The insulin receptor substrate-1-related 4PS substrate but not the interleukin-2R gamma chain is involved in interleukin-13-mediated signal transduction

Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3- dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin- like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL- 13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4R alpha) and lack expression of the IL-2 receptor gamma subunit (IL-2R gamma), resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. These results indicate that IL-13 does not use the IL-2R gamma subunit in its receptor complex and that expression of IL-2R gamma enhances, but is not absolutely required for mediating IL-4-induced tyrosine phosphorylation of IRS-1/4PS.     

Localization of the G-CSF gene on chromosome 17 proximal to the breakpoint in the t(15;17) in acute promyelocytic leukemia

The human granulocyte-colony stimulating factor gene (G-CSF) is localized at 17q11.2-q21, the region of one of the breakpoints in the 15;17 chromosome translocation specific for acute promyelocytic leukemia (APL). As G-CSF induces differentiation and loss of tumorigenicity in myeloid leukemic cells or cell lines, it was possible that the translocation in APL involved the DNA of the G-CSF coding region or its regulatory region. In situ hybridization to chromosomes with the t(15;17) from patients with the APL translocation using a G- CSF cDNA clone revealed that the coding region of this gene is proximal to the t(15;17) breakpoint on chromosome 17. Southern analysis of DNA from patients with the APL translocation showed no differences in hybridization between normal and leukemic cells. These results indicate that the G-CSF coding sequence is not disrupted by the chromosomal rearrangement characteristic of APL.     

Proteolytic degradation of von Willebrand factor after DDAVP administration in normal individuals

The infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) in normal individuals is followed by an increase in factor VIII/von Willebrand factor (vWF) in plasma, by an increase in intensity of all sizes of multimers, and by the appearance of larger multimers of vWF than those seen in the resting state. Since the larger multimers are rapidly cleared and proteolysis is known to cause disaggregation of large multimers, we evaluated the degree of vWF proteolysis after DDAVP administration. DDAVP was infused into eight normal adult volunteers, and the relative proportions of the intact 225 kilodalton (kDa) subunit and the 189, 176, and 140 kDa vWF fragments were compared before and at different times after DDAVP infusion. The relative proportion of the 176 kDa fragment was increased, whereas that of the other species was decreased, thereby indicating that proteolytic fragmentation had occurred. However, plasmin did not appear to be responsible because the vWF fragments characteristically produced by this enzyme could not be detected. Concomitant analysis of vWF multimeric structure showed that these changes were accompanied by an increase in the relative proportion of the satellite bands, which suggests that they were proteolytically generated. Proteolysis may explain, at least in part, rapid clearance of larger vWF multimers released by DDAVP.     

The human myeloid cell nuclear differentiation antigen gene is one of at least two related interferon-inducible genes located on chromosome 1q that are expressed specifically in hematopoietic cells

We have previously shown that the human myeloid cell nuclear differentiation antigen (MNDA) is expressed at both the antigen and mRNA levels specifically in human monocytes and granulocytes and earlier stage cells in the myeloid lineage. A 200 amino acid region of the MNDA is strikingly similar to a region in the proteins encoded by a family of interferon-inducible mouse genes, designated Ifi-201, Ifi- 202, Ifi-203, etc, that are not regulated in a cell- or tissue-specific fashion. However, a new member of the Ifi-200 gene family, D3, is induced in mouse mononuclear phagocytes but not in fibroblasts by interferon. The same 200 amino acid region, duplicated in the mouse Ifi- 200 gene family, is also repeated in the recently characterized human IFI 16 gene that is constitutively expressed specifically in lymphoid cells and is induced in myeloid cells by interferon gamma. The 1.8-kb MNDA mRNA, which contains an interferon-stimulated response element in the 5' untranslated region, was significantly upregulated in human monocytes exposed to interferon alpha. Characterization of the MNDA gene showed that it is a single-copy gene and localized to human chromosome 1q 21-22 within the large linkage group conserved between mouse and human that contains the Ifi-200 gene family. The IFI 16 gene is also located on human chromosome 1q. Our observations are consistent with the proposal that the MNDA is a member of a cluster of related human interferon-regulated genes, similar to the mouse Ifi-200 gene family. In addition, one mouse gene in the Ifi-200 gene family and the human MNDA and IFI 16 genes show expression and/or regulation restricted to cells of the hematopoietic system, suggesting that these genes participate in blood cell-specific responses to interferons.     

