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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 901 records · Page 50Linked to original sources

Genetic heritability and shared environmental influences of type A measures in the NHLBI Twin Study.

Data from the NHLBI Twin Study were used to investigate the genetic component in a number of Type A measures given to these twins during a second cardiovascular examination. Specifically, the objective of the current study was to determine the extent to which various Type A measures are influenced by genetic effects and by measurable environmental and cultural factors. Analyses of these data for twins yielded a number of results. First, the Type A behavior pattern as assessed by the structured interview was only weakly associated with self-report inventories developed as alternatives to the structured interview. Second, among the self-report measures of Type A, only the Thurstone Temperament Schedule Active scale showed a clear significant genetic component. Most important, a number of demographic and social characteristics known to be associated with the various Type A scales had a differential effect on twin similarities. Specifically, for the job involvement subscale of the Jenkins Activity Survey, twins of both zygosities became equally similar after adjustments for covariates, while no effect on twin similarity was noted for the Thurstone Temperament Schedule Active scale. It is concluded that a complex constellation of genetic predispositions and acquired behaviors underlies the Type A behavior construct.

Aged↗

Klinefelter's syndrome: an analysis of the origin of the additional sex chromosome using molecular probes.

The results of our study of the origin of the additional X chromosome in 39 males with a 47,XXY chromosome constitution are reported. We used a total of 20 X-linked RFLPs and successfully determined the origin of all 32 patients in whom DNA from both parents was available, and a further 3 in whom DNA was available from the patient and mother only. Males whose additional X chromosome was maternal in origin were further investigated using an X-linked centromere specific probe to determine the cell division at which the error occurred. Our results showed 53% of the non-disjunction to be attributable to pat mei I errors, 34% to mat mei I errors, 9% to mat mei II errors and 3% to a post-zygotic mitotic error. In the great majority of patients resulting from an error of maternal meiosis there was clear evidence of recombination involving the non-disjoined chromosomes, suggesting that absence of recombination is not an important aetiological factor in non-disjunction of the X chromosome in female meiosis. There was no alteration of parental age associated with the paternally derived 47,XXY males but a marked increase in maternal age among the maternally derived 47,XXY males, the increase being associated with mat mei I but not mat mei II errors. The proportion of paternally and maternally derived cases was similar among different ascertainment classes, suggesting that there is no dramatic effect of parental origin of the additional X chromosome on the phenotype of 47,XXY males.

Age Factors↗

A cytogenetic study of 47,XXY males of known origin and their parents.

A number of patients with both sex chromosome aneuploidy and the fragile X syndrome have been reported and this has led to the hypothesis that females heterozygous for the fragile X mutation have an increased rate of meiotic nondisjunction. Furthermore the suggestion has frequently been made that a predisposition to meiotic nondisjunction is associated with an increase in mitotic nondisjunction. We have tested these two hypotheses by examining the chromosomes of a series of 47,XXY males and their parents. In the majority the parental origin of the additional sex chromosome was known. The cells were cultured under conditions suitable for demonstrating the fragile X and 100 cells were scored 'blind' from the patients and both parents. No fragile X individual was seen and there was no difference in the proportion of aneuploid cells between the parents in whom the nondisjunction event occurred and the control parents. Therefore, our results lend no support to the suggestions that the fragile X is associated with an increase in sex chromosome aneuploidy or that individuals in whom meiotic nondisjunction occurs have an increased level of mitotic nondisjunction.

Adolescent↗

Transient neonatal hypothyroidism due to transplacental transfer of maternal immunoglobulins that inhibit TSH binding, TSH-induced cAMP increase and cell growth.

