Leukolectins support lifelong innate immunity in lower vertebrates, and reveal dichotomies of several leukocytic lineages.

Innate immunity is vital for animal homeostasis and survival. First-line immuno-defense for fish larvae involves mucus enriched with leukolectin (LL) secreted by dermal lectocytes. Later during the critical transition from yolk-nutrition to feeding, additional larval immuno-protection in zebrafish (zF) is provided by macrophages containing LL (lectophages). This work investigated new LL-expression in embryos and in blood, structures of fish leukocytic LL and LL-genes, and LL-presence in chicken leukocytes. In zF-embryos, lectophages appear ∼10 hpf, while later, cells co-expressing myeloperoxidase- and LL-mRNA were detected (∼19 hpf). Furthermore, protein-extracts of Atlantic salmon (Ssal) leukocytes contained LL-proteins, compartmentalized in the cytosol. Cloning and sequencing revealed 94 % nt-sequence identity between variants of Ssal-leukolectins. Highly conserved LLs allowed production of epitope-specific anti-LL IgGs. Immuno-fluorescence-analysis demonstrated that most Ssal-bloodcells were LL-negative, but both some large cells with protrusions and some small, rounded cells did express LL. Immunoperoxidase-staining method confirmed LL-expression in some Ssal-leukocytes, identified as macrophages, PMN-leukocytes, thrombocytes and dendritic cells. However, closer examination revealed a dichotomy of these cell-categories into either LL-positive, or LL-negative variants. In situ hybridization demonstrated profuse LL-expression in Ssal head kidney interstitial tissue, while LL-transcripts were absent in large kidney tubules. Both hematopoietic (non-pigmented) marrow cells and melano-macrophages expressed LL-mRNA, implying that leukolectins provide lifelong innate immuno-protection. PCR-amplification using Ssal-leukocytic DNA as template, and direct sequencing yielded a leukocytic ll-gene. Some cells in salmon, cod, halibut, oikopleura and zebrafish embryos express LL-proteins and/or LL-mRNA, and LL-mRNA is detected in salmon, cod and chicken leukocytes. However, current genomes for these species lack recognizable LL-loci except the Ssal_v3.1 Genome-assembly. The data demonstrate an unexpected dichotomy of some leukocyte lineages into LL-positive or LL-negative cell-variants. Such dichotomies suggest exploring differential impacts from the duplicated leukocyte-lineages in health and disease.

Leukolectin is expressed in lectophages, a distinct population of zebrafish embryonic macrophages.

Leukolectins (LL) belong to the tectonin-family of proteins, with functions in innate immunity. Fish larvae compensating for loss of maternal chorionic protection post-hatching, provide a model-system for studying how lectins contribute to immunity. Atlantic salmon (Ssal) LL-proteins function after secretion in mucus from dermal lectocytes, as this mucus envelops embryos and larvae. The Ssalll-gene possesses multiple putative binding sites for diverse transcription-factors, suggestive of LL-functions in non-epithelial cells. Since zebrafish (zF) perivitelline fluid (PVF) contains LL-proteins, this study aims to characterize zF-leukolectins, their cellular origin, expression and gene structure. Extracts of (10 hpf) zF-embryos contained LL-proteins, and whole mount immuno-histochemistry revealed dispersed LL-positive cells including zF-lectocytes, accounting for exocrine LL-secretion by embryos. Lectocytes are lcp1-negative, but other zF-cells co-expressed LL-proteins and lcp1-transcripts, which (at this stage) identified such non-lectocytes as early macrophages (termed lectophages). In sections, LL-expression characterized large macrophage-progenitors and smaller colonizing macrophages. RT- and RACE-PCR yielded zF-LLcDNA including parts of untranslated regions. ORF encoded 255 AAs including (19 AA) signal peptide. Processing of a primary LL-transcript to (∼1.300 nt) LL-mRNA was suggested by Northern blots. Most zebrafish-egg lectins (zFELs) possess four TECPR-domains, while five TECPR-domains were predicted for zF-LL. Minor sequence variations suggested nearly identical zF-LL isoforms. Alignment of zFEL-proteins predicted a zFEL-tree with a separate leukolectin-branch. LL-amplification using zF-DNA, revealed five exons and four introns. Predicted structures of zF- and Ssal-leukolectins showed strong structural conservation (92% sequence-identity) with shorter zF-introns 2&4, but identical introns 1&3. Non-lectocytic LL-functions were investigated further by dual in situ hybridization, revealing that only some embryonic lcp1-expressing cells in early zF-embryos co-expressed LL-transcripts. Macrophages from erythro-myeloid progenitor (EMP) are known to colonize zebrafish tissues as resident macrophages (TRM), e.g. nervous system (CNS) and epiderm. Unlike Ssal-larvae relying on yolk for months, zF-larvae switch within days to nutrition from the digestive-tract, necessitating additional immuno-protection possibly from TRMs. EMP also gives rise to microglia, the TRM of CNS. The neural tube of zF-embryos exhibited numerous small, LL-positive cells, presumably stemming from lectophage-progenitors. Functions of these LL-positive embryonic microglia (lectoglia) appear more relevant for tissue remodelling than for pathogenic threats. Lectoglia sustaining CNS-neurons suggests physiological LL-roles relevant for adult health and disease. The data focus the need for resolving whether lectophages represent an unrecognized myelogenic lineage, or whether instead, LL-expression occurs in a subpopulation of the early macrophage-lineage.

