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T Bock

Publications and source records attributed to T Bock.

At least 37 records · Page 2Linked to original sources
PubMed1999

Previous maternal abortion, longer gestation, and younger maternal age decrease the risk of type 1 diabetes among male offspring.

OBJECTIVE: To identify possible influences and interactions of perinatal determinants in the subsequent development of type 1 diabetes. RESEARCH DESIGN AND METHODS: The data were obtained from children born in Denmark during the periods 1978-1982 and 1984-1986 and admitted to a Danish hospital with newly diagnosed type 1 diabetes between 1978 and 1995; 857 patients fulfilled the criteria. The study was conducted by combining and analyzing two national registries: the National Patient Registry and the Medical Birth Registry. For each diabetic child, two control children were randomly selected, matched by sex, time, and district of delivery. RESULTS: By multivariate logistic regression analysis, the following significant determinants were identified. Male offspring showed decreased risk when born of mothers who had had one or more abortions (odds ratio [OR] 0.66 [95% CI 0.48-0.92]) and with long duration of gestation (linearly with OR 0.91 per week [0.85-0.99]), while increased risk was found for high maternal age (linearly with OR 1.03 per year [1.00-1.06]). Female offspring showed no such association. No significant differences between diabetic patients and control subjects were found with respect to paternal age, maternal parity, placental weight or any of the birth size parameters, or interventions and complications during delivery. CONCLUSIONS: The findings show that perinatal determinants may influence the risk of subsequent development of type 1 diabetes in a sex-specific manner.

Abortion, Spontaneous↗
PubMed1999

Intermittent feeding and fasting reduces diabetes incidence in BB rats.

Food intake may be one of several factors which influence the risk of development of insulin dependent diabetes mellitus, but the influence of the pattern of food supply has not been studied previously. The aim of the present study was to investigate the effect of intermittent feeding and fasting upon diabetes in BB rats. This study included three groups. Group 1 served as control and included 77 animals, 79% became diabetic. In groups 2 and 3, after weaning, food but not water was withdrawn from the animals: 24 h twice a week in group 2; 24 h every second day in group 3. Group 2 included 40 BB rats, 50% (p < 0.004) became diabetic. Group 3 included 44 BB rats, 52% (p < 0.01) became diabetic. No differences were seen between sexes. Degree of insulitis was not influenced by changed food supply. Regarding blood glucose, no influence was seen among diabetic animals, among non-diabetic animals changed food supply reduced blood glucose values obtained at the end of the study. Intermittent feeding and fasting tended to reduce mean age at the time of diagnosis of diabetes, significance was reached only in female animals from group 3 compared to group 1. Body weight was obtained weekly. Intermittent feeding and fasting caused a reduced weight gain in group 2 as well as in group 3 compared to control animals; however, most pronounced in group 3 and also more pronounced among males compared to females. For pre-diabetic and non-diabetic animals comparable influence on body weight was seen. The main conclusion in the study is that intermittent feeding and fasting reduced diabetes incidence in BB rats.

Age Factors↗
PubMed1998

Short-term effects of early-acting and multilineage hematopoietic growth factors on the repair and proliferation of irradiated pure cord blood (CB) CD34+ hematopoietic progenitor cells.

