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L Berg

Publications and source records attributed to L Berg.

At least 55 records · Page 3Linked to original sources

TNF-alpha, TSH, and aging regulate TGF-beta synthesis and secretion in FRTL-5 rat thyroid cells.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine produced by macrophages in response to a variety of pathological conditions, can inhibit thyroid cell function in vitro and in vivo. TNF-alpha induction of transforming growth factor-beta 1 (TGF-beta 1) in rat endothelial cells suggested that TGF-beta, a known mediator of inflammatory effects of TNF-alpha, may be involved in the sensitivity of aged thyroid cells to TNF-alpha (G. Chen, A. E. Pekary, and J. M. Hershman. Endocrinology 131: 863-870, 1992). To determine whether TNF-alpha induces TGF-beta production in FRTL-5 cells, young (< 20 passages) and aged (> 40 passages) FRTL-5 cells were grown to near confluency in medium containing 2 U/l of bovine thyroid-stimulating hormone [TSH; 6-hormone (6H) medium] or no TSH [5-hormone (5H) medium]. TNF-alpha (0-100 ng/ml) was added 0-48 h before total RNA was extracted. Northern blots were hybridized with 32P-TGF-beta 1, -beta 2, and -beta 3 cDNAs. In aged cells TNF-alpha increased their TGF-beta 1 (and -beta 2 and -beta 3) mRNA levels 5.4-fold (and > 10-fold), respectively, while in young cells all TGF-beta mRNAs remained almost undetectable during incubation with TNF-alpha. In contrast, TNF-alpha and TSH had a highly significant stimulatory effect on the secretion rate of TGF-beta precursors in both young and old cells as measured in the mink lung cell bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Health promotion in schools: policies and practices in Stockholm county, 1990.

A survey was undertaken of the policies and practices concerning organisation and implementation of health education and health promotion in schools in 151 of the total 213 Local Educational Areas (LEAs) in Stockholm county in 1990. Health education was included in the workplan of 49% of the responding LEAs, while 39% of respondents had a local action programme or guidelines for health education. Topic areas taught to all pupils and considered most important included alcohol, drug abuse, smoking, sex education, bullying, nutrition and physical exercise. Most senior level schools (55-83%) had written policies concerning pupils using alcohol, drugs or smoking in school, and 68% of LEAs had restrictions on staff smoking in school. Continuing health education was desired by 87% of the respondents. A written programme/plan regarding health education was identified as an important indicator of interest and commitment in health education and health policy issues by the local school.

Adolescent↗

Antitumor actions of interferon-gamma and interleukin-1 beta on human papillary thyroid carcinoma cell lines.

To test the hypothesis that interferon-gamma (IFN gamma) and interleukin-1 beta (IL-1 beta) possess antitumor activity on human papillary thyroid carcinoma cells, we studied the in vitro effects of IFN gamma and IL-1 beta on the proliferation and invasiveness of two human PTC cell lines, TPC-1 (TP) and NPA (NP) cells. TP and NP cells were treated with various concentrations of IFN gamma and IL-1 beta alone and in combination. Cell proliferation was assessed by [3H]thymidine incorporation and cell number measurement. Tumor cell invasion was assessed by the ability of cells to penetrate through a Matrigel membrane. Both IFN gamma and IL-1 beta inhibited [3H]thymidine incorporation into TP cells in a dose-dependent manner and decreased TP cell number. In NP cells, treatment with IFN gamma and IL-1 beta also decreased [3H]thymidine incorporation and cell number. The inhibitory effects of IFN gamma and IL-1 beta on tumor cell proliferation were additive in both cell lines. In the invasion experiments, IFN gamma and IL-1 beta reduced the invasiveness of TP and NP cells. Again, the inhibitory effects of IFN gamma and IL-1 beta on tumor cell invasion were additive in both cell lines. In summary, the results showed that both IFN gamma and IL-1 beta are potent inhibitors of the proliferation and invasiveness of TP and NP cells. The additive effects of IFN gamma and IL-1 beta are evidence that they act through different pathways. Our findings suggest that IFN gamma and IL-1 beta are two of the anticancer factors that act to suppress the proliferation and reduce the invasive potential of human papillary thyroid carcinoma cells.

