the highest titres of IgM and IgA antibody, and these parameters did not discriminate between those with and without symptoms any better than the IgG titre. This was also true for the IgG subclasses where activity was predominantly measured in IgG1. Quantifying the IgG antibody allowed us to demonstrate a significant correlation with years of work exposure (P less than 0.001). There was no significant association between antibody and cigarette smoking, as assessed by smoking history and confirmed objectively by serum cotinine levels. There was a significant correlation with total IgG level (P less than 0.001) suggesting that a non-specific immune enhancement may accompany the specific response. The antibody titres were followed up to 3 years after modification of the humidification systems, and during this time symptoms resolved and the antibody levels progressively fell to undetectable levels. The EIA was adapted to measure antigen at nanogram levels thus providing a rapid test for screening of humidifer water as well as a technique that may help identify the nature of the antigens involved.

Air Conditioning↗
PubMed1990

Chromosomal structure is altered by mutations that suppress or enhance position effect variegation.

We examined the genetic, morphological, and molecular effects of position effect variegation in Drosophila, and the effects of mutations that either suppress [Su(var)] or enhance [E(var)] this phenomenon. All eight Su(var) mutations examined strongly suppress the inactivation of variegating alleles of the genes white [In(l) wm4], brown [In(2R) bwVDe2] and Stubble [T(2; 3) SbV]. The E(var) mutation enhances variegation of these loci. The chromosomal region 3C-E (26 bands) which includes the white locus is usually packaged as heterochromatin in salivary glands of the variegating strain wm4. Addition of any of the Su(var) mutations restores a more euchromatic morphology to this region. In situ hybridization to polytene chromosomes and DNA blot analyses of gene copy number demonstrate that the DNA of the w+ gene is less accessible to its probe in the variegating wm4 strain than it is in the wild-type or variegation-suppressed strains. Blot analysis of larval salivary gland DNA indicates that the white gene copy number does not vary among the strains. Hence, the differences in binding of the w+ gene probe in the variegating and variegation-suppressed strains reflect differences in chromosomal packaging rather than alterations in gene number. The effects of variegation and the Su(var) mutations on chromatin structure were analyzed further by DNAse I digestion and DNA blot hybridization. In contrast to their dramatic effects on chromosomal morphology and gene expression, the Su(var) mutations had negligible effects on nuclease sensitivity of the white gene chromatin. We suggest that the changes in gene expression resulting from position effect variegation and the action of the Su(var) mutations involve alterations in chromosomal packaging.

Animals↗
PubMed1990

Estimation of paraproteins by immunoturbidimetry and electrophoresis followed by scanning densitometry.

A comparison of paraprotein estimation by immunoturbidimetry (IT) and electrophoresis followed by scanning densitometry (EFD) showed significant differences in concentration for IgG, IgA, and IgM paraproteins. Overestimation of IgM paraproteins by IT was particularly marked. Our data suggest that both techniques should be used for IgG and IgA paraproteins but for IgM paraproteins IT was found to be unsuitable and EFD is the method of choice.

Blood Protein Electrophoresis↗
PubMed1989

The evaluation of suspected renal colic: ultrasound scan versus excretory urography.

Patients commonly present to the emergency department with a suspected diagnosis of renal colic. A prospective study of 98 patients presenting with acute flank or abdominal pain or both was conducted to determine the diagnostic accuracy of ultrasound scan compared with excretory urography for the diagnosis of urinary tract calculi. All patients underwent standardized ultrasound scan and excretory urography as independent procedures. Two staff radiologists who reported the procedures were blinded to the results of the other diagnostic test and ultimate clinical outcome. All patients discharged home from the ED were followed to the hospital urology clinic. The diagnosis of urinary calculus was made only by identification of calculus at surgery or by reported passage of a stone by the patient. Of 85 patients available for follow-up study (56 men, 29 women; mean age, 40.5 years; range 18 to 77 years), calculi were identified in 69 (81%). Ultrasound identified calculi in 44 patients (sensitivity, 64%; specificity, 100%). Excretory urography identified calculi in 44 patients (identical sensitivity and specificity). When the presence of obstructive hydronephrosis only was used to diagnose renal calculi, ultrasound scan identified 59 patients (sensitivity, 85%; specificity, 100%) and excretory urography identified 62 patients (sensitivity, 90%; specificity, 94%). When the results of both diagnostic modalities were combined, calculi were identified in 59 patients (sensitivity, 85%; specificity, 100%) and hydronephrosis was seen in 66 patients (sensitivity, 95%; specificity, 94%). Our study shows that the diagnostic abilities of these procedures are equal in the detection of renal calculi.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Climate, intermittent humidification, and humidifier fever.

