Expression of Tn and sialyl Tn antigens in synovial tissues in rheumatoid arthritis.

OBJECTIVES: The carbohydrate chains represented by mucins (MUCs) are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. Tn and sialyl Tn antigens are tumour-associated carbohydrate antigens which are borne on the core proteins of mucins. The purpose of this study is to investigate the existence of tumour-associated carbohydrate antigens in rheumatoid arthritis (RA). METHODS: . We examined the expression of Tn and sialyl Tn antigens in synovial tissues from RA and osteoarthritis (OA) patients by immunohistochemistry. In addition, mucins from synovial fluid (SF) from RA patients are purified by gel filtration and density gradient ultracentrifugation and the existence of these antigens examined by dot and Western blotting. RESULTS: We found that Tn and sialyl Tn antigens were strongly expressed in synovial cells and infiltrating mononuclear cells on the sublining layer and lymphoid follicles in synovial tissues in RA compared with those in osteoarthritis. Tn and sialyl Tn antigens were detected in purified mucins of SF from RA patients. CONCLUSIONS: Tumour-like synovial hyperplasia cells expressed Tn and sialyl Tn antigens. This finding suggests that the mucins exhibiting with abnormal glycosylation may be in part responsible for synovial hyperplasia, leading to the joint destruction in the pathogenesis of RA.

15-deoxy-delta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and have a dominant regulatory role in adipocyte and monocyte differentiation. PPAR-gamma agonists are also negative regulators of macrophage activation and have modulatory effects on tumorigenesis. In this study we demonstrate that synovial tissue localized expression of PPAR-gamma in patients with rheumatoid arthritis (RA). We detected markedly enhanced expression of PPAR-gamma in macrophages, as well as modestly enhanced expression in the synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR-gamma by 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the synthetic PPAR-gamma ligand (troglitazone) induced RA synoviocyte apoptosis in vitro. Moreover, intraperitoneal administration of these PPAR-gamma ligands ameliorated adjuvant-induced arthritis with suppression of pannus formation and mononuclear cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ(2) were more potent than troglitazone. These findings suggest that PPAR-gamma may be an important immunoinflammatory mediator and its ligands, especially 15d-PGJ(2), may be useful in the treatment of RA.

Two distinct phosphatidylinositol-specific phospholipase Cs from Streptomyces antibioticus.

Two phosphatidylinositol-specific phospholipase C (PI-PLC) genes from Streptomyces antibioticus were cloned by a shotgun method using Streptomyces lividans TK24 as a host. The genes of the two PI-PLCs (named as PLC1 and PLC2) were adjoined and opposite in the direction of transcription/translation. Both of them were confirmed to be expressed in S. antibioticus. The two enzymes were different in the following properties. (i) PLC2 had considerable sequence similarity to other bacterial PI-PLCs, while PLC1 had a short stretch that was similar to PI-PLCs of eukaryotes rather than the other bacterial enzymes. (ii) PLC1 was Ca2+-dependent, whereas PLC2 was not. (iii) PLC1 generated myo-inositol-1-phosphate and myo-inositol-1:2-cyclic phosphate simultaneously from PI, but PLC2 showed sequential formation of them. (iv) PLC2 has GPI-anchor-degrading activity while PLC1 does not have. Both enzymes did not hydrolyze phosphatidylcholine, phosphatidylinositol-4-monophosphate and phosphatidylinositol-4,5-bisphosphate. Both PLC1 and PLC2 contained two histidine residues that might be catalytic residues. PLC1 has residues that possibly form a Ca2+-binding site. Then it was suggested that both PLC1 and PLC2 act according to the catalytic mechanism using the two histidine residues as proposed in both eukaryotic and prokaryotic enzymes, but that PLC1 has a more 'eukaryotic' mechanism in which Ca2+ participates than that of the Ca2+-independent bacterial enzymes. Thus, we propose that PLC2 is a conventional 'bacteria-type' enzyme, while PLC1 is more closely related to the eukaryotic enzymes rather than the bacterial enzymes.

Urocortin expression in synovium of patients with rheumatoid arthritis and osteoarthritis: relation to inflammatory activity.