Carcinoma, Papillary↗

Cytokines modulate type I iodothyronine deiodinase mRNA levels and enzyme activity in FRTL-5 rat thyroid cells.

Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interferon-gamma (INF-gamma) have inhibitory effects on thyroid function both in vivo and in vitro. We have studied the effects of these cytokines on type I 5'-deiodinase (5'-DI) mRNA expression and enzyme activity in FRTL-5 cells maintained in standard cell culture medium containing 0 (5H) or 2 mIU/ml bovine TSH (6H). Northern blots were hybridized with 5'-DI cDNA. 5'-DI mRNA levels were reduced to 20% of control values after treating cells with 100 ng/ml TNF-alpha in 6H for 2 days while the corresponding enzyme activity was reduced 50%. Other cytokines, including IL-1beta and interferon-gamma, also significantly inhibited expression of 5'-DI in FRTL-5 cells grown in 6H medium. Because the majority of circulating T3 in the rat is secreted by the thyroid gland, the highly significant decline in the serum T3/T4 ratio following in vivo administration of cytokines may be due to their direct inhibitory effect on thyroidal 5'-DI expression.

Animals↗

Thyrotropic activity of basic isoelectric forms of human chorionic gonadotropin extracted from hydatidiform mole tissues.

hCG is known to have thyroid-stimulating activity and may cause hyperthyroidism in patients with trophoblastic diseases. hCG occurs in normal and molar pregnancy with breaks or nicks in the alpha- or beta-subunit peptide linkage and with substantial heterogeneity in the composition and degree of branching within the oligosaccharide side-chains. The bioactivity of hCG is markedly influenced by these structural variations. We purified hCG from five hydatidiform moles, using chromatofocusing separation after gel filtration. The hCG molecules were fractionated according to their isoelectric points, with a linear pH gradient from 3.2-6.1 and a final 1.0 mol/L NaCl step elution. The hCG immunoreactivity of each fraction was measured by RIA, and the thyroid-stimulating activity of hCG was determined by means of the cAMP response in Chinese hamster ovary cells expressing functional human TSH receptors (Chinese hamster ovary-JP09 cells). The chromatofocusing profile showed that hCG from the moles was eluted in six or seven major peaks at pH 6.1, 5.5, 5.3, 4.8, 3.8, and 3.2 and with 1.0 mol/L NaCl, whereas hCG extracted from serum of hydatidiform moles and standard hCG preparation CR-127 extracted from pregnancy urine showed only small peaks at pH greater than 5.3. Each fraction increased cAMP production significantly in Chinese hamster ovary-JP09 cells. The relative bioactivity/immunoreactivity, represented as the ratio of cAMP/hCG (picomoles per IU), was significantly higher in basic components (pI 6.1, 6.2 +/- 1.2; pI 5.5, 4.4 +/- 2.7; pI 5.3, 5.8 +/- 0.3) than in hCG CR-127 (bioactivity/immunoreactivity, 0.42; P < 0.05). The difference in pI of each hCG isoform was attributable to the extent of sialylation; basic hCG isoforms contained less sialic acid by immunological detection using lectins. These results indicate that isoforms of hCG with more thyrotropic activity were produced by trophoblastic tissues in patients with hydatidiform mole. We speculate that these isoforms of hCG may be responsible for the hyperthyroidism in some patients with hydatidiform moles.

Adult↗

Effect of peptide nicking in the human chorionic gonadotropin beta-subunit on stimulation of recombinant human thyroid-stimulating hormone receptors.

It is now generally accepted that human chorionic gonadotropin (hCG) has thyroid-stimulating activity. Heterologous forms of the hCG molecule occur in the purified preparations extracted from urine of pregnant women and patients with trophoblastic diseases. This work was undertaken to determine the effect of peptide nicking in the hCG-beta subunit on its thyrotropic potency. Using Chinese hamster ovary cells expressing functional human thyroid-stimulating hormone (TSH) receptors, we examined the effect of nicked hCG on cycliC AMP (cAMP) production and receptor binding. The effect of human leukocyte elastase (hLE), a nicking enzyme, on standard hCG also was examined in the cAMP assay and on receptor binding. We studied five hCG preparations extracted from the urine of normal pregnancy (CR-127 and P8) and trophoblastic diseases (C2, C5 and M4). Two preparations (C2, 96% nicked and M4, 100% nicked in the beta 44-49 region) showed about a 1.5-fold potency of standard hCG CR-127, which is also 20% nicked in the same region. Non-nicked hCG (P8) had the weakest potency among all of the samples tested. Treatment of standard hCG with hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE increased the cAMP response about two-fold. Dose-dependent displacement of bovine [125I]TSH by standard hCG and hLE-digested hCG was observed and was almost identical. We have confirmed the increased in vitro thyrotropic activity of hCG nicked in the beta-intercysteine loop on recombinant human TSH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Referral notes used as a tool for evaluating the co-operation between general practitioners and hospital physicians.

