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K Lindberg

Publications and source records attributed to K Lindberg.

At least 19 recordsLinked to original sources
PubMed2001

Suppressor of cytokine signaling 3 (SOCS-3) protects beta -cells against interleukin-1beta - and interferon-gamma -mediated toxicity.

Suppressor of cytokine signaling 3 (SOCS-3) is a negative feedback regulator of IFN-gamma signaling, shown up-regulated in mouse bone marrow cells by the proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IFN-gamma. IL-1beta and IFN-gamma alone, or potentiated by TNF-alpha, are cytotoxic to the insulin producing pancreatic beta-cells and beta-cell lines in vitro and suggested to contribute to the specific beta-cell destruction in Type-1 diabetes mellitus (T1DM). Using a doxycycline-inducible SOCS-3 expression system in the rat beta-cell line INS-1, we demonstrate that the toxic effect of both IL-1beta or IFN-gamma at concentrations that reduced the viability by 50% over 3 days, was fully preventable when SOCS-3 expression was turned on in the cells. At cytokine concentrations or combinations more toxic to the cells, SOCS-3 overexpression yielded a partial protection. Whereas SOCS-3-mediated inhibition of IFN-gamma signaling is described in other cell systems, SOCS-3 mediated inhibition of IL-1beta signaling has not previously been described. In addition we show that SOCS-3 prevention of IL-1beta-induced toxicity is accompanied by inhibited transcription of the inducible nitric oxide synthase (iNOS) by 80%, resulting in 60% decreased formation of the toxic nitric oxide (NO). Analysis of isolated native rat islets exposed to IL-1beta revealed a naturally occurring but delayed up-regulated SOCS-3 transcription. Influencing SOCS-3 expression thus represents an approach for affecting cytokine-induced signal transduction at a proximal step in the signal cascade, potentially useful in future therapies aimed at reducing the destructive potential of beta-cell cytotoxic cytokines in T1DM, as well as other cytokine-dependent diseases.

Animals↗
PubMed2001

Porcine small intestinal submucosa (SIS): a bioscaffold supporting in vitro primary human epidermal cell differentiation and synthesis of basement membrane proteins.

The growth pattern of human epidermal cells, fibroblasts or Swiss mouse 3T3/J2 fibroblasts cultured upon the extracellular matrix (ECM) derived from small intestinal submucosa (SIS) was evaluated. The cell/SIS composites were grown submerged, then maintained in air/liquid interface for 2, 7, 10 or 14 days. The presence of differentiation-related keratins 10, 14 and 16, FN, laminin, collagen type VII and collagen type IV was determined by immunohistochemical methods in SIS alone and in the SIS/cell composite. Only FN could be detected in SIS alone. SIS supported the formation of an epithelial structure with suprabasal expression of K16 and regional suprabasal expression of K10. The epidermal cells were K14 positive and tended to 'invade' the SIS to various degrees. Following the growth of epidermal cells and fibroblasts on the SIS substratum, immunolabeling of FN, laminin, collagen type VII and collagen type IV was observed in a cell-associated pattern. The fibroblasts commonly invaded the SIS, when co-cultivated with epidermal cells on the opposite side of the SIS. The ability of SIS to support epidermal cell/fibroblast attachment, migration and/or proliferation and differentiation with deposition of basement membrane (BM) components indicates that the composite model may be useful for studying cell-matrix interactions and for investigation as a dermal substitute.

3T3 Cells↗
PubMed2001

Impact of IgG replacement therapy and antibiotic treatment on the colonization of non-encapsulated Haemophilus influenzae in the nasopharynx in patients with hypogammaglobulinaemia.

Non-typable Haemophilus influenzae (NTHI) and Streptococcus pneumoniae are regarded as the main pathogens in patients with humoral immunodeficiency. These patients have been given IgG replacement therapy since the 1950s. However, a number of individuals still suffer from recurrent episodes of respiratory tract infections. Nasopharyngeal cultures were obtained on a regular basis over a 3-6-month period from 11 patients with common variable immunodeficiency disease in 1989 and 1998. The proportion of cultures positive for NTHI decreased from 56% in 1989-90 to 16% in 1998-99 (p < 0.003). After 9 y of IgG therapy, 7 of the 11 patients were free from NTHI in the nasopharynx. Specific NTHI strains were analysed by pulsed-field gel electrophoresis and compared, with regard to genetic relatedness, on an intra-individual basis. In 1 patient the same NTHI strain was found in both 1989 and 1999. The apparent absence of NTHI from the nasopharynx in most of the patients was assumed to be due to subcutaneous IgG treatment, as well as adequate antibiotic treatment.