Peripherally produced CRH acts as a local auto/paracrine proinflammatory agent. Urocortin is a new member of the CRH family that acts through the family of CRH receptors. In this study, we demonstrated that the expression of urocortin mRNA in synovia of patients with rheumatoid arthritis was greater than that of patients with osteoarthritis. Also, we detected urocortin and CRH receptor immunoreactivity in the synovial lining cell layer, subsynovial stromal cells, blood vessel endothelial cells, and mononuclear inflammatory cells from the joints of rheumatoid arthritis and osteoarthritis patients. The expression of immunoreactive urocortin was significantly greater in rheumatoid arthritis than osteoarthritis (P < 0.0001) and correlated with the extent of inflammatory infiltrate. CRH receptor immunoreactivity was strong in mononuclear inflammatory cells of rheumatoid arthritis synovia. Urocortin stimulated IL-1beta and IL-6 secretion by human peripheral blood mononuclear cells in vitro. These findings suggest that, like CRH, urocortin is present in peripheral inflammatory sites, such as rheumatoid synovium, and acts as an immune-inflammatory mediator.

Blood flow patterns in the rat pancreas: a simulative demonstration by injection replication and scanning electron microscopy.

Scanning electron microscopy of vascular casts prepared by arterial injections of intentionally reduced amounts of resin showed that in the rat pancreas, the casting medium fills blood capillaries in the endocrine islets more promptly than those in the exocrine lobules and secretory ducts. Furthermore, the exocrine lobules containing endocrine islets allowed a more rapid resin flow through the insulo-acinar portal route than those lobules lacking an islet. The capillaries of secretory ducts were the last portions to be filled with resin. Since the resin used in this study was as viscous as blood and injected under a physiological pressure, the microcirculatory patterns demonstrated by the present method reflect the physiological flow pattern of blood in the pancreas.

Preferential inhibition of cyclooxygenase-2 by meloxicam in human rheumatoid synoviocytes.

The aim of this study was to evaluate the anti-inflammatory effect of 4-hydroxy-2-methyl-N-[5-methyl-2-thiazolyl]-2H-1, 2-benzothiazine-3-carboxamide-1,1-dioxide (meloxicam) using cultured rheumatoid synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with meloxicam in the presence or absence of interleukin-1beta. Meloxicam had no effect on both cyclooxygenase-1 and -2 expression as determined by Western blot analysis, immunohistochemical staining, and reverse transcription polymerase chain reaction (RT-PCR). Even the lower doses of meloxicam inhibited cyclooxygenase-2 activity, but only the higher doses of meloxicam inhibited cyclooxygenase-1 activity as determined by prostaglandin E(2) synthesis assay. So meloxicam had a preferential inhibitory effect of cyclooxygenase-2 relative to cyclooxygenase-1 on cultured rheumatoid synoviocytes without affecting cyclooxygenase expression. On the other hand, indomethacin had no selectivity and dexamethasone inhibited the expression of cyclooxygenase-2. Our data indicate that clinical efficacy and safety of meloxicam for rheumatoid arthritis may result from its preferential inhibition of cyclooxygenase-2 activity relative to cyclooxygenase-1 on rheumatoid synoviocytes.

Auranofin inhibits interleukin-1beta-induced transcript of cyclooxygenase-2 on cultured human synoviocytes.

The aim of this study was to characterize the effects of auranofin (2,3,4,6-tetra-O-acetyl-l-thio-beta-D-gluco-pyranosato-S) on cyclooxygenase expression and prostaglandin E(2) synthesis on cultured human synovial fibroblast-like cells (synoviocytes). Synoviocytes were treated with auranofin in the presence or absence of interleukin-1beta. Cultured supernatants were harvested for prostaglandin E(2) synthesis. Cyclooxygenase-1 and -2 expression was analyzed with Western and Northern blotting. Translocation of nuclear factor-kappa B p65 was determined by immunostaining. Cytotoxicity was measured with 51Cr release assay. Auranofin attenuated interleukin-1beta-induced prostaglandin E(2) production of the cells in a dose-dependent fashion. Auranofin selectively suppressed interleukin-1beta-induced cyclooxygenase-2 mRNA and protein expression of the cells without alteration of cyclooxygenase-1 expression. Also, auranofin interfered with interleukin-1beta-induced translocation of nuclear factor-kappa B. These inhibitory effects did not originate in the cytotoxicity of the agent. Our data indicate that auranofin inhibits interleukin-1beta-induced prostaglandin E(2) synthesis and cyclooxygenase-2 expression via suppression of nuclear factor-kappa B activation on synoviocytes.

Meloxicam inhibits the growth of non-small cell lung cancer.