Leukolectin-proteins are synthesized and secreted by lectocytes, a distinct category of fish embryonic mucus cells.

Fish perivitelline fluid (PVF) is a vital extra-embryonic compartment. At hatching, PVF-contents dissolve into the hatching fluid (HF). Analysis of Atlantic salmon HF reveals nearly a hundred distinct proteins, most of which were identified by advanced mass-spectrometry. However, one entity with an apparent molecular weight 26 kDa, necessitated identification from its tryptic peptides. Subsequent cloning and sequencing revealed novel leukolectin-proteins. From bioinformatic analysis, leukolectins (LL) belong in the tectonin protein-family, with recognized functions in innate immunity. This study aims to identify LL-expressing cells in diverse fish species, and to characterize the LL-gene in order to predict bio-functions of leukolectins. LL-proteins were detected in HF from several fish species and one invertebrate, using polyclonal LL-specific IgGs. Embryonic LL-immunoreactive cells were numerous in Atlantic salmon, rainbow trout, fewer in Atlantic cod, and rare in Atlantic halibut and Oikopleura dioica. LL-immunoreactive cells were termed lectocytes, which corresponded to peridermal mucuscells stained by PAS, but unstained by eosin. Hence, lectocytes and hatching-gland cells were clearly distinguished. Northern blots revealed two salmon LL-transcripts at mid-embryogenesis. Such transcripts were detected in epithelial cells of the periderm, gills and oral cavity. LL-transcripts predominated in the periderm, while choriolysin-transcripts were dominant in the gills. No co-expression of choriolysins and LL-transcripts was detected. BAC-library screening yielded salmon LL's genestructure with 4 introns, 5 exons, TATA-box, multiple upstream putative transcription-factor bindingsites and polyadenylation site. LL-gene location on chromosome ssa17 was identified in Ssal_v3.1, the 2021version of the salmon genome. In conclusion, larvae from several fish species are outfitted with mucus enriched by LL-proteins. Mucus cells are present in embryos of all fishes, but embryonic lectocyte-numbers are far higher in species with near total larval survival. When (maternal) chorionic first-line immuno-defence is lost at hatching, leukolectin-enriched mucus may provide vital protection for larvae.

Choriolytic and non-choriolytic proteases during hatching of Atlantic Salmon embryos.

Fish embryonic hatching glands (HGs) secrete choriolysin-zymogens, which when activated degrade the chorion, allowing larval exit. Thus, hatching encompasses two dissimilar choriolysin-processes: pre-choriolysis including activated choriolysins accessing the perivitelline space (PVS), followed by choriolysis. Discovery of serine-proteolytic zonase in Atlantic salmon hatching fluid (HF) raises questions concerning its participation in hatching. This work aims to identify salmon choriolysins, and evaluate their role and that of zonase during hatching. Precocious salmon hatching occurs under alkaline conditions, producing an HF containing similar metallo- and serine- proteolytic activities. Purified zonase is selectively inhibited by peFabloc, whose MW (580 Da) allows diffusion through the chorion into the PVS. Without apparent toxicity, brief peFabloc-pretreatment (2 mM) of salmon eggs reduced precocious hatching substantially, compatible with a zonase-relevance for hatching. Atlantic salmon differed from other fishes since their HGs were not immuno-stained by polyclonal antibodies against pike choriolysins. However, cloning and sequencing experiments revealed a single low choriolytic enzyme (LCE) of 69% identity to pike LCE. Similar experiments with high choriolytic enzymes (HCEs) revealed two types (HCE-1 and HCE-2) with respectively 71% and 91% identity to pike HCE-1 & HCE-2. In situ hybridization revealed typical HGs. However, zebrafish-choriolysis is achieved by HCE-class choriolysins alone. Another zebrafish choriolysin (HE2) was not expressed. Peptide-bond hydrolysis by non-choriolytic zonase mimicks HCE-action generating hydrophilic sites for LCE-choriolytic catalysis. Ultimately, precise definitions of choriolytic and pre-choriolytic catalysis requires developmental genetics. Our data are compatible with a complex pre-choriolytic hatching-stage in Atlantic salmon, before LCE-choriolysis degrades the chorion.