PURPOSE: Hematopoietic growth factor(s) (GF) may exert positive effects in vitro or in vivo on the survival of hematopoietic stem and progenitor cells after accidental or therapeutic total body irradiation. METHODS AND MATERIALS: We studied the clonogenic survival and DNA repair of irradiated (0.36, 0.73, and 1.46 Gy) CD34+ cord blood (CB) cells after short-term incubation (24 h) with GFs. CD34+ cells were stimulated with basic fibroblast growth factor (bFGF), stem cell factor/c-kit ligand (SCF), interleukin-3 (IL-3), IL-6, leukemia inhibitory factor (LIF), and granulocyte-monocyte colony stimulating factor (GM-CSF) alone or in combination in short-term serum-free liquid suspension cultures (LSC) immediately after irradiation and then assayed for clonogenic progenitors. DNA repair was evaluated by analysis of DNA strand breaks using the comet assay. Survival of CFU-GM, BFU-E, and CFU-Mix was determined and dose-response curves were fitted to the data. RESULTS: The radiobiological parameters (D[0] and n) showed significant GF(s) effects. Combination of IL-3 with IL-6, SCF or GM-CSF resulted in best survival for CFU-GM BFU-E and CFU-Mix, respectively. Combinations of three or more GFs did not increase the survival of clonogenic CD34+ cells compared to optimal two-factor combinations. The D[0] values for CFU-GM, BFU-E, and CFU-Mix ranged between 0.56-1.15, 0.41-2.24, and 0.56-1.29 Gy, respectively. As for controls, the curves remained strictly exponential, i.e., all survival curves were strictly exponential without any shoulder (extrapolation numbers n=1 for all tested GF(s). DNA repair capacity of CD34+ cells determined by comet assay, was measured before, immediately after irradiation, as well as 30 and 120 min after irradiation at 1 Gy. Notably, after irradiation the 2-h repair of cytokine-stimulated and unstimulated CD34+ cells was similar. CONCLUSION: Our data indicate that increased survival of irradiated CB CD34+ cells after short-term GF treatment is mediated through proliferative GF effects on the surviving fraction but not through improved DNA repair capacity.

Cell Survival↗
PubMed1998

Expression of intercellular adhesion molecule-1 on the vascular endothelium in nasal polyps before, during and after topical glucocorticoid treatment.

Nasal polyposis is a result of a chronic inflammatory disorder in the upper airways. In vitro studies have revealed that extravasation of leucocytes requires interactions between several sets of adhesion molecules expressed on the circulating leucocytes and the vascular endothelium. Therefore, the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) in biopsies from polyps and inferior turbinates was investigated by the use of immunohistochemical staining. Biopsies were obtained from 11 patients suffering from nasal polyposis before, during and after treatment with 100 microg budesonide (Rhinocort Turbuhaler) in each nostril twice daily. Before, during and after treatment, ICAM-1 was expressed in the majority of vessels in polyps and mucosa of inferior turbinates. The intensity of endothelial ICAM-1 expression in polyps was significantly reduced during topical glucocorticoid treatment compared with the pretreatment and posttreatment levels (p < 0.005). In biopsies from the inferior turbinates, the intensity of the endothelial ICAM-1 expression was lower during treatment than after discontinuation of medical treatment (p < 0.005). In conclusion, topical budesonide treatment seems to downregulate ICAM-1 expression on the vascular endothelium in nasal polyps. Such an effect may interfere with leucocyte extravasation and partially account for the anti-inflammatory effect of local glucocorticoid treatment in human nasal polyposis.

Administration, Topical↗
PubMed1997

Purging of peripheral blood progenitor cell autografts and treatment of minimal residual disease.

Clinical success of autologous peripheral blood progenitor cell (PBPC) transplantation is challenged by relapse of malignant disease which might at least in part be mediated by graft-contaminating tumor cells. Although the clinical efficacy of tumor cell depletion still remains to be demonstrated, multiple purging strategies are currently pursued in the context of autologous stem cell transplantation. This report discusses ex vivo manipulations of PBPC transplants with respect to purging of tumor cells, including positive selection of CD34+ cells with or without negative depletion of tumor cells as well as ex vivo expansion techniques. Moreover, strategies with an adoptive immunotherapy using ex vivo-generated autologous dendritic cells for the treatment of minimal residual disease after stem cell transplantation will be discussed here.

Antigens, CD34↗
PubMed1997

Physicochemical properties and in vitro toxicity of cationic liposome cDNA complexes.

