Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long term follow-up results.

Determining the viability of residual tumor masses is a great challenge after primary treatment of Hodgkin lymphoma. FDG-PET may play a crucial role in this procedure. In this study, files of 128 Hodgkin lymphoma patients were reviewed, who were treated in three Hungarian hematology centers between January 1995 and February 2005. CT scan showed residual tumor mass by all of them. Their median follow-up was 75.5 months from PET examination. The number of true-positive, true-negative, false-positive, false-negative subjects were 29, 83, 10, 6, respectively. Sensitivity of post-treatment FDG-PET was 83 %, specificity 93 %, positive predictive value 74 %, negative predictive value 93 %, and accuracy 88 %. The difference between the event free survival of PET positive and negative cases is highly significant (p=0.0000), according to the Mantel-Cox test. Our results in the largest cohort of patients, in accordance with literature, clearly indicates that patients with negative FDG-PET results are unlikely to progress or relapse during the longest follow-up.

Nociceptin inhibits uterine contractions in term-pregnant rats by signaling through multiple pathways.

The actions of the endogenous peptide nociceptin (PNOC; previously abbreviated as N/OFQ) on the myometrium have not been investigated previously. Our aim was to study the presence and functional role of PNOC in the modulation of uterine contractility in pregnant rats at term. The presence of PNOC and its receptors (OPRL1; previously called NOP) in the uterus were detected by radioimmunoassay and radioligand-binding experiments. The PNOC-stimulated G protein activation was assessed by a [(35)S]GTPgammaS-binding technique. The effects of PNOC in uterine rings precontracted with KCl or oxytocin were also tested in vitro. Uterine levels of cAMP were measured by enzyme immunoassay. The K(+) channel blockers tetraethylammonium and paxilline were used to study the role of K(+) channels in mediating the uterine effects of PNOC. Both PNOC and OPRL1 were present in the uterus. PNOC revealed a maximum contraction inhibition of approximately 30%, which was increased to 40% by naloxone. Naloxone and pertussis toxin significantly attenuated the G protein-stimulating effect of PNOC. The uterine cAMP levels were elevated by PNOC and naloxone and after preincubation with pertussis toxin. Tetraethylammonium and paxilline reduced the contraction-inhibiting effect of PNOC and naloxone to approximately 10% and 15%, respectively. We presume that PNOC plays a role in regulating uterine contractility at term. Its effect is mediated partly by stimulatory heterotrimeric G (G(s)) proteins coupled to OPRL1 receptors and elevated cAMP levels, and also by Ca(2+)-dependent K(+) channels. Our results demonstrate a novel action and signaling pathway for PNOC that might be a potential drug target.

Early vegetation development after grassland restoration by sowing low-diversity seed mixtures in former sunflower and cereal fields.

We studied the early vegetation dynamics in former croplands (sunflower and cereal fields) sown with a low-diversity seed mixture (composed of 2 native grass species) in Egyek-Pusztakócs, Hortobágy National Park, East-Hungary. The percentage cover of vascular plants was recorded in 4 permanent plots per field on 7 restored fields between 2006 and 2009. Ten aboveground biomass samples per field were also collected in June in each year. We addressed two questions: (i) How do seed sowing and annual mowing affect the species richness, biomass and cover of weeds? (ii) How fast does the cover of sown grasses develop after seed sowing? Weedy species were characteristic in the first year after sowing. In the second and third year their cover and species richness decreased. From the second year onwards the cover of perennial grasses increased. Spontaneously immigrating species characteristic to the reference grasslands were also detected with low cover scores. Short-lived weeds were suppressed as their cover and biomass significantly decreased during the study. The amount of litter and sown grass biomass increased progressively. However, perennial weed cover, especially the cover of Cirsium arvense increased substantially. Our results suggest that grassland vegetation can be recovered by sowing low diversity mixtures followed up by yearly mowing. Suppression of perennial weed cover needs more frequent mowing (multiple times a year) or grazing.

HbA1c levels and erythrocyte transport functions in complication-free type 1 diabetic children and adolescents.