OBJECTIVE: To study what proportion of clinical visits to a general practitioner working at a Swedish health centre leads to a referral to a specialist, the adequacy of the reason for the referral, the quality of the referral notes, and the quality of the answers by the specialists to whom the patients had been referred. DESIGN: A referee committee representing the different medical specialists and the general practitioners studied all referral notes dealing with internal medicine, surgery, orthopaedics, and otorhinolaryngology during a defined period from two health centres as to adequacy of the reason for referral, the quality of the referral notes, and the quality of the answers to the referrals. SETTING AND PARTICIPANTS: Altogether 188 consecutive referral notes and 171 answers to these referrals from two Swedish health centres were evaluated. RESULTS: Of the visits to a general practitioner, 7-8% resulted in a referral to a hospital specialist, and 90% of these were answered by letter. The referee committee agreed that the vast majority of the reason for referral were adequate, and that the referral notes as well as the answers to these with few exceptions were adequately formulated. CONCLUSIONS: The referrals from primary health care to different medical specialists worked adequately, but it was concluded that it may be further improved. When evaluating the co-operation between two medical systems, it is important that the evaluation as well is made in co-operation by representatives from the two systems.

Family Practice↗

A wish list.

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Aged↗

Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older.

Subjects with clinically diagnosed senile dementia of the Alzheimer type (n = 37) and healthy controls (n = 5) were assessed clinically until death. Postmortem examination of the brain was performed at age 80 years or older. The brains of all of the group with dementia (except one that was found to have a non-Alzheimer dementia) had substantial densities of neocortical senile plaques regardless of dementia severity; the control brains had very few senile plaques. In those subjects with Alzheimer's disease, moderate correlations were found between dementia duration and severity (cognitive portion of the Blessed Dementia Scale and the Sum of Boxes from the Clinical Dementia Rating) and certain neuropathological lesions, both gross and microscopic. Densities of neocortical neurofibrillary tangles were related to degree of dementia; densities of neocortical senile plaques were unrelated. We conclude that (1) neocortical senile plaque densities differentiate very old subjects with Alzheimer's disease from nondemented controls, but there is a need for more postmortem studies of older persons who are free of dementia; and (2) among the microscopic lesions studied, densities of neocortical neurofibrillary tangles were most closely related to the degree and duration of dementia.

Aged↗

Influence of age on clinical and psychometric assessment of subjects with very mild or mild dementia of the Alzheimer type.

OBJECTIVE: The influence of age on performance on clinical and psychometric assessments is examined in groups of nondemented persons and individuals with either very mild or mild dementia of the Alzheimer type (DAT). DESIGN: Initial clinical and psychometric assessments of persons enrolled in longitudinal studies of DAT and nondemented control subjects. SETTING: Alzheimer's Disease Research Center at Washington University, St Louis, Mo. PARTICIPANTS: Volunteer samples of 108 people (44 men, 64 women) with mild DAT, 61 people (30 men, 31 women) with very mild DAT, and 122 healthy nondemented people (45 men, 77 women) were recruited between 1979 and 1991. Age ranged from 54 to 87 years. Persons with confounding medical, neurologic, or psychiatric disorders were excluded. Dementia severity was staged using the Clinical Dementia Rating scale. MAIN OUTCOME MEASURES: Five brief quantitative clinical tests included in the 90-minute clinician administered protocol, as well as 14 tests included in a 2-hour psychometric test battery. RESULTS: Dementia severity affected performance on all measurements. Age did not influence performance on clinical assessments. There was a significant interaction between age and dementia severity on 10 of 14 psychometric measures. In general, older nondemented individuals performed less well than younger nondemented individuals while older mildly demented persons performed about the same as, or slightly better than, their younger counterparts. CONCLUSIONS: Age does not affect performance on brief clinical assessment instruments. However, age affects psychometric performance differently in cognitively intact persons when compared with persons with DAT. As a result, psychometric differentiation between cognitively normal and demented individuals is more difficult in older populations.

