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Abstract Background Approximately half of the mitochondrial genome inherent within 546 individual Atlantic salmon (Salmo salar) derived from across the species' North Atlantic range, was selectively amplified with a novel combination of standard PCR and pyro-sequencing in a single run using 454 Titanium FLX technology (Roche, 454 Life Sciences). A unique combination of barcoded primers and a partitioned sequencing plate was employed to designate each sequence read to its original sample. The sequence reads were aligned according to the S. salar mitochondrial reference sequence (NC_001960.1), with the objective of identifying single nucleotide polymorphisms (SNPs). They were validated if they met with the following three stringent criteria: (i) sequence reads were produced from both DNA strands; (ii) SNPs were confirmed in a minimum of 90% of replicate sequence reads; and (iii) SNPs occurred in more than one individual. Results Pyrosequencing generated a total of 179,826,884 bp of data, and 10,765 of the total 10,920 S. salar sequences (98.6%) were assigned back to their original samples. The approach taken resulted in a total of 216 SNPs and 2 indels, which were validated and mapped onto the S. salar mitochondrial genome, including 107 SNPs and one indel not previously reported. An average of 27.3 sequence reads with a standard deviation of 11.7 supported each SNP per individual. Conclusion The study generated a mitochondrial SNP panel from a large sample group across a broad geographical area, reducing the potential for ascertainment bias, which has hampered previous studies. The SNPs identified here validate those identified in previous studies, and also contribute additional potentially informative loci for the future study of phylogeography and evolution in the Atlantic salmon. The overall success experienced with this novel application of HT sequencing of targeted regions suggests that the same approach could be successfully applied for SNP mining in other species.

A letter to the editor is presented in response to the article concerning the therapeutic use of lithium manic-depressive illness, published in the previous issue.

The success of genome-wide association studies (GWAS) in identifying common, low-penetrance variant-cancer associations for the past decade is undisputed. However, discovering additional high-penetrance cancer mutations in unknown cancer predisposing genes requires detection of variant-cancer association of ultra-rare coding variants. Consequently, large-scale next-generation sequence data with associated phenotype information are needed. Here, we used genotype data on 166,281 Icelanders, of which, 49,708 were whole-genome sequenced and 408,595 individuals from the UK Biobank, of which, 41,147 were whole-exome sequenced, to test for association between loss-of-function burden in autosomal genes and basal cell carcinoma (BCC), the most common cancer in Caucasians. A total of 25,205 BCC cases and 683,058 controls were tested. Rare germline loss-of-function variants in PTPN14 conferred substantial risks of BCC (OR, 8.0; P = 1.9 × 10 -12 ), with a quarter of carriers getting BCC before age 70 and over half in their lifetime. Furthermore, common variants at the PTPN14 locus were associated with BCC, suggesting PTPN14 as a new, high-impact BCC predisposition gene. A follow-up investigation of 24 cancers and three benign tumor types showed that PTPN14 loss-of-function variants are associated with high risk of cervical cancer (OR, 12.7, P = 1.6 × 10 -4 ) and low age at diagnosis. Our findings, using power-increasing methods with high-quality rare variant genotypes, highlight future prospects for new discoveries on carcinogenesis. SIGNIFICANCE: This study identifies the tumor-suppressor gene PTPN14 as a high-impact BCC predisposition gene and indicates that inactivation of PTPN14 by germline sequence variants may also lead to increased risk of cervical cancer., (©2021 American Association for Cancer Research.)

Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10 -8 ); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.