Higher erythrocyte sodium-lithium countertransport activity (SLC) is implicated in the development of diabetic nephropathy. Altered glucose homeostasis and genetic susceptibility are claimed to play a role in the elevation of SLC. We aimed to test whether metabolic control or the genetic variants of G protein beta 3 (Gb3) subunits determine SLC and other erythrocyte transport activities in complication-free stage of type 1 diabetes. A total of 96 complication-free type 1 diabetic children and adolescents were enrolled. SLC, Na(+)/K(+)-ATPase (NAK) and Ca(2+)-ATPase (CA) were measured by functional assays in erythrocytes. Gb3-C825T polymorphism was determined by PCR-RFLP. Results were related to HbA(1c) and were compared to those of 97 healthy controls. SLC activity was higher in diabetics (387+/-146 vs. 280+/-65 mmol/RBC. hour) and correlated with HbA(1c) levels (y=0.004x+6.42, r=0.33, n=96, p<0.01). NAK and CA activities were unaltered. The prevalence of (825)T allele was similar in the patient and control groups (0.34 vs 0.37) and no differences in enzyme activities were observed between the (825)T allele-positive and negative subjects. Although metabolic control correlated with SLC, other membrane functions were not affected. Therefore we hypothesize that the relationship between advanced glycation and SLC elevation is not causative. Rather, a genetic susceptibility for the coexistence of poor metabolic control and higher SLC is more likely. However, the presence of Gb3-C825T variant is not likely to be a risk factor for SLC-elevation and altered metabolic control diabetes.

Second malignancies after treatment for Hodgkin's disease.

The occurrence of treatment-related second malignancy following Hodgkin's disease (HD) has now been recognized as a major problem. The purpose of this study was to review our experience with second malignancies in patients treated for Hodgkin's disease, comparing the results with the international literature data. Six hundred and sixty five patients with HD were treated in our department, between 1978 and 1996. Second neoplasm developed in 32 cases (4.8%). Seven secondary hematological malignancies were observed: four acute nonlymphocytic leukemias, two non-Hodgkin's lymphomas and one chronic myeloid leukemia. Among patients with second hematological malignancies, the mean age at diagnosis of HD was 44 years and the mean interval until the development of second malignancy was 6.1 years. Five patients received chemo- and radiotherapy and in two cases chemotherapy was used. Three of the seven patients are alive. Twenty-five patients have had solid tumors, affecting lung (5), breast (3), colon (3), stomach (2), urinary bladder (2), head-and-neck (1), thyroid gland (1), esophagus (1), liver (1), pancreas (1), furthermore, three sarcomas and two malignant melanomas were observed. Their mean age at the diagnosis of HD was 46 years and the mean period of latency was 8.3 years. Chemotherapy was applied to nine patients, 16 patients received both chemo- and radiotherapy. Eleven patients had solid tumors in the region irradiated earlier. Ten out of the 25 patients are alive, three patients' present state is unknown. Since alkylating agents increase the risk of leukemia and irradiation contributes mainly to other malignancies, future treatment protocols should attempt to reduce the most serious consequence of therapy without compromising the survival. It is necessary to investigate the impact of additional risk factors. Careful, lifelong observation is indicated for patients with HD, with special attention given to new clinical signs and symptoms.

[Clinical features and guidelines of treatment of mucosa-associated lymphoid tissue lymphoma of stomach] / A primer gyomor MALT limfóma klinikuma és korszerû kezelésének irányelvei.

The mucosa-associated lymphoid tissue (MALT) lymphoma is a very indolent disease. Its most common site is the stomach. The lymphoma begins as a reactive lymphocyte accumulation mostly due to an infection of Helicobacter pylori (HP). Through repeated mutations this tissue is transformed into the characteristic MALT lymphoma. At the time of the diagnosis the lymphoma is usually localised, but in one third of the patients the disease has already been disseminated. There are not any commonly accepted guidelines of therapy concerning this primary gastric MALT lymphoma, but certain general tendencies have already been defined. In the early disease the aim of the treatment is curative with the preservation of the stomach as much as possible. In a considerable number of cases, when the surface of the stomach is affected by HP, one can achieve histological and molecular biologic remission after eliminating the bacteria. However, there is no such therapeutic consequence to be expected in case of a deeply invasive tumour. The optimal treatment of patients of this group as well as those whose disease is resistant to HP eradication treatment together with those who are HP negative is radiotherapy or surgery with chemotherapy. In this latter case quality of life becomes worse. In an advanced case cure is impossible and chemotherapy is the most effective to ease the patient's state.

