Systemic lupus erythematosus complicating autoimmune pulmonary alveolar proteinosis that was worsened by immunosuppressive therapy.

A 26-year-old Japanese woman developed autoimmune pulmonary alveolar proteinosis (PAP) during glucocorticoid therapy for systemic lupus erythematosus (SLE). Intensive immunosuppressive therapy worsened the PAP. De-escalation of immunosuppressive therapy improved the PAP. Autoimmune PAP is rarely associated with systemic autoimmune diseases, and the present case is the first case of autoimmune PAP associated with SLE. Moreover, the present case suggests that immunosuppressive therapy should be avoided or used carefully for the treatment of patients with anti-GM-CSF antibody, such as those with autoimmune PAP.

Subacute sarcoid myositis with ocular muscle involvement; a case report and review of the literature.

Sarcoidosis is a chronic granulomatous disease that can affect multiple organs. The lungs, eyes, and skin are known to be highly affected organs in sarcoidosis. There have been reports based on random muscle biopsy that 32-80% of systemic sarcoidosis comprises noncaseating granulomas; however, muscle involvement in sarcoidosis is generally asymptomatic and has an unknown frequency. We describe a case of acute to subacute sarcoid myositis of the skeletal and extraocular muscles. Typical ophthalmic involvement (manifested by infiltration of the ocular adnexa, intraocular inflammation, or infiltration of the retrobulbar visual pathways) and extraocular sarcoid myositis (as with the present case) is infrequently reported. It is important to keep in mind the rare yet perhaps underestimated entity of sarcoid myositis, and to utilize muscle biopsy and imaging tests for appropriate diagnosis and management of patients with sarcoidosis.

Insulin stimulates the expression of basic fibroblast growth factor in rat brown adipocyte primary culture.

The effect of insulin on the hyperplasia of brown adipose tissue (BAT) was investigated using the primary culture of rat brown adipocyte precursor cells (RBAC). Results showed insulin to significantly increase the number of RBAC, but not bovine capillary endothelial cells, in the presence of fetal bovine serum. Insulin also increased the expression of basic fibroblast growth factor (bFGF) mRNA and the related protein in the primary culture of RBAC. In addition, insulin enhanced the capillary growth in an in vitro angiogenesis model in which microvascular fragments and RBAC isolated from rat BAT were grown in coculture. The level of bFGF-related protein in the coculture was higher in the presence of insulin than in the absence of insulin. These findings suggest that insulin may play an important role in the proliferation as well as in the differentiation of brown adipocytes, with resulting hyperplasia of BAT (including the formation of new capillaries) through increased production of bFGF in brown adipocytes.

Relationship between cold tolerance and generation of suppressor macrophages during acute cold stress.

Acute cold stress induces suppressor macrophages expressing large numbers of receptors to the crystallizable fragment (Fc) portion of immunoglobulin G (MAC-1+ FcgammaRII/IIIbright cells), resulting in the immunosuppression of splenocyte mitogenesis. The generation of MAC-1+ FcgammaRII/IIIbright cells is mediated by the action of glucocorticoids (GCs) through the GC-receptor. In the present study, the generation of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cells was closely related to the decrease of rectal temperature during 3-day exposure to 5 degrees C. We next investigated the effects of improved cold tolerance on the generation of MAC-1+ FcgammaRII/IIIbright cells during acute cold stress. Mice were adapted to cold by exposure to 5 degrees C for 3 wk (cold-acclimated mice) and then reexposed to 5 degrees C for 3 h (acute cold stress) after living at 25 degrees C for 24 h. The rectal temperature of cold-acclimated mice was not decreased by the acute cold stress. In addition, the proportion of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cell population from cold-acclimated mice was unaffected by the acute cold stress. The cold acclimation significantly attenuated the increases in serum corticosterone levels and the expression of the GC-receptor mRNA on peritoneal exudate cells in response to acute cold stress. These results suggest that the altered GC response to acute cold stress by the improvement of cold tolerance inhibits the generation of suppressor macrophages during acute cold stress.