Background: Alpha-fetoprotein (AFP), cancer antigens 15.3, 19.9, and 125, carcinoembryonic antigen, and alkaline phosphatase (ALP) are widely measured in attempts to detect cancer and to monitor treatment response. However, due to lack of sensitivity and specificity, their utility is debated. The serum levels of these markers are affected by a number of nonmalignant factors, including genotype. Thus, it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects., Methods: We performed genome-wide association studies of serum levels of AFP ( N = 22,686), carcinoembryonic antigen ( N = 22,309), cancer antigens 15.3 ( N = 7,107), 19.9 ( N = 9,945), and 125 ( N = 9,824), and ALP ( N = 162,774). We also examined the correlations between levels of these biomarkers and the presence of cancer, using data from a nationwide cancer registry., Results: We report a total of 84 associations of 79 sequence variants with levels of the six biomarkers, explaining between 2.3% and 42.3% of the phenotypic variance. Among the 79 variants, 22 are cis (in- or near the gene encoding the biomarker), 18 have minor allele frequency less than 1%, 31 are coding variants, and 7 are associated with gene expression in whole blood. We also find multiple conditions associated with higher biomarker levels., Conclusions: Our results provide insights into the genetic contribution to diversity in concentration of tumor biomarkers in blood., Impact: Genetic correction of biomarker values could improve prediction algorithms and decision-making based on these biomarkers., (©2019 American Association for Cancer Research.)

Introduction: Many factors influence the nursing needs and survival of nursing home residents, including the admission criteria. The aim of the study was to compare health, survival and predictors for one- and two-year survival of people entering Icelandic nursing homes between 2003-2007 and 2008-2014., Material and Methods: Retrospective, descriptive, comparative study. The data was obtained from a Directorate of Health database for all interRAI assessments of Icelandic nursing homes from January 1, 2003, to December 31, 2014 (N = 8487)., Results: There was a significant difference in the health and survival of new nursing home residents before and after December 31, 2007. In the latter period, the mean age was 82.7 years. In the previous period, it was 82.1 years, and the prevalence of Alzheimer's disease, ischemic heart disease, heart failure, diabetes and COPD increased between the periods. One-year survival decreased from 73.4% to 66.5%, and two-year survival decreased from 56.9% to 49.1%. The strongest mortality risk factors were heart failure and chronic obstructive pulmonary disease, as well as high scores on the CHESS scale and ADL long scale., Conclusion: After 2007, new residents were older, in poorer health, and their life expectancy was shorter than for those moving to nursing homes before that. The results suggest that the aim of the regulatory change was achieved, i.e., to prioritise those in worst health. Their care needs may therefore be different and greater than before.

Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth.

Introduction: Organ transplant is often the only viable treatment for patients with end-stage organ failure. Until now, Icelandic legislation has required informed consent for organ donors, but a new parliamentary bill has been put forth to change the laws to presumed consent. The goal of this study was to investigate the attitude of the Icelandic population towards legislative changes to presumed consent., Materials and Methods: Descriptive cross-sectional study using a questionnaire. The study population included all Icelanders, 18 years and older. The sample involved 1400 persons randomly selected from a Capacent Gallup mailing-list. The response rate was 63% or 880 answers., Results: The majority of Icelanders are in favour of the proposed legislative change (more than 80%). Women were more likely to support presumed consent than men, 85% versus 76% respectively. Younger participants were more likely to be positive towards the new law, but no significant difference was found in attitude by family income, demographics or education. Persons who knew someone close to them that had received a transplanted organ were 50% more likely to be in complete agreement with the proposed legislation. Only 5% of participants were currently registered organ donors - 29 women and 15 men., Conclusion: Icelanders are very positive towards changing the law to include presumed consent in organ donation. Women and younger people tended to be more in favour and similarly those who know someone that has received donated organs. A majority of responders are willing to donate their organs, but very few are registered as donors.

A cross-sectional school-based survey study (N=13,284; 53% females; mean age 15.8±0.7) of 14-17-year-old adolescents was conducted in seven European countries (Greece, Spain, Poland, Germany, Romania, the Netherlands, and Iceland). The aim of the study was to investigate the prevalence of Internet addictive behavior (IAB) and related psychosocial characteristics among adolescents in the participating countries. In the study, we distinguish two problematic groups: adolescents with IAB, characterized by a loss of control over their Internet use, and adolescents "at risk for IAB," showing fewer or weaker symptoms of IAB. The two groups combined form a group of adolescents with dysfunctional Internet behavior (DIB). About 1% of adolescents exhibited IAB and an additional 12.7% were at risk for IAB; thus, in total, 13.9% displayed DIB. The prevalence of DIB was significantly higher among boys than among girls (15.2% vs. 12.7%, p<0.001) and varied widely between countries, from 7.9% in Iceland to 22.8% in Spain. Frequent use of specific online activities (e.g., gambling, social networking, gaming) at least 6 days/week was associated with greater probability of displaying DIB. Multiple logistic regression analysis indicated that DIB was more frequent among adolescents with a lower educational level of the parents, earlier age at first use of the Internet, and greater use of social networking sites and gaming sites. Multiple linear regression analysis showed that externalizing (i.e., behavioral) and internalizing (i.e., emotional) problems were associated with the presence of DIB.