Transient neonatal hypothyroidism due to transplacental transfer of maternal blocking type TSH receptor antibodies (TRAb) was found in a baby born to a 27-yr-old mother, who had been receiving thyroxine medication for primary myxedema. Maternal IgG inhibited radiolabelled TSH binding to its receptor (TBII), TSH-stimulated thyroid adenylate cyclase (AC) activation (TSII) and TSH-stimulated 3H-thymidine uptake (TGII) in cultured rat thyroid cells (FRTL-5). At birth, the baby's IgG showed similar activities to maternal IgG but all these activities decreased gradually, and disappeared from her serum within 12 weeks of age. In the baby, initially nonvisualized thyroid was clearly visualized on 99 m-Tc thyroid scintigraphy when all these blocking activities disappeared, TSII and TGII being decreased more slowly than TBII, and the baby remained euthyroid after discontinuation of thyroxine. This study suggests that such IgGs induced hypothyroidism and thyroid atrophy in the mother and were responsible for transient neonatal hypothyroidism in the baby.

Adult↗

Comprehensive clinical and statistical analysis of hemophilia in Korea.

A Total of 498 cases of hemophilia which were reported by sixteen medical centers in Korea were reviewed and analyzed. Hemophilia A comprised 425 cases (85.3%) and the remaining 73 cases (14.7%) were hemophilia B. One case was female and all other cases were male. There were known hemophilia patients in the family in 43.0% of cases and the involved members were brothers, maternal cousins, maternal uncles, and maternal grandfathers in descending order of frequency. The major symptoms of the patients were hemorrhagic, such as easy bruising and hemarthrosis followed by prolonged bleeding after trauma and soft tissue hematoma. The incidence of hemarthrosis increased significantly with age. The pediatric age group below the age of 15 consisted of 67.1% of the cases. According to the age at diagnosis, half (54.2%) of the severe cases were diagnosed before the age of 1 year. APTT was prolonged over 40 seconds in all cases and 291 cases showed severe prolongation over 80 seconds. Of 498 cases 273 cases (54.8%) belonged to the severe form (factor VII or IX level, less then 1%), whereas 182 cases (36.5%) and 43 cases (8.7%) belonged to the moderate (factor VIII or IX, 2-5%) and mild form (factor VIII or IX, 6-25%), respectively, Chronic arthropathy was present in 236 cases (49.6%), and the incidence increased significantly with age. The management of chronic arthropathy most commonly employed was rehabilitation in 25.4% of cases, but in 50.8% no management was given at all. The involved joints in descending order of frequency were knees, elbows and ankles. The complications were intracranial hemorrhage, Gl bleeding and nerve palsy in 48, 24, and 13 cases, respectively.

Adolescent↗

Refractoriness to platelet transfusion after single-donor consecutive platelet transfusions and its relationship to platelet antibodies.

In thirty patients with acute leukemia and severe aplastic anemia receiving random single donor platelet transfusions, the development of refractoriness by consecutive platelet transfusions with cytapheresis and its relationship to the appearance of anti-platelet antibodies were investigated. The median number of platelet transfusions inducing refractoriness was 13 times, and 20% of the patients remained unrefractory despite of the repeated multiple platelet transfusions up to 20 to 25 times. The results of anti-platelet antibody tasts by the enzyme-linked immunosorbent assay(ELISA) and immunofluorescent techniques(IFT) showed no statistically significant relationship with the refractoriness (p greater than 0.1). Although there was significant correlation between the results of ELISA and IFT, both tests were insufficient to find out refractoriness even with the use of pooled platelets from multiple donors as target cells. This study shows that 13 single donor platelet transfusions result in refractoriness, that both ELISA and IFT are insufficient to detect refractoriness despite of their significant correlation, and that other methods than these are needed in order to detect alloimmunization.

Adolescent↗

Pathologic activity of Plasmodium berghei prevented but not reversed by dexamethasone.