Enhancement in cognitive function recovery by granulocyte-colony stimulating factor in a rodent model of traumatic brain injury.

Traumatic brain injury (TBI) is characterized by neuronal damage and commonly, secondary cell death, leading to functional and neurological dysfunction. Despite the recent focus of TBI research on developing therapies, affective therapeutic strategies targeting neuronal death associated with TBI remain underexplored. This study explored the efficacy of granulocyte-colony stimulating factor (G-CSF) as an intervention for improving cognitive deficits commonly associated with TBI. Although G-CSF has been studied with histological techniques, to date, its effects on functional outcome remain unknown. To this end, we used a closed head injury (CHI) model in Wistar rats that were randomly assigned to one of four groups (untreated TBI, G-CSF treated TBI, G-CSF treated Control, Control). The treatment groups were administered subcutaneous injections of G-CSF 30 min (120 µg/kg) and 12 h (60 µg/kg) post-trauma. The Morris Water Maze test was used to measure any treatment-associated changes in cognitive deficits observed in TBI animals at days 2-6 post-injury. Our findings demonstrate a significant improvement in cognitive performance in the G-CSF treated TBI animals within a week of injury, compared to untreated TBI, indicative of immediate and beneficial effect of G-CSF on cognitive performance post CHI. Our model suggests that early G-CSF exposure may be a promising therapeutic approach in recovery of cognitive deficits due to TBI.

Multi-modal approach for investigating brain and behavior changes in an animal model of traumatic brain injury.

Use of novel approaches in imaging modalities is needed for enhancing diagnostic and therapeutic outcomes of persons with a traumatic brain injury (TBI). This study explored the feasibility of using functional magnetic resonance imaging (fMRI) in conjunction with behavioral measures to target dynamic changes in specific neural circuitries in an animal model of TBI. Wistar rats were randomly assigned to one of two groups (traumatic brain injury/sham operation). TBI rats were subjected to the closed head injury (CHI) model. Any observable motor deficits and cognitive deficits associated with the injury were measured using beam walk and Morris water maze tests, respectively. fMRI was performed to assess the underlying post-traumatic cerebral anatomy and function in acute (24 hours after the injury) and chronic (7 and 21 days after the injury) phases. Beam walk test results detected no significant differences in motor deficits between groups. The Morris water maze test indicated that cognitive deficits persisted for the first week after injury and, to a large extent, resolved thereafter. Resting state functional connectivity (rsFC) analysis detected initially diminished connectivity between cortical areas involved in cognition for the TBI group; however, the connectivity patterns normalized at 1 week and remained so at the 3 weeks post-injury time point. Taken together, we have demonstrated an objective in vivo marker for mapping functional brain changes correlated with injury-associated cognitive behavior deficits and offer an animal model for testing potential therapeutic interventions options.

