Biomedical subjects

Y P Jin

Publications and source records attributed to Y P Jin.

14 recordsLinked to original sources

PubMed2003

Predicting multiple sclerosis at optic neuritis onset.

Using multivariate analyses, individual risk of clinically definite multiple sclerosis (CDMS) after monosymptomatic optic neuritis (MON) was quantified in a prospective study with clinical MON onset during 1990-95 in Stockholm, Sweden. During a mean follow-up time of 3.8 years, the presence of MS-like brain magnetic resonance imaging (MRI) lesions and oligoclonal immunoglobulin (Ig) G bands in cerebrospinal fluid (CSF) were strong prognostic markers of CDMS, with relative hazard ratios of 4.68 [95% confidence interval (CI) 2.21-9.91] and 5.39 (95% CI 1.56-18.61), respectively. Age and season of clinical onset were also significant predictors, with relative hazard ratios of 1.76 (95% CI 1.02-3.04) and 2.21 (95% CI 1.13-3.98), respectively. Based on the above two strong predictors, individual probability of CDMS development after MON was calculated in a three-quarter sample drawn from a cohort, with completion of follow-up at three years. The highest probability, 0.66 (95% CI 0.48-0.80), was obtained for individuals presenting with three or more brain MRI lesions and oligoclonal bands in the CSF, and the lowest, 0.09 (95% CI 0.02-0.32), for those not presenting with these traits. Medium values, 0.29 (95% CI 0.13-0.53) and 0.32 (95% CI 0.07-0.73), were obtained for individuals discordant for the presence of brain MRI lesions and oligoclonal bands in the CSF. These predictions were validated in an external one-quarter sample.

Adult↗

PubMed2001

Multiple sclerosis: deficient in vitro responses of blood mononuclear cells to IFN-beta.

IFN-beta may modify the clinical course of multiple sclerosis (MS) but is not curative, and there are also patients whose disease does not respond to IFN-beta as currently administered. Tests are warranted with a capacity to early discriminate responders from non-responders, thereby altering treatment option for the individual patient. In vitro effects of IFN-beta on expression of activation-associated cell surface markers and cytokine production need to be explored in this context. Here we report on the influence in vitro of IFN-beta on blood mononuclear cells (MNC) prepared from MS patients and healthy controls. MNC were subjected to short-term culture in the presence of IFN-beta at concentrations of 100 U/ml and 1000 U/ml. Expression of cell surface molecules CD40, CD69, CD80, CD86, CD95 and HLA-DR was measured by flow cytometry. IL-10 and IL-12 p40 production in culture supernatants was measured by ELISA. MNC exposed to IFN-beta in vitro enhanced expression of the co-stimulatory CD80, CD86, the early activation antigen CD69 and the cell death receptor CD95. Expression of CD40 and HLA-DR was not influenced. IFN-beta increased IL-10 but suppressed IL-12 p40 production. In vitro effects of IFN-beta on MNC were similar in MS patients and in healthy subjects, except that IFN-beta-induced augmentation of CD86 and CD69 expression was less pronounced in MS, in particular in untreated MS patients. Individual MS patients clearly responded differently to IFN-beta in vitro in comparison with the majority of patients in this cross-sectional study. In conclusion, anti-inflammatory effects of IFN-beta on blood MNC include augmentation of IL-10 production and suppression of IL-12 p40 production, which are accompanied by enhancement of CD69, CD80, CD86 and CD95 expression. The less pronounced IFN-beta-induced effects on CD86 and CD69 expression in MS vs controls might reflect a defect in immunoregulation in MS. Larger groups should be evaluated, and follow-up studies performed in MS patients before/during IFN-beta treatment in relation to clinical outcome measures to evaluate the usefulness of these markers for possible differentiation between responders and non-responders to IFN-beta treatment.

Adult↗

PubMed2001

Altered phenotype and function of blood dendritic cells in multiple sclerosis are modulated by IFN-beta and IL-10.