The purpose of this study was to elucidate the interaction of cationic liposomes and plasmid cDNA by examining their ultrastructure, zeta potential, stability in aqueous media and protection from DNaseI digestion; their potential for hemolysis and platelet aggregation was evaluated as it may serve as an in vitro toxicity screen. Liposomes consisting of N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) or 3 beta-[N-(N',N'-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and dioleylphosphatidylethanolamine (DOPE) were complexed with plasmid constructs of ovine prostaglandin G/H synthase (pCMV4-PGH) or human alpha 1-antitrypsin (pCMV4-AAT) at lipid:plasmid (L/P) ratios of 3:1-8:1 (w/w). The electron micrographs showed bead-like attachment of liposomes to cDNA and coating of plasmid strands. The zeta potential showed isoelectric points at L/P ratios of 3.5-4 (DOTMA/DOPE) and 5.5-6.5, corresponding to a pKa of 6.45 (DC-Chol/DOPE). Liposome cDNA complexes were stable in water, saline and 5% dextrose for 48 h, but precipitated instantaneously in PBS. An increase in the L/P ratio corresponded with increased protection from DNaseI digestion. DOTMA/DOPE liposomes alone were highly hemolytic and DC-Chol/DOPE liposomes moderately hemolytic; hemolysis was abolished by cDNA complexation, with the exception of very high (> or = 7:1) L/P ratios. Both liposomes alone and cDNA complexes caused transient serum turbidity, while none caused platelet aggregation. It was concluded that current cationic lipid cDNA formulations are metastable and appear to have very little if any toxicity with respect to hemolytic potential and untoward interaction with other blood components.

DNA, Complementary↗
PubMed1997

Total number and size distribution of motor neurons in the spinal cord of normal and EMC-virus infected mice--a stereological study.

The encephalomyocarditis virus of the diabetogenic M-strain (EMC-M) is known to cause diabetes in mice. The EMC-M virus has also been shown to cause paresis in some of the infected animals. The clinical features include an acute ascending predominantly motor paralysis, developing within days. This resembles acute idiopathic polyneuritis. The alpha motor neurons would be a possible target for the virus, so two parameters, the total number and the size distribution of motor neurons, were therefore selected for further investigation in 6 mice with neurological involvement and compared with 6 control mice. The optical fractionator method was applied for estimating the total number of motor neurons and the 3D size distribution was estimated using the rotator method in a vertical design. No difference was found in the total number of motor neurons and the size distributions were similar in the 2 groups. This design can be used as a model for the estimation of the total number of motor neurons and their size distribution in other experimental animal models.

Animals↗
PubMed1997

Assembly of adeno-associated virus type 2 capsids in vitro.

Capsid proteins VP1, VP2 and VP3 of adeno-associated virus type 2 (AAV-2) were separately expressed by recombinant baculoviruses, purified under denaturing conditions and renatured in the presence of 0.5 M arginine, followed by dialysis against buffers of physiological ionic strength. At a protein concentration of 0.05 mg/ml, the three capsid proteins predominantly formed monomers and, to a lesser extent, oligomers, as determined by sedimentation analysis. Oligomerization increased at higher protein concentrations. The capsid protein oligomers consisted of globular, non-capsid-like structures, as detected by electron microscopy. Addition of a HeLa cell extract significantly stimulated oligomerization of the capsid proteins, probably due to interactions with HeLa cell proteins. Characterization of structures sedimenting around 60S by immunoprecipitation and electron microscopy showed that, in addition to other aggregates, empty capsid-like structures were formed in vitro. The identity of these structures as empty AAV capsids was verified by immunoelectron microscopy. Analysis of capsid formation in HeLa cells by transfection of VP expression constructs allowing separate expression of VP1, VP2 and VP3 showed that they were able to form capsids, although with a reduced efficiency as compared to VP proteins expressed from the wt cap gene. This finding suggests that the mutations introduced to allow separate capsid protein expression reduced the efficiency of capsid assembly in vivo and might also explain the reduced recovery of empty capsids employing the in vitro assembly procedure.