Interaction of thyrotropin (TSH) and gonadotropins in the function of genital organs I. Investigations in the frog.

Earlier data indicate that TSH, which has a structure similar to that of gonadotropins, is able to evoke ejaculation in the frog (Galli-Mainini reaction). The present experiments provide evidence that TSH, in a dose that by itself is ineffective, is able to potentiate the effect of HCG. This action of TSH is more pronounced if the drug is administered prior to HCG; it is less evident upon simultaneous administration. Since FSH + LH has similar effects the experiments provide further evidence for the concept that TSH acts like gonadotropin in this system.

Interaction of thyrotropin (TSH) and gonadotropins in the function of genital organs. Effect of TSH and gonadotropin pretreatment (hormonal imprinting) of newborn rats on hormonal overlap in adult animals.

At the age of 25 days the TSH-gonadotropin overlap is minimal in rats and extremely high doses of TSH are required to produce gonadotropin-like responses. Although the effect may be due also to some occasional contamination, nevertheless a single treatment of newborn animals (hormonal imprinting) with either hormone augmented the response to a second treatment with either hormone performed at 25 days of age. Newborn rats pretreated with either TSH or gonadotropin were exposed to a second TSH challenge at the age of 25 days exhibited responses which were not commeasurable to those observed after gonadotropin treatment alone. However, the amplifying action of TSH pretreatment with regard to the second response to gonadotropin was comparable or even more apparent than that of gonadotropin pretreatment.

Expression of a single major histocompatibility complex locus controls the immune response to poly-L-(tyrosine, glutamic acid)-poly-DL-alanine-poly-L-lysine.

Genetic control of the immune response linked to the major histocompatibility (H-2) complex in the mouse has been described for synthetic polypeptide antigens and for low doses of native proteins. The phenomenon is well documented(1,2). Extensive screening of intra-H-2 crossover-derived recombinant strains has localized H-2-linked immune response (Ir) genes to the I-immune response region of the H-2 complex (3). For most antigens, Ir genes are autosomal, dominant, and they segregate as single loci. It is not known whether these crossover-defined loci respresent single genes with multiple alleles or clusters of tightly linked genes (4). In 1972, Stimpfling and Durham (5) postulated that two interacting loci within the H-2 complex were required for the response to the alloantigen, H-2.2 (6), and, in 1975, Dorf et. al. (7) observed a responder phenotype in a recombinant derived from two strains which were nonresponders to the synthetic linear terpolymer, L-glutamic acid, L-lysine, L-phenylaline (GLPhe). Analysis of additional recombinants and complementation tests with F(1) hybrids clearly demonstrated that genes in two intra-I-region loci controlled the immune response to GLPhe. Subsequently, requirement for genes mapping in two intra-I-region loci were reported for porcine LDH(B)(8), the alloantigen Thy-1.1 (9), and for the synthetic terpolymers L-glutamic acid, L-lysine, L-tyrosine and L-glutamic acid, L-lysine, L- leucine (6,10). Demonstration that responses to both synthetic polypeptide and native protein antigens can be controlled by genes in two distinct I-region loci prompted speculation that the phenotypic expression of two I-region genes is a general phenomenon which may provide the key for understanding the mechanism of Ir gene function and cellular collaboration in the immune response. Benacerraf and Dorf (10) have shown that Ir gene complementation is often more effective in the cis than in the trans configuration. This concept is further supported by the data reported for GLPhe (10-12) which indicate that both of the complementing genes must be expressed in each of the cell types participating in the interaction. Failure to detect complementation for the majority of antigens under H-2-linked Ir-gene control might be attributed to the limited number of available intra-I- region recombinant strains.

Genetic control of cell-mediated responsiveness to an AKR tumor-associated antigen: mapping of the locus involved to the I region of the H-2 complex.

