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T Bock

Publications and source records attributed to T Bock.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1991

Reduction of diabetes incidence in NOD mice by neonatal glucose treatment.

The aim of this study was to investigate whether neonatal glucose treatment influences the incidence of diabetes in NOD mice. Thirty-nine NOD mice (19 males, 20 females) were treated with 8 g glucose/kg BW/day administered by subcutaneous injections twice a day for the first six days of life. Thirty-six untreated NOD mice (20 males, 16 females) served as a control group. In the glucose-treated group, 33% became diabetic compared with 58% in the control group (X2 = 5.3, p = 0.021). Among the glucose-treated males, 16% became diabetic compared with 50% of the untreated males (X2 = 5.5, p = 0.019), whereas 50% of the glucose-treated females became diabetic compared with 69% of the untreated females (X2 = 1.1, NS). We conclude that neonatal glucose treatment can reduce the diabetes incidence in NOD mice. These results could have implications for the prevention of type 1 diabetes mellitus in humans.

Animals↗
PubMed1991

[Subjective perception of psychotic events. Illness concepts of patients, relatives, therapists in comparison].

The study explains, from an academic and psychiatric point of view, the need of qualitative research in the field of self-perception when suffering from an psychosis. It compares illness concepts and the subjective assessment (diagnosis) voiced by patients, their close relatives and the responsible medical staff. Surprising conclusions, which are carefully discussed, are the result of the study. When looking at future research on this issue, the need of stronger consideration of psychotic matters and the biographical as well as institutionalised context becomes obvious.

Adaptation, Psychological↗
PubMed1990

Prevention of diabetes mellitus in BB rats by neonatal stimulation of beta cells.

Antigen expression in type 1 (insulin-dependent) diabetes may depend on the functional state of beta cells. At birth, beta cells are immature, produce only a basal amount of insulin, and are unresponsive to glucose--but are sensitive to glucagon and arginine. beta cells of spontaneously diabetic BB rats were stimulated for the first 6 days after birth by glucose with glucagon or arginine to accelerate beta cell maturation, and possibly to induce antigen expression and tolerance. Over the first 200 days of life, only 23% of glucose and glucagon-treated BB rats, and 20% of glucose and arginine-treated BB rats developed diabetes, compared with 65% of untreated controls. This finding may explain the observation that children of mothers who have type 1 diabetes are three times less likely to develop the disease than children of fathers with type 1 diabetes. Earlier maturation of beta cells during the diabetic pregnancy may protect against diabetes in later life.

Animals↗
PubMed1987

Increased thromboplastic potential in diabetes: a multifactorial phenomenon.

Coagulation parameters, platelet aggregation, and thromboxane production as well as metabolic parameters were measured in 31 diabetic patients, 12 without and 19 with clinically manifest late complications, and in 14 healthy control subjects. Spontaneous in vitro aggregation as well as ADP, collagen, and arachidonic acid induced aggregation were higher in both groups of diabetic patients, without an increase in thromboxane B2 production. In diabetic patients with late complications an increase in fibrinogen, fibrinogen cyanogen bromide peptide, factor VIII related antigen, C1-esterase inhibitor, and antithrombin III was observed in comparison to healthy subjects. Fibrinogen, C1-esterase inhibitor, and factor VIII related antigen were already elevated in diabetic patients without clinically manifest late vascular complications. No strict correlations were found between serum glucose, glycosylated hemoglobin, and glycosylated albumin, on the one hand, and coagulation promoting or inhibiting factors, aggregation or thromboxane B2 production, on the other, in either control or diabetic subjects. Also no correlations existed between the coagulation parameters and the aggregation results. In vitro incubation of pooled normal plasma with different glucose concentrations had no influence on the methods by which the coagulation parameters were measured. These data indicate that rather early in the diabetic state many changes take place in different phases of the thrombostatic process, all resulting in an increased hemostatic diathesis.

Adult↗