Responses In Various Organs Research Articles

Organ-dependent responses of Periploca sepium to repeated dehydration and rehydration

Plant responses to water deficit occur in a complex framework of organ interactions, but few studies focus on the effect of drought stress on all organs in a whole-plant. The effects of repeated dehydration and rehydration (DH) on physiological and biochemical responses in various organs of Periploca sepium Bunge ( P. sepium) were investigated. The leaf relative water content decreased significantly during drought, but recovered and showed an increase when compared to well-watered control plants. The malondialdehyde (MDA) content increased in mature and old leaves, but decreased in young leaves, new stems and fine roots during drought, indicating that the young and vigorous tissues of a whole-plant are protected preferentially from the oxidative stress. Among all organs, the fine roots showed the highest levels of proline, total free amino acids (TFAA) and Na +, while the leaves showed the highest levels of total soluble sugars (TSS), soluble proteins (SP), Ca 2+ and Mg 2+. The response to DH differed in different organs, both in magnitude and in the type of solutes involved. Drought stress increased the contents of proline, TFAA, TSS, SP and K + in all organs of P. sepium plants, while the accumulation amounts were obviously different among the organs. The storage starch in stems and roots plays an important role in providing carbohydrates for growth. Changes in Na +, Ca 2+ and Mg 2+ under DH presented a high degree of organ specificity. Our data indicates that response strategies are different between different organs; therefore, evidence the needs to integrate all the information in order to better understand plant tolerance mechanisms.

Cediranib/AZD2171 Inhibits Bone and Brain Metastasis in a Preclinical Model of Advanced Prostate Cancer

Late stage or aggressive cancers exhibit metastatic growth at multiple sites, and the characterization of treatment response in various organs to drugs with potentially wide-ranging efficacy is needed. Tumor cells that induce angiogenesis are a common characteristic of metastatic disease, and clinically, antiangiogenic therapies have shown value in the setting of advanced cancer. However, recent preclinical studies have suggested that exposure to antiangiogenic drugs can increase tumor invasiveness and metastasis, making it important to determine which contexts antiangiogenic therapy is most appropriate. We describe here the effects of cediranib, a receptor tyrosine kinase inhibitor, in a model of advanced prostate cancer metastatic to skeleton and brain. Treatment with cediranib decreased metastatic tumor burden in the brain and bone, decreased cerebral vasogenic edema, and improved survival, despite increasing the invasive histology of brain metastases. Short-duration cediranib treatment given at the time of tumor cell dissemination was sufficient to inhibit the establishment and subsequent growth of bone metastases, although brain metastases were subject to rebound growth after the discontinuation of cediranib. Distinct growth patterns at different organ sites in the same animal showed that certain tumor microenvironments such as bone may be most amenable to interventions by anti-vascular endothelial growth factor (VEGF) therapies. In addition, anti-VEGF treatment may be of utility in decreasing the rapid growth of solid brain metastases and vasogenic edema in patients with advanced cancer, leading to reduced morbidity and associated clinical benefit.

Experimental Evaluation of Whole Body Vibration Exposure from Tracked Excavators with Hydraulic Breaker Attachment in Rock Breaking Operations

Ever expanding technological growth has led to an increase in the use of tracked excavators for construction, demolition, material handling, rock breaking etc. Excavator operators are exposed to a variety of risk factors that may lead to health problems. A major health hazard among operators is whole-body vibration. Human response to vibration is very complex and nonlinear. Whole Body Vibration in the range of 2 to 30 Hz corresponds to most of the resonant responses of various organs and parts of the human body. The objective of this paper is to assess whole body vibration for the tracked excavator with hydraulic breaker. The job safety analysis conducted through questionnaires for different industrial vehicle operators revealed the presence of a health risk among the operators in rock breaking machinery. To quantify the level of vibration, field tests are performed on four tracked excavators with hydraulic breaker attachments in two different work locations. Accelerometer, a real-time signal conditioning / processing and PULSE data acquisition software are used for vibration measurement. The frequency of vibration exposure is observed to be between 6.8 and 12 Hz. Acceleration levels measured were in the range of 0.87 −2.2 m/s2 for a tracked excavator operator with breaker. The total vibration exposure calculated was between 0.621 and 1.932 m/s2. The vibration dose value recorded was 17.6 −62.72 m/s1.75. Whole body vibration exposure of the breaker operator was much higher and lies beyond the upper limit as given in ISO 2631–1. The ranges of vibration parameters measured were concomitant with frequent lower back pain, other muscular-skeletal injuries like leg pain etc which are prevalent among these operators.