Neuroprotection by freezing ischemic penumbra evolution without cerebral blood flow augmentation with a postsynaptic density-95 protein inhibitor.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether neuroprotection is feasible without cerebral blood flow augmentation in experimental permanent middle cerebral artery occlusion. METHODS: Rats were subjected to permanent middle cerebral artery occlusion by the suture occlusion method and were treated 1 hour thereafter with a single 5-minute intravenous infusion of the postsynaptic density-95 protein inhibitor Tat-NR2B9c (7.5 mg/kg) or saline (n=8/group). Arterial spin-labeled perfusion-weighted MRI and diffusion weighted MRI were obtained with a 4.7-T Bruker system at 30, 45, 70, 90, 120, 150, and 180 minutes postmiddle cerebral artery occlusion to determine cerebral blood flow and apparent diffusion coefficient maps, respectively. At 24 hours, animals were neurologically scored (0 to 5), euthanized, and the brains stained with 2-3-5-triphenyl tetrazolium chloride to ascertain infarct volumes corrected for edema. Additionally, the effects of Tat-NR2B9c on adenosine 5'-triphosphate levels were measured in vitro in neurons subjected to oxygen-glucose deprivation. RESULTS: Final infarct volume was decreased by 30.3% in the Tat-NR2B9c-treated animals compared with controls (P=0.028). There was a significant improvement in 24 hours neurological scores in the Tat-NR2B9c group compared with controls, 1.8±0.5 and 2.8±1.0, respectively (P=0.021). Relative to controls, Tat-NR2B9c significantly attenuated diffusion-weighted imaging lesion growth and preserved the diffusion-weighted imaging/perfusion-weighted imaging mismatch (ischemic penumbra) without affecting cerebral blood flow in the ischemic core or penumbra. Tat-NR2B9c treatment of primary neuronal cultures resulted in 26% increase in cell viability and 34% greater adenosine 5'-triphosphate levels after oxygen-glucose deprivation. CONCLUSIONS: Preservation of adenosine 5'-triphosphate levels in vitro and neuroprotection in permanent middle cerebral artery occlusion in rats is achievable without cerebral blood flow augmentation using a postsynaptic density-95 protein inhibitor.

Visualization of clot lysis in a rat embolic stroke model: application to comparative lytic efficacy.

BACKGROUND AND PURPOSE: The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model and to compare tissue plasminogen activator (tPA)-based clot lysis with and without recombinant Annexin-2 (rA2). METHODS: In experiment 1 we used in vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50 µL in 250 µL blood. In experiment 2, we used in vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot imaging were conducted before and during treatment with vehicle (n=6), tPA (n=8), or rA2 plus tPA (n=8) at multiple time points. Brains were removed for ex vivo clot localization. RESULTS: Clots created with 25 µL Magnevist were the most stable and provided the highest contrast-to-noise ratio. In the vehicle group, clot length as assessed by T1-weighted imaging correlated with histology (r=0.93). Clot length and cerebral blood flow-derived ischemic lesion volume were significantly smaller than vehicle at 15 minutes after treatment initiation in the rA2 plus tPA group, whereas in the tPA group no significant reduction from vehicle was observed until 30 minutes after treatment initiation. The rA2 plus tPA group had a significantly shorter clot length than the tPA group at 60 and 90 minutes after treatment initiation and significantly smaller cerebral blood flow deficit than the tPA group at 90 minutes after treatment initiation. CONCLUSIONS: We introduce a novel MRI-based clot imaging method for in vivo monitoring of clot lysis. Lytic efficacy of tPA was enhanced by rA2.

Characterization of gadolinium-based dynamic susceptibility contrast perfusion measurements in permanent and transient MCAO models with volumetric based validation by CASL.

Perfusion imaging is crucial in imaging of ischemic stroke to determine 'tissue at risk' for infarction. In this study we compared the volumetric quantification of the perfusion deficit in two rat middle-cerebral-artery occlusion (MCAO) models using two gadolinium-based contrast agents (P1152 (Guerbet) and Magnevist (Bayer-Schering, Pittsburgh, PA, USA)) as compared with our well established continuous arterial spin labeling (CASL) perfusion imaging technique. Animals underwent either permanent MCAO or transient MCAO with 80-min reperfusion. Imaging was performed at four different time points after MCAO. A region-of-interest (ROI) analysis of the subregions of the ischemic zone (core, penumbra, transient reversal (TR), and sustained reversal (SR)) using P1152 showed significant reduction in blood flow in the core and TR subregions relative to the penumbral and SR subregions while occluded. After reperfusion, a significant increase in blood flow was recorded at all time points after reperfusion in all regions except TR. From the ROI analysis the threshold for the penumbra was determined to be -62+/-11% and this value was subsequently used for quantification of the volumetric deficit. The ischemic volume as defined by dynamic susceptibility contrast (DSC), was only statistically different from the CASL-derived ischemic volume when using Magnevist at post-reperfusion time points.

Granulocyte-colony stimulating factor delays PWI/DWI mismatch evolution and reduces final infarct volume in permanent-suture and embolic focal cerebral ischemia models in the rat.