Aged↗

ARACHnase. An evaluation of a positive control for platelet neutralization procedure testing with seven commercial activated partial thromboplastin time reagents.

ARACHnase (Hemostasis Diagnostics International Co., Denver, CO) is a normal plasma that contains a venom extract from the brown recluse spider, Loxosceles reclusa, which mimics the presence of a lupus anticoagulant (LA). Seven activated partial thromboplastin time (APTT) reagents were used for platelet neutralization procedure (PNP) testing with ARACHnase: Automated APTT (Organon-Teknika, Durham, NC); Thrombofax and Thrombosil (Ortho, Raritan, NJ); Actin and Actin FSL (Dade, Aguado, PR); and Thromboscreen-Kontact and Thromboscreen-APTT LS (Pacific-Hemostasis, Ventura, CA). ARACHnase consistently displayed a positive PNP result of greater than 5 seconds correction of the initial baseline APTT. Thus, ARACHnase may provide a positive control for LA testing, regardless of the choice of APTT reagent and activator/phospholipid combination.

Adult↗

Interlaboratory histopathologic assessment of Alzheimer neuropathology: different methodologies yield comparable diagnostic results.

Three investigators have applied different histopathologic methods (modified Bielschowsky silver methods, Congo red-gallocyanin) to differentiate Alzheimer's disease (AD) (n = 7 subjects; four with very mild dementia and three with moderate to advanced dementia) neuropathology from brain changes associated with aging in three nondemented individuals who had been evaluated using a validated dementia severity staging instrument [Washington University Clinical Dementia Rating (CDR)] generally within a year of death. The presence of elevated numbers of neocortical (frontal and temporal) diffuse, mature, and total senile plaques (SP) was strongly correlated with the presence of clinical AD but did not equate with CDR dementia severity. Neocortical neurofibrillary tangle (NFT) density as well as hippocampal NFT and SP density in this small series did not differentiate statistically between AD and controls. NFT density appeared to correlate with CDR better than SP density. Quantitative histopathologic assessment of AD markers in only a few brain regions can accurately predict the presence of clinical AD, including the very mild form of the disease. This is especially true for SP in the neocortex.

Aged↗

Serum thyrotropin and thyroid hormone levels in elderly and middle-aged euthyroid persons.

OBJECTIVE: To determine whether serum thyrotropin (TSH) levels are altered in euthyroid older persons compared with middle-aged adults. DESIGN: Serum TSH and thyroid hormone levels were measured in a large group of older persons (> 70 years old, n = 216) and their middle-aged offspring (40-60 years old, n = 211) after excluding those with clinical or historical evidence of thyroid disease or abnormal thyroid function. MEASUREMENTS: Serum TSH, thyroxine (T4), free T4 index, estimated free T4, triiodothyronine (T3), estimated free T3, and ferritin levels were measured on the Abbott IMx instrument. Peroxidase and thyroglobulin antibodies were measured by radioimmunoassay using Kronus kits. MAIN RESULTS: Overall, serum TSH showed a log-normal distribution. The geometric mean TSH (mU/L) and 95% confidence limits in the older persons, 1.24 (0.29-5.4), did not differ significantly from that in the middle-aged, 1.45 (0.54-3.9). The mean TSH in the 264 women, 1.37 (0.34-5.5), was similar to that of the 163 men, 1.30 (0.48-3.5). The mean TSH in older women, 1.21 (0.22-6.6), was slightly but significantly lower than that in middle-aged women, 1.52 (0.55-4.2). However, when euthyroid women with positive antibodies were excluded, this difference was not significant. Four of the 123 older women had TSH < 0.1 mU/L, but none of the men or middle-aged women had a suppressed serum TSH. The mean TSH in older men, 1.28 (0.43-3.8), was similar to that in middle-aged men, 1.32 (0.55-3.2). Free T4 was slightly higher in older women than middle-aged women. There were no significant correlations between TSH and any thyroid hormone level. Serum ferritin, measured as a potential marker for the action of thyroid hormone, did not correlate with any measure of thyroid function. At least one antibody level was > 10 U/mL in 14.6% of older women, 15.6% of middle-aged women, 4.3% of older men, and no middle-aged men. When those with milder elevations of antibody levels were included (at least one level > 1 U/mL), the prevalence was 32% of older women, 43.3% of middle-aged women, 15% of older men, and 11.4% of middle-aged men. CONCLUSIONS: Euthyroid older persons have about the same levels of serum TSH as younger ones, although older euthyroid women have a slightly lower serum TSH than middle-aged women. We recommend that the normal range of serum TSH in the elderly be considered to be the same as that in healthy middle-aged subjects.