Two summer outbreaks of humidifier fever (HF) are described in a microprocessor factory (factory A) and a printing factory (factory B). The air in each factory was humidified intermittently and controlled by present humidistats operating to maintain a relative humidity of 45% by an air handler incorporating a spray humidifier in factory A and two ceiling mounted spray humidifiers in factory B. Questionnaire data from each workforce suggested that although symptoms apparently occurred most commonly in both factories on return from holiday (41/57, 71.9%), many subjects (24/40, 60%) in factory A also had intermittent symptoms of ill defined periodicity for some time before the disorder was recognised. Similar intermittent symptoms with no discernible pattern occurred in factory B in a smaller number of subjects (4/17, 23.5%), all of whom were night or rotating shift workers. Both episodes of humidifier fever after return from summer holiday developed when nocturnal air temperatures were unseasonably low; not on the day of return to work but two days later (factory A) and one day later (factory B). Symptoms were most common in most workers who had circulating serum IgG antibody measured by ELISA to humidifier sludge in factory B (14/17, 82.9%) but were most common in IgG antibody negative subjects in factory A (27/40, 67.5%). A more classic form of humidifier fever redeveloped in factory B during winter when meteorological recordings suggested that humidification of intake air was more continuous. Humidifier fever in winter may have been the major influence on the formulation of the symptom pattern thought to be relevant for recognition of the disorder. A form of the illness, however, can occur during the summer which is camouflaged by intermittent humidification when the symptoms appear to be more closely associated with cool nocturnal air intake and unrelated to the pattern of attendance at work.

Air Conditioning↗
PubMed1989

Oligoclonal immunoglobulins in HIV infection.

We tested 150 patients infected with human immunodeficiency virus (HIV) for the presence of oligoclonal bands in serum, prompted by reports that these abnormal proteins may have prognostic significance. Sixty HIV-negative individuals from "at-risk" groups were tested along with 80 HIV-negative, healthy blood donors for the presence of these bands. All sera were tested by isoelectric focusing, because it is more sensitive for this purpose than more-conventional electrophoretic techniques. In the HIV-positive group, 61% of the sera had oligoclonal bands; in the HIV-negative "at-risk" group, 36% had bands. No bands were detectable in sera from the healthy blood-donor group. Some patients were also followed for differing periods throughout their infection, and changes in their oligoclonal banding patterns could not be correlated with disease progression. The fact that oligoclonal bands were found to be present without HIV infection in a substantial number of individuals from within the "at-risk" groups leads us to conclude that the presence of oligoclonal bands in HIV infection is of limited prognostic significance.

HIV Seropositivity↗
PubMed1988

The defect of lymphocyte locomotion in chronic lymphocytic leukaemia: studies of polarization and growth-dependent locomotion.

This paper reports a study of the locomotor behaviour of the lymphocytes from 17 patients with chronic lymphocytic leukaemia (CLL). The cells were studied both immediately after separation from blood and after culture for 24 to 48 h with a range of growth activators. Cells direct from blood were tested for polarization in fetal calf serum (FCS 20%), phorbol myristate acetate (PMA 10(-7)M) and colchicine (10(-5)M). The polarization of lymphocytes from CLL patients with high white cell (WBC) counts (greater than 10 X 10(9)/litre) was very poor in FCS and PMA, though the cells from about half of these patients responded well to colchicine. The response of cells from patients with low white cell counts was the same as that of controls. The growth activators, PHA (1 micrograms/ml), anti-CD3 antibody (OKT3 2.5 ng/ml), Cowan strain Staphylococcus aureus (SAC; 1.5 X 10(7)/ml) and PMA (10(-8)M) induced an increase in the proportion of locomotor lymphocytes from controls and from CLL patients with low white cell counts during 24 h of culture. Cells from patients with high white cell counts showed very little increase in locomotor forms in any activator including PMA and the B cell mitogen SAC. This defect was seen in both polarization assays and collagen gel invasion assays. The findings suggest that CLL lymphocytes have a defect of locomotion demonstrable at two levels: (a) the cells fail to respond by polarizing immediately upon stimulation; colchicine treatment reverses this defect in some cases; (b) they also fail to acquire locomotor capacity during culture with activators of growth.

