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Biomedical subjects

D Daniel

Publications and source records attributed to D Daniel.

At least 37 records · Page 2Linked to original sources
PubMed1994

Insulin-specific T cells are a predominant component of islet infiltrates in pre-diabetic NOD mice.

Numerous investigation have demonstrated that T cells are involved in destruction of beta cells in the NOD mouse, a widely studied model of type I diabetes. In this report we describe a series of islet-specific T cell lines established from islet-infiltrating lymphocytes obtained from individual pre-diabetic NOD mice as well as a large panel of clones derived from these lines. Proliferation assays indicated that these nominally islet-specific lines responded vigorously to porcine insulin. Furthermore, of 40 islet-specific clones derived from lines established from 12-week-old mice, 22 (55%) responded to insulin. A similar analysis of islet-specific clones established from 7-week-old mice indicated that 2 of 14 (14%) were insulin specific. These findings demonstrate that insulin-specific T cells can comprise a major portion of the spontaneously arising T cell response to islets in NOD mice.

Animals↗
PubMed1994

Analysis of the spontaneous T cell response to insulin in NOD mice.

Insulin-specific T cells have been found to be present in high frequency among nominally islet-cell-specific T cells in the islet infiltrates that accumulate in NOD mice. In a previous report in which clones obtained from 7- and 12-week-old mice were examined, we identified a 15-residue peptide of the B chain as the dominent epitope for this response. Despite the fact that the response to insulin appears to be directed toward this single peptide, diverse TCR V beta usage was observed. That insulin-specific T cells contribute to beta cell damage is suggested by the fact that all clones tested could mediate beta cell destruction upon adoptive transfer. In the present report we extend this examination of insulin-specific T cells to lines and clones established from mice ranging in age from 4-12 weeks. These clones were found to be very similar to those from 7- and 12-week-old mice. The response was directed to the same peptide and most were found to produce IFN gamma, but none produced IL-4.

Age Factors↗
PubMed1994

[Malignant tumors of the small intestine. Diagnostic problems and differentiated surgical therapy].

The data of 27 patients who suffered from malignant tumors of the small bowel between 1970 and 1992 were retrospectively documented and evaluated. In the mainly elderly patients (5th to 8th decade of life) the tumor was most frequently localized in the ileum (41%), followed by the jejunum (30%) and the duodenum (22%). Adenocarcinoma was the most frequent histological diagnosis. Only 28% of the tumors were limited to the intestinal wall. 40% had metastases, local or to other organs. Due to diagnostic problems only 30% of these tumors were found preoperatively. In 22% of the cases an explorative laparotomy and in 33% an emergency operation because of ileus and/or peritonitis led to the correct diagnosis. Still, in 64% of the patients a R0-resection was possible. Nevertheless, the median period of survival was only 24.8 months. But patients who were R0-resected survived 65 months.

Adenocarcinoma↗
PubMed1993

Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF-alpha, and IL-1 beta.

Neutrophils are possibly involved in the pathogenesis of various lung diseases through the release of numerous mediators. In the present study, we studied the regulation of IL-8 gene induction and protein secretion in human blood neutrophils. Northern blot analysis revealed that LPS increased IL-8 mRNA levels in neutrophils, with a maximal fivefold increase by 2 h. IL-8 mRNa levels returned to baseline values within 12 h. In contrast, LPS-stimulated monocytes demonstrated a sustained increase of IL-8 mRNA levels for more than 24 h. TNF-alpha, IL-1 beta, and phorbol myristate acetate also increased IL-8 mRNA levels in neutrophils. Immunohistochemical analysis confirmed that IL-8 was localized within stimulated neutrophils. IL-8 secretion by neutrophils and monocytes was quantified using a specific ELISA for IL-8. Resting neutrophils secreted minimal IL-8 activity. However when cells were stimulated with LPS, TNF-alpha, or IL-1B, neutrophils secreted IL-8. IL-8 secretion was most marked during the first 2 h after stimulation and decreased thereafter. In contrast, monocytes maintained a high rate of IL-8 secretion over 12 h. Although a single monocyte secreted 70-fold more IL-8 than did a single neutrophil after 4 h of incubation, the high abundance of neutrophils in peripheral blood made the neutrophil-secreted IL-8 more significant. During the first 2 h, neutrophils secreted approximately 40% of the IL-8 released by monocytes in the same volume of blood. This ratio decreased to 9% after 12 h. Neutrophil-secreted IL-8 may play an autocrine or paracrine role during the initial stage of inflammation.

Cells, Cultured↗
PubMed1993

Establishment of islet-specific T-cell lines and clones from islet isografts placed in spontaneously diabetic NOD mice.