Multiple sclerosis (MS) is assumed to result from autoaggressive T cell-mediated immune responses, in which T helper type 1 (Th1) cells producing cytokines, e.g. IFN-gamma and lymphotoxin promote damage of oligodendrocyte-myelin units. Dendritic cells (DCs) as potent antigen presenting cells initiate and orchestrate immune responses. Whether phenotype and function of DCs with respect to Th1 cell promotion are altered in MS, are not known. This study revealed that blood-derived DCs from MS patients expressed low levels of the costimulatory molecule CD86. In addition, production of IFN-gamma by blood mononuclear cells (MNCs) was strongly enhanced by DCs derived from MS patients. IFN-beta and IL-10 inhibited the costimulatory capacity of DCs in mixed lymphocyte reaction (MLR) and showed additive effects on suppression of IL-12 production by DCs. Correspondingly, DCs pretreated with IFN-beta and IL-10 significantly suppressed IFN-gamma production by MNCs. IFN-beta in vitro also upregulated CD80 and, in particular, CD86 expression on DCs. In vitro, anti-CD80 antibody remarkably increased, while anti-CD86 antibody inhibited DC-induced IL-4 production in MLR. We conclude that DC phenotype and function are altered in MS, implying Th1-biased responses with enhanced capacity to induce Th1 cytokine production. In vitro modification of MS patients' DCs by IFN-beta and IL-10 could represent a novel way of immunomodulation and of possible usefulness for future immunotherapy of MS.

Adult↗

PubMed2001

Dendritic cells derived from patients with multiple sclerosis show high CD1a and low CD86 expression.

Dendritic cells (DC) are important antigen presenting cells (APC) and play a major role in initiating and orchestrating immune responses by priming T cells. Little is known about involvement of DC in multiple sclerosis (MS), where auto-aggressive T cells against myelin autoantigens are considered to contribute to inflammation and demyelination in the central nervous system. In this study, we compared phenotype and cytokine secretion of DC from patients with MS, other neurological diseases (OND) and healthy subjects. DC were generated from blood adherent mononuclear cells (MNC) by culture for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield and morphology of DC were similar in MS patients and controls. In both, the DC phenotype was that of immature myeloid lineage, comprising CD1a+ and CD11c+. The proportion of CD1a+ DC, being important for presentation of lipid antigens to T cells, was higher in MS patients compared to controls. The proportion of CD86+ DC, a co-stimulatory molecule that is assumed to promote Th2 differentiation, was low in MS. Low proportions of CD86+ DC were only observed in untreated MS patients but not in patients treated with IFN-beta. Production of IL-10 and IL-12 p40 by DC did not differ in MS patients and controls. These findings indicate that alterations of functionally important surface molecules on DC are associated with MS.

Adult↗

PubMed2000

Changes of lead levels in 24-h urine from 1985 to 1998 in Japanese adults.

To determine whether current environmental lead (Pb) levels are causing any progressive changes in urinary Pb levels, 24-h urine samples were collected from 277 subjects (159 men and 118 women) in 1985, 312 subjects (155 men and 157 women) in 1993, and 311 subjects (156 men and 155 women) in 1998. All of the subjects worked in the same factory. The urinary Pb concentration was analyzed by flameless atomic absorption spectrophotometry. The geometric means for men were 4.74, 2.67 and 1.31 microg/day; 3.17, 1.78 and 1.04 microg/g creatinine; and 3.18, 1.99 and 0.98 microg/l urine in 1985, 1993 and 1998, respectively. The values for women were 3.22, 2.14 and 0.97 microg/day; 3.35, 2.26 and 1.15 microg/g creatinine; and 2.49, 1.86 and 0.83 microg/l urine, respectively. These results demonstrated that Pb levels in 24-h urine decreased significantly in the 13-year period (P<0.01).

