Different thermal conditions of the extremities affect thermoregulation in clothed man

The effects of different types of clothing on human deep body temperature were studied with six healthy male subjects in a supine posture. Two clothing ensembles were employed for the present study: A covered the whole body area with garments except the face (1.97 clo) and B covered only the trunk and the upper half of the extremities with garments (1.53 clo). The experiment was carried out in a climatic chamber at 55% ± 5% relative humidity under cooling and warming temperatures: the temperature was changed from 22°C to 10°C (cooling) and returned to 22°C again (warming). The major findings were: rectal temperature (T _re) continued to decrease gradually in A throughout the experiment, whereas in B it increased during cooling, and returned to previous levels during warming. As a result, Tre and chest skin temperature were maintained at a higher level in B than in A. Internal tissue conductances were greater in A than in B both during cooling and during warming. Thermal comfort appeared to have been influenced more by the rate of skin temperature change than by the level of skin temperature per se. It was concluded that peripheral vasoconstriction in B induced less heat flow from core to shell, and, thus, the core temperature was maintained at a higher level in B than in A.     

Alteration of gene expression in intervertebral disc degeneration of passive cigarette- smoking rats: separate quantitation in separated nucleus pulposus and annulus fibrosus.

OBJECTIVE: We constructed a passive cigarette-smoking model with rats to investigate the molecular mechanism of intervertebral disc degeneration, and found by gene expression analysis that passive cigarette smoking stimulated the stress-responsive signal pathway and inhibited the apoptotic pathway. In this study, to clarify that these changes were derived from either nucleus pulposus (NP) or annulus fibrosus (AF), we separately collected NP and AF and quantitatively analyzed gene expression. METHODS: Total RNA was extracted from NP and AF of the lumbar intervertebral discs from rats which were kept in a smoking box for 4 and 8 weeks. Gene expression was measured by real-time PCR of cDNA synthesized from the total RNA. RESULTS: Stress-responsive protein, heat shock protein 70, was expressed similarly in NP and AF, and was upregulated to the same degree after 8 weeks of passive cigarette smoking. The protein tyrosine phosphatase gene was expressed more strongly in AF than in NP, and was upregulated after 8 weeks of smoking in both tissue parts. The type II collagen and aggrecan genes were predominantly expressed in AF and NP, respectively. CONCLUSION: These results indicate that passive cigarette smoking stimulates both NP and AF, and induces the stress-responsible genes such as heat shock protein 70 and protein tyrosine phosphatase in both.     

Molecular mechanisms underlying IFN-{gamma}-mediated tumor growth inhibition induced during tumor growth inhibition induced during tumor immunotherapy with rIL-12

The present studnt Investigates the molecular by which IFN-produced as a result of in vitroIL-12 addministration exertsits anty-tumor,rIL-12 was administered three or five times intomice bearing CDA1M fibrosarcoma, OV-HM ovarian carcinoma orMCH-1-A1 fibosarcoma. This regimen induced complete regressionof CSA1M and OV-HM tumors but only transient growth inhibitionof MCH-1-A1 tumors. The anty-tumor effects of Il-12 were associatatedwith enhanced induction of IFN-becouse these effects were abrogatedby pretreatment of hosts with anti-IFN- antibody.Exposure inin vitro of the three types of tumor cells to rIFN- resultedin moderate to potent inhibition of tumor cell growth.IFNstimulatedthe expression of mRNAs for an inducible type of NO synthasa(INOS)in CSA1M cells and indoleamine 2,3-dioxygenasa (IDO),an enzyme capable of degrading tryptophan, in OV-HM cells ,but induced only marginal levels of these mRNAs in MCH-I-ALcells. In association withiNOS gene expression, INF--stimulatedCSA1M cells produced a large amount of NO which functioned toinhibit their own growth in vitro. Although OV-HM and MCH-1-A1cells did not produce NO, they also exhibited NO susceptibility.Whereasthe tumor masses from IL-12-treated CSA1M-bearing mice inducedhigher levels of INOS (for CSA1M) or IDO and iNOS (for OV-HM)mRNAs,the MCH-1-A1 tumor mass expressed lower levels of iNOS mRNAalone.Moreover, massive infiltration of CD4⁺and CD8⁺ T cellsand Mac-1⁺ cells was seen only in the CSA1M and OV-HM tumors.Thus, these results indicate that IFN- produced after IL-12treatment induces the expression of various genes with potentialto modulate tumor cells and growth by acting directly on tumorecells or stimulating tumor-infiltrating lymphold cells and thatthe effectiveness of IL12 therapy is assoiated with the operation if these mechanisms.     

Dedifferentiated adenoid cystic carcinoma: a clinicopathologic study of 6 cases.

Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade "dedifferentiated" carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34-70 y). The mean size of the tumors was 3.5 cm (range, 1.7-6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6-69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immunoreactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of 1 case, which was positive for p53 immunostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma.     

