ISOLATED ADRENOCORTICOTROPIC HORMONE (ACTH) DEFICIENCY

The case to be reported is that of a 72-year-old woman with isolated adrenocorticotropic hormone (ACTH) deficiency, who complained of anorexia and generalized malaise. The secretions of human growth hormone(HGH), prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) were all within normal limit. In spite of the extremely low level of Cortisol, the plasma level of AGTH would not rise sufficiently, but a marked response of Cortisol to AGTH stimulation was recognizaed. The postmortem examination revealed a decrease In basophilic or PAS-positive cells of the anterior pituitary gland which also showed a selective loss of AGTH-secreting cells over immunohistochemical study. Electron microscope could easily visualize somatotroph, mammotroph, thyrotroph, FSH- and LH-gonadtroph, but corticotroph was difficult to be discerned. Adrenocortical cells demonstrated atrophy and degeneration, for which the zona fasciculata and zona reticularis were narrowed. The zona glomerulosa was slightly enlarged In width.     

Adjuvant Activity of 6-Amino-6-Deoxy-Muramyldipeptides and Their Acylamino Derivatives on the Induction of Delayed Hypersensitivity to Azobenzenearsonate-N-Acetyl-l-Tyrosine in Guinea Pigs

The 6-amino-6-deoxy-N-acetylmuramyldipeptides and their 6-acylamino derivatives were shown to be active as adjuvants on the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-l-tyrosine in guinea pigs. However, 6-acylamino-6-deoxy-N-(acyl)muramyldipeptides were inactive as adjuvants.     

Lectin histochemical study on the olfactory organ of the newt,Cynops pyrrhogaster,revealed heterogeneous mucous environments in a single nasal cavity

Expression patterns of glycoconjugates were examined by lectin histochemistry in the nasal cavity of the Japanese red-bellied newt, Cynops pyrrhogaster. Its nasal cavity consisted of two components, a flattened chamber, which was the main nasal chamber (MNC), and a lateral diverticulum called the lateral nasal sinus (LNS), which communicated medially with the MNC. The MNC was lined with the olfactory epithelium (OE), while the diverticulum constituting the LNS was lined with the vomeronasal epithelium (VNE). Nasal glands were observed beneath the OE but not beneath the VNE. In addition, a secretory epithelium was revealed on the dorsal boundary between the MNC and the LNS, which we refer to as the boundary secretory epithelium (BSE) in this study. The BSE seemed to play an important role in the construction of the mucous composition of the VNE. Among 21 lectins used in this study, DBA, SBA and Jacalin showed different staining patterns between the OE and the VNE. DBA staining showed remarkable differences between the OE and the VNE; there was intense staining in the free border and the supporting cells of the VNE, whereas there was no staining or weak staining in the cells of the OE. SBA and Jacalin showed different stainings in the receptor neurons for the OE and the VNE. Furthermore, UEA-I and Con A showed different stainings for the nasal glands. UEA-I showed intense staining in the BSE and in the nasal glands located in the ventral wall of the MNC (VNG), whereas Con A showed intense staining in the BSE and in the nasal glands located in the dorsal and medial wall of the MNC (DMNG). The DMNG were observed to send their excretory ducts into the OE, whereas no excretory ducts were observed from the VNG to the OE or the VNE. These results suggested that the secretion by the supporting cells as well as the BSE and the DMNG establishes that there are heterogeneous mucous environments in the OE and the VNE, although both epithelia are situated in the same nasal cavity.     

CD69-null mice protected from arthritis induced with anti-type II collagen antibodies

CD69, known as an early activation marker antigen on T and B cells, is also expressed on platelets and activated neutrophils, suggesting certain roles in inflammatory diseases. In order to address the role of CD69 in the pathogenesis of arthritis, we established CD69-null mice. CD69-null mice displayed a markedly attenuated arthritic inflammatory response when injected with anti-type II collagen antibodies. Cell transfer experiments with neutrophils, but not T cells or spleen cells, from wild-type mice into CD69-null mice restored the induction of arthritis. These results indicate a critical role for CD69 in neutrophil function in arthritis induction during the effector phase. Thus, CD69 would be a possible therapeutic target for arthritis in human patients.     

Airway responsiveness and airway remodeling after chronic exposure to procaterol and fenoterol in guinea pigs in vivo

BACKGROUND: Chronic exposure to fenoterol (FEN), a beta(2)-adrenergic receptor (beta(2)-AR) agonist, was shown to induce both airway hyperresponsiveness and airway remodeling in experimental animals. OBJECTIVE: We wanted to know the effects of chronic exposure to procaterol (PRO), a beta(2)-AR agonist, on airway function and structure, because this agent is widely used as a bronchodilator in Japan. For comparison, the effects of FEN were also examined. METHODS: Aerosolized PRO (0.1 or 1 mg/ml), FEN (1 mg/ml) or vehicle (0.9% NaCl) was given to guinea pigs 3 times a day for 6 weeks. Sublaryngeal deposition of these agents was calculated using radioisotopes. At 72 h after the last inhalation of PRO, FEN or vehicle, the dose-response relationship between lung resistance (R(L)) and intravenously administered acetylcholine (ACh) was measured. After measuring R(L), histological changes in noncartilaginous airway dimensions were evaluated. RESULTS: The amount of sublaryngeal deposition of 0.1 mg/ml PRO in the present study was speculated to be 100 times larger than that of therapeutic dose. ACh concentrations causing 2-fold, 10-fold and maximal increases in R(L) were not different in 4 groups tested. In the smaller membranous airways (<0.4 mm in diameter), but not the larger ones, thickening of adventitial areas was significantly greater in animals treated with beta(2)-AR agonists than in control animals (23 and 25, and 96% higher in animals treated with 0.1 and 1 mg/ml PRO or 1 mg/ml FEN, respectively). The degree of the increase was significantly less in PRO-treated animals than in FEN-treated animals (p < 0.01). CONCLUSION: Our results did not provide any evidence that regular inhalation of PRO at the therapeutic dose might induce bronchial hyperresponsiveness. In addition, huge amounts of PRO only caused a mild thickening of the adventitial areas, suggesting that PRO may be a weak inducer of airway remodeling compared with FEN.     