Adult↗
PubMed2000

Children with recurrent episodes of acute otitis media: the effect of local administration of immunoglobulin G on acute otitis media, colonization and turnover of non-encapsulated Haemophilus influenzae in the nasopharynx.

In most children with recurrent episodes of acute otitis media (AOM), tube treatment is successful, but there are those who nevertheless suffer from middle ear infections. The aim of the present study was to ascertain whether local administration of immunoglobulin could reduce the number of episodes of otorrhoea in otitis-prone infants <2 years old who were treated with tubes, or whether it could affect the nasopharyngeal colonization and turnover of bacterial pathogens in the nasopharynx. IgG or placebo were also administered intranasally daily for 6 months to 50 infants, randomized in a double-blind study. An arbitrarily primed polymerase chain reaction (AP-PCR) was used to characterize the different isolates of NTHI (non-encapsulated, non-typable Haemophilus influenzae). Three infants in the IgG group and six infants in the control group suffered from > or =3 episodes of acute otitis media. No effect on the nasopharyngeal colonization or the turnover of non-encapsulated H. influenzae in the nasopharynx could be detected in either group.

Acute Disease↗
PubMed2000

Personal sampling in parallel with open-face filter cassettes and IOM samplers for inhalable dust--implications for occupational exposure limits.

Parallel personal sampling was carried out with the open-face filter cassette and the IOM sampler for inhalable dust for nine types of organic dust. Parallel samples numbering 749 were obtained from 152 plants. Extremely large values and outliers were disregarded, and the remaining data for each type of dust were divided into subsets according to type of product or work task, and analyzed with the aid of linear regression. The coefficient of regression for each subset ranged between 0.2 and 0.7. Hypothetical occupational exposure limits (OELs) for inhalable dust were calculated based on the linear relation obtained between the dust concentrations measured with the open-face filter cassette and the IOM sampler. The fraction of person days with time-weighted average (TWA) concentrations exceeding the calculated hypothetical OELs for inhalable dust was obtained from the distribution of measured TWA inhalable dust concentrations. Based on the results of this study and the difference in sampling efficiency for large particles between the two samplers, it was concluded that the numerical value of the OEL for inhalable dust may be set at approximately twice the numerical value of the corresponding limit value for "total dust." Additional consideration of recently discovered health effects, and technical and economical factors may result in other numerical values of future OELs for inhalable dust.

Air Pollutants, Occupational↗
PubMed1999

What is wrong in chronic adenoiditis/tonsillitis immunological factor.

The local immune response in adenoid and tonsil tissue can be visualized and the complexity of the cytokine network and effector molecule expression has not been illustrated in several different tonsillar entities. Many factors still remain to be learned in order to help us to understand the interactions between microorganisms and host in peripheral lymphatic tissue.

Adenoids↗
PubMed1999

Hyperferritinaemia-cataract syndrome.

The first family with hyperferritinaemia-cataract syndrome in Scandinavia is described. We discuss the etiology and point at this diagnosis as a differential diagnosis in case of hereditary cataract.

Cataract↗
PubMed1999

Assembly of very low density lipoprotein: a two-step process of apolipoprotein B core lipidation.

The liver plays a primary role in lipid metabolism. Important functions include the synthesis and incorporation of hydrophobic lipids, triacylglycerols and cholesteryl esters into the core of water-miscible particles called lipoproteins and the secretion of these particles into the circulation for transport to distant tissues. In this article, we present a brief overview of one aspect of the assembly process of very low density lipoproteins, namely, possible mechanisms for combining core lipids with apolipoprotein B. This is a complex process in which apolipoprotein B interacts with core lipids to form very low density lipoproteins by a two-step process that can be dissociated biochemically.

Animals↗
PubMed1999

Enzymatic dissociation of keratinocytes from human skin biopsies for in vitro cell propagation.