Adult↗

Activation of the thyrotropin (TSH) receptor by human chorionic gonadotropin and luteinizing hormone in Chinese hamster ovary cells expressing functional human TSH receptors.

It is well known that peptide heterogeneity exists in the hCG-beta subunit in pregnancy and in patients with trophoblastic diseases. To elucidate the differences in thyrotropic activity of hCG molecules, we examined cAMP accumulation and TSH receptor binding of intact hCG, hLH, and a recombinant hCG that lacked the C-terminal extension on the beta-subunit, hCG (alpha wt/beta delta T), using Chinese hamster ovary (CHO) cells transfected with hTSH receptors. hLH, which shares 85% sequence identity with the hCG-beta molecule except for the C-terminal amino acid residue extension of the hCG-beta subunit, bound to the TSH receptor and stimulated adenylate cyclase about 10 times more potently than hCG on a molar basis. This was consistent with the result that cAMP stimulation by mutant hCG (alpha wt/beta delta T) was greater than intact hCG. hLH also increased iodide uptake and thymidine incorporation in FRTL-5 rat thyroid cells more potently than intact hCG. These results demonstrate that hLH is a more potent TSH than hCG and that the C-terminal extension of the hCG beta-subunit can interfere with hCG interaction with the hTSH receptor. hCG lacking the C-terminal extension of the beta-subunit occurs in the mixture of heterogeneous hCG molecular forms of pregnancy and trophoblastic diseases and may contribute to the hyperthyroidism in patients with hydatidiform mole, choriocarcinoma, and hyperemesis gravidarum.

Analysis of Variance↗

In vivo primary induction of virus-specific CTL by immunization with 9-mer synthetic peptides.

A primary cytotoxic T lymphocyte (CTL) response in vivo requires antigen presentation by cytosolic processing and can not in general be obtained by vaccination with soluble proteins. In the present work we have found that vaccination of mice with pre-processed synthetic peptides, corresponding to endogenous 9-mers produced in influenza A virus-infected cells, resulted in strong primary CTL responses. The generated CTL efficiently killed virus-infected target cells with preference for viral strains having the identical amino acid sequences to the peptides used for immunization. The optimal conditions for a primary in vivo CTL response was obtained with 100 micrograms peptide dissolved in incomplete Freund's adjuvant and injected s.c. at the base of tail. Spleen cells which had been primed 7-10 days earlier were restimulated for 5 days in vitro, using an optimal low peptide concentration (0.05 microM) and tested against virus-infected and peptide-treated target cells. The peptide-induced CTL were major histocompatibility complex class I restricted and CD8 positive.

Amino Acid Sequence↗

Mild senile dementia of the Alzheimer type. 4. Evaluation of intervention.

The design of trials of interventions intended to slow or arrest the progression of senile dementia of the Alzheimer type must be based on analysis of the natural history of the disease. Using a random coefficients statistical model, we analyzed the natural history of senile dementia of the Alzheimer type in carefully defined subjects with mild disease (n = 68) for periods of up to 10 years. Subject performance was assessed longitudinally on batteries of clinical and psychometric measures. The characteristics of these measures were analyzed relevant to their utility as outcome measures for long-term trials in patients with senile dementia of the Alzheimer type. Estimates were made of sample sizes required to show arrest, and 50% or 25% slowing in the progression of mild disease. We suggest that a clinically relevant global measure, such as the Sum of Boxes of the Clinical Dementia Rating scale, and a performance-based clinical scale or psychometric measure would be appropriate in a 12- or 24-month trial enrolling subjects with mild senile dementia of the Alzheimer type.

Actuarial Analysis↗