Antibodies to human T-cell leukemia virus type III in hemophiliacs from Spain

We tested serum samples from 50 hemophiliacs from Sevilla, Spain, for antibody to HTLV-III by indirect membrane immunofluorescence (IMI) and radioimmunoprecipitation with SDS polyacrylamide gel electrophoresis (RIP-SDS/PAGE). All had received commercial clotting factors from the United States with the exception of one hemophiliac who had never been transfused. Thirty-four (68%) reacted with HTLV-III-infected cells (H9/HTLV-III) by both methods, but not with the uninfected line (H9). Of 41 hemophilia-A patients tested, 28 (68%) were positive, and of nine hemophilia-B patients, six (66%) were positive. The nontransfused hemophilia-B patient was negative for antibody to HTLV-III by both methods. One patient with clinical AIDS tested positive as did six of seven with chronic unexplained lymphadenopathy. The eight individuals with AIDS or lymphadenopathy all had hemophilia A. We conclude that exposure to HTLV-III is widespread among asymptomatic hemophiliacs in Spain.     

Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias

The t(11;14)(q13;q32) translocation and its molecular counterpart, BCL- 1 rearrangement, are consistent features of intermediate lymphocytic lymphoma (ILL). Rearrangement is thought to deregulate the nearby PRAD- 1/BCL-1 proto-oncogene that is a newly identified member of the cyclin family. To characterize further the association between rearrangement of chromosome 11q13 and over-expression of BCL-1. Southern blot analysis was performed in 33 cases of ILL, 5 cases of t(11;14)- associated leukemias, and 1 case of leukemia carrying a variant translocation t(11;19)(q13;q13) using three separate BCL-1 locus probes. When RNA was available, BCL-1 expression was assessed by Northern blot analysis. DNA from 19 of 33 ILL (57%) showed BCL-1 rearrangement, 16 involving the major translocation cluster (MTC) region and 3 involving a new breakpoint cluster located in the 5' flanking region of the BCL-1 gene. DNA from 3 of 6 t(11q13)-associated leukemias demonstrated a rearrangement involving the MTC. Northern blot analysis showed that BCL-1 was overexpressed in 14 of 15 ILL and in all leukemias analyzed (included the t(11;19) leukemia) relative to normal and malignant lymphoid tissues. These results constitute additional elements in favor of the role of BCL-1 in lymphoid neoplasia and allow us to speculate about its mechanisms of activation.     

Development of Scales to Measure Beliefs of Diabetic Patients

In this article health belief concepts are identified and previous attempts to construct scales for measuring these concepts are critiqued. Using an initial sample of 156 diabetic patients, factor analytic techniques were used to develop measures of the basic concepts of the Health Belief Model. The derived scales from this sample were cross-validated on a second sample of 92 diabetic patients. The scales were tested for unidimensionality, internal and external consistency, and stability across both samples. The application of these scales to nursing research and practice are discussed.     

Hepatitis C virus infection in the elderly

We studied hepatitis C virus (HCV)-related disease in older people because the treatment rationale for younger asymptomatic patients is based on the long-term prognosis of infection. Of the HCV-antibody-positive patients seen at Freeman Hospital 1990-1994, 25 were >65 years old; 24 were Caucasian and one was Afro-Caribbean. Median age at presentation was 67 years, and five were female. Nine were asymptomatic at presentation, six presented with varices, five with malaise, three with abdominal pain one with pruritis and one with oedema. Risk factors identified were: transfusion (7), haemodialysis (1), health care worker (dentist) (1), and tattoos (2). There was no recognized risk factor for infection in 14, but five of these had done military service in areas of high HCV prevalance. Liver biopsy in 20 showed chronic hepatitis in two, cirrhosis in 12, and cirrhosis and hepatocellular carcinoma in six. Three additional patients also developed hepatocellular carcinoma. HCV genotyping was done in 19 and all were type 1 (1a, 4; 1b, 14; 1 untypable, 1). Eleven died, at median age 71 years (range 65-94 years), five of HCV liver-related deaths and two from HCV-associated non hepatic disorders (non-Hodgkin's lymphoma and fibrosing alveolitis).      