BACKGROUND AND PURPOSE: Granulocyte-colony stimulating factor (G-CSF) is used clinically to attenuate neutropenia after chemotherapy. G-CSF acts as a growth factor in the central nervous system, counteracts apoptosis, and is neuroprotective in rodent transient ischemia models. METHODS: We assessed the effect of G-CSF on ischemic lesion evolution in a rat permanent-suture occlusion model with diffusion- and perfusion-weighted magnetic resonance imaging and the neuroprotective effect of G-CSF in a rat embolic stroke model. RESULTS: With a constant perfusion deficit, vehicle-treated animals showed an expanding apparent diffusion coefficient lesion volume that matched the perfusion deficit volume at approximately 3 hours, with the 24-hour infarct volume equivalent to the perfusion deficit. In G-CSF-treated rats, the apparent diffusion coefficient lesion volume did not increase after treatment initiation, and the infarct volume at 24 hours reflected the initial apparent diffusion coefficient lesion volume. In the embolic model, we observed a significant decrease in infarct volume in G-CSF-treated animals compared with the vehicle-treated group. CONCLUSIONS: These results confirm the potent neuroprotective activity of G-CSF in different focal ischemia models. The magnetic resonance imaging data demonstrate that G-CSF preserved the perfusion/diffusion mismatch.

Normobaric hyperoxia and delayed tPA treatment in a rat embolic stroke model.

In a rat embolic stroke (eMCAO) model, the effects of 100% normobaric hyperoxia (NBO) with delayed recombinant tissue plasminogen activator (tPA) administration on ischemic lesion size and safety were assessed by diffusion- and perfusion (PWI)-weighted magnetic resonance imaging. NBO or room air (Air) by a face mask was started at 30 mins posteMCAO and continued for 3.5 h. Tissue plasminogen activator or saline was started at 3 h posteMCAO. Types and location of hemorrhagic transformation were assessed at 24 h and a spectrophotometric hemoglobin assay quantified hemorrhage volume at 10 h. In NBO-treated animals the apparent diffusion coefficient/PWI mismatch persisted during NBO treatment. Relative to Air groups, NBO treatment significantly reduced 24 h infarct volumes by approximately 30% and approximately 15% with or without delayed tPA, respectively (P<0.05). There were significantly more hemorrhagic infarction type 2 hemorrhages in Air/tPA versus Air/saline animals (P<0.05). Compared with Air/tPA, the combination of NBO with tPA did not increase hemorrhage volume at 10 h (4.0+/-2.4 versus 6.6+/-2.6 microL, P=0.065) or occurrence of confluent petechial hemorrhages at 24 h (P>0.05), respectively. Our results suggest that early NBO treatment in combination with tPA at a later time point may represent a safe and effective strategy for acute stroke treatment.

Laser Doppler flowmetry predicts occlusion but not tPA-mediated reperfusion success after rat embolic stroke.

BACKGROUND AND PURPOSE: Laser Doppler flowmetry (LDF) is increasingly used to assess adequate occlusion after embolic stroke (ES) in rats. METHODS: Employing LDF, relative regional cerebral blood flow (rCBF) was continuously monitored during the first 2 h following ES and correlated with 24 h 2,3,5-triphenyltetrazolium chloride (TTC)-staining of corrected infarct volume. In a preliminary experiment (n=18), it was demonstrated that rCBF-reduction to 37% or less of baseline correctly identified occlusion success in the suture middle cerebral artery occlusion (sMCAO) model. Using the same methodology, we then assessed whether LDF allowed for identification of animals with successful ES (experiment 2, n=26) and tissue plasminogen activator (tPA)-mediated reperfusion following ES (experiment 3, n=28). RESULTS: In ES rats, 3 infarct patterns were identified: small (<150 mm(3)), medium ( approximately 250 mm(3)), and large (>400 mm(3)). Rats with an rCBF below 45% of preocclusion values had an 80% probability of developing medium to large infarcts, whereas rats with an rCBF above the 45%-threshold had a 100% chance of developing small infarcts. LDF did not reliably detect reperfusion in tPA-treated animals (sensitivity=40%), because it apparently occurred within brain areas remote from the LDF-monitoring site as indicated by TTC-staining and magnetic resonance angiography in a subset of animals. CONCLUSION: LDF is an excellent screening method to identify animals with successful ES; however, distinction of medium from large infarcts is not possible, the critical threshold for identifying adequate occlusion is higher than in the sMCAO model, and LDF poorly predicts tPA-mediated reperfusion.

Antithrombin III in fetuses and newborn children.