Dexamethasone has recently been shown to block the production of cachectin (implicated in the pathogenesis of cerebral malaria) if administered prior to endotoxin induction of mouse macrophages. Using the hamster cheek pouch-cerebral malaria model, we tested the hypothesis that dexamethasone is effective as a therapeutic agent in severe malaria if given before some yet undefined trigger point in the disease. Infected hamsters were treated with dexamethasone (0.7 mg/kg) daily on days 7-12, 4-12, or 1-12 post-challenge. When treatment was started on day 1, whole body oxygen consumption (used as a measure of erythrocyte transport to sites of diffusion) on day 12 was greater than (P less than 0.05) that of infected control animals, though the degree of anemia was no different in treated and untreated groups. Furthermore, treatment produced a reduction in monocyte accumulation, capillary malfunction, and monocyte/red blood cell aggregate formation observable in the cheek pouch in vivo and a similar reduction in monocyte presence, capillary pathologic change, and multifocal hemorrhage in the brain on postmortem. These data suggest that mediator(s), whose production can be blocked by pretreatment with dexamethasone, are involved in the pathogenesis of disease leading to death of the Plasmodium berghei infected hamster.

Animals↗

Use of avidin-biotin-glucose oxidase complex to detect antimalarial antibody in serum by light microscopy.

An immunohistochemical assay was developed combining an avidin-biotin-glucose oxidase complex procedure (ABC-GO) with light microscopy to detect specific antibody against Plasmodium falciparum. Thin blood films were prepared from culture material of P. falciparum and fixed with acetone. Antibody was detected by successive incubations with test serum, biotinylated goat antihuman antibody, avidin-biotin-glucose oxidase complex, and glucose oxidase substrate. In the presence of reactive serum, a blue precipitate formed on the parasites and could be visually observed with a 40x objective. Sera from patients with single infections for P. vivax or P. ovale were unreactive. No cross-reactivity was observed with sera from patients with rheumatoid arthritis, filariasis, amebiasis, schistosomiasis, dengue, scrub typhus, leptospirosis, or toxoplasmosis. The sensitivity of ABC-GO is comparable to that of the indirect fluorescent antibody test.

Animals↗

The ELISA-U: an enzyme-linked immunosorbent assay using urease as the enzyme marker for rapid detection of Plasmodium falciparum antibody in human serum.

A visual, enzyme-linked immunosorbent assay using urease (ELISA-U) as the enzyme marker was adapted for rapid detection of antibody against Plasmodium falciparum. Flat-bottom, 96-well microtiter plates were coated with P. falciparum soluble antigen obtained by saponin and NP-40 treatment of parasite cultures. Antibody was detected by successive incubations with test sera, urease-conjugated rabbit-human antibody, and urease substrate. Reactive sera developed a definite and easily visualized purple color. Sera from patients with single infections of P. vivax or P. ovale were unreactive. No cross-reactivity was noted with sera from patients with rheumatoid arthritis, filariasis, amebiasis, schistosomiasis, dengue, scrub typhus, leptospirosis, or toxoplasmosis. The procedure can be performed at room temperature and completed within 1 hr. The sensitivity of the assay is comparable to that of the indirect fluorescent antibody test at all but the lowest dilutions tested.

Animals↗

Interaction of Malaysian sera with Plasmodium vivax sporozoite antigen.

A seroepidemiologic survey of Plasmodium vivax and Plasmodium falciparum transmission was conducted in 94 Orang Asli children and adults. The prevalence of malaria was 46% in this population, and infections due to P. vivax and P. falciparum occurred with equal frequency. Multi-species infection was common, particularly in children less than 10 years of age. Circumsporozoite (CS) antibodies to P. vivax were detected by ELISA, using the recombinant protein NS181V20, in sera from 53-95% of all subjects in this study. The specificity of reactivity to NS181V20 was confirmed by immunofluorescence using air-dried sporozoites. CS antibodies to P. falciparum were present in less than 50% of the population less than 30 years of age. These data support further testing of this protein as a candidate vivax vaccine.

Adolescent↗

Lipoprotein structural abnormalities in chronic renal failure with and without hemodialysis.

