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Biomedical subjects

L U Lamm

Publications and source records attributed to L U Lamm.

At least 19 recordsLinked to original sources
PubMed1995

Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein.

Mannan-binding protein (MBP) is a serum lectin participating in the innate immune defense by opsonizing various microorganisms for phagocytosis. Opsonization defect due to MBP deficiency and low levels of the protein can partially be explained by the dominant effect of three different mutations in the structural part of the MBP gene. Large interracial differences in the frequencies of these variants have previously been described, but they cannot explain the large interindividual variation in MBP serum concentration. We describe the existence of additional polymorphisms at positions -550 (H/L variants) and -221 (X/Y variants) in the promoter region of the gene. The promoter haplotypes, HY, LY, and LX, show associations with high, medium, and low levels of MBP serum concentrations, respectively. Moreover, this represents a genetic system with additive effect of haplotypes in which a low producing LX haplotype in the homozygous state down-regulates the basal expression of MBP as effectively as a single structural variant. Populations of pure Eskimos, Caucasoids, and black Africans show marked interethnic differences in the frequencies of promoter haplotypes regulating the expression of the normal peptide, with the HY haplotype frequency varying from 0.83 in Eskimos via 0.33 in Caucasoids to 0.08 in Africans. The LY haplotype frequency varies from 0.04 in Eskimos via 0.39 in Caucasoids to 0.23 in Africans. The LX haplotype frequency varies from 0.03 in Eskimos via 0.24 in Caucasoids to 0.23 in Africans. The effect of the promoter variants can explain almost all of the ethnic differences not explainable by the structural variants alone.

Base Sequence↗
PubMed1995

Cancer risk after renal transplantation in the Nordic countries, 1964-1986.

The theory that cancer may arise under conditions of reduced immune capacity is supported by observations of humans with immune deficiencies such as occur following organ transplants. However, no study on humans has been done in which the reference population was the same as that in which the cancer cases arose and in which there was a sufficiently long period of follow-up. Information on 5,692 Nordic recipients of renal transplants in 1964-1982 was linked with the national cancer registries (1964-1986) and population registries. Person-years at risk were calculated from the date of first transplantation until death or the end of the study period and were multiplied by the appropriate age- and calender-specific incidence rates to obtain the expected numbers of cancers. Standardized incidence ratios (SIR) were calculated after stratification by a number of recorded variables. Altogether, 32,392 person-years were accrued, and 471 cancers occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95% CI, 4.0 to 5.2) for females. Significant overall 2- to 5-fold excess risks in both sexes were seen for cancers of the colon, larynx, lung and bladder, and in men also for cancers of the prostate and testis. Notably high risks, 10-fold to 30-fold above expectation, were associated with cancers of the lip, skin (non-melanoma), kidney and endocrine glands, also with non-Hodgkin's lymphoma, and in women also with cancers of the cervix and vulva-vagina. Among a number of donor and recipient variables studied, including tissue types and compatibility (ABO, HLA, DR), age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites. Kidney transplantation increases the risk of cancer in the short and in the long term, consistent with the theory that an impaired immune system allows carcinogenic factors to act. The tumor risk is small in comparison with the benefits of transplants, but patients should be followed up for signs of cancer.

Adult↗
PubMed1992

Diallelic polymorphism may explain variations of the blood concentration of mannan-binding protein in Eskimos, but not in black Africans.

Mannan-binding protein (MBP) is a lectin which, upon binding to certain carbohydrates, activates the classical pathway of complement without the involvement of antibody or C1q. Deficiency of the MBP is associated with an opsonic defect and recurrent infections during early life. An amino acid substitution in the exon 1 at codon 54 in the MBP gene (GGC [glycine] to GAC [aspartic acid]) has been shown to be closely associated with low MBP concentration in Caucasoids. The gene frequency of the mutant allele in this population has been estimated at 0.13. In the study described here, we investigated the association between the mutant allele and MBP protein concentration in Eskimos from East-Greenland and black Africans from the Baringo District in Kenya. The frequency of the GAC allele was identical in Eskimos and Caucasoids (0.13). No overlap with regard to MBP concentration between the genotypes was found in the Eskimos. In contrast, the Africans revealed a low frequency of the GAC allele (0.009). However, the median MBP protein concentration was approximately 5 times lower among the Africans than the Eskimos. In 12.6% of the Africans and in 2.5% of the Eskimos, MBP was undetectable. Thus, MBP deficiency is the most frequent immunodeficiency so far described. The high prevalence of MBP deficiency among healthy individuals indicates that MBP deficiency also confers some selective advantages. We advance the hypothesis that MBP deficiency is maintained in populations because MBP deficiency decreases the infectivity of some intracellular micro-organisms which are dependent on opsonization.

