Expression of CD83 in the murine immune system

CD83 is used as a marker for mature dendritic cells (DC) in man. We have developed a new monoclonal antibody (mAb), Michel-17, that specifically recognizes mouse CD83. We show that murine CD83 is expressed mainly on mature DC and on activated T cells. Histological analysis of serial spleen sections revealed a CD83 expression pattern resembling that of MIDC-8, a known murine DC marker molecule. In contrast to other costimulatory receptors, cross-linking of CD83 with the mAb Michel-17 on DC or T cells does not induce any activation signals. Our data describe for the first time the expression pattern of murine CD83, which is comparable to that of human CD83.The unique mAb Michel-17 will help to elucidate the biological functions of the CD83 molecule in more detail.     

Usefulness of high-resolution comparative genomic hybridization (CGH) for detecting and characterizing constitutional chromosome abnormalities

Comparative genomic hybridization (CGH) is a technique for detection of chromosomal imbalances in a genomic DNA sample. We here report the application of the recently developed method of high-resolution CGH on DNA samples from 66 children having various degrees of delayed psychomotor development with or without clear dysmorphic features and congenital malformations. In 5 of 50 patients with apparently normal karyotypes, a deletion or duplication was revealed by CGH. Only one of these cases had a subtelomeric rearrangement. In one of seven cases with a de novo apparently balanced translocation, deletions were found. In all nine cases where the origin of a marker chromosome or additional chromosomal material was difficult to determine, CGH gave a precise identification. The following findings were from cases having a deletion or duplication as the sole chromosomal imbalance; dup(2)(p16p21), del(4)(q21q21), del(6)(q14q15), del(6)(p12p12), dup(6)(q24qter), and dup(15)(q11q13). One case had dup(9)(p11pter) combined with a very small subtelomeric deletion on 6q. In our hands, CGH is highly useful not only for identifying known chromosomal imbalances, but also for finding elusive deletions or duplications in the large group of children with developmental delay with or without congenital abnormalities. In such cases, the diagnostic yield of CGH appears to be higher than what has been reported from subtelomeric FISH screening.     

Reelin-immunoreactivity in the hippocampal formation of 9-month-old wildtype mouse: effects of APP/PS1 genotype and ovariectomy

Reelin, an extracellular matrix protein has an important role in the migration, correct positioning and maturation of neurons during development. Though it is generally down-regulated in the postnatal period, expression of this large glycoprotein continues in the adult brain in some cell populations. In the present study, we examined the distribution of reelin-immunoreactivity (-ir) in the hippocampal formation of 9-month-old wildtype mice (WT). Then, reelin-ir in normal mice was compared to that of transgenic mice (APP/PS1) carrying mutated human APP and PS1 genes, which are linked to the familial form of Alzheimer's disease (AD). The APP/PS1 mice were additionally burdened with a second risk factor for AD, namely depletion of circulating gonadal hormones by ovariectomy (APP/PS1 + OVX). The analyses revealed that in adult WT reelin-ir is expressed by Cajal-Retzius cells and a subgroup of interneurons throughout the hippocampal formation. In addition, layer II projection neurons in the lateral entorhinal subfields are reelin-ir. Interestingly, ovariectomy decreases the number of reelin-ir cells in the hilus in WT mice, whereas AD-related genotype alone induces only a non-significant reduction. Unexpectedly, additional stress, e.g., depletion of gonadal hormones, does not aggravate the slight reduction in the reelin cell number in the APP/PS1 mice. We propose that the changes in normal reelin-ir are linked to disturbances in repair mechanisms in which APP/PS1 and gonadal hormones are involved and which are perturbed in neurodegenerative conditions, namely AD.     

Assessment of HER‐2/neu overexpression and/or gene amplification in breast carcinomas: should in situ hybridization be the method of choice?

AIMS: Since the release of Herceptin, pathology laboratories have been requested to test breast carcinomas for HER-2/neu overexpression and/or gene amplification. Standardized IHC and FISH are mandatory in order to get reliable results, but there are problems even with standardized procedures. We decided to evaluate the two methods to determine which, or possibly if both, should be the primary investigation method(s). METHODS AND RESULTS: The material consisted of 215 primary invasive breast carcinomas with complete clinical follow-up of 15 years. HER-2/neu protein expression was determined for all specimens, whereas FISH for assessing HER-2/neu gene signal number was done in 165 cases. IHC was double-checked with two or three different antibodies in 35 tumours, including all cases with discrepancies between IHC and FISH. Among these, there were discrepancies in a third. IHC overexpression of HER-2/neu was found in 13% and gene amplification in 18%. Discordance between IHC and FISH was found in 11 cases (8%). Five tumours were IHC+/FISH- and six were IHC-/FISH+. IHC and FISH positive cases as well as FISH only positive tumours had the same prognosis respecting survival. Tumours with >2 but 4 gene signals per nucleus. In contrast, cases with IHC overexpression without gene amplification had a prognosis similar to that of IHC-/FISH- tumours. CONCLUSIONS: From our data, it seems to be more important to assess HER-2/neu gene amplification than IHC overexpression. Failure to detect FISH-amplified (IHC-negative) cases would have an adverse effect on the survival of these patients. On the other hand, IHC overexpression tumours without gene amplification appear to belong to a better prognostic group, and failure to detect them would probably not have a negative effect on the survival of these women. Even though FISH is a more complex and expensive procedure, it should be considered the method of choice for primary assessment of HER-2/neu status in breast cancer patients.     