Actin assembly is a crucial factor for superoxide anion generation from adherent human eosinophils

BACKGROUND: Cellular adhesion is crucial for eosinophil effector functions. OBJECTIVE: We sought to elucidate the role of the actin cytoskeleton in cellular adhesion and superoxide anion generation by human eosinophils. METHODS: Eosinophils were stimulated with platelet-activating factor (PAF) or complement component 5a on human serum albumin-coated plates with or without an actin-polymerization inhibitor, cytochalasin B (CB), or cytochalasin D (CD). Superoxide anion generation was measured on the basis of reduction of absorbance associated with cytochrome c.2 Eosinophil adhesion was assessed on the basis of eosinophil protein X content in adherent cells. Transient stimulus-induced increase of intracellular calcium and translocation of protein kinase C (PKC) betaII, PKC delta, PKC zeta, and p47 phagocyte oxidase (a component of nicotinamide adenine dinucleotide phosphate oxidase) were also investigated. RESULTS: CB, CD, or antibodies against CD18 (the beta2 chain of integrin, alphaMbeta2) inhibited stimulus-induced eosinophil superoxide anion generation. Stimulus-induced eosinophil adhesion was unaltered by CB, whereas it was significantly suppressed by CD or anti-CD18 antibodies. Transient PAF-induced intracellular calcium increase was also unaffected by CB or CD, but stimulus-induced eosinophil shape changes and translocation of PKCs and p47 phagocyte oxidase to the cell membrane region were completely inhibited by CB. PAF-induced eosinophil degranulation was inhibited by CB, CD, or anti-CD18 antibodies, whereas complement component 5-induced degranulation was not suppressed by CB. CONCLUSION: By itself, beta2 integrin-dependent cellular adhesion is not sufficient for promoting eosinophil effector function. Adequate actin assembly is required for eosinophil adhesion and also for full superoxide anion generation in eosinophils.     

Expression of CD10 by stromal cells during colorectal tumor development

CD10 is a cell surface metalloprotease expressed by a variety of normal cell types, including lymphoid precursor cells, germinal center B lymphocytes, and some epithelial cells. We noticed that stromal cells of some cancers are positive for CD10. In this study, we investigated the role of CD10 produced by the stromal cells of colorectal neoplasms in the progression of colorectal neoplasms. Immunohistochemical examination of CD10 and p53 was performed in 169 colorectal epithelial neoplasms representing various stages of carcinogenesis. The results were correlated with the morphologic characteristics of the neoplasms. There was no expression of CD10 in the stromal cells of normal colorectal tissue. CD10-positive stromal cells were present adjacent to the tumor cells in 16 of 73 adenomas with mild or moderate dysplasia. More frequent expression of CD10 by the stromal cells was detected in adenomas with severe dysplasia (12 of 17), intramucosal carcinomas (10 of 16), and invasive carcinomas (50 of 63) than in adenomas with mild or moderate dysplasia (P < 0.0001). Expression of CD10 by > 10% of the stromal cells was detected only within the area of the invasive growth front of invasive carcinomas, not in adenomas and in only 1 of the intramucosal carcinomas. The difference between invasive and non invasive tumors was significant (P < 0.0001). The stromal expression of CD10 was significantly associated with the accumulation of p53 and a larger tumor size. These results indicate that CD10 expression is an integral part of colorectal carcinogenesis. CD10 expression seems to contribute to the invasion and thus probably facilitates metastasis.     

Nuclear accumulation of beta-catenin in intestinal-type gastric carcinoma: correlation with early tumor invasion

Mutation of the adenomatous polyposis coli gene, which is known to be an early event in the carcinogenesis of intestinal-type gastric carcinoma, leads to accumulation of beta-catenin. In addition, beta-catenin has been found to activate down stream signaling molecules in the wingless/Wnt pathway. In this study, the clinical significance of nuclear accumulation of beta-catenin was evaluated in gastric carcinoma. Immunohistochemical staining showed nuclear localization in 16 (12%) of 139 (94 intestinal-type and 45 diffuse-type) gastric carcinomas, and all 16 lesions with nuclear staining were intestinal-type adenocarcinomas. Of the 16 cases, 15 were in the early clinical stage. In the remaining case, the lesion had invaded the subserosal layer and showed strong nuclear staining at the invasive front. In 14 of the 16 cases with nuclear localization, there were no abnormal mobility shifts detected using polymerase chain reaction-single strand conformational polymorphism analysis. This was confirmed using direct sequencing analysis, which revealed the wild-type sequence in the 12 cases tested. Nuclear accumulation of beta-catenin did not correlate with lymph node metastasis or 5-year survival. These findings suggest that high intranuclear levels of beta-catenin protein play an important role in early tumor growth and may function in initiation of invasive processes in intestinal-type gastric carcinoma.     

α2-Macroglobulin secretion enhanced in rat hepatocytes by partially characterized factor from Kupffer cells

Isolated rat Kupffer cells produced a factor which stimulated the synthesis of ₂-macroglobulin (2M) in primary cultured rat hepatocytes. Although Kupffer cells placed in culture produced the factor without stimulation by lipopolysaccharide (LPS), the LPS-stimulated cells produced larger amounts of the factor. On the other hand, the production of the factor was inhibited by addition of actinomycin D. The induction of2M synthesis by cultured hepatocytes was enhanced in the presence of dexamethasone (Dex), in that hepatic synthesis of2M increased by addition of the factor alone and with Dex 1.5 and three- to four-fold, respectively. The factor was nondialyzable and stable at 60°C for 30 min. When the factor was fractionated using the molecular sieve method, the activity recovered in the fraction had a molecular weight of over 30,000.     

T cell immunity and primary biliary cirrhosis

T lymphocytes play a pivotal role in the autoimmune response in primary biliary cirrhosis (PBC). Recent studies have shown that there is overlapping in the PDC-E2-specific T and B cell epitopes. In addition, helper T and cytotoxic T cell epitopes all contain a shared peptide sequence. In addition, recognition of exogenous antigens including bacterial antigens by autoantigen-specific T cell and the mechanism of molecular mimicry provide a clue to clarifying the pathogenesis of PBC. Furthermore, the findings that autoantigen-immune complexes cross present and also that the presentation of autoantigen is of a higher relative efficiency, define a unique role of autoantibodies in the pathogenesis of the autoimmune disease. The mechanism of immune-mediated bile duct damage in PBC, including the possible role of T cell-mediated cytotoxicity and molecular mimicry is discussed.