Adolescent↗
PubMed1991

Clinical applicability of the immunomagnetic beads technique for serological crossmatching in renal transplantation.

The aim of the present prospective study was to investigate the clinical applicability of the immunomagnetic (IM) beads technique for serological crossmatching (XM) in renal transplantation. The IM XM were read after various periods of incubation, and the results were compared with those obtained by the conventional Kissmeyer-Nielsen (KN) technique. A total of 132 sera from 96 potential recipients were tested against cells from 62 donors. Eight-nine KN T-cell XM-negative renal allograft transplantations were performed, and the IM XM results were related to clinical 3-month follow-up data (incidence of primary non-function, never functioning grafts, graft losses and rejection episodes). The IM technique was clearly more sensitive than KN, and sensitivity increased markedly with increasing duration of incubation. KN-, IM+ reactions were predominantly found among sera from patients with panel-reactive antibodies (PRA, 2p less than 0.01), and thus probably caused by HLA antibodies. However, positive IM XM, appearing after more than 35 min of incubation, did not influence the overall clinical outcome in the observation period. With reading after exactly 35 min of incubation, XM results obtained by IM and KN techniques correlated well. Thus, we believe, that the IM XM technique will be as safe and effective in avoidance of hyperacute rejections as the conventional assay. In the present material, the incidence of primary nonfunction was significantly (2p = 0.0023) higher among PRA+ recipients compared to PRA- patients. To conclude, we recommended the IM technique with reading after exactly 35 min of incubation for easy, fast (70 min) and reliable XM, that is always possible to perform using peripheral blood.

Cell Separation↗
PubMed1991

HLA-DR/RFLP compatible corneal grafts.

Fifty-one elective high risk transplantations were matched according to HLA/DR antigens and RFLP-subtypes. The 18 months survival of the grafts are 93% in the matched group compared to 50% in a non-matched compatible historical control group.

Adolescent↗
PubMed1990

Pregnancy zone protein: a re-evaluation of serum levels in healthy women and in women suffering from breast cancer or trophoblastic disease.

Pregnancy zone protein (PZP) and alpha 2-macroglobulin (alpha 2M) serum concentrations were studied in healthy female donors, in women suffering from benign and malignant breast tumours, and in relation to normal and abnormal pregnancies. PZP was found to be useless as a tumour marker. Thus, PZP levels in breast cancer patients did not differ from those of fibroadenoma patients or healthy women. There was no correlation between PZP (or alpha 2M) concentrations and the pTNM-classification or metastatic burden of the breast cancer patients. Moreover, PZP levels were unaffected by cancer treatment and the course of disease. Neither patients nor control donors showed any age-dependent increase in circulating PZP and the mean serum value (8.38 +/- 4.83 mg/l, mean +/- SD) determined in a population of 154 non-pregnant women was considerably lower than that of most previous reports. Serum concentrations were unchanged during the normal menstrual cycle, but increased during pregnancy. However, late pregnancy sera (35th gestational week) contained significantly less PZP than previously reported by others, and non-pregnancy levels were observed in one out of 22 cases. Results obtained in hydatidiform mole patients were similar to findings in normal pregnancy. Neither serum 17 beta-oestradiol nor morphological differentiation between complete and partial mole showed any correlation with circulting PZP levels. Apart from a moderate increase during gestation, alpha 2M concentrations showed little variation between the populations examined.

Adult↗
PubMed1990

Ciclosporin-induced immunosuppression in vitro. II. Variation in sensitivity and binding capacity.