Animals↗
PubMed1994

Perinatal determinants among children who later develop IDDM.

OBJECTIVE: The aim of this study was to investigate whether children who develop insulin-dependent diabetes mellitus (IDDM) differ in some aspects from a matched control group at the time of birth. RESEARCH DESIGN AND METHODS: We studied all children who were born in Denmark during the period 1973-1977 and admitted to a Danish hospital with a diagnosis of IDDM during 1978-1989. The study was conducted by combining two nationwide registries, The National Patient Registry and The Birth Registry. RESULTS: The criteria were fulfilled by 837 children. Data regarding the age of the parents, the number of previous pregnancies of the mother, the month of birth, and the birth weight and length of the children who developed IDDM were compared with the data of an age- and sex-matched control group of 837 children without IDDM. We did not detect any significant differences between the two groups with respect to the parameters studied. CONCLUSIONS: No differences in perinatal determinants could be demonstrated among Danish children who develop IDDM compared with children without diabetes.

Adolescent↗
PubMed1994

High juvenile body weight and low insulin levels as markers preceding early diabetes in the BB rat.

Diabetes incidence in BB rats is 60-80% and our aim was to investigate whether it is possible to characterize those rats destined to develop diabetes. While the genetic background as well as the environmental factors affecting BB-rat littermates are very similar, body weight reflects some existing variance. The study involved 151 BB rats, and the body weight of each animal was measured daily from birth. Thirty-four animals became diabetic before 100 days of age, and their body weight showed a 5-10% increase compared to the non-diabetic animals for each day of life from day 1 to day 45 (p values 0.0001 to 0.05). This increased body weight in individuals destined for diabetes was seen in both sexes. When investigating whether juvenile body weight has any predictive value, we found that the incidence of diabetes at 100 days of age increased from 22.5% to 46.7% (p < 0.01) when the heaviest animals in each litter were selected. Insulin content in pancreas was examined at day 10 and 20, and was found to be significantly reduced in the BB rats with highest body weight compared with rest of the litter (p = 0.02 and p = 0.0005, respectively). The insulin concentration in peripheral blood was significantly reduced in the BB rats with highest body weight at 20 days of age (p = 0.002). When early and late diabetic BB rats were compared at time of diagnosis regarding blood glucose, degree of insulitis and number of small and large islets, no significant differences were found between the groups.

Age of Onset↗
PubMed1994

The first fatal case of Vibrio vulnificus infection in Denmark.

Vibrio vulnificus can cause severe infections in humans and persons with preexisting liver disorders are especially at risk. In this paper we report what is to our knowledge the first fatal case of V. vulnificus infection in Denmark. The patient was a 68-year-old man with a history of chronic lymphatic leukemia and hepatic cirrhosis. Physicians should be aware of the clinical manifestations of this disease and should be especially attentive to patients at risk of acquiring the infection if there has been possible exposure to V. vulnificus by contact with seawater or contaminated material such as eels.

Aged↗
PubMed1992

No risk of diabetes after insulin-shock treatment.

Prophylactic insulin treatment is effective in preventing diabetes in animal models of insulin-dependent diabetes mellitus (IDDM) but the safety of such preventive treatment in prediabetic human subjects remains unclear; insulin is a potential autoantigen that could accelerate beta-cell decompensation and onset of IDDM. We have investigated whether insulin treatment of non-diabetic subjects increases the risk of subsequent development of diabetes in a retrospective study of Danish patients who received insulin-shock treatment for psychiatric disorders. Mean age of the 481 patients at insulin-shock treatment was 32.6 (range 12.9-69.6) years. The patients received 59 (6-200) injections of 78 (16-261) IU bovine/porcine insulin. Hospital records provided an average of 22.0 (0.6-51.2) years' observation. During the observation time, IDDM developed in only 1 patient; 1.3 cases would be expected from Danish incidence data (p = 0.75). Similarly, there was no significant difference between the observed number of cases of non-insulin-dependent diabetes mellitus (NIDDM) and the number expected from Danish prevalence data (12 vs 10.2; p = 0.45). We collected blood samples from 27 of the patients. All but 2 (who had previously diagnosed NIDDM) had normal fasting blood glucose and plasma insulin concentrations, none had islet-cell antibodies, and only 2 had detectable insulin antibodies. Thus, the risk of diabetes was not increased by the use of many insulin injections in these non-diabetic subjects. We conclude that clinical trials on prevention of IDDM by prophylactic insulin treatment can be regarded as safe.