Cyclooxygenase (COX)-2 has been reported to play an important role in carcinogenesis. Meloxicam (preferential COX-2 inhibitor) inhibits the growth of COX-2 positive and COX-1 negative colorectal cancer cells. We evaluated the effects of meloxicam on the growth of lung cancer cells. By reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, COX-2 but not COX-1 was expressed in human non-small cell lung cancer (NSCLC) cell lines (A549 and PC14). In human small cell lung cancer (SCLC) cell line (H841), both COX-1 and COX-2 were not detected. MTT assay and prostaglandin (PG) E2 enzyme immunoassay showed that meloxicam inhibited the growth and PGE2 production of both A549 and PC14, but not H841 cells. These findings suggest that COX-2 may play an important role in the pathogenesis and progression of NSCLC, and that meloxicam may be a useful therapeutic agents in the treatment of NSCLC.

Expression of peroxisome proliferator-activated receptor (PPAR)-gamma in human lung cancer.

The peroxisome proliferator-activated receptor (PPAR)-gamma is a member of the steroid nuclear receptors. Recent studies have demonstrated that PPAR-gamma is expressed in several cancer cells. We examined the PPAR-gamma expression in both normal lung and major types of human lung cancer. The expression of PPAR-gamma mRNA was detected in 2 out of 3 normal lung tissues and its protein was detected in 3 out of 5 normal lung tissues. In contrast, a small cell carcinoma cell line and all other types of lung cancer tissues expressed PPAR-gamma mRNA and its protein. Immunoreactive PPAR-gamma is strongly expressed in cancer cells and moderately in mononuclear cells, endothelial cells and fibroblasts of lung cancer tissues. Our results suggest that PPAR-gamma may play an important role in the pathogenesis and/or progression of lung cancer, and may be a novel therapeutical target for therapy of lung cancer.

Perineuronal sulfated proteoglycans, cell surface glycoproteins and dark neurons in the cingulate cortex of newborn and adult rats.

Many neurons in the adult rat cingulate cortex possess perineuronal sulfated proteoglycans detectable with cationic iron colloid and aldehyde fuchsin, or cell surface glycoproteins reactive to lectin Vicia villosa or soybean agglutinin. The perineuronal sulfated proteoglycans develop three to four weeks after birth. The cell surface glycoproteins develop at earlier stage or two to three weeks after birth. Dark or active neurons begin to appear three to four weeks after birth. These findings indicate that the brain matures after birth or during weaning period.

Perineuronal sulfated proteoglycans in the adult rat brain: histochemical and electron microscopic studies.

Neurons of cerebellar nuclei in the rat brain had a marked surface coat which was stained with cationic iron colloid or aldehyde fuchsin. Neurons with a similar surface coat were also noted in the retrosplenial cortex. The surface coat was stained doubly with cationic iron colloid and aldehyde fuchsin. Digestion with hyaluronidase eliminated the stainability of the surface coat to both agents. Combined digestion with chondroitinase ABC, heparitinase and keratanase eliminated the cationic iron colloid staining but did not interfere with the aldehyde fuchsin staining. Electron microscopy of ultrathin sections revealed that the iron particles were deposited in the perineuronal tissue spaces. These findings indicate that the surface coat consists of sulfated proteoglycans which occupy, as the extracellular matrix, the perineuronal tissue spaces. Many neurons in the retrosplenial cortex were labeled with lectin Vicia villosa agglutinin. Double staining revealed that these lectin-labeled neurons are usually reactive to cationic iron colloid. Few neurons in the cerebellar nuclei were labeled with lectin V. villosa agglutinin.

Rat parathyroid gland, with special reference to its blood vascular bed, pericapillary space and intercellular space.

The blood vascular bed, perivascular space and intercellular space of the rat parathyroid gland were studied using scanning electron microscopy of vascular casts, freeze-cracked tissue samples, and NaOH-digested tissue blocks. The findings were supplemented by transmission light and electron microscopy of iron colloid-treated or enzyme-digested tissue sections. The rat parathyroid gland contained a rich network of capillaries. These capillaries were surrounded by marked pericapillary spaces which were demarcated by basal lamina of both capillaries and parenchymal cells. The pericapillary spaces contained numerous collagen fibrils, and issued many crista-like projections which ran deep into the sheets of parenchymal cells. The intercellular spaces of parenchymal cells contained neither basal lamina nor collagen fibrils. The surfaces of the parenchymal cells showed strong negative charging, and maintained the intercellular spaces. The luminal surfaces of the capillary endothelium also showed strong negative charging, and maintained the capillary lumen.

A re-examination of Raffles's statistics on the population of Java in the early nineteenth century: some problems of early censuses.