Aged↗
PubMed1987

Lymphocyte migration in murine malaria during the primary patent parasitaemia of Plasmodium chabaudi infections.

Inoculation of adult C57/BC mice with 10(6) red cells infected with Plasmodium chabaudi induces an acute primary parasitaemia peaking around the 8th or 9th day and lasting 10-14 days. Concomitantly, the spleen enlarges to reach 6-7 times its normal weight by the 11th day. The major component of this increase is between day 9 and 11, due primarily to an increase in erythropoietic cells in the red pulp. Although initially the white pulp increases in size, by day 11 it shows partial lymphocyte depletion which coincides with the occurrence of massive absolute lymphocytosis in the peripheral blood. 3H-Thymidine labelling in vivo suggests that this lymphocytosis is not due to lymphocytopoiesis. Collectively, these findings suggest a redistribution of lymphocytes. Lymphocyte migration was investigated around peak parasitaemia, using enriched populations of T and B cells labelled with 51Cr. The traffic patterns of these cells were followed over 36 h. These studies show decreased uptake (or decreased retention) of T and B cells by spleens of infected mice. Concomitantly, there is increased retention of T and B cells in the liver and lungs of infected mice, suggesting a complex redistribution of these cells. Lymphocyte migration to lymph nodes was unimpaired in these animals. Similar changes in T and B cell migration do not occur in Babesia microti infections in C57/BL mice. We relate our findings to histological and histochemical changes in the liver and spleen of malarious mice and discuss the significance of these findings to immunosuppression in malaria and to the development of parasiticidal immunity.

Animals↗
PubMed1986

Quantitation of monoclonal immunoglobulins by immuno-isoelectric focusing and its application for monitoring secretory B cell neoplasia.

A scheme for quantitation of serum and urinary paraproteins is described using isoelectric focusing and scanning densitometry. Paraproteins could be quantified using this system when present at concentrations ranging from 1 mg/ml to 26 mg/ml, depending on the immunoglobulin class. The relevance of these results to monitoring secretory B cell neoplasia and the distinction between monoclonal gammopathy of undetermined significance and myeloma is discussed.

Antibodies, Monoclonal↗
PubMed1986

The incidence, clonal origin and secretory nature of serum paraproteins in chronic lymphocytic leukaemia.

Immuno-isoelectric focusing (IIEF) showed a 61% incidence of serum paraproteinaemia in 56 patients with chronic lymphocytic leukaemia (CLL). A strong correlation between the serum paraprotein heavy chain isotypes and those of the cytoplasmic heavy chain immunoglobulins was observed with no discrepancy noted in light chain expression. Density gradient ultracentrifugation analysis of selected sera containing monoclonal IgM showed that the IgM paraproteins were mostly 19S, secretory IgM but one patient was found to have both 19S and 8S monoclonal IgM. When the cellular origin of the IgM and IgD paraproteins found in one patient was investigated, both paraproteins were found to share the same idiotype and originate from the neoplastic clone. These findings confirm the view that there is an incomplete maturation block in chronic lymphocytic leukaemia and that in vivo secretion of paraproteins by the neoplastic cells is a relatively common occurrence.

Adult↗
PubMed1986

The incidence of monoclonal gammopathy in a population over 45 years old determined by isoelectric focusing.

Immuno-isoelectric focusing (IIEF), a technique previously shown to be sensitive for the detection of paraproteinaemia, was used to test 200 individuals over the age of 45, without history of B cell neoplasm, for the presence of serum paraproteinaemia. 11% of these individuals had evidence of paraproteinaemia detectable by IIEF compared with only 2% by zonal and immunoelectrophoresis. A further 12% had oligoclonal immunoglobulins and the remainder had no qualitative abnormality of the immunoglobulin profile. These results are discussed with particular reference to the aetiology, diagnosis and monitoring of potential B cell neoplasm in high risk individuals or groups.

Aged↗