Antithrombin III (AT III) was measured in plasma of healthy fetuses between 20-29 weeks of gestation, in plasma of suspected growth retarded or malformed fetuses between 30-39 weeks of gestation, in healthy newborn infants after delivery, and in healthy infants during the first year of life. Measurements were performed with an AT III assay (Orion Diagnostica, Espoo, Finland Turbox) on nephalometer Turbox. The results were expressed as a percentage of the mean adult value (300 mg/l) and statistically analysed with the non-parametric Kruskal-Walles test. AT III levels in fetuses were low but increasing. They continued to increase after birth (F = 34.53 p < 0.001) and reached adult values in the age between the tenth and twelfth month of life.

[T lymphocyte subpopulations in women with spontaneous abortions]. / Subpopulacije T limfocita u zena sa spontanim pobacajima.

Investigations were carried out to observe changes in the functional T-lymphocyte activity, as well as the presence of single T-lymphocyte subpopulations in the first trimester of pregnancy in 10 pregnant women with recurrent abortions in their previous pregnancies, compared to 8 healthy pregnant women in the first trimester and 20 of them in the third trimester of pregnancy, and in 30 healthy nonpregnant women at the fertile age. The functional T-lymphocyte activity (PHA-test) was decreased in pregnant women with recurrent abortions (54 +/- 0.99) and in healthy pregnant women (56 +/- 2.50) compared to healthy nonpregnant women (76 +/- 4.80). The total number of lymphocytes in the first trimester was decreased in the investigated group (22 +/- 5.38) and also in healthy pregnant women (25 +/- 1.55) in relation to nonpregnant women (33 +/- 3.15). The percentage of T-lymphocytes was similar (59 +/- 4.32 and 58 +/- 1.96 in relation to 80 +/- 2.80). Helper T-lymphocytes (T-4) were significantly decreased in the investigated group (28 +/- 4.25) compared to the group of healthy pregnant women in the first trimester (32 +/- 1.60) and healthy nonpregnant women (55 +/- 2.37). Suppression T-lymphocytes (T-8) were significantly increased in the investigated group (30 +/- 3.11) in relation to healthy pregnant women in the first trimester (25 +/- 2.45) and to healthy nonpregnant women (23 +/- 1.95). The ratio of helper T-lymphocytes and suppression T-lymphocytes (T4:T8) was significantly lower in pregnant women with recurrent abortions compared to healthy pregnant women in the first trimester and to healthy nonpregnant women.

[Levels of serum IgE and eosinophilic granulocytes in women with cancer of the uterine cervix]. / Vrijednosti serumskog IgE i eozinofilnih granulocita u zena s rakom grla maternice.

In a homogeneous group of patients with diagnosis ca cervicis uteri III B and eosinophilia the concentration of IgE in serum was studied before and during therapy with radiation. In the group of 17 patients in whom concentrations of IgE before radiation were within normal limits (mean = 40.6), after radiation they did not essentially change (mean = 37.1; t less than tgr; P greater than 0.05) and eosinophilia significantly increased at the end of therapy (t = 3.38; P less than 0.05). In the second group of 16 patients higher concentrations of IgE were found before radiation (means = 251.8) and a significant decrease after radiation (mean = 184.6; t = 2.55; P less than 0.05). Eosinophilia had increased here as well (mean = 12.88; t = 8.29; P less than 0.05). Higher concentrations of IgE and eosinophilia are probably partly due to the lack of specific T-suppressor cells for IgE but also partly due to tumour antigens.

[Immunoglobulins in women with cancer of the uterine body (before treatment)]. / Imunoglobulini u zena s rakom trupa maternice (prije lijecenja).

Thirty-five women aged 40 to 79 years with the carcinoma of the body of the uterus were before treatment examined for humoral immunity to find out if the diminished function of the immunological system and immunodeficiency lead to an increased proneness to malignant diseases. Concentrations of total serum proteins, electrophoresis of proteins, and the quantitative determination of G-, A-, and M- immunoglobulins were performed. Lower mean values of IgG (11.94 g/L) and IgA (1.91 g/L) were observed, whereas IgM concentrations did not reveal a statistically significant difference compared with healthy women. The classes, light and heavy chains, as well as immunoglobulin fragments were investigated by immunoelectrophoresis with monospecific antisera. The results revealed a significant accumulation of certain parts of the immunoglobulin molecule, such as gamma heavy chains (in 63% of patients), kappa (77%) and lambda light chains (37%), and fragments--Fab (37%), Fc (57%) i Fd (40%), showing no antibody properties in comparison with the control group of healthy women.