Targeting Interleukin-21 in Immune-Mediated Pathologies

Interleukin (IL)-21, a cytokine mostly produced by activated CD4+ T cells, has been reported to play an important role in the tissue-damaging immune response in various organs. This pathogenic effect is strictly linked to the ability of IL-21 to control the functional activities of multiple immune and non-immune cells. For instance, IL-21 regulates the differentiation and function of effector CD4+ T helper cells; controls activation, proliferation, and survival of B cells and enhances the cytotoxic activity of CD8+ T cells and NK cells. IL-21 also inhibits the differentiation of inducible regulatory T cells (Tregs) and makes effector CD4+ T cells resistant to the Tregs-mediated immunesuppression. Additionally, IL-21 stimulates epithelial cells and fibroblasts to make chemokines and extracellular matrix proteases, respectively. Consistently, studies from various laboratories have documented the beneficial effect of IL-21 neutralization on the progression of inflammatory diseases in mice. Here we review the present knowledge on the expression and role of IL-21 in immune-mediated pathologies.

The microRNA miR-696 regulates PGC-1α in mouse skeletal muscle in response to physical activity

MicroRNAs (miRNAs) are small noncoding RNAs involved in posttranscriptional gene regulation that have been shown to be involved in growth, development, function, and stress responses of various organs. The purpose of this study was to identify the miRNA response to physical activity, which was related to functions such as nutrient metabolism, although the miRNAs involved are currently unknown. C57BL/6 mice were divided into exercise and control groups. The exercise group performed running exercise, with a gradual increase of the load over 4 wk. On the other hand, to examine the effect of muscle inactivity, the unilateral hindlimbs of other mice were fixed in a cast for 5 days. Microarray analysis for miRNA in gastrocnemius revealed that miR-696 was markedly affected by both exercise and immobilization, showing opposite responses to these two interventions. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), which was increased by exercise and decreased by immobilization in the protein level, was predicted as a target regulated by miR-696. In cultured myocytes, intracellular miR-696 variation led to negative regulation of PGC-1alpha protein along with the expression of mRNAs for downstream genes. In addition, we found decreases in the biogenesis of mitochondria and fatty acid oxidation in miR-696-overexpressing myocytes compared with normal control myocytes. These observations demonstrate that miR-696 is a physical activity-dependent miRNA involved in the translational regulation of PGC-1alpha and skeletal muscle metabolism in mice.

The lymphatic system controls intestinal inflammation and inflammation-associated colon cancer through the chemokine decoy receptor D6

Background and aimsInflammatory CC chemokines have long been associated with cancer, but unequivocal evidence of a role in clinically relevant models of carcinogenesis is lacking. D6, a promiscuous decoy receptor...

Enhanced induction of a histamine-forming enzyme, histidine decarboxylase, in mice primed with NOD1 or NOD2 ligand in response to various Toll-like receptor agonists

We investigated the immunopharmacological aspects of innate immune responses via Toll-like receptors (TLRs), NOD1 and NOD2, in terms of induction of the histamine-forming enzyme, histidine decarboxylase (HDC), activity in mice. Intravenous injection of TLR4-agonistic synthetic lipid A definitely induced HDC activity in the liver, spleen, and lungs, especially the lungs, in mice, where maximum activity was induced about 3 h after the injection of lipid A. The TLR2/6 agonistic synthetic diacyl-type lipopeptide FSL-1 and TLR3-agonistic poly I:C were also effective in inducing HDC, while the NOD2-agonistic synthetic muramyldipeptide (MDP) and NOD1-agonistic synthetic FK156 and FK565 exhibited only weak activities in this respect. Mice primed with intravenous injection of NOD1 or NOD2 agonists produced higher HDC activity following the 4-6 h later intravenous challenge with the above TLR agonists. Among the priming agents, FK565 exhibited the strongest activity, and it was effective via various administration routes - intraperitoneal, subcutaneous, intramuscular, as well as intravenous injection; furthermore, oral (gastric) administration was effective, although it needed a dose 10 times higher than that required for other administration routes. These findings suggest that HDC is induced in association with TLRs and NOD1/2, and that the newly formed histamine by the induced HDC might play important roles in the regulation of inflammatory and immune responses in various organs.

MicroRNAs: novel regulators in cardiac development and disease

MicroRNAs (miRNAs) are endogenous, small ribonucleotides regulating the translation of target messenger RNAs that have been shown to be involved in orchestrating growth, development, function, and stress responses of various organs, including the heart. Muscle miRNAs are mainly controlled by a network of myogenic transcription factors, and throughout cardiac development they fine-tune regulatory protein levels in a spatiotemporal manner. Recent profiling studies revealed that miRNA expression patterns are derailed in both human cardiac disease and animal models of cardiac hypertrophy and failure. Modulation of miRNA expression in vitro as well as in vivo has revealed an important role of miRNAs in regulating heart function, particularly cardiac growth and conductance. Here, we overview the recent findings on miRNAs in cardiac development and disease and report the latest advances in the identification and validation of miRNA targets, which are important for a comprehensive understanding of cardiac miRNA function. Finally, we focus on the development and use of miRNA antagonists (antagomirs) to target miRNAs in vivo, which may translate into novel therapeutic strategies for heart disease in the future.

Organ-dependent responses of the african rice to short-term iron toxicity: Ferritin regulation and antioxidative responses

Hydroponically grown African rice (Oryza glaberrima) was exposed for 72 h to a high Fe2+ concentration (500 mg dm(-3)) to identify the first steps of iron toxicity response in various organs. Iron accumulated in all plant parts analysed and had only a limited impact on absorption and translocation of other nutrients. The content of the iron-storage protein ferritin increased as a consequence of transcription stimulation or increase in mRNA stability and culminated after 48 h of treatment in laminae and to a lesser extent in sheaths but was not detected in roots. Although endogenous iron concentrations were similar in sheaths and laminae, superoxide dismutase activity was stimulated only in sheaths while ascorbate peroxidase activity increased mainly in laminae. It is concluded that both ferritin synthesis and antioxidative response may play a key role in the resistance of Oryza glaberrima to iron toxicity but that their relative importance are not the same in all organs.

Sequential Periods of Preconditioning Decrease Laparoscopy-Related Elevations in Hepatic TNF-α and IL-6 Levels in Rats

Laparoscopy induces an ischemia/reperfusion (I/R) injury that elicits the production of inflammatory cytokines. The aim of this study was to test whether laparoscopic preconditioning (LP) could change hepatic inflammatory response. Twenty-four male Spraque Dawley rats were assigned into one of three experimental groups: the control group (C) was subjected to sham operation; the I/R group was subjected to 60 minutes of pneumoperitoneum followed by 45 minutes of desufflation; and the ischemic preconditioning (IP) group was subjected to preconditioning prior to the induction of I/R. Preconditioning was defined as two cycles of 5 minutes of pneumoperitoneum followed immediately by 5 minutes of desufflation. Hepatic tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 levels were evaluated as an inflammatory response. Hepatic TNF-alpha levels increased in the I/R group compared with the C group (9.64 +/- 0.77 pg/mg protein vs. 6.53 +/- 0.48 pg/mg protein, P < 0.01). The decreased TNF-alpha levels in the IP group were not statistically significant when compared to the I/R group (8.09 +/- 0.74 pg/mg protein). Hepatic IL-6 levels increased in the I/R group compared to the C group (4.17 +/- 0.31 pg/mg protein vs. 2.93 +/- 0.20 pg/mg, P < 0.05). IP reduced the hepatic IL-6 levels significantly compared to the I/R group (3.31 +/- 0.22 pg/mg protein vs. 4.17 +/- 0.31 pg/mg protein, P <0.05). Laparoscopy induces cytokine response in various organs including the liver. LP could alter the production of cytokines prior to sustained laparoscopic procedures. Preconditioning may be advisable, especially for elderly or other patients with hepatic, renal, or cardiac dysfunction. Further studies are needed to adapt this concept to clinical settings.

Up-Regulation of Endothelial Nitric Oxide Synthase Inhibits Pulmonary Leukocyte Migration Following Lung Ischemia-Reperfusion in Mice

Endogenous nitric oxide (NO) is known to modulate post-ischemic inflammatory response in various organs. However, the role of nitric oxide synthase isoforms (NOS) in mediating pulmonary post-ischemic inflammatory response is poorly understood. We therefore studied post-ischemic endothelial adhesion molecule expression and leukocyte migration in endothelial NOS knockout (eNOS-KO) mice subjected to pulmonary ischemia and reperfusion in vivo. Under anesthesia and mechanical ventilation, the left pulmonary hilum in wild-type (WT) and eNOS-KO mice was clamped for 1 hour, followed by reperfusion for up to 24 hours. In WT mice, we observed a selective up-regulation of both eNOS mRNA and protein in lung tissue, while inducible NOS (iNOS) and neuronal NOS (nNOS) remained unchanged. Survival in eNOS-KO mice was reduced due to severe pulmonary edema, underlining an increased susceptibility to ischemia-reperfusion (I/R) injury. Interstitial tissue infiltration by CD18- and CD11a-positive white blood cells as well as lung tissue water content peaked at 5 hours of reperfusion and were found significantly higher than in WT mice. Enhanced leukocyte-endothelial interaction was associated with pronounced up-regulation of vascular cell adhesion molecule (VCAM) in eNOS-KO mice during post-ischemic reperfusion. We conclude that eNOS attenuates post-ischemic inflammatory injury to the lung most probably via inhibition of endothelial adhesion molecule expression.

β1/β2-Adrenergic Receptor Heterodimerization Regulates β2-Adrenergic Receptor Internalization and ERK Signaling Efficacy

Beta(1)- and beta(2)-adrenergic receptors (beta(1)AR and beta(2)AR) are co-expressed in numerous tissues where they play a central role in the responses of various organs to sympathetic stimulation. Although the two receptor subtypes share some signaling pathways, each has been shown to have specific signaling and regulatory properties. Given the recent recognition that many G protein-coupled receptors can form homo- and heterodimers, the present study was undertaken to determine whether the beta(1)AR and beta(2)AR can form dimers in cells and, if so, to investigate the potential functional consequences of such heterodimerization. Using co-immunoprecipitation and bioluminescence resonance energy transfer, we show that beta(1)AR and beta(2)AR can form heterodimers in HEK 293 cells co-expressing the two receptors. Functionally, beta-adrenergic stimulated adenylyl cyclase activity was found to be identical in cells expressing beta(1)AR, beta(2)AR, or both receptors at similar levels, indicating that heterodimerization did not affect this signaling pathway. When considering ERK1/2 MAPK activity, a significant agonist-promoted activation was detected in beta(2)AR- but not beta(1)AR-expressing cells. Similarly to what was observed in cells expressing the beta(1)AR alone, no beta-adrenergic stimulated ERK1/2 phosphorylation was observed in cells co-expressing the two receptors. A similar inhibition of agonist-promoted internalization of the beta(2)AR was observed upon co-expression of the beta(1)AR, which by itself internalized to a lesser extent. Taken together, our data suggest that heterodimerization between beta(1)AR and beta(2)AR inhibits the agonist-promoted internalization of the beta(2)AR and its ability to activate the ERK1/2 MAPK signaling pathway.

Neonatal exposure to antigen primes the immune system to develop responses in various lymphoid organs and promotes bystander regulation of diverse T cell specificities.

Neonatal exposure to Ag has always been considered suppressive for immunity. Recent investigations, however, indicated that the neonatal immune system could be guided to develop immunity. For instance, delivery of a proteolipid protein (PLP) peptide on Ig boosts the neonatal immune system to develop responses upon challenge with the PLP peptide later. Accordingly, mice given Ig-PLP at birth and challenged with the PLP peptide as adults developed proliferative T cells in the lymph node that produced IL-4 instead of the usual Th1 cytokines. However, the spleen was unresponsive unless IL-12 was provided. Herein, we wished to determine whether such a neonatal response is intrinsic to the PLP peptide or could develop with an unrelated myelin peptide as well as whether the T cell deviation is able to confer resistance to autoimmunity involving diverse T cell specificities. Accordingly, the amino acid sequence 87-99 of myelin basic protein was expressed on the same Ig backbone, and the resulting Ig-myelin basic protein chimera was tested for induction of neonatal immunity and protection against experimental allergic encephalomyelitis. Surprisingly, the results indicated that immunity developed in the lymph node and spleen, with deviation of T cells occurring in both organs. More striking, the splenic T cells produced IL-10 in addition to IL-4, providing an environment that facilitated bystander deviation of responses to unrelated epitopes and promoted protection against experimental allergic encephalomyelitis involving diverse T cell specificities. Thus, neonatal exposure to Ag can prime responses in various organs and sustain regulatory functions effective against diverse autoreactive T cells.

Systemic and mucosal immune responses in mice after mucosal immunization with group B streptococcus type III capsular polysaccharide-cholera toxin B subunit conjugate vaccine.

Group B streptococci (GBS) colonize the female genital and rectal tracts and can cause invasive infection in susceptible newborns. An optimally effective GBS vaccine should induce mucosal and systemic immunity. In this study, we investigate the local and systemic immune responses to GBS type III capsular polysaccharide (CPS) after mucosal vaccination of mice via intranasal, peroral, rectal, and vaginal routes, with GBS type III CPS conjugated with recombinant cholera toxin B subunit (GBS III CPS-rCTB). Cholera toxin (CT) was added as an adjuvant. Immunoglobulin G (IgG) and IgA antibodies to the CPS were tested in serum, lungs, and intestinal, rectal, and vaginal extracts by enzyme-linked immunosorbent assay. The conjugated CPS administered by intranasal, peroral, rectal, and vaginal routes was much more effective at inducing both mucosal and systemic antibody responses to GBS III CPS than was unconjugated CPS. The CPS-specific immune responses in various organs were dependent on the route of immunization. Generally, the highest levels of IgA and IgG were generated in the regions or sites of the conjugate exposure. Thus, intranasal vaccination elicited the highest anti-CPS IgA and IgG antibody levels in the lungs, whereas peroral administration in the intestinal site and vaginal vaccination elicited the highest antibody levels in the vagina. Rectal vaccination was superior to the other routes in inducing high antibody levels in the rectum. The four routes of mucosal vaccination also induced distant antibody responses to CPS. Rectal vaccination induced high specific IgA levels in the vagina and intestine, and oral administration induced high specific IgA levels in the lungs and rectum. All four routes of vaccination with the conjugate elicited similarly high levels of anti-CPS IgG in serum. Intranasal vaccination with different doses of the conjugate (10, 30, and 80 microg of CPS) did not have a significant influence on the anti-CPS specific antibody responses. Intranasal immunization induced better antibody responses when one dose of the conjugate was divided and given on three consecutive days compared to administration of the full dose on one occasion. In conclusion, rectal and vaginal vaccination may be the best way of stimulating anti-CPS immune responses in the rectal and vaginal tracts, while high levels of anti-CPS antibodies in the lungs can be achieved after intranasal administration. The vaccination regimen thus might influence the mucosal immune response to CPS. This conjugate may serve as an effective mucosal vaccine for preventing mucosal colonization and invasive infection caused by GBS.

Serum levels of basic fibroblast growth factor and vascular endothelial growth factor in children and adolescents with type 1 diabetes mellitus.

Diabetes mellitus is characterized by microangiopathy and increased angiogenic response in various organs. Basic fibroblast growth factor (bFGF) as well as vascular endothelial growth factor (VEGF) are both angiogenic and are involved in vascular endothelial cell growth. The purpose of this study was to determine serum levels of bFGF and VEGF, in children and adolescents (youngsters) with type 1 diabetes mellitus, and correlate them with parameters reflecting the severity of the disease. Forty diabetic youngsters without clinical evidence of complications were compared with 30 healthy control subjects (mean age +/- SD, 14.3 +/- 3.6 and 13.8 +/- 3.6 y, respectively). Diabetes duration and metabolic control (expressed by glycosylated Hb) were (mean +/- SD) 6.2 +/- 3.8 y and 9.6 +/- 1.8%, respectively. bFGF and VEGF (pg/mL) were measured in serum samples by enzyme immunoassays, and both were not significantly different between the type 1 diabetes mellitus and the control group (p = 0.952 and p = 0.559, respectively). Restricting the analysis to the type 1 diabetes mellitus group, neither the duration nor the metabolic control of the disease showed any correlation with bFGF and VEGF serum levels, whereas a significantly positive correlation was found between the two examined angiogenic factors both in the diabetic (r = 0.3464, p = 0.025) and the control group (r = 0.4619, p = 0.0013). In conclusion, serum levels of bFGF and VEGF were not found to vary significantly in diabetic youngsters in relation to controls and had no correlation with the duration and metabolic control of the disease. Nevertheless, a positive correlation was found between these two angiogenic factors both in the type 1 diabetes mellitus and the control group.

Extension-growth responses and expression of flavonoid biosynthesis genes in the Arabidopsis hy4 mutant.

The hy4 mutant of Arabidopsis thaliana (L.) Heynh. was previously shown to be impaired in the suppression of hypocotyl extension specifically by blue light. We report here that hy4 is altered in a range of blue-light-mediated extension-growth responses in various organs in seedlings and mature plants: it shows greater length of bolted stems, increased petiole extension and increased leaf width and area in blue light compared to the wild type. The hy4 mutant shows decreased cotyledon expansion in both red and blue light compared to the wild type. Anthocyanin formation and the expression of several flavonoid biosynthesis genes is stimulated by blue light in the wild type but to a much lower extent in hy4. The results indicate that the HY4 gene product is concerned with the perception of blue light in a range of extension-growth and gene-expression responses in Arabidopsis.

Formoguanamine-induced blindness and photoperiodic responses in the Japanese quail,Coturnix coturnix japonica

We administered a blindness-inducing substance (formoguanamine hydrochloride) to Japanese quail in order to find whether it is effective to induce retinal degeneration in avian species other than the chicken. We also investigated its effects on the photoperiodic response of various organs including gonads and the entrainment of circadian locomotor activity rhythms. Histological observation revealed conspicuous degeneration of the photo-receptor outer segments and pigment epithelium. Behavioural responses of formoguanamine hydrochloride-treated birds to visual stimuli were completely abolished. These results proved that this chemical substance is effective to induce blindness in avian species other than the chicken. In formoguanamine hydrochloride-treated birds, the locomotor activity rhythm was entrained to light-dark cycles and the photoperiodic gonadal response was almost normal, suggesting that the extraretinal photoreceptors remained intact even after the formoguanamine hydrochloride-treatment.

The Genitourinary Spheroidal Membrane: An Experimental Study of a new Percutaneously Inserted Prosthetic Device for the Control of Urinary Incontinence

The genitourinary spheroidal membrane, composed of silicone rubber, has been developed along with a mechanical delivery instrument that allows transcutaneous insertion of the prosthetic sphere in the periurethral tissues to enhance outlet resistance in incontinent patients. An experimental study was undertaken in six female mongrel dogs to evaluate the safety and efficacy of this concept. The leak-point pressure increased from five to 38cm. H2O (mean increase, 16.8cm. H2O). This increase is statistically significant (p < 0.024, two-sided t test). During the 90-day experiment, there was no migration of the spheres, minimal local inflammatory response, and no granuloma formation or inflammatory response in various organs studied. Although the leak-point pressure was increased in all of the dogs, none developed difficulty voiding. We conclude that the design concept is sound and safe, the delivery system is reliable, and it is possible to place the spheroidal membrane into an anatomic location that will increase outlet resistance.

Morphological and enzymatic heterogeneity of suramin-induced lysosomal storage disease in some tissues of mice and rats

Suramin-induced lysosomal storage disease reproduced in the rat was extended to the mouse with the attempt to characterize enzymatically and morphologically heterogeneous responses of various organs to the drug. Suramin administration strikingly decreased (3–6 days afterward) the activity of β-glucuronidase in all tissues studied (kidney, liver, heart, and skeletal muscle). The enzymatic responses were small in the activities of β- N-acetyl-glucosaminidase. The activity of arylsulfatase A decreased to a varying degree in mouse tissues, but in rats the activity increased in liver and skeletal muscle. The activity of cathepsin D increased in rat tissues. Suramin induced morphological changes characteristic to lysosomal storage diseases in kidney and liver but not in heart and skeletal muscle of both mice and rats. Kidney was appreciably more susceptible to suramin than liver. The occurrence of lysosomal accumulations, membranous lamellar inclusions, and granular material were most prominent in tubular cells of kidney and in Kupffer cells of liver. These cells also presented intensive Alcian blue staining. Interestingly, the enzymatic and morphological responses did not corelate with each other, which may reflect differences in the regulation of lysosomal functions in various cell types.

Systemic Expression of Cutaneous Basophil Hypersensitivity

Guinea pigs primed for cutaneous basophil hypersensitivity (CBH) with several soluble proteins or with sheep erythrocytes developed a systemic, delayed-onset, maculopapular rash when challenged parenterally with specific antigen. The rash was most readily induced 5 to 7 days after immunization, at a time when local CBH skin test reactivity was also optimal. Miscroscopically, the rash resembled local CBH skin test reactions, being comprised of a papillary dermal infiltrate of basophils and lymphocytes and a striking dilatation and compaction of superficial venules. In addition to the systemic rash, animals expressing systemic CBH (SCBH) exhibited a striking eosinophilia at 24 hr which gave way to basophilia at 48 hr. Focal collections of eosinophils, and of smaller numbers of basophils, were found in the lungs and spleen; both eosinophils and basophils infiltrated the medulla of the thymus. Thus, basophil-rich infiltrations are favored in the skin even after systemic challenge with antigen and occur only to a much smaller extent in other organs where eosinophils may predominate. These differences in the response of various organs to challenge with parenteral antigen suggest that as yet unidentified local factors play a determinative role in regulating the inflammatory response. The pathogenesis of SCBH is not yet established, but it shares many of the properties of local CBH: histology, carrier specificity, development early after sensitization in the absence of detectable antibodies. Passive transfer has not been accomplished with serum alone but has been achieved irregularly with cells plus serum. SCBH may serve as a useful model for several disease states in man characterized by a systemic rash and eosinophilia, including certain types of drug reaction.