Multiple sclerosis: Assessment of colonic and anorectal function in the presence of faecal incontinence

Six females suffering from Multiple Sclerosis (MS) with symptoms of constipation and faecal incontinence were investigated using anal manometry, proctometrogram, proctography and large bowel transit time estimates (using inert markers). Results were compared to a control group (4 females, 2 males). Resting anal sphincter pressure (internal sphincter function) was reduced, but not significantly so, compared with controls (46±12.6 vs. 68±8.2 mm Hg: P>0.1). Maximum squeeze increment pressure (external sphincter function) was significantly diminished in the patient group (13.5±4.5 vs. 82.5±12.3 mm Hg: P>0.0001). Radiological imaging of the anorectum demonstrated an abnormal position of the pelvic floor at rest, with moderate descent in most cases during straining. Measurement of anorectal angles (puborectalis muscle function) indicated a normal angle at rest (76±10.4 degrees), but with little change on maximum contraction (74±3.5 degrees) and on straining (79±4.6 degrees). Rectal sensory parameters did not differ from controls either for minimum sensation, 44.5±5.2 vs. 30±5.8 ml (P>0.1), or at maximum tolerable volume, 163±34.5 vs. 148±22 ml (P>0.2). Four of six patients failed to empty 100% of simulated stool at proctography, at which the only anatomical defect was the presence of a rectocele in two patients. Large bowel transit studies revealed abnormally slow transit in 82% of patients, all of whom had delay in the distal colon. These physiological studies demonstrate that in patients with MS who had anorectal dysfunction, there is a marked impairment of external anal sphincter function with moderate changes in pelvic floor musculature. Delayed distal colonic transit may be associated with inability to completely evacuate the rectum.

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Résumé Six femmes souffrant de scléroses en plaques avec des symptômes de constipation, et d'incontinence fécale ont été étudiées par manométrie anale, proctométrogramme, défécographie et temps de transit intestinal (utilisant des marqueurs inertes). Les résultats ont été comparés à un groupe contrôle (4 femmes et 2 hommes). La pression anale de repos (fonction sphinctérienne interne) était réduite mais de façon non significative comparée au contrôle (46±12.6 vs. 68±8.2 mm Hg: P>0.1). La pression maximale de rétention (fonction sphinctérienne externe) etait significativement diminuée dans le groupe de malades (13.5±4.5 vs. 82.5±12.3 mm Hg: P>0.0001). Les images radiologiques montraient une position anormale du plancher pelvien au repos avec une descente modérée dans la plupart des cas au cours de l'effort. La mesure de l'angle anorectal (fonction du muscle puborectal) indiquait un angle normal au repos (76±10.4 degré) mais avec peu de changement lors de la contraction maximum (74±3.5 degré) ou de l'effort d'évacuation (79±4.6 degré). Les paramétres sensitifs rectaux ne différaient pas des contrôles soit pour la sensation minimale (44.5±5.2 vs. 30±5.8 ml, P>0.1) ou le volume maximum tolérable (163±34.5 vs. 148±22 ml, P>0.2). 4 des 6 patients ne pouvaient évacuer 100% de la selle factice à la défécographie, au cours de laquelle le seul défaut anatomique était la presence d'une rectocèle chez 2 patients. Le temps de transit colique révélait un transit anormalement lent chez 82% des patients, tous ayant un retard dans le colon distal. Ces études physiologiques montrent que chez les patients avec sclérose en plaque et mauvais fonctionnement anorectal, il y a une altération marquée de la fonction sphinctérienne externe avec des modifications modérées de la musculature du plancher pelvien. Le retard au temps de transit colique peut être associé avec l'impossibilité d'évacuer complètement le rectum.

     

石斛类叶鞘的显微鉴定研究

商品石斛的植物来源复杂,规格繁多,外形鉴定较困难。为了准确鉴定石斛的品种,对常作为药用的16种石斛属(Dendrobium Sw)植物的叶鞘进行了显微观察,发现其表皮细胞的形状,大小,所含草酸钙结晶的形状、大小、分布等种间区别较明显,可作为鉴别石斛种类的科学依据之一。本文对金钗石斛D.nobile Lindl。等16种石斛的叶鞘表面特征加以描述,并附主要特征图和检索表。