Four techniques for dissociation of skin biopsies were compared to identify the method of choice for optimal expansion of isolated keratinocytes. Equivalent biopsies were obtained from 4 healthy human subjects and each divided into four parts. One part was minced and placed in a trypsinizing flask containing 0.05% trypsin and 0.01% ethylenediaminetetraacetic acid (EDTA). Released cells were harvested hourly. With the other parts, the epidermis was separated from the dermis after treatment with 0.5 mg/nml thermolysin, 2.5 mg/ml Dispase, or 0.17% trypsin and the epidermal portions were minced and incubated for 1 h in trypsin:EDTA. The cells were cocultivated with irradiated 3T3 fibroblasts to study the keratinocytes proliferative capacity. Freshly isolated cells were immunostained with anti-vimentin antibodies or grown in fibroblast-supportive conditions to detect the presence of human dermal fibroblasts. The mean number of cells dissociated per cm2 biopsy was higher after trypsin:EDTA digestion of a dermis-containing biopsy using a trypsinizing flask (4.0x 10(6) cells/cm2) compared to a biopsy where dermis-epidermis had been separated by thermolysin (2.8x 10(6) cells/cm2), Dispase (2.3x 10(6) cells/cm2) or trypsin (1.1 x 10(6) cells/cm2). Between 0.5% and 4% of the cells dissociated from a dermis-containing biopsy were human fibroblasts. This comprised more than twice the number of fibroblasts obtained by using epidermal/dermal split techniques. The proliferative capacity in primary and secondary culture was higher in cells isolated by trypsin:EDTA incubation in the trypsinizing flask or after epidermal-dermal separation using thermolysin, suggesting that Dispase or trypsin may have a more detrimental effect on the isolated keratinocytes. Our results show that dissociating the cells by trypsin:EDTA incubation in a trypsinizing flask or after epidermal-dermal separation using thermolysin, are preferable methods for isolating keratinocytes from human skin.

3T3 Cells↗
PubMed1999

Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins.

In this study we have investigated the role of suppressor of cytokine signaling (SOCS) proteins in GH receptor-mediated signaling. GH-induced transcription was inhibited by SOCS-1 and SOCS-3, while SOCS-2 and cytokine inducible SH2-containing protein (CIS) had no effect By using chimeric SOCS proteins it was found that the ability of SOCS proteins to inhibit GH-mediated transcription was located in the amino-terminal 40-80 amino acids. In SOCS-3, 46 amino acids C-terminal to the SH2 domain were required for the inhibitory activity, while a truncated SOCS-1 having only 2 amino acids C-terminal to the SH2 domain was able to inhibit GH-mediated transcription. Both SOCS-1 and SOCS-3 were able to inhibit GH-induced STAT5 (signal transducer and activator of transcription) activation. SOCS-1 inhibited the tyrosine kinase activity of Janus kinase 2 (JAK2) directly, while SOCS-3 only inhibited JAK2 when stimulated by the GH receptor. All four SOCS proteins were able to bind to a tyrosine-phosphorylated glutathione-S-transferase-GH receptor fusion protein, and SOCS-3 required the same 46 C-terminal amino acids for GH receptor binding as it did for inhibition of GH-mediated transcription and STAT5 activation. These data suggest that SOCS-1 and -3 can suppress GH-induced transcriptional activity, presumably by inhibiting the kinase activity of JAK2 either directly in the case of SOCS-1 or via binding to the tyrosine-phosphorylated GH receptor in the case of SOCS-3.

Amino Acid Sequence↗
PubMed1998

Comparative studies of DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or primarily heat tobacco.