Adult↗

PubMed1999

Incidence of optic neuritis in Stockholm, Sweden, 1990-1995: II. Time and space patterns.

OBJECTIVES: To describe the time and space patterns of patients with monosymptomatic optic neuritis (MON) in Stockholm County, Sweden, and to explore the role of environmental factors in the etiology of MON and multiple sclerosis. DESIGN: Population-based and prospective incidence survey. SETTING: Census based on referrals from 1.68 million inhabitants of Stockholm County. PATIENTS: One hundred forty-seven new patients with MON were consecutively referred by ophthalmologists and neurologists from January 1, 1990, through December 31, 1995. A standardized questionnaire was used for data collection. MAIN OUTCOME MEASURES: Evaluations consisted of annual incidence, statistical significance of temporal aggregation, Knox test, likelihood score test applied to the ratio of the highest to lowest seasonal proportion of registered events, and standardized morbidity ratio for municipalities. RESULTS: We observed a seasonal pattern of MON incidence, with the highest incidence (31%) in the spring and the lowest (17%) in the winter (ratio of highest to lowest seasonal proportion, 1.84; 95% confidence interval, 1.13-3.01; P = .007). The seasonal monthly incidences were correlated with the average number of sunny hours and the temperature. The presence of positive immune activity markers (i.e., mononuclear pleocytosis and oligoclonal IgG bands in the cerebrospinal fluid) seemed to be linked to the onset of MON in winter. No aggregation by time, space, or month of birth was detected. CONCLUSIONS: Monosymptomatic optic neuritis in Stockholm County occurred at an uneven frequency across the seasons, with the highest incidence in spring and the lowest in winter. This seasonal pattern is compatible with that described in most previous reports. Environmental and probable infectious factors unevenly distributed by season may play a role in the etiology and early clinical course of MON.

Adult↗

PubMed1999

An angiotensin-converting enzyme gene polymorphism suggests a genetic distinction between ischaemic stroke and carotid stenosis.

BACKGROUND: Ischaemic cerebrovascular disease (ICVD) is a heterogeneous syndrome to which different genetic factors may contribute. We have investigated the distribution of alleles of the angiotensin-converting enzyme (ACE) gene, which has been suggested to be of possible importance in ischaemic stroke or cardiovascular disease, in groups of patients with ischaemic stroke and carotid artery stenosis (CS). MATERIALS AND METHODS: One hundred and thirty patients with ischaemic stroke and 68 patients with more than 50% stenosis of the internal carotid artery were investigated and compared with age- and sex-matched healthy control subjects. Alleles of an insertion/deletion polymorphism of the ACE gene were determined by one-stage polymerase chain reaction and visualized on agarose gels. RESULTS: There was a significant difference (P < 0.05) in the distribution of ACE alleles, homozygosity for the presumed susceptibility deletion allele being more common in patients with CS than in healthy control subjects. There was also a significant difference (P < 0.05) in patients with CS in comparison with matched ICVD patients without CS, both in allelic frequencies and in homozygosity for the deletion allele. CONCLUSIONS: Our results indicate that the ACE gene polymorphism may be a risk factor for the development of CS. The observed difference in ACE allele distribution may be seen as evidence for a genetic distinction between ICVD and CS, two clinically related conditions, which further supports the hypothesis that genetic factors are of importance for this group of diseases.

Aged↗

PubMed1999

Nidovirus infections: experimental model systems of human neurologic diseases.

The presence of terminally differentiated slow- and non-dividing cells in the central nervous system (CNS) provides a safe harbor for viral persistence and latency and constitutes a unique immunologic environment for viral infections. Studies of experimental model systems of viral infections of the CNS provide insight into mechanisms of viral persistence and immune-mediated pathology. Nidoviruses are comprised of 2 families of viruses, coronaviruses and arteriviruses, and are common pathogens of humans and a variety of animal species. Both families of viruses contain neurotropic strains that produce experimental neurologic diseases in rodents. These include acute meningitis and encephalitis; acute poliomyelitis; and chronic inflammatory, immune-mediated, demyelination. Coronavirus-induced demyelinating disease mimics many of the pathologic features of Multiple Sclerosis (MS).