Due to an improved understanding of past climatological conditions, it has now become possible to study the potential concordance between former climatological models and present-day genetic structure. Genetic variability was assessed in 26 samples from different rivers of Atlantic salmon in Iceland (total of 2,352 individuals), using 15 microsatellite loci. F-statistics revealed significant differences between the majority of the populations that were sampled. Bayesian cluster analyses using both prior information and no prior information on sampling location revealed the presence of two distinguishable genetic pools - namely, the Northern (Group 1) and Southern (Group 2) regions of Iceland. Furthermore, the random permutation of different allele sizes among allelic states revealed a significant mutational component to the genetic differentiation at four microsatellite loci (SsaD144, Ssa171, SSsp2201 and SsaF3), and supported the proposition of a historical origin behind the observed variation. The estimated time of divergence, using two different ABC methods, suggested that the observed genetic pattern originated from between the Last Glacial Maximum to the Younger Dryas, which serves as additional evidence of the relative immaturity of Icelandic fish populations, on account of the re-colonisation of this young environment following the Last Glacial Maximum. Additional analyses suggested the presence of several genetic entities which were likely to originate from the original groups detected.

Background: Approximately half of the mitochondrial genome inherent within 546 individual Atlantic salmon (Salmo salar) derived from across the species' North Atlantic range, was selectively amplified with a novel combination of standard PCR and pyro-sequencing in a single run using 454 Titanium FLX technology (Roche, 454 Life Sciences). A unique combination of barcoded primers and a partitioned sequencing plate was employed to designate each sequence read to its original sample. The sequence reads were aligned according to the S. salar mitochondrial reference sequence (NC&#95;001960.1), with the objective of identifying single nucleotide polymorphisms (SNPs). They were validated if they met with the following three stringent criteria: (i) sequence reads were produced from both DNA strands; (ii) SNPs were confirmed in a minimum of 90% of replicate sequence reads; and (iii) SNPs occurred in more than one individual., Results: Pyrosequencing generated a total of 179,826,884 bp of data, and 10,765 of the total 10,920 S. salar sequences (98.6%) were assigned back to their original samples. The approach taken resulted in a total of 216 SNPs and 2 indels, which were validated and mapped onto the S. salar mitochondrial genome, including 107 SNPs and one indel not previously reported. An average of 27.3 sequence reads with a standard deviation of 11.7 supported each SNP per individual., Conclusion: The study generated a mitochondrial SNP panel from a large sample group across a broad geographical area, reducing the potential for ascertainment bias, which has hampered previous studies. The SNPs identified here validate those identified in previous studies, and also contribute additional potentially informative loci for the future study of phylogeography and evolution in the Atlantic salmon. The overall success experienced with this novel application of HT sequencing of targeted regions suggests that the same approach could be successfully applied for SNP mining in other species.

This article documents the addition of 228 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Anser cygnoides, Apodemus flavicollis, Athene noctua, Cercis canadensis, Glis glis, Gubernatrix cristata, Haliotis tuberculata, Helianthus maximiliani, Laricobius nigrinus, Laricobius rubidus, Neoheligmonella granjoni, Nephrops norvegicus, Oenanthe javanica, Paramuricea clavata, Pyrrhura orcesi and Samanea saman. These loci were cross-tested on the following species: Apodemus sylvaticus, Laricobius laticollis and Laricobius osakensis (a proposed new species currently being described)., (© 2010 Blackwell Publishing Ltd.)