PIP: The author evaluates the reliability of the population statistics for early nineteenth-century Java, Indonesia, which were published in 1817 by T. S. Raffles. Data on household size, sex ratio, age structure, and Chinese and other nationalities are analyzed. It is noted that a main problem with the data is underestimation of household sizes.^ieng

[A note on the population mobility and sex ratio of the people of South Sulawesi].

PIP: Some aspects of recent migration trends among the Buginese people of South Sulawesi, Indonesia, are described in this paper. The effect of out-migration on the sex ratio at the place of origin is analyzed. Characteristics of the internal migration process at selected places of destination, including Kabupaten Luwu and South Sumatra, are also examined. (summary in ENG)^ieng

[Population of Southeast Asia in the mid-nineteenth century: population counts appearing in the Journal of the Indian Archipelago and Eastern Asia].

"This paper aims to compile and evaluate the information on the population of Southeast Asia in the Mid-nineteenth century appearing in the Journal of the Indian Archipelago and Eastern Asia, which was published from 1847 to 1860 in Singapore. The journal contains considerable numbers of population figures for the pre-census period,...[concerning] Sumatra, the Malay Peninsula, the Straits Settlements, Java, Bali, Lombok, Sulawesi, Borneo, and other parts of insular Southeast Asia. The general tendency of the population counts of insular Southeast Asia in this period by the Europeans is toward underestimation. This is especially true for the inland areas of the larger islands, which were remote from the European sphere of influence. Populations of the small islands located on commercial routes are reported relatively accurately or even overestimated. Populations of the European settlements are sometimes overestimated and their growth rates tend to be exaggerated." (SUMMARY IN ENG)

[[Multihouseholdcompounds in a Malay village in Kelantan, 1971-1991]].

The author describes changes in the size and characteristics of multiple-household compounds in Kelantan, Malaysia, during the period 1971-1991. It is found that "in Malay villages, multihouseholdcompounds were in earlier times...based on a bilateral residence rule in which one or more children, either male or female, would stay in the compound of their parents....A recent trend has been for more females to remain in the parental compound than males, reflecting the orientation toward independence among the males." (SUMMARY IN ENG)

[[A re-examination of Raffles's statistics on the population of Java in the early nineteenth century]].

The author analyzes the accuracy of the population data published by Sir Thomas Raffles concerning early nineteenth-century Java, Indonesia. Specific topics considered include "a. errors in computation, b. distribution of household size by sub-district, c. distribution of sex-ratio by sub-district, d. variation of age-structure by sub-district, [and] e. problems of Chinese population. Special attention was given to the consistency of the definition of categories and the distribution patterns of the reported figures." (SUMMARY IN ENG)

[On the mobile character of the Malay village population: a feature of the post-settlement population of Galok, Kelantan].

The author examines migration trends in Malay villages. "This report deals with the case of Galok, a settlement opened in the last decade of nineteenth century about 40 kilometers up the Kelantan River, based on field data collected in 1970/71 and 1984." The low rate of population growth due to migration is analyzed, with a focus on the impact of rural-urban migration and changes in household composition. (SUMMARY IN ENG)

[[Changes in population and households in a Malay village, 1971-1991]].

"The Malay village of Galok in Kelantan was revisited [in]...1991 to investigate the changes in the population and households in the 20 years since the first intensive community study was conducted there in 1970/71. Major economic activities in 1970/71 were paddy cultivation in rain-fed fields, small scale rubber tapping, and newly introduced tobacco cultivation. The village's population increased from 690 in 1971 to 1,100 in 1991, and the number of households from 145 to 211. Despite the increase in population and households, the households cultivating paddy decreased from 71 to 36, those tapping rubber from 94 to 53, and those growing tobacco from 124 to 40, while regular employment, irregular wage labor in the surrounding areas, and temporary migratory work in Singapore increased remarkably. Many people moved out of the village and many others moved in. Though the former exceed the latter in number, the village population is still increasing owing to the high fertility...." (SUMMARY IN ENG)

[The population and character of traditional communities in insular Southeast Asia].

"This article discusses the character of population distribution and its relation to the structure of societies and states in Insular Southeast Asia in the early and mid nineteenth century. Except in Java and Bali, populations were characterized by sparsity, diversity, smallness, and mutual independence. Despite the effects of crisis mortality, the long-term population growth in the traditional period seems not to have been much different from [that] in India and China, which suggests the smallness of the original or early populations." The author notes that new communities were formed by the separation of settlements in frontier regions and that these patterns continued into the middle of the nineteenth century. The traditional order seems to have broken down in the late nineteenth century as a result of the combined pressures of colonialism and population increase. (summary in ENG)