Immobilization of biocatalysts with poly(vinyl alcohol) supports.

Two polymer materials, poly(vinyl alcohol) (PVA) superfine fibers and photocrosslinkable PVA bearing styrylpyridinium groups, have been developed to immobilize biocatalysts. The former has a large surface consisting of relatively large-size pores and the fibers can immobilize a large amount of biocatalyst on their surface by ionic interaction. The latter entraps many kinds of biocatalysts by cyclodimerization caused by visible light irradiation. The biocatalysts on/in these supports maintain high activity and thermal stability. These materials can easily be formed into various shapes suitable for various applications. A new bioreactor system was constructed for evaluating a variety of biocatalysts and supports.

Exocytosis: the common release mechanism of secretory granules in glandular cells, neurosecretory cells, neurons and paraneurons.

Exocytotic granule release in glandular cells (exocrine and endocrine), neurosecretory cells, neurons and paraneurons was discussed. Attention was focused on the neurosecretory terminals in the mammalian posterior pituitary gland and adrenomedullary cells. The concept of "exocytosis-vesiculation sequence" proposed by Douglas and Nagasawa was introduced. This theory states that the exocytotic release of secretory granules was followed by the mechanism of granule membrane recovery; this process occurred at the bottom of the exocytotic pit in the form of coated microvesicles. Experimental results were presented which substantiated the theory for the transformation of coated microvesicles into smooth microvesicles. The origin and the nature of long enigmatic "synaptic vesicles" in the posterior pituitary gland was thus explained. The exocytotic release probably operates as the general and perhaps sole mechanism of granule release in a variety of glandular cells, neurosecretory cells, neurons and paraneurons.

Immunosorbent consisting of DNA immobilized on oxirane-activated sepharose.

The preparation of adsorbents for DNA antibodies is described. The degree of immobilization of native DNA on Sepharoses activated with epichlorohydrin or bisoxirane was investigated as a function of pH, temperature, time, concentration of DNA, and oxirane content in the supports. The maximum amount of DNA bound was obtained after 8 h at 40-50 degrees C at pH 11-11.5. The amount bound was increased by raising either the concentration of DNA or the oxirane content of the supports, and could reach 300 mg/g dry support. The immobilized DNA was applied to the adsorption of DNA antibodies using either commercial human serum with anti-native DNA activity or the sera of patients with systemic lupus erythematosus. The amount of antibody adsorbed depended on the amount of DNA. The thermal stability of the immobilized DNA was also examined. After heating at 80 degrees C, the leakage of DNA was slight and the adsorption of antibodies was not affected.

Immobilization of DNA via covalent linkage for use as immunosorbent.

DNA was immobilized covalently to Sepharose by several methods using epichlorohydrin, cyanogen bromide, carbodiimide, hydroxysuccinimide, carbonyldiimidazole, trichlorotriazine, and diazonium salt. These immobilizing methods were compared from the standpoint of the preparation of immunosorbent for anti-DNA antibodies. Among these methods, that involving epichlorohydrin was the most suitable because of large coupling capacity, stability of bound DNA, and nonadsorption of anti-DNA by the support itself.

Time course of in vivo insulin sensitivity after a single bout of exercise in rats.

After a single bout of treadmill running (20 m.min-1, 1 hour), the time course of the in vivo insulin sensitivity was determined in previously untrained rats. The glucose infusion rate (GIR, mg.kg-1.min-1) as an index of insulin sensitivity was assessed by the euglycemic insulin clamp technique 1 (1h-post-Ex group), 3 (3h-post-Ex), 6 (6h-post-Ex) and 24 hours after exercise (24h-post-Ex), n = 8 in each group. GIRs increased with time from 5.72 +/- 1.02 (1h-post-Ex), to 7.58 +/- 1.07 (3h-post-Ex), 10.31 +/- 1.52 (6h-post-Ex) and 10.23 +/- 1.62 (24h-post-Ex) vs control (5.51 +/- 0.63); the GIR in the 6h-post-Ex and the 24h-post-Ex were significantly higher than those in the control and the 1h-post-Ex groups (p less than 0.05). The rate of increase was equivalent to that observed after long-term training in our previous study. GIR of alpha-adrenergic blockade infused 1 hour after exercise (1h-post-Ex alpha) significantly increased (8.32 +/- 0.96) compared to the control and no exercise alpha-blocker-infused control (C alpha) (p less than 0.05). But no significant difference was shown between 1h-post-Ex and 1h-post-Ex alpha groups. In the beta-blocker-infused group, GIR did not show a significant increase. These results indicate that an increase in the in vivo insulin sensitivity after a single bout of exercise is not evident until 6 hours post-exercise. The delay in the sensitivity might partly be explained by the suppression caused by catecholamines via the alpha-mechanism.