We report the development of new PCR assays and loading panels for the Atlantic salmon using 15 microsatellite loci. A total of 8, 3 and 4 loci were coamplified in three separate PCRs using labelled primers and loaded on the ABI DNA analyzer in two separate panels. Amplified alleles were clearly typed, and easily interpretable results were obtained. The method was successfully applied in different laboratories, even when different types of DNA polymerase were employed. The method is useful for analysing paternity, population genetics and conservation as well as for selective breeding programmes., (© 2009 Blackwell Publishing Ltd.)

The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

Salmonella osteomyelitis is rare in the immunocompetent host, even though Salmonella is not an infrequent public health problem. Invasive salmonellosis has in general a poor outcome in pregnancy with regard to fetal survival. We report the case of a healthy woman who developed Salmonella osteomyelitis of the iliac bone four weeks after a febrile gastroenteritis in the first trimester of pregnancy. Diagnosis was confirmed by magnetic resonance imaging scanning of the iliac bone and a growth of Salmonella enteritidis in blood culture. The patient recovered fully after six weeks treatment with intravenous antibiotics and delivered a healthy infant at 40 weeks.

Eighteen new microsatellite loci consisting of 10 di-, 5 tri-, 2 tetra- and 1 heptanucleotide repeats are introduced for the Atlantic cod (Gadus morhua L.). All loci were co-amplified in two polymerase chain reactions (plus two previously published microsatellites) and all products were typed clearly. The number of alleles per locus ranged from six (PGmo130) to 45 (PGmo76) and the observed heterozygosity ranged from 0.356 (PGmo130) to 0.957 (PGmo95). All loci except one followed Hardy-Weinberg expectations. Genetic linkage disequilibrium analysis between all pairs of loci did not yield any significant values., (© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.)

Inducible hematopoietic stem/progenitor cell lines represent a model for studying genes involved in self-renewal and differentiation. Here, gene expression was studied in the inducible human CD34+ acute myelogenous leukemia cell line KG1 using oligonucleotide arrays and suppression subtractive cloning. Using this approach, we identified Dlg7, the homolog of the Drosophila Dlg1 tumor suppressor gene, as downregulated at the early stages of KG1 differentiation. Similarly, Dlg7 was expressed in normal purified umbilical cord blood CD34+CD38- progenitors but not in the more committed CD34+CD38+ population. Dlg7 expression was not detected in differentiated cells obtained from hematopoietic colonies, nor was expression detected in purified T-cells, B-cells, and monocytes. When analyzed in different types of stem cells, Dlg7 expression was detected in purified human bone marrow-derived CD133+ progenitor cells, human mesenchymal stem cells, and mouse embryonic stem (ES) cells. Overexpression of Dlg7 in mouse ES cells increased their growth rate and reduced the number of EBs emerging upon differentiation. In addition, the EBs were significantly smaller, indicating an inhibition in differentiation. This inhibition was further supported by higher expression of Bmp4, Oct4, Rex1, and Nanog in EBs overexpressing Dlg7 and lower expression of Brachyury. Finally, the Dlg7 protein was detected in liver and colon carcinoma tumors but not in normal adjacent tissues, suggesting a role for the gene in carcinogenesis. In conclusion, our results suggest that Dlg7 has a role in stem cell survival, in maintaining stem cell properties, and in carcinogenesis. Disclosure of potential conflicts of interest is found at the end of this article.

A single founder mutation in each of the BRCA genes has been identified in Iceland. The frequency of the BRCA1 G5193A and BRCA2 999del5 mutations in all ovarian cancer patients diagnosed over the period 1991-2000 was determined. Mutation status was correlated with family history, tumour morphology and age at diagnosis. Samples from 86% of cases (179 carcinomas and 74 borderline tumours) were available. In the carcinomas, BRCA1 and BRCA2 mutations were present in 1.2% and 6% of cases, respectively. No BRCA mutations were found in the borderline tumours. Odds Ratio (OR) of developing ovarian cancer was 20.65 for BRCA2 carriers. Family history of breast/ovarian cancer was present for 70% of BRCA2 carriers and approximately 14% for non-carriers with carcinoma. In conclusion, BRCA2 999del5 is present in 6% of ovarian cancer cases in Iceland and is associated with a 20-fold increase in the risk of the disease. The BRCA1 G5193A mutation is too rare to contribute significantly to ovarian cancer in Iceland.