Animals↗

PubMed1998

Incidence of optic neuritis in Stockholm, Sweden 1990-1995: I. Age, sex, birth and ethnic-group related patterns.

We studied the incidence of monosymptomatic optic neuritis (MON) in Stockholm county, Sweden and its variation with person-related factors. Patients with suspected or diagnosed MON between January 1, 1990 and December 31, 1995 were referred from ophthalmologists and neurologists to a research registry. The diagnosis was based on accepted clinical criteria only, and verified by an ophthalmologist who examined all the patients. Data were collected by interview using a structured questionnaire. The crude mean annual incidence, based on 147 patients, 118 females and 29 males, diagnosed with MON, was 1.46 per 100,000 person-years, 2.28 for females and 0.59 for males. The corresponding age-adjusted incidences were 1.40, 2.28 and 0.53. The age-specific incidence curve for both sexes suggested a bimodal distribution with peaks at 30-34 years and 45-49 years. The smoothed cumulative incidences in 1 year birth cohorts showed a notchy profile, related to bimodality. The incidence among residents born out of the Nordic countries was low, 0.28 per 100,000. Patients with onset of MON before 40 years of age had a significantly higher frequency of mononuclear pleocytosis in cerebrospinal fluid and shorter duration to conversion to multiple sclerosis. In summary, MON occurred in Stockholm at a relatively low frequency, particularly among males. The presence of particular birth date and birth place related patterns might be etiologically relevant.

Adult↗

PubMed1997

Lead levels in 24-h urine in Japanese adults.

Samples of 24-h urine were collected from 278 subjects (159 males and 119 females) in 1985, and 321 subjects (161 males and 160 females) in 1993 in the same factory with no occupational exposure to lead (Pb) in Japan. The age range of the subjects was 20-59 years. The urinary Pb concentrations were analyzed by flameless atomic absorption spectrophotometry after wet digestion followed by solvent extraction. The Pb levels in 24-h urine were distributed log-normally with geometric means (geometric S.D.) of 4.74 (1.46) and 2.67 (1.98) micrograms/day for males; and 3.22 (1.42) and 2.14 (2.05) micrograms/day for females in 1985 and 1993, respectively. No age-related changes in Pb levels in 24-h urine in either sex from 20 to 59 years were apparent. Pb levels in 24-h urine were significantly higher in males than in females (P < 0.01). Analysis of male smokers together with age-matched non-smokers failed to show an elevation of Pb levels in 24-h urine as related to smoking habits. Comparison of the Pb levels in 24-h urine in 1985 and 1993 disclosed that the Pb levels in 24-h urine were significantly lower in 1993 than in 1985 in both sexes (P < 0.01).

Adult↗

PubMed1996

Differential activation of extracellular signal-regulated kinase (ERK) 1, ERK2, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinases by bacterial peptidoglycan.

Soluble staphylococcal peptidoglycan (sPGN) is an inducer of cytokine secretion and may activate macrophages through the CD14 lipopolysaccharide (LPS) receptor. To elucidate sPGN-activated signal transduction pathways, stimulation of mitogen-activated protein (MAP) kinases by sPGN was studied in mouse RAW264.7 macrophages. sPGN strongly activated extracellular signal-regulated kinase (ERK) 1 and ERK2, moderately activated c-Jun NH2 terminal kinase (JNK), and weakly activated p38 MAP kinase, in contrast to LPS, which strongly activated all of these kinases, and phorbol 12,13-dibutyrate (PDB), which strongly activated ERK1 and ERK2 but did not activate p38 or JNK. sPGN- and LPS-induced activation of ERK1 and ERK2, unlike PDB-induced activation, was sensitive to inhibition by herbimycin A and insensitive to inhibition by increased intracellular cAMP. These results demonstrate differential activation of MAP kinases by sPGN, similar but not identical activation of signal transduction pathways by sPGN and LPS, and different mechanisms of MAP kinase activation by bacterial stimulants and phorbol esters.