Effect of training and detraining on in vivo insulin sensitivity.

Insulin sensitivity was determined in rats to clarify the effect of detraining at 1 (trained state), 2, 3, and 7 days (7 rats each) and 14 days (n = 8) after five weeks of voluntary training using euglycemic insulin clamp technique. The relationship between basal insulin and glucose shifted towards a decrease in metabolic insulin needs compared to untrained controls (n = 20). During the insulin clamp study, to maintain comparable plasma glucose and insulin levels in all groups, the glucose infusion rate had to be increased significantly (p less than 0.01) to 9.92 +/- 1.12 mg.kg-1.min-1 compared to control group (6.57 +/- 0.57). This improved sensitivity persisted for 2 days after training but was significantly lowered in the 7-days-after group (p less than 0.01). In summary, this study shows that training effect on insulin sensitivity can be determined after voluntary training in rat. This training effect lasted 2 days after training.

Long-lasting effect of training on insulin responsiveness in the rat.

In vivo insulin sensitivity and responsiveness were assessed in rats one day (Day 1), seven days (Day 7), and 3 weeks (Day 21) after cessation of training, using a 2-stage sequential hyperinsulinemic euglycemic clamp technique (insulin infusion rate: 4.4 mU.kg-1.min-1 and 26.4 mU.kg-1.min-1). The day after the last bout of exercise, the glucose infusion rate (GIR-L: 4.4 mU-dose), which is an index of insulin sensitivity, was significantly higher in the trained group (11.5 +/- 1.1 mg.kg-1.min-1) than in the control group (6.1 +/- 0.6 mg.kg-1.min-1; p < 0.01). Detraining decreased GIR-L significantly, to 7.4 +/- 0.5 (Day 7: p < 0.01) and 7.4 +/- 0.5 mg.kg-1.min-1 (Day 21: p < 0.05). Insulin responsiveness, assessed by response to a 26.4 mU-dose of insulin (GIR-H), was also increased by training, from 21.8 +/- 1.2 mg.kg-1.min-1 (control) to 32.9 +/- 1.2 (Day 1, p < 0.01). Seven days after cessation of training period the level was nearly identical (33.4 +/- 1.0 mg.kg-1.min-1) and remained high 3 weeks after training (30.8 +/- 1.0: p < 0.01, vs control). These data indicate that insulin responsiveness remains elevated for 3 weeks after training, although insulin sensitivity is reversed within seven days. These results may be attributed to changes in body composition or long-lasting changes in post-receptor mechanisms.

Determination of transcoronary circulatory transport function.

A method is described to determine the transcoronary circulatory transport function (h(t)) from input (Ci'(t)) and output (Co'(t)) dye-dilution curves obtained at the inlet and outlet of the coronary circulation. Assuming the mathematical linearity and stationarity of the coronary circulation, it is demonstrated that h(t) can be computed in terms of lagged normal density curve as a model from the sole measurement of the first to third moments of Ci'(t) and Co'(t) when recorded by a pair of our dye sampling systems that have shown to have identical response to step function. The method is useful because of its simplicity in practice. The physiological meaning of the determination of h(t) is discussed. It could be helpful to the estimation of the change in coronary path-length distribution under some conditions, although the method is still of limited value at present, because the averaged path-length through the coronary circulation cannot be evaluated correctly.