Adolescent↗
PubMed1992

Interleukins increase surface ganglioside expression of pancreatic islet cells in vitro.

This experiment was conducted in order to investigate whether expression of gangliosides on islet cell surface in vitro is influenced by cytokines, especially interleukin 1. Islets from adult Lewis rats were incubated with different concentrations of recombinant-derived human cytokines. Following dispase treatment, the single cells were labeled with monoclonal antiganglioside antibodies A2B5 or R2D6, and conjugate. Both are directed against beta cells; A2B5 is recognized to bind specifically to pancreatic islet cells, while R2D6 is shown to bind no other pancreatic cells than beta cells. Surface labeling was evaluated in blind trials using a fluorescence microscope and a fluorescence-activated cell sorter (FACS). A2B5 staining demonstrated a significantly higher number of labeled cells after incubation with interleukin 1 alpha (14.9% +/- 2.8; p less than 0.005), interleukin 1 beta (23.2% +/- 4.2; p less than 0.0005) or TNF alpha (16.1% +/- 4.0; p = 0.005) compared to endotoxin controls (4.1% +/- 1.1). Interleukin 1 beta (9.5% +/- 1.5; p less than 0.005) showed a significantly increased number of R2D6-stained cells (control: 2.3% +/- 1.3). A similar but not significant effect was seen with interleukin 1 alpha and TNF alpha. Interleukin 6 had no effect on the antigen expression. The intensity of labeling was elevated among interleukin 1 beta-incubated cells compared to control samples. Thus, treatment of islets with different cytokines, especially interleukin 1 beta, increases surface antigen expression. We suggest that this mechanism of action in vitro may be of importance for the putative diabetogenic effect of interleukin 1.

Animals↗
PubMed1992

Beta-cell expression of 65-kDa heat-shock protein mRNA is function- and age-dependent.

This study examined the expression of mRNA coding for the 65-kDa heat-shock protein (HSP) in rat islet cells of different functional states and different ages. In addition, beta cells and non-beta cells purified by fluorescence-activated cell sorting were studied. Total RNA from islet cells and insulin-producing RINm5F cells was isolated and analyzed by Northern blotting using a cDNA probe coding for the human homologue to the mycobacterial 65-kDa HSP, after which blots were quantified by densitometric scanning. Isolated beta cells were found to express 65-kDa HSP mRNA. The expression was increased in Lewis islet cells exposed to heat shock or high glucose concentration, four- and three-fold, respectively (p < 0.01). In isolated beta cells cultured at high glucose concentration a doubling in the content of 65-kDa HSP mRNA was seen compared with islets cultured at low glucose concentration (p < 0.05). In islets from Lewis rats fasted for 24 h, the content of 65-kDa HSP mRNA was 42% lower than in islets isolated from normally fed Lewis rats (p < 0.01). Both in BB rats and Wistar Furth rats the content of 65-kDa HSP mRNA was found to be higher in the 30- and the 60-day-old rats compared with the neonatal animals (p < 0.01). The expression of 65-kDa HSP mRNA was increased in RINm5F cells following heat shock, while no induction was seen after stimulation with glucose, TPA or IBMX. It is concluded that the 65-kDa heat-shock protein belongs to the family of inducible functional antigens in beta cells, which strengthens the interest in 65-kDa HSP as an antigen possibly involved in the initiation of autoimmune beta-cell destruction.

Age Factors↗