1-Methyl-3-isobutylxanthine↗

PubMed1995

Peptidoglycan induces transcription and secretion of TNF-alpha and activation of lyn, extracellular signal-regulated kinase, and rsk signal transduction proteins in mouse macrophages.

In soluble peptidoglycan (PGN) from staphylococcal cell walls as well as soluble PGN (sPGN) secreted by staphylococci in the presence of beta-lactam antibiotics induced TNF-alpha mRNA and secretion of bioactive TNF-alpha in the murine RAW264.7 macrophage cell line, PGN and sPGN also induced rapid and dose-dependent tyrosine phosphorylation of several cellular proteins, including lyn and mitogen-activated protein kinases (extracellular signal-regulated kinases; but not hck, fgr, or vav) and increased the activities of mitogen-activated protein and rsk kinases. These PGN- and sPGN-induced effects were qualitatively similar to the effects induced by ReLPS, but higher concentrations of PGN and sPGN than ReLPS were required. In contrast to the ReLPS-induced effects, the PGN- and sPGN-induced effects were not inhibited by polymyxin B. All PGN-, sPGN-, and ReLPS-induced effects were serum independent, since they were observed both in RAW264.7 cells grown and stimulated in the presence of serum and in the cells adapted to growth and stimulated in a serum- and albumin-free medium. These results indicate that lyn, extracellular signal-regulated kinase, and rsk signal transduction molecules may be involved in macrophage activation by PGN and further support the idea that PGN and LPS may activate the cells through similar mechanisms.

Animals↗

PubMed1993

[Effect of baoyuantang on level of serum lipid peroxide and vitamin E in chronic glomerulonephritis].

Serum lipid peroxide (LPO) and vitamin E (VE) were determined in 18 patients with chronic glomerulonephritis (CGN) before and after treatment with Baoyuantang (BYT). It was found that before treatment the level of serum LPO (4.89 +/- 1.85 mumol/L) was higher, while the content of serum VE (4.27 +/- 1.84 micrograms/ml) was lower than those of normal controls (3.36 +/- 0.59 mumol/L, P < 0.001; 7.03 +/- 0.69 microgram/ml, P < 0.05). After treatment with BYT, the level of LPO lowered to 3.76 +/- 1.49 mumol/L, P < 0.05, as compared with the value before treatment, while the content of VE was increased to 5.33 +/- 2.45 micrograms/ml, but without statistical significance. A negative correlation was found between LPO level and VE content both before and after treatment (r = -0.495,P < 0.05; r = -0.522, P < 0.05). The results indicated chronic deficiency of VE in association with an increase in the level of LPO in the kidney in CGN patients and inhibition of LPO by BYT. After treatment complete remission was observed in 5 cases, basic remission in 3, and partial remission in 7.

Adult↗

PubMed1992

[Effect of baoyuantang on erythroid progenitor and clinical observation in chronic renal failure patients].

The erythroid colony formating ability and the therapeutic efficacy were investigated in patients with chronic renal failure (CRF) before and after treatment with baoyuantang. The results showed that the number of CFU-E, BFU-E of bone marrow was found lower in CRF patients than that in normal controls, and there was inhibitory action in the CRF serum on the number of CFU-E, BFU-E of normal human bone marrow. After treatment with baoyuantang, the amount of Hb was increased and creatinine decreased in CRF patients, and its effective rate reached 83.3%. The above-mentioned inhibitory action in CRF serum was also reduced post-treatment. The results indicated that baoyuantang could increase the ability for proliferation and differentiation of erythroid progenitor and adjust anemia in CRF patient.

Adult↗