Antibiotics from Algae XXXIII1: Phlorotannins of the Brown Alga Himanthalia elongata2,3

It is possible to obtain approximately 0.2% (relative to dry weight) phenols soluble in ethyl acetate from HIMANTHALIA ELONGATA. After removal of a fraction containing high-molecular weight substances, a total of 17 oligomeric phlorotannins with 2 to 8 aromatic rings can be isolated from the mixture of the acetylated phenol fraction. Apart from 2 derivatives belonging to the fucol group, diphlorethol and a tetraphlorethol not yet fully identified, all the other substances are fucophlorethols. Amongst these substances, a phenoxylated therphenyl derivative and several fucophlorethols with two-fold phenoxy-substituted biphenyl moieties were identified for the first time.     

Beta-oxidation of 1-[14C]-17-[131I]-iodoheptadecanoic acid following intracoronary injection in humans results in similar release of both tracers

Radioiodine labelled 17-iodo-heptadecanoic acid (IHA) is used for non-invasive study of myocardial metabolism in coronary heart disease and cardiomyopathy. Yet in the interpretation of in vivo myocardial tracer kinetics, it is controversial whether the intracellular degradation of IHA or the removal of iodide across cellular membranes is the rate-limiting step in iodide release from the myocardium. In five patients undergoing coronary sinus catheterization, a mixture of about 40 kBq of [¹²³I] NaI was injected into the left coronary artery. During the following 15-min period, frequent blood samples were taken from the aorta and the coronary sinus. In the aqueous phase of the venous blood, ¹⁴CO₂ and inorganic ¹³¹I appeared nearly in parallel, with a peak time of 4–5 min. Moreover, as shown by the AV difference, there was no significant back diffusion of IHA and no significant non-specific deiodination detectable over the period of observation. There was myocardial retention of inorganic iodide (¹²³I) injected into the left coronary artery. The data strongly support the premise that lipid turnover through -oxidation is the rate-limiting step in the externally measured release of iodide after IHA injection, provided that recirculating inorganic radioactive iodide is corrected for. In addition, 15 volunteers were studied using [¹¹C]palmitic acid and [¹²³I]IHA using PET and dynamic planar camera scintigraphy with iodide correction. There was no significant difference between the mean values of the elimination half-times, and also no significant correlation between half-times of both fatty acids for single individuals.     

Prevalence of antibodies against SARS‐CoV‐2 in the Norwegian population,August 2021

BackgroundOne year into the COVID‐19 pandemic, the cumulative number of confirmed COVID‐19 cases in Norway was still low. In January 2021, when the Norwegian COVID‐19 vaccination campaign started, the national seroprevalence estimate of SARS‐CoV‐2 antibodies was 3.2%. We have conducted a nationwide cross‐sectional study in August 2021 to investigate the overall prevalence of SARS‐CoV‐2 antibodies in Norway after 8 months of COVID‐19 mass vaccination and a third wave of SARS‐CoV‐2 infection.MethodsResidual sera were collected from laboratories across Norway in August 2021. In IgG antibodies against the spike protein, the spike receptor binding domain (RBD) and the nucleocapsid protein of SARS‐CoV‐2 were measured by a bead‐based flow cytometric assay.ResultsIn total, 1926 residual sera were collected from individuals aged 0–98 years; 55.1% were from women. The overall national estimated seroprevalence from vaccination and/or infection was 62.6% (credible interval [CrI] 60.1%–65.2%) based on having antibodies against both spike and RBD. Estimated seroprevalence increased with age. Among all samples, 11.7% had antibodies against nucleocapsid. For unvaccinated children <12 years, the seroprevalence estimate due to SARS‐CoV‐2 infection was 12.5% (95% CrI 9.3%–16.1%). Of seropositive samples from the unvaccinated children, 31.9% lacked anti‐nucleocapsid antibodies.ConclusionsThe high overall SARS‐CoV‐2 seroprevalence estimates are in line with Norwegian registry data. Vaccination, not infection, contributed the most to the high seroprevalence in August 2021. Lack of antibodies against nucleocapsid should not automatically be interpreted as absence of previous infection as this could lead to underestimation of COVID‐19 cases in seroprevalence studies.     

Reference ranges for serial measurements of umbilical artery Doppler indices in the second half of pregnancy

OBJECTIVE: The purpose of this study was to construct new reference ranges for serial measurements of commonly used umbilical artery Doppler indices (pulsatility index, resistance index, and systolic:diastolic ratio). STUDY DESIGN: This was a prospective longitudinal study of the umbilical artery Doppler indices that were obtained serially at the free-loop of umbilical cord at 4-week intervals at 19 to 42 weeks of gestation in 130 low-risk singleton pregnancies. A total of 513 observations were used to construct the reference ranges with the use of multilevel modeling. RESULTS: Longitudinally established percentiles of Doppler indices from the present study show a continuous reduction throughout the second half of pregnancy without any plateau or increase near term, as reported previously. There was a significant negative association between Doppler indices and placental weight and neonatal birth weight, but not with gender. The intraobserver coefficients of variation for the umbilical artery pulsatility index, resistance index, and systolic:diastolic ratio were 10.5%, 6.8 %, and 13.0 %, respectively. CONCLUSION: New reference ranges for umbilical artery Doppler indices that are based on longitudinal observations appear to be slightly different from cross-sectional studies and are more appropriate for serial evaluation of fetal hemodynamics.