Objective: There has been significant weight gain among Western populations during the past few decades, including children and adolescents. The aim of this research was to investigate the possibility of discovering a correlation between the weight of primary school children and their well-being and performance in studies. There was also an interest in determining the weight development of children and adolescents during a period of thirty years and attempting to answer the question whether they were still putting on weight., Methods and Materials: The target population of the research project comprised pupils in the 4th, 7th and 10th grades of primary schools within the service area of Akureyri Health Centre during the winter of 2000-2001. The above classes were chosen on the basis of the fact that they all sat the national coordinated examination. Data were collected to discover Body Mass Index (BMI, weight/height&#95;, kg/m&#95;), measure performance in studies (the results in nationally coordinated examinations in Icelandic and arithmetic) and assess well-being by means of a questionnaire (Youth Self Report, YSR), which was only presented to the 7th and 10th grade. Furthermore, BMI was determined for corresponding groups from the school years 1970-71, 1980-81 and 1990-91, using information obtained from school health reports for the pupils in question., Results: This group consisted of 819 pupils and information was available on 568 of those, or about 70%. The weight gain which turned out to have occurred between the years 1970 and 1990 did not occur in the final decade of the 20th century and this applies to all three year groups. No difference was between those living in urban and rural areas. This was found to be the case, both when comparing the average BMI of the year groups and the proportion of children who are above a certain threshold of criteria. Furthermore, it was found that excessive weight/obesity is related to slack study results and a poor state of well-being among pupils in the 10th grade of the primary school. Such a relationship, however, did not exist among students in the 7th grade. Heavier pupils in the 4th grade perform better in their studies than their lighter peers, although this difference is not statistically significant., Conclusions: The unfavourable trend towards weight gain that we have seen in the past may now be changing. Other research pointing in the same direction has not been found, however, and more results are needed before this can be stated as a fact. Weight has a stronger influence on the well-being of adolescents in their upper teens, or towards the end of primary school, than is the case with younger pupils. This research does not explain why, although it may be assumed that the social environment of older children and adolescents is a significant factor in this respect. As the children grow older, a correlation begins to appear between being overweight and having less performance in studies and none of the heavier pupils show excellent school performance.

Objective: Cervical cancer is a disease caused in part by an infection with an oncogenic subtype of human papillomavirus (HPV). In this study we analysed all cervical cancer samples diagnosed in Iceland during two periods, 1958-1960 and 1995-1996, and asked whether significant changes in viral or immunological parameters had occurred over a period that spanned both significant changes in sexual attitude and the implementation of organized screening for cervical cancer., Methods: Samples from 47 patients (46 squamous cell carcinomas (SCC) and 1 adenosquamous carcinoma (ASC)) in the first period and 30 patients (20 SCC, 4 ASC, and 6 adenocarcinomas (AC)) in the later period were analysed for viral subtype and expression of Fas, FasL, MHC class I, p53 and apoptosis., Results: AC and ASC are proportionately much more common today than 40 years ago (30% vs 2%). The distribution of HPV in cervical cancer is similar in both periods, with HPV16 found in 75% and HPV18 in 13% of cases. Other HPV types found were 31,33,45, and 59. No significant differences were found in the immunological profiles of tumors from the two periods except that a higher fraction of SCC in the later period stained positive for FasL. When SCC are compared with AC/ASC, the latter have less expression of MHC class I, less expression of Fas, and stronger FasL expression., Conclusions: AC/ASC tumors show some immunological features that suggest that they are more resistant to immune attack than SCC.

Bioactivity-guided fractionation of extracts of Schinus molle leaves, using an in vitro assay, led to the isolation of ACE-inhibitory steroidal triterpenes of the euphane type, identified by means of NMR spectroscopic methods. One of the triterpenes was isolated as an equilibrium mixture of epimeric aldehydes. The triterpenes showed moderate ACE-inhibitory activity (IC(50) about 250 microM).