Nine patients with chronic renal failure in maintenance hemodialysis (CRF-HD) and nine without hemodialysis (CRF) showed similar modifications in the structure and composition of VLDL and LDL isolated by density gradient centrifugation as compared to normal controls. In very low density lipoproteins (VLDL), the ratios of triglycerides to protein and of cholesterol to protein were strongly correlated. All patients, independently of their cholesterol and triglyceride levels, presented a "beta-VLDL" caused by an increment in the isoelectric point of the particles in the density range 1.006-1.019 g/ml. This was probably due to the augmented proportion of apoB in them and is not associated with the E2 phenotype. The results indicate that the structural modifications of VLDL and low density lipoprotein (LDL), present in chronic renal failure, are not changed by maintenance hemodialysis and that they are not necessarily associated with hyperlipidemia.

Adult↗

The half-lives of IgG subclasses and specific antibodies in patients with primary immunodeficiency who are receiving intravenously administered immunoglobulin.

With the increased use of immunoglobulin for intravenous use (IGIV) as replacement therapy for patients with primary immunodeficiencies, a natural concern is whether such preparations demonstrate a normal turnover rate with regard to total IgG, individual IgG subclasses, and specific antibody titers. We have conducted such a pharmacokinetic study on a cohort of eight patients with an IGIV preparation, Gammagard. For total IgG, the half-life found was 25.8 days; for IgG1 it was 29.7 days; for IgG2 it was 26.9 days; and for IgG3 it was 15.7 days. The results are similar to those reported for endogeneous IgG. Half-lives for antibodies to S. minnesota (Re 595 mutant), cytomegalovirus, and S. pneumoniae were of the same order of magnitude as that for total IgG. We conclude that this IGIV preparation is catabolized in patients with primary immunodeficiency at a rate similar to that of native IgG in normal individuals.

Adolescent↗

Bcl-1 gene rearrangements in B cell lymphoma.

We analyzed 50 B cell lymphoma samples by Southern blot analysis, using the bcl-1 and heavy chain immunoglobulin (JH) probes with two or more restriction endonucleases. All samples showed JH rearrangement, and three samples (two diffuse small lymphocytic lymphomas and one diffuse large cell lymphoma probably transformed from a diffuse small lymphocytic lymphoma) demonstrated rearranged bcl-1 sequences. The three samples showed the t(11;14)(q13;q32) chromosome translocation, and all three contained rearranged JH fragments that comigrated with the rearranged bcl-1 fragment. The breakpoint of the translocation occurred within a 1.6-kb region on chromosome 11 in the three cases. Two of the three patients had primary refractory disease. Two of the three patients had gastrointestinal involvement. Bcl-1 rearrangement may identify an unusual subset of patients with primary refractory disease with gastrointestinal involvement. It may also describe a unique subset of large cell lymphoma patients transformed from diffuse small cell histology.

B-Lymphocytes↗

[Dissecting aortic aneurysm of DeBakey type II diagnosed by color Doppler flow imaging and treated by a Bentall surgical procedure: a case report].

A 33-year-old man with known annuloaortic ectasia was admitted to the hospital because of chest pain. A dissecting aortic aneurysm was strongly suspected, but angiography was not performed because of his history of allergic reaction to iodine contrast material. Two-dimensional echocardiography demonstrated a markedly dilated basal aorta. The aortic wall immediately above the right sinus of Valsalva appeared to divide the aortic lumen into anterior and posterior channels. A defect in the intimal flap with a diameter of two cm was also detected six cm above the aortic ring. Color Doppler flow mapping showed blood flow passing through a probable entrance tear from the true lumen into the false lumen. Reentry could not be detected by Doppler imaging. All major aortic tributaries were presumed patent and supplied via the true lumen. The patient underwent successful emergency Bentall surgical procedure and recovered. It is emphasized that in some cases of DeBakey type I or II aortic dissection, color Doppler flow imaging is helpful for determining indications for emergency surgery.

Adult↗