One impediment to detailed characterization of islet-specific T cells from the NOD mouse model of diabetes is the difficulty encountered in isolation of such cells. This report describes a method that allows routine isolation of relatively large numbers of T cells highly enriched for reactivity toward islet antigens. The method involves renal subcapsular transplantation of spontaneously diabetic NOD mice with NOD islets. These grafts are rapidly destroyed in a tissue-specific manner and this destruction is accompanied by lymphocytic infiltration. Here we demonstrate that the islet graft infiltrates are an excellent source of islet-specific T cells and that islet-specific T-cell lines and clones can be established from these cells. Islet-specific T-cell clones isolated from a T-cell line established from the islet graft infiltrates were capable of adoptive transfer of diabetes to NOD/LtSz-scid recipients.

Animals↗
PubMed1991

Structure of (+/-)-3-benzyloxy-2,3,3a,7a-tetrahydrobenzo[b]thiophen-5 (4H)-one 1,1-dioxide.

C15H16O4S, (1), Mr = 292.35, orthorhombic, Pbca, a = 5.9496 (10), b = 11.483 (3), c = 40.262 (7) A, V = 2750.7 (10) A3, Z = 8, Dx = 1.41 g cm-3, mu = 2.340 cm-1, Mo K alpha radiation, lambda = 0.7107 A, F(000) = 1232, T = 198 K, R = 0.0451 for 1703 reflections [Fo greater than or equal to 4 sigma (Fo)]. The two rings are cis-fused with the ring junction torsion angles being -38.2 (3) degrees for C3--C3a--C7a--S1 and -38.4 (4) degrees for C4--C3a--C7a--C7. The thiophene ring assumes the envelope conformation [C3a is 0.590 (3) A from the plane through S1, C2, C3 and C7a] while the cyclohexanone moiety is in the sofa conformation [C3a is 0.530 (3) A from the plane through C4, C5, C6, C7 and C7a].

Crystallization↗
PubMed1990

Structures of two diastereomers of the tetrahydrobenzothiophene moiety of breynolide.

(1) (+/-)-3-Triisopropylsiloxy-2,3,3a,7a-tetrahydrobenzo[b]thiophen -5(4H)-one 1,1-dioxide, C17H30O4SSi, Mr = 358.57, triclinic, P1, a = 7.4383 (14), b = 8.1000 (15), c = 16.895 (3) A, alpha = 80.202 (14), beta = 88.800 (15), gamma = 76.231 (14) degrees, V = 974.0 (3) A3, Z = 2, Dx = 1.22 g cm-3, Mo K alpha, lambda = 0.7107 A, mu = 2.339 cm-1, F(000) = 388, T = 298 K, R = 0.0436 for 3086 reflections [F0 greater than or equal to 4 sigma(F0)]. (2) (+/-)-3-tert-Butyldiphenylsiloxy-2,3,3a,7a-tetrahydrobenzo[b]th iophen- 5(4H)-one 1,1-dioxide, C24H28O4SSi, Mr = 440.63, triclinic, P1, a = 9.113 (2), b = 11.020 (2), c = 12.551 (3) A, alpha = 74.01 (2), beta = 70.83 (2), gamma = 88.70 (2) degrees, V = 1141.4 (4) A3, Z = 2, Dx = 1.28 g cm-3, Mo K alpha, lambda = 0.7107 A, mu = 2.125 cm-1, F(000) = 468, T = 298 K, R = 0.0424 for 4262 reflections [F0 greater than or equal to 4 sigma(F0)]. The two rings are cis-fused with the cyclohexenone ring in the sofa conformation and the tetrahydrothiophene ring in the half-chair conformation for both (1) and (2). However, the bulky siloxy groups assume different orientations in the two compounds. In (1), the triisopropylsiloxy group is equatorial and close intramolecular contacts between H2A and H4B [2.29 (3) A], O11 and C4 [2.934 (3) A] and O9 and C7 [2.979 (3) A] are observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗
PubMed1989

Structure of a functionalized tetrahydrobenzothiophene.

(+-)-4-(tert-Butyldimethylsiloxy)-3a,4,7,7a-tetrahydrobenzo[b] thiophen -3(2H)-one 1,1-dioxide, C14H24O4SSi, Mr = 316.49, monoclinic, P2(1)/n, a = 7.1431 (7), b = 19.643 (2), c = 12.528 (1) A, beta = 104.810 (8) degrees, V = 1699.4-(3) A3, Z = 4, Dx = 1.24 g cm-3, Mo K alpha radiation, lambda = 0.71073 A, mu = 2.597 cm-1, F(000) = 680, T = 298 K, R = 0.0566 for 2733 reflections [Fo greater than or equal to 4o-(fo)]. The two rings are cisfused with the cyclohexene ring in the half-chair conformation while the thiophene moiety has the envelope conformation. The endocyclic bond angles of the cyclohexene ring are enlarged, especially at the bridgehead C atoms, C3a and C7a, which have angles 116.0 (2) and 116.8 (2)o, respectively. There are several close intramolecular contacts: C3...O11 2.614 (3), O10...O11 3.137 (3), O10...C7 3.073 (4) A. Adjacent molecules related by 1-x, 1-y, 2-z stack so that the carbonyl O and C atoms of one molecule lie directly over the carbonyl C and O atoms of the second molecule. The C