Monkshood, Aconitum napellus L. (Ranunculaceae), is considered one of the most poisonous plants growing in Europe. Monkshood and other Aconitum species are still used in Oriental and homeopathic medicine as analgesics, febrifuges and hypotensives. The neurotoxin aconitine is the principal alkaloid in most subspecies of monkshood. A review is presented, which includes historical aspects of monkshood as a poisonous and medicinal plant, the mode of action of aconitine, symptoms of toxicity, treatment and reports of recent poisoning incidents. In addition, results of quantitative HPLC examination of hypogeous and epigeous organs from a population of A. napellus ssp. vulgare cultivated in Iceland are discussed. The fact that children in Iceland have commonly been known to eat the sweet tasting nectaries in monkshood prompted an investigation of the alkaloidal content of these organs specifically. The low aconitine content found in the nectaries as well as in whole flowers accords with the absence of reported toxicity arising from the handling of flowers and consumption of nectaries from A. napellus in this country.

In 1991, three cases of anaphylactoid reactions among vaccinators of farmed fish were registered in Norway. The reactions developed after repeated accidental self-injection of vaccine against salmon furunculosis. In 1991, some 60 million salmon were vaccinated against furunculosis at approximately 50 grams body weight. Following such self-injection of vaccine, inflammatory reactions are seen in the injected finger, also spreading occasionally to the hand. More seldom a "flu" like syndrome with fever, muscle aches, and general malaise is experienced probably caused by endotoxins in the vaccine. Devices to protect the fingers against accidental self-injection have been developed and, so far, the results are promising.

Heterosexual transmission of HIV-1 is likely to involve transmission of virus present in seminal fluid to inflammatory cells, particularly macrophages, present in the endometrium and peritoneal cavity. We have investigated the susceptibility of peritoneal macrophages and the corresponding autologous blood monocytes from normal women to infection by the BA-L strain of HIV-1. In 10 of 18 examples, peritoneal macrophages showed signs of infection within 4-5 days, which was earlier than the autologous monocytes. In contrast to peritoneal macrophages, lung macrophages from 10 of 11 normal donors failed to show significant reverse transcriptase (RT) values 3 weeks post infection. Monolayer cultures of monocytes cultured for 5 days prior to infection developed RT values similar overall to those of freshly isolated cells although individual donors varied as to which culture condition was optimal. The ease of infection of peritoneal macrophages did not correlate with levels of CD4 antigen or degree of pelvic inflammatory development, nor were macrophages harvested from women early in the menstrual cycle significantly more susceptible to infection than those collected from midcycle on. This unexplained heightened infectibility of peritoneal macrophages in a proportion of normal women suggests that those individuals could be more at risk for heterosexual transmission of HIV-1 infection.

Class I antigen expression by ovarian epithelial neoplasms was determined by flow cytometric analysis and an immunoperoxidase technique for each specimen. The numbers of class I positive tumors determined by the methods were compared. The more subjective immunohistochemical analysis and the more objective flow cytometric technique revealed similar results as long as strict criteria for the interpretation of results was applied. Most of the tumor specimens revealed a homogeneous Gaussian distribution of green fluorescence, class I antigen expression, by flow cytometry. There were two specimens that exhibited a less than characteristic type of membrane staining. The antigen-antibody reaction product was expressed in the extracellular matrix, as well as on the cell membrane of certain cells. This may represent a defect in antigen expression and, if so, might alter the immune response to these tumors.

Epithelial ovarian cancers with aneuploid DNA content are associated with a poorer clinical course than diploid tumors. Flow cytometric analysis may further categorize aneuploid tumors based on the relative expression of cell surface histocompatibility (HLA) antigens. Surgical specimens from 20 patients with aneuploid tumors were stained using an indirect immunofluorescence method with primary murine monoclonal antibodies W36/22 (class I HLA surface antigens) and L5.1 (irrelevant antibody), counterstained with propidium iodide (DNA stain), and analyzed with the flow cytometer using a computer program to correct staining intensity for cell size. Patients with high or low class I expression were similar with respect to age, stage, histology, grade, and residual disease following surgical debulking; all patients were treated with cisplatin-based chemotherapy. Women with low class I HLA antigen expression had higher progression rates and death rates than patients with high class I HLA expression. Low class I HLA antigen expression is a poor prognostic factor among patients with aneuploid ovarian cancers.