A new cigarette (Eclipse) that primarily heats rather than burns tobacco has been developed. Since Eclipse primarily heats tobacco, the smoke chemistry is much simplified, consisting of 80% glycerol and water. With the simplified smoke chemistry, it would be expected that toxicological activity would be reduced. Smoke and smoke condensate from Eclipse have consistently yielded markedly reduced mutagenicity and cytotoxicity in in vitro tests when compared to smoke and smoke condensate from the 1R4F Kentucky reference cigarette, which is representative of typical low 'tar' cigarettes sold in the U.S. today. The objective of the present study was to evaluate the potential of mainstream cigarette smoke condensate (CSC) of Eclipse to produce DNA adducts in lung, heart and skin tissue of dermally-exposed mice and to compare the results with those obtained with CSC from the 1R4F Kentucky reference cigarette. CSC from Eclipse or 1R4F cigarettes was applied dermally to SENCAR mice three times a week for 30 weeks. Amounts of CSC applied were 30, 60 or 120 mg 'tar' per animal per week. Tissues were collected after 1, 4, 14 and 29 weeks of CSC application. DNA adducts were analyzed in lung, heart and skin tissues using the 32P-postlabeling method with P1 nuclease modification. Distinct time and dose-dependent diagonal radioactive zones (DRZ) were observed in the DNA from lung, heart and skin tissues of animals treated with 1R4F CSC. The relative adduct labeling (RAL) values of lung, heart and skin DNA from reference CSC-treated animals were significantly greater (p<0.05) than those of the solvent control animals. No corresponding DRZs were observed at any dose from the DNA of animals treated with CSC from Eclipse or solvent control (acetone) and the RAL values observed following application of Eclipse were not increased relative to the solvent control. These results provide additional evidence that the smoke condensate from the Eclipse cigarette is markedly less genotoxic than smoke condensate from tobacco-burning cigarettes representative of those currently sold in the U.S.

Administration, Cutaneous↗
PubMed1998

The microsomal triglyceride transfer protein catalyzes the post-translational assembly of apolipoprotein B-100 very low density lipoprotein in McA-RH7777 cells.

In cells in which the lipoprotein assembly process had been inactivated by brefeldin A (BFA), membrane-associated apoB-100 disappeared without forming lipoproteins or being secreted, indicating that it was degraded. Reactivation of the assembly process by chasing the cells in the absence of BFA, gave rise to a quantitative recovery of the membrane-associated apoB-100 in the very low density lipoprotein (VLDL) fraction in the medium. These results indicate that the membrane-associated apoB-100 can be converted to VLDL. A new method was developed by which the major amount (88%) of microsomal apoB-100 but not integral membrane proteins could be extracted. The major effect of this method was to increase the recovery of apoB-100 that banded in the LDL and HDL density regions, suggesting that the membrane-associated form of apoB-100 is partially lipidated. We also investigated the role of the microsomal triglyceride transfer protein (MTP) in the assembly of apoB-100 VLDL using a photoactivatable MTP inhibitor (BMS-192951). This compound strongly inhibited the assembly and secretion of apoB-100 VLDL when present during the translation of the protein. To investigate the importance of MTP during the later stages in the assembly process, the cells were preincubated with BFA (to reversibly inhibit the assembly of apoB-100 VLDL) and pulse-labeled (+BFA) and chased (+BFA) for 30 min to obtain full-length apoB-100 associated with the microsomal membrane. Inhibition of MTP after the 30-min chase blocked assembly of VLDL. This indicates that MTP is important for the conversion of full-length apoB-100 into VLDL. Results from experiments in which a second chase (-BFA) was introduced before the inactivation of MTP indicated that only early events in this conversion of full-length apoB-100 into VLDL were blocked by the MTP inhibitor. Together these results indicate that there is a MTP-dependent "window" in the VLDL assembly process that occurs after the completion of apoB-100 but before the major amount of lipids is added to the VLDL particle. Thus the assembly of apoB-100 VLDL from membrane-associated apoB-100 involves an early MTP-dependent phase and a late MTP-independent phase, during which the major amount of lipid is added.

Animals↗
PubMed1998

Small intestinal submucosa: a substrate for in vitro cell growth.

The extracellular matrix (ECM) of the small intestinal submucosa (SIS) was harvested by removing the superficial layers of the mucosa and the external muscular layers. The remaining 80 microns thick sheet was disinfected and sterilized by methods which removed all cellular components. The SIS-ECM, retaining its native 3-dimensional microarchitecture and composition, was evaluated for its ability to support in vitro cell growth. Six separate cell types were seeded either alone or in coculture with other cells upon this matrix, grown in selected media, a examined daily for time periods ranging from 48 h to 2 weeks. The six cell types tested were NIH Swiss mouse 3T3 fibroblast, NIH 3T3/j2 fibroblasts, primary human fibroblasts, primary human keratinocytes, human microvascular endothelial cells (HMECs), and an established rat osteosarcoma (ROS) cell line. All cell types showed the ability to attach a proliferate. All fibroblast cell line and the keratinocytes proliferated and/or migrated into the 3-dimensional scaffold of the SIS matrix. The ROS cells and the HMECs were confined in their growth pattern to the surface of the matrix. Coculturing of NIH 3T3/J2 fibroblasts and primary human keratinocytes resulted in a distinctive spatial orientation of the two cell types. The fibroblast populated the mid-substance of the 3-dimensional matrix and the keratinocytes formed an epidermal structure with rete ridge-like formation and stratification when the composite was lifted to an air liquid interface in culture. In summary, SIS provides a substratum with a 3-dimensional scaffold that allows for cell migration and spatial organization. The substratum is suitable for in vitro studies of the interaction between epithelial or mesenchymal cells and a naturally occurring extracellular matrix.