The purpose of the present study was to analyse and correlate variations in lymphocyte sensitivity to, and binding of, ciclosporin (CsA) in vitro. Peripheral blood lymphocytes from healthy individuals were harvested over a 5-week period and activated with purified protein derivative (PPD) or alloantigens in the presence or absence of CsA (1 microgram/ml). Sensitivity to CsA was expressed as the ability of the drug to suppress cell proliferation ([3H]thymidine incorporation) and high-affinity interleukin-2 receptor (IL-2R) expression. Binding capacity was tested in a [3H]CsA binding assay. A significant variability in both sensitivity and binding capacity was recorded between individuals (P less than 0.001). There was no correlation between high sensitivity and high binding capacity. The intraindividual day-to-day variability did not differ significantly from the experimental (intra- and interassay) variability. The CsA-induced suppression of high-affinity IL-2R expression varied between 57.1 and 98.9%, while suppression of [3H]thymidine incorporation varied between 81.0 and 97.4%. Specific binding of 10 nM [3H]CsA at 37 degrees C varied between 5.4 and 10.7%.

Analysis of Variance↗
PubMed1989

Female haemophilia A in a family with seeming extreme bidirectional lyonization tendency: abnormal premature X-chromosome inactivation?

We studied a female child with mild classical haemophilia A, presenting with a F VIII deficiency similar to that detected in her maternal grandfather. Investigations on several occasions showed that the obligate carrier mother of the proposita had normal VIII:C activity, whereas her likewise obligate carrier sister had a typical carrier VIII:C/vWf:Ag pattern. The child was a phenotypically normal female with normal karyotype. Her father had no clinical or biochemical signs of haemophilia A. RFLP-analysis using DX13 and St14 probes each elicited one allele (5.8 and 3.4 kb, respectively) segregating along with the affected F VIII gene from the hemizygous grandfather to both his daughters and further to the haemophilic female child. The paternity of the child was analyzed using various red cell and HLA antigens and RFLP by p29C, a probe detecting polymorphic hypervariable TaqI and PstI fragments in the pseudoautosomal areas of the X- and Y-chromosomes. All results obtained were concordant with the declared paternity. RFLP-analysis, using single (Pst I) and double digestion (Pst I/Hha I) of DNA and a PGK probe, revealed a remarkable difference in hybridization fragments, strongly suggesting hypermethylation, and in consequence, preferential X-chromosome inactivation in the proposita. This points to extreme lyonization as the most plausible explanation for haemophilia A in this female child. A familial tendency to abnormal premature X-chromosome inactivation is speculated.

Child, Preschool↗
PubMed1988

Segregation of HLA-DR, -DQ and -DP phenotypes and restriction fragment length polymorphic fragments in two recombinant families.

Members of two families were typed for HLA-DR, -DQ and -DP specificities by means of sera and local PLT bulk reagents. One B:C and one DR:DP cross-over were identified in both families. The restriction fragment length polymorphism (RFLP) was analyzed by southern blotting and the use of DR beta, DR alpha, DQ beta, DQ alpha, DP beta and DP alpha probes. Previous observations concerning typical RFLP patterns for serological DR/DQ- and cellular DP-specificities were confirmed. With respect to recombinant haplotypes, RFLP was informative in both families. All polymorphic fragments-(DRB, DQA and B as well as DPA and B)-segregated together in the HLA-B:DR cross-overs. In the DR:DP recombinant children, the DR and DQ fragments were separated from DP fragments, demonstrating that DP-types as defined by PLT and RFLP map close together. No cross-hybridization between the segregating fragments was detected with the various probes.

Female↗
PubMed1988

HLA-DR typing using restriction fragment length polymorphism (RFLP) with one enzyme and two probes.

A panel of 43 homozygous and 36 heterozygous highly selected cells, representing the most common DR-specificities, were investigated with the DNA hybridization technique. By using a single restriction enzyme, TaqI, and two probes, DR beta and DQ alpha, it was possible to construct assignment criteria giving a reasonable definition of DR1, 3, 4, 5, 7 + w9, w8, w10 and w11. The criteria sometimes require that certain bands must not be present. Therefore, in certain genotypic combinations, the presence or absence of the particular specificity on one haplotype cannot be decided. This is a problem only for DR2 and DRw6, which for this reason cannot be assigned in about 1/3 to 1/4 of the cases. The association between RFLP assignment and serological assignment is not absolute, the correlation coefficients ranking from 0.62 to 1.0. In the case of false negative RFLP assignment, this may be due to genetic heterogeneity, as in the case of a DR2 individual who proved to be Dw12 and not Dw2 associated. It is often stated that interpretation of the RFLP pattern is particularly difficult in random or heterozygous individuals compared to proven homozygotes. This is not the case in the present study, where in fact correlation coefficients between RFLP and serologically determined DR specificities were higher in the heterozygotes (range 0.79-1.00).

DNA↗