The role of H-2-linked genes in controlling resistance to murine leukemia viruses has been studied by measuring the cell-mediated immune response of F1 hybrid mice (between AKR and various C3H and C57BL/10 derived, H-2 congenic strains) to an AKR tumor cell line, BW5147. The studies have shown that the ability to generate a primary or secondary cell-mediated response to an AKR tumor cell antigenic determinant is under H-2 linked control. The locus determining CML responsiveness maps in the I-J subregion. Nonresponsiveness is associated with the H-2q/k and H-2b/k hybrid genotypes, whereas responsiveness is associated with the H-2k/k homozygous genotype. Nonresponsiveness may result from (a) dominant suppression; (b) recessive responsiveness; or (c) an alternate mechanism not yet understood. This type of control may be one of several H-2-associated mechanisms of defense against virus-induced neoplasms.

Genetic control of radiation leukemia virus-induced tumorigenesis. I. Role of the major murine histocompatibility complex, H-2.

Resistance to radiation leukemia virus-induced leukemogenesis is associated with the H-2D region of the H-2 complex, or with closely linked loci. The H-2Dd allele confers resistance ot the disease, while the H-2D-Q and H-2Ds alleles are associated with susceptibility. It is not clear whether Ir genes, or an alternative mechanism are responsible for the observed H-2-linked resistance to the disease.

Genetic control of radiation leukemia virus-induced tumorigenesis II. Influence of Srlv-1, a locus not linked to H-2.

A single locus, tentatively denoted Srlv-1 (susceptibility to radiation leukemia virus [RadLV]-1), confers dominant susceptibility to RadLV-induced leukemogenesis. Srlv-1 is not linked to H-2, and appears to be distinct from Fv-1 and Fv-2. Preliminary data suggest that Srlv-1 affected virus proliferation. A striking feature of this system is that Srlv-1 overrides the protection afforded by the H2D-associated dominant resistance to RadLV-induced neoplasia.

Mapping of the genetic control of murine response to low doses of the dinitrophenyl conjugates of ovomucoid and bovine gamma-globulin.

The antibody responses in mice to low doses of the DNP-conjugates of ovomucoid (OM) and bovine gamma-globulin (BGG) were measured for a number of inbred strains carrying independent and recombinant H-2 haplotypes. This permitted mapping the gene(s) controlling the response to low doses of OM (Ir-1-OM) within the I-A subregion of the H-2 complex. Similarly, it was possible to map the primary gene(s) controlling the response to low doses of BGG (Ir-1-BGG) within the I-A and/or I-B subregions. Further localization of the Ir-1-BGG gene(s) to the I-A or I-B subregion of the H-2 complex was not possible due to the ambiguous response of the B10.A(4R) strain of mice.

Genetic control of the immune response. Mapping of the Ir-1 locus.

Eleven strains of mice bearing recombinant H-2 chromosomes derived from known crossover events between known H-2 types were immunized with a series of branched, multichain, synthetic polypeptide antigens [(T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L]. Results with nine of the eleven H-2 recombinants indicated that the gene(s) controlling immune response to these synthetic polypeptides (Ir-1) is on the centromeric or H-2K part of the recombinant H-2 chromosome. Results with two of the eleven recombinant H-2 chromosomes indicated that Ir-1 was on the telomeric or H-2D part of the recombinant H-2 chromosome. Both of these recombinants were derived from crossovers between the H-2K locus and the Ss-Slp locus near the center of the H-2 region. One of these recombinants, H-2(y), was derived from a known single crossover event. These results indicate that Ir-1 lies near the center of the H-2 region between the H-2K locus and the Ss-Slp locus. The results of a four-point linkage test were consistent with these results. In 484 offspring of a cross designed to detect recombinants between H-2 and Ir-1, only two putative recombinants were detected. Both of these recombinants were confirmed by progeny testing. Extensive analysis of one of them has shown that the crossover event occurred within the H-2 region. (Testing of the second recombinant is currently under way.) Thus, in the linkage test, recombinants between H-2 and Ir-1 are in fact intra-H-2 crossovers. These results permit assignment of Ir-1 to a position between the H-2K locus and the Ss-Slp locus.