3T3 Cells↗
PubMed1997

Growth hormone and prolactin stimulate the expression of rat preadipocyte factor-1/delta-like protein in pancreatic islets: molecular cloning and expression pattern during development and growth of the endocrine pancreas.

GH and PRL have been shown to stimulate proliferation and insulin production in islets of Langerhans. To identify genes regulated by GH/PRL in islets, we performed differential screening of a complementary DNA library from neonatal rat islets cultured for 24 h with human GH (hGH). One hGH-induced clone had 96% identity with mouse preadipocyte factor-1 (Pref-1, or delta-like protein (Dlk)]. The size of Pref-1 messenger RNA (mRNA) in islets was 1.6 kilobases, with two less abundant mRNAs of 3.7 and 6.2 kilobases. The Pref-1 mRNA content of islets from adult rats was only 1% of that in neonatal islets. Pref-1 mRNA was markedly up-regulated in islets from pregnant rats from day 12 to term compared with those from age-matched female rats. Two peaks in mRNA expression were observed during gestation, one on day 14 and the other at term, whereafter it decreased to nonpregnant levels. Pref-1 mRNA was up-regulated 3- to 4-fold in neonatal rat islets of Langerhans after 48-h culture with hGH, as found also with bovine GH or ovine PRL. During the development of pancreas from embryonic day 12 (E12) to postnatal day 4, we observed a 2-fold increase in Pref-1 mRNA on E17 and a 5-fold increase at birth, followed by a rapid decline on postnatal day 4. Pref-1 immunoreactivity was found in a subpopulation of insulin cells of neonatal islets of Langerhans. At an early embryonal stage (E13), most cells of the pancreatic anlage were Pref-1 positive, becoming predominantly restricted to the insulin-producing cells during development. In conclusion, these findings suggest that Pref-1 is involved in both differentiation and growth of beta-cells.

Amino Acid Sequence↗
PubMed1996

A one-site, two-state model for the binding of anions in photosystem II.

Photosystem II membranes, dialyzed against a Cl(-)-free buffer to remove bound Cl-, lost about 65% of the control activity. A light-intensity study of the Cl(-)-free membranes showed that all PS II centers were able to evolve oxygen at about 35% of the control rate when measured in Cl(-)-free medium. The Cl(-)-depleted membranes were immediately (< 15 s) reactivated to 85-90% of the original activity by the addition of fairly high concentrations of Cl- (Kd = 0.5 mM), but both Cl- and the activity were promptly lost when the membranes immediately after reactivation were diluted in a Cl(-)-free medium. However, stabilization of Cl(-)-binding could be accomplished by prolonged incubation in the presence of Cl-. The transition to stable binding, followed using 36Cl-, occurred over several minutes. The stable binding was further characterized by a Kd of 20 microM and a t1/2 for dissociation of about 1h [Lindberg et al. (1993) Photosynth. Res. 38, 401-408]. The effects on S2 signals of removal of Cl- were studied using EPR. The depletion of Cl- was accompanied by a shift in intensity toward the g = 4.1 signal at the expense of the multiline signal. When Cl- or Br- but not F- was added to the depleted PS II membranes, the original distribution of the signals was immediately (< 30 s) restored. We propose that Cl(-)-binding responsible for high oxygen-evolution activity and normal EPR properties of the S2 state may occur either as high affinity (Kd = 20 microM) and slowly exchanging (t1/2 = 1 h), or as low affinity (Kd = 0.5 mM) and rapidly exchanging (t1/2 < 15 s). Our results suggest that Br- but not F- has a mode of binding similar to that of Cl-. The high-affinity state is the normal state of binding, but once Cl- has been removed, it will first rebind as low-affinity, rapidly exchanging followed by conversion into a high-affinity, slowly exchanging mode of binding.

Anions↗