Biomedical subjects

H Borg

Publications and source records attributed to H Borg.

At least 19 recordsLinked to original sources

PubMed2006

HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden.

AIMS/HYPOTHESIS: The World Health Organization considers an aetiological classification of diabetes to be essential. The aim of this study was to evaluate whether HLA-DQB1 genotypes facilitate the classification of diabetes as compared with assessment of islet antibodies by investigating young adult diabetic patients. SUBJECTS AND METHODS: Blood samples were available at diagnosis for 1,872 (90%) of the 2,077 young adult patients (aged 15-34 years old) over a 5-year period in the nationwide Diabetes Incidence Study in Sweden. Islet antibodies were measured at diagnosis in 1,869 patients, fasting plasma C-peptide (fpC-peptide) after diagnosis in 1,522, while HLA-DQB1 genotypes were determined in 1,743. RESULTS: Islet antibodies were found in 83% of patients clinically considered to have type 1 diabetes, 23% with type 2 diabetes and 45% with unclassifiable diabetes. After diagnosis, median fpC-peptide concentrations were markedly lower in patients with islet antibodies than in those without (0.24 vs 0.69 nmol/l, p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies of at least one of the risk-associated HLA-DQB1 genotypes compared with patients without. Antibody-negative patients with risk-associated HLA-DQB1 genotypes had significantly lower median fpC-peptide concentrations than those without risk-associated genotypes (0.51 vs 0.74 nmol/l, p=0.0003). CONCLUSIONS/INTERPRETATION: Assessment of islet antibodies is necessary for the aetiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in differentiating between idiopathic type 1 diabetes and type 2 diabetes.

Adolescent↗

PubMed2006

Islet antibodies associated with pancreatic B-cell dysfunction at and 3 years after diagnosis of diabetes in subjects aged 35-64 years old: degree of impairment less severe than in those aged 0-34 years old.

AIMS: To determine differences in pancreatic B-cell function in relation to islet antibodies at diagnosis of diabetes and 3 years later in subjects aged 35-64 years old compared with those aged 0-34 years. METHODS: From a population-based diabetes register, 46 (0-34 years old) and 323 (35-64 years old) incident diabetic patients were investigated at diagnosis and 3 years later. Islet cell antibodies (ICA, GADA and IA-2A) and fasting plasma C-peptide were measured. RESULTS: Islet antibodies were found in 80% of the subjects aged 0-34 years and in 11% of those aged 35-64 years at diagnosis. ICA and GADA was the only combination of two islet antibodies detected in those aged 35-64 years and was, with or without IA-2A, associated with significantly lower median fasting C-peptide values than in those without or with only one antibody [0.35 nmol/l, interquartile range (IQR) 0.63 vs. 0.85 nmol/l, IQR 0.49; P = 0.0004]. However, fasting C-peptide in subjects aged 35-64 years old with multiple islet antibodies was higher than in those aged 0-34 years with islet antibodies (median 0 nmol/l, IQR 0.16, P = 0.0019). After 3 years' follow-up, fasting C-peptide was even lower in subjects aged 35-64 years old with three islet antibodies (median 0.14 nmol/l, IQR 0.27; P = 0.05). CONCLUSIONS: Islet antibodies were common in adults at diagnosis of diabetes. The combination of ICA and GADA indicates impaired B-cell function at diagnosis of diabetes in those aged 35-64 years old.

Adolescent↗

PubMed2005

Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes.

OBJECTIVE: To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. MATERIAL AND METHODS: Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. RESULTS: Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p<0.001). CONCLUSIONS: Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis.

Adolescent↗

PubMed2004

Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden.

OBJECTIVES: To establish the prevalence of remaining beta-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. DESIGN: Population-based cohort study. SETTING: Nationwide from all Departments of Medicine and Endocrinology in Sweden. SUBJECTS: A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. MAIN OUTCOME MEASURE: Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved beta-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies - were measured. RESULTS: Amongst 269 islet antibody positives (ab+) at diagnosis, preserved beta-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining beta-cell function. Amongst the 241 patients without detectable beta-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. CONCLUSIONS: Sixteen per cent of patients with autoimmune type 1 diabetes had remaining beta-cell function 8 years after diagnosis whereas 5.8% with beta-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.

Adolescent↗

PubMed2003

Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 yrs) in the Diabetes Incidence Study in Sweden (DISS).

AIMS/HYPOTHESIS: We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. METHODS: During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. RESULTS: In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up. CONCLUSION/INTERPRETATION: Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.

Adolescent↗

PubMed2002

Insulin autoantibodies are of less value compared with islet antibodies in the clinical diagnosis of autoimmune type 1 diabetes in children older than 3 yr of age.

BACKGROUND: Insulin autoantibodies (IAA), antibodies against endogenous insulin, may be detected in type 1 diabetic children before the start of insulin treatment. OBJECTIVE: To relate IAA to islet antibodies (i.e., islet cell antibodies [ICA], and antibodies against two ICA-related islet antigens, glutamic acid decarboxylase 65 [GADA] and protein tyrosine phosphatase IA-2 [IA-2 A]) at diagnosis, and to endogenous beta-cell function at follow-up after diagnosis in diabetic children. SUBJECTS: We investigated 74 children, aged 1-15 yr, at the diagnosis of diabetes and 1-10 yr later. Insulin treatment may induce antibody development against exogenous insulin. Patients with insulin treatment > or = 1 wk (n = 5) were therefore excluded from the final analysis. METHODS: Radioligand-binding assays based on human recombinant antigen were used to measure IAA, GADA, and IA-2 A. ICA were determined with indirect immunofluorescence. RESULTS: IAA were detected at a significantly lower frequency (43%; p < or = 0.001) than ICA (86%), GADA (72%), and IA-2 A (80%). In agreement, IAA measurements only marginally increased the frequency of positive autoimmune markers at diagnosis of diabetes (from 97 to 99% positive for at least one autoantibody). Preserved beta-cell function (detectable fasting p-C-peptide levels) was found in only nine patients, who were older (13 +/- 3 vs. 7 +/- 6 yr, p = 0.002) and had fewer of the antibodies (IAA, GADA, IA-2 A, ICA) in high titer (> median) compared with 60 patients with undetectable p-C-peptide levels. CONCLUSIONS: Insulin autoantibodies are of less clinical value compared with islet antibodies in the diagnosis of autoimmune type 1 diabetes in children.

Journal Article↗

PubMed2001

Telemark skiing injuries: an 11-year study.

This study evaluated telemark injuries in a Swedish ski area in terms of injury ratio, location, and causes over time. During the seasons of 1989-2000 all injured telemark skiers ( n=94) who attended the medical center in Tärnaby, Sweden, within 48 h after the accident were registered and asked to fill in an injury form. A control group of noninjured telemark skiers were interviewed in the season of 1999-2000. The most common cause of injury was fall (70%) and the injury ratio was 1.2. There was a higher proportion of beginners in the injured population, and they had a fall/run ratio of 0.7, compared with 0.3 for average and advanced skiers. Ankle/foot injuries were most common (28% of injuries) followed by knee (20%) and head/neck (17%). The ankle/foot injuries decreased from 35% to 22% in the seasons 1989-1995 to 1995-2000. Beginners had more ankle/foot injuries than skilled participants. The severity of ankle/foot injuries classified as the Abbreviated Injury Scale group 2 or higher decreased from 33% to 21% during the study period. Twenty-seven percent used plastic and 73% leather boots. We found no association between boot material and ankle/foot injuries. The proportion of high boots with two or more buckles was 51%. High boots appeared to be protective against ankle/foot injuries. The proportion of high boots increased from 24% to 67% during the study period. Thus ankle/foot injuries were the most common injury location, but have decreased over time. The severity of these injuries has also decreased. A possible explanation could be the increased use of high boots.

Abbreviated Injury Scale↗

PubMed2001

Islet autoantibodies in the prediction of diabetes in school children.

In 1987 serum was collected from 1031 non-diabetic schoolchildren in the Southeast area of Sweden with the aim of evaluating islet autoantibody status (ICA, GADA and IA2-ab) in the prediction of diabetes in schoolchildren. The clinical development of Type 1 diabetes in the children was assessed in 1994 and 1997. The combination of ICA, GADA and IA2-ab were found in four subjects whereas six had two and 35 children one of these antibodies. After 10 years, six of the 1031 children had developed clinical diabetes and five of these six children were positive for islet antibodies. Two were positive for all three antibodies, two were positive for ICA and GADA, and one was positive for GADA. Among the individual autoantibodies, ICA showed the highest positive predictive value (29%) whereas the predictive value for the combination of two autoantibodies was highest for GADA and ICA (40%). Thus, GADA and ICA measurements may be a rational approach to detect schoolchildren at risk for developing diabetes.

Adolescent↗

PubMed2001

High levels of antigen-specific islet antibodies predict future beta-cell failure in patients with onset of diabetes in adult age.

It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict beta-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete beta-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete beta-cell failure, whereas low GADA levels predict slowly progressive beta-cell insufficiency.

Adult↗

PubMed2000

Islet cell antibody frequency differs from that of glutamic acid decarboxylase antibodies/IA2 antibodies after diagnosis of diabetes.

The combination of glutamic acid decarboxylase (GAD) 65 antibodies (GADA) and protein tyrosine phosphatase-like protein IA2 antibodies (IA2-ab), measured by radioligand binding assays, has been suggested to replace islet cell antibodies (ICA), measured by indirect immunofluorescence, as a marker for autoimmune type I diabetes. The aim of this study was to compare the frequency of ICA and GADA and/or IA2-ab not only at, but also after the diagnosis of diabetes. ICA, GADA and IA2-ab were therefore assessed at and up to 11 y after the diagnosis of diabetes in 86 children (1-15-y-old). At diagnosis, ICA were found in 74 (86%) and GADA and/or IA2-ab in 79 (92%) of the diabetic children. Hence, there was no major difference in frequency between ICA and GADA and/or IA2-ab at diagnosis of diabetes. At follow-up, however, ICA were less frequent than GADA and/or IA2-ab; 1-3 y after diagnosis ICA were found in 12 (44%) and GADA and/or IA2-ab in 24 (89%) of 27 children (p=0.001); 4-6 y after diagnosis ICA were found in 7 (24%) and GADA and/or IA2-ab in 27 (93%) of 29 children (p < 0.0001); 7-11 y after diagnosis ICA were found in 4 (13%) and GADA and/or IA2-ab in 21 (70%) of 30 children (p < 0.0001). We conclude that the frequency of ICA does not always correspond to that of GADA and/or IA2-ab. Many years after diagnosis of diabetes, measurements of GADA and IA2-ab, but not ICA, detect autoimmunity in high frequency.

Adolescent↗

PubMed1997

Measurement of antibodies against glutamic acid decarboxylase 65 (GADA): two new 125I assays compared with [35S]GAD 65-ligand binding assay.

Recently, 65-kDa glutamic acid decarboxylase (GAD 65) antibodies (GADA) have been introduced as autoimmune markers in blood to confirm the diagnosis of insulin-dependent diabetes mellitus (IDDM). In this study, to evaluate two new assays that use 125I-labeled GAD 65, we assayed samples from 100 children with recent onset of diabetes and 100 control children, the results were compared with those of a [35S]GADA assay and with results for islet cell antibodies (ICA), the conventional autoimmune marker. Receiver operating characteristic (ROC) curve analysis showed one of the new assays (from RSR) to be more sensitive (P = 0.01) than the comparison ([35S]GADA) assay, whereas the second new assay (from Elias) was less sensitive (P < 0.001). The GADA frequency at 97.5% specificity was greatest in the comparison assay: 63 of 100 vs 41 of 100 (P < 0.01) and 53 of 100 (P = 0.16) in the RSR and Elias assays, respectively. Almost all GADA-positive patients had ICA, but one-third of the ICA-positive patients was GADA-negative. Accordingly, adding GADA analysis results to ICA testing increased the frequency of detection of autoimmune markers only slightly (from 81% to 85%). In conclusion, at 97.5% specificity the [35S]GADA assay seemed to be more efficient than the 125I assays, although the difference was significant only for the Elias 125I assay. Antigen-specific antibodies other than GADA may explain the difference in GADA and ICA frequencies.

Adolescent↗

PubMed1997

Protein tyrosine phosphatase-like protein IA2-antibodies plus glutamic acid decarboxylase 65 antibodies (GADA) indicates autoimmunity as frequently as islet cell antibodies assay in children with recently diagnosed diabetes mellitus.

Islet cell antibodies (ICA), the classical autoimmunity marker for insulin-dependent diabetes mellitus (IDDM), are detected in approximately 85% of children with recently diagnosed diabetes. Because the ICA assay is semiquantitative and difficult to standardize, alternative assays are needed. When glutamic acid decarboxylase 65 (GAD 65) was discovered as a major islet antigen, the measurement of antibodies to GAD 65 (GADA) was considered a good alternative to ICA. Recently, however, we showed that 1 in 3 ICA-positive diabetic patients do not have GADA. Now, antibodies against the protein tyrosine phosphatase-like protein IA2 (IA2-ab) have been detected in IDDM. To find out whether measurements of IA2-ab combined with those of GADA could detect autoimmunity to the same extent as ICA, we have measured all three kinds of antibodies (using radioligand binding assays for IA2-ab and GADA) in 100 recently diagnosed diabetic and 100 control children: ICA were found in 87, IA2-ab in 69, and GADA in 66 of the 100 diabetic patients, whereas in the 100 control children ICA were found in 2, IA2-ab in 1, and GADA in 3. Among the 87 ICA-positive patients, 45 (52%) had both IA2-ab and GADA, 21 (24%) had only IA2-ab, and 16 (18%) had only GADA, whereas 5 (6%) lacked both IA2-ab and GADA. Among the 13 ICA-negative patients, 1 (8%) had both IA2-ab and GADA, 2 (15%) had only IA2-ab, and 4 (31%) had only GADA. Thus, 6 of the 100 patients had neither ICA, IA2-ab, nor GADA. Combining the IA2-ab and GADA assays gave positive results for autoimmunity in 89 of the 100 patients, compared with 87 by the ICA assay. The combination of the IA2-ab and GADA assays appears to be an effective alternative to the ICA assay.

Autoantibodies↗

PubMed1987

Tissue culture of human fetal pancreas. Effects of human serum on development and endocrine function of isletlike cell clusters.

The human fetal pancreas represents a source of insulin-producing beta-cells with a potential for transplantation to diabetic patients. It has previously been shown that such cells can be viably maintained in tissue culture media containing fetal calf serum (FCS) and that these explants continue to synthesize and release insulin. In this study the effects of human serum (HS) on the growth and function of human fetal pancreatic explants have been compared with those of FCS. For this purpose, pancreatic glands, obtained after prostaglandin-induced abortions, were briefly exposed to collagenase, and the digest was cultured in RPMI-1640 medium plus 10% pooled HS or FCS. The outgrowth of isletlike cell clusters (ICCs) was monitored. In 31 of 58 consecutively explanted glands, development of ICCs was observed. In the presence of FCS the outgrowth of ICC took place on top of a fibroblast monocellular cell layer; HS effected less growth of fibroblasts and increased the formation of ICCs about sevenfold compared with explants from the same glands maintained in FCS. However, in the explant cultures with HS, the cell number per ICC, expressed as DNA content, was reduced by 50%. In both FCS and HS the insulin content of the medium showed great variability and progressively declined from day 2 to day 5. The medium glucagon concentration also decreased but not to the same extent as that of insulin. Immunocytochemical-stained ICCs showed insulin- and glucagon-positive cells scattered among most nonstained, presumably nonendocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood↗

PubMed1985

Evidence for IFN-beta heterogeneity in a substrain of Namalwa cells.

A substrain of Namalwa cells, denoted substrain B, was grown in fermentors up to the 100-L scale, and was induced with Sendai virus to produce interferon (IFN). The titer of the crude IFN varied extensively between different batches; part of the variation was caused by a differential expression of IFN-alpha and IFN-beta. More than 80% of the IFN activity was IFN-beta by several criteria. A two-step purification procedure was developed and the resulting preparation had a specific activity of approximately 10(6) U/mg protein. The IFN-beta type was found to be heterogeneous, and could be separated into several components, which probably represented post-translational modifications of one molecule.

Adsorption↗

PubMed1985

Tissue culture of human fetal pancreas. Development and function of B-cells in vitro and transplantation of explants to nude mice.

The present study evaluates the development and function of human fetal B-cells in vitro with a view to using such cells in future attempts for transplantation of human fetal pancreas to diabetic patients. A method previously described in our laboratory for preparing islets in vitro from the fetal rat pancreas has been applied and modified for use with human fetal pancreas. Pancreatic glands of different gestational ages were obtained from 37 consecutive prostaglandin-induced abortions. After a mild collagenase treatment, the partially disintegrated tissue was maintained in culture for 7 days in tissue culture medium RPMI 1640 plus 20% fetal calf serum to permit cell attachment and out-growth of endocrine cells. In 17 of the 37 consecutively cultured fetal pancreatic glands, islet-like cell clusters were formed. The 20 remaining glands were lost because of either bacterial contamination or lack of viability already before dissection had occurred. Sections of the newly formed cell clusters revealed well-preserved pancreatic cells showing frequent mitotic figures. The tissue exhibited a high rate of (pro)insulin biosynthesis and a modest insulin response to secretory stimuli, suggesting that the mechanism of glucose regulation by the fetal B-cells is not yet fully developed. Electron micrographs showed a large number of granule-containing cells, some of which were identified as B-cells. In nine cases, harvested cell clusters were implanted beneath the kidney capsule of nude mice. When these animals were killed after 2 mo, seven mice showed a considerable growth of the grafts with numerous islet-like structures containing insulin- and glucagon-positive cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Long-term effects of cyclosporin A on cultured mouse pancreatic islets.

In the light of recent attempts to treat newly-diagnosed Type 1 (insulin-dependent) diabetic patients with cyclosporin A, and reports suggesting an impaired glucose tolerance following immunosuppression therapy with cyclosporin A, we investigated the long-term effects of cyclosporin A on islet beta-cell morphology and function in vitro. Collagenase-isolated mouse pancreatic islets were cultured free-floating for 7 days in medium RPMI 1640 + 10% calf serum in the presence of cyclosporin A (0.1 or 1.0 mg/l). Islets cultured in the presence of the higher cyclosporin A concentration had impaired islet proinsulin biosynthesis and insulin release when challenged with high glucose concentration. Moreover, the insulin content of the drug-exposed islets was decreased and so was the rate of DNA synthesis. The glucose oxidation and respiratory rates, however, remained unaffected, suggesting that the impaired insulin production was not a result of defective oxidative metabolism. There were no changes in the ultrastructure or phospholipid biosynthesis of the islets after the drug treatment. These data indicate that cyclosporin A affects islets in culture, the clinical implications of which are so far difficult to assess. The inhibitory effect of cyclosporin A on islet cell DNA synthesis must nevertheless be considered in attempts to ameliorate Type 1 (insulin-dependent) diabetes, and when grating islet cells in numbers primarily insufficient to cure the recipient.

Animals↗

PubMed1982

B-cell growth factor: distinction from T-cell growth factor and B-cell maturation factor.

A T-cell hybridoma was derived by somatic cell hybridization between concanavalin A-activated BALB/c spleen cells and the AKR thymoma BW 5147. Media conditioned by hybridoma cells, even at high dilutions (1:1,000) support the growth of lipopolysaccharide-stimulated B-cell blasts but not that of T-cell growth factor (TCGF)-reactive T-cells. This activity, herein designated B-cell growth factor (BCGF), has a Mr of approximately equal to 20,000 and it can readily be separated from TCGF (Mr approximately equal to 30,000) by gel filtration. BCGF is constitutively produced by the hybridoma cells, it is removed from conditioned media by incubation with target cells at +4 degrees C, and it is equally effective on B-cell blasts carrying different major histocompatibility complex and Ig haplotypes. BCGF shows no T-cell replacing factor (TRF) activity, and it is poor in supporting the development of Ig-secreting plaque-forming cells in B-cell blast cultures. Terminal maturation, however, can be induced in BCGF-dependent blasts by addition of conditioned media from normal helper T cell cultures, suggesting that two distinct factors are involved in the helper cell-dependent growth and maturation of B lymphocytes.

Animals↗

PubMed1981

Human interferon for clinical trials: removal of pyrogen by a simple two-step procedure.

Commonly used preparations of human interferon are pyrogenic when used in humans for clinical trials. We describe a simple two-step procedure for the purification of human fibroblast interferon, employing Blue Sepharose chromatography and high-speed centrifugation. Such preparations are devoid of pyrogenic activity in a rabbit test system and are much more suitable for use in human clinical trials than previously used preparations.

Animals↗