Monocarboxylate transporter 1 (MCT1) plays a direct role in short-chain fatty acids absorption in caprine rumen

Despite the importance of short-chain fatty acids (SCFA) in maintaining the ruminant physiology, the mechanism of SCFA absorption is still not fully studied. The goal of this study was to elucidate the possible involvement of monocarboxylate transporter 1 (MCT1) in the mechanism of SCFA transport in the caprine rumen, and to delineate the precise cellular localization and the level of MCT1 protein along the entire caprine gastrointestinal tract. RT-PCR revealed the presence of mRNA encoding for MCT1 in all regions of the caprine gastrointestinal tract. Quantitative Western blot analysis showed that the level of MCT1 protein was in the order of rumen ≥ reticulum > omasum > caecum > proximal colon > distal colon > abomasum > small intestine. Immunohistochemistry and immunofluorescence confocal analyses revealed widespread immunoreactive positivities for MCT1 in the caprine stomach and large intestine. Amongst the stratified squamous epithelial cells of the forestomach, MCT1 was predominantly expressed on the cell boundaries of the stratum basale and stratum spinosum. Double-immunofluorescence confocal laser-scanning microscopy confirmed the co-localization of MCT1 with its ancillary protein, CD147 in the caprine gastrointestinal tract. In vivo and in vitro functional studies, under the influence of the MCT1 inhibitors, p -chloromercuribenzoate (pCMB) and p -chloromercuribenzoic acid (pCMBA), demonstrated significant inhibitory effect on acetate and propionate transport in the rumen. This study provides evidence, for the first time in ruminants, that MCT1 has a direct role in the transepithelial transport and efflux of the SCFA across the stratum spinosum and stratum basale of the forestomach toward the blood side.     

Incidence and characterization of age related amyloid deposits in the human anterior pituitary gland

Summary To identify amyloid deposits in the anterior pituitary gland, we have immunohistochemical, histochemical and alkaline Congo red staining. The anti-human P component reacted positively with these amyloid deposits, while antisera against prealbumin, AA type amyloid fibril protein and various anterior pituitary hormones were negative. A combination of Congo red and anti-human P component staining was most sensitive and reliable for detection of amyloid in the anterior pituitary glands of 300 randomly autopsied patients. Amyloid deposits increased in parallel with the age of the patients, however, they appeared earlier and more frequently than heretofore reported. Deposition of amyloid was seen initially in the 3rd decade and the positivity rate of amyloid deposits was 73% in the 5th decade. The histochemical characteristics of these pituitary amyloid deposits differed from those of cerebral and systemic deposits, particularly those found in the amyloid of senile systemic amyloidosis.This study was supported in part by a grant from the Fundation for Advancement of Clinical Medicine and Ministry of Health and Welfare of Japan     

Rat strain differences in the early stage of porcine-serum-induced hepatic fibrosis.

Rat strain differences in the early development of porcine serum (PS)-induced hepatic fibrosis were histologically and immunohistochemically examined using Brown Norway (BN), Sprague Dawley (SD) and Wistar rats. They were injected i.p. with 0.5 ml sterile PS twice a week for 4 and 8 weeks. In addition, rats treated with physiological saline in the same way served as controls. At 4 weeks, hepatic fibrosis accompanying fibrous septa mainly composed of type III collagens developed in BN and SD rats but not in Wistar rats. In addition, the numbers of eosinophils, CD3-positive cells and ED-1-positive cells significantly increased in BN and SD rats, that of CD45RA-positive cells in BN rats, and that of alpha-smooth muscle actin (SMA)-positive cells in SD rats, respectively. Such differences in the number of inflammatory cells may be related with the absence of hepatic fibrosis in Wistar rats at 4 weeks. At 8 weeks, hepatic fibrosis with formation of many small-sized pseudolobules was observed in all strains at almost similar degree, and the numbers of infiltrating cells increased in all strains of rats with some exception. In addition, the main location of inflammatory cells was different, suggesting a different role of each inflammatory cell in the process of hepatic fibrosis.     

Microanatomical localization of PD-1 in human tonsils

PD-1 is an immunoinhibitory receptor, which belongs structurally to the CD28 family. PD-1-deficient mice show breakdown of peripheral tolerance and manifest multiple autoimmune symptoms. We previously described expression of PD-1 on activated T and B lymphocytes and myeloid cells. However, little is known about the microanatomical distribution of PD-1 in lymphoid organs. In this study, we performed immunohistochemistry using monoclonal antibodies against human PD-1. In human tonsils, PD-1 was expressed on most of T cells and a small subset of centrocytes in the light zone of germinal centers (GCs), where clonal selection of centrocytes takes place. These results suggest that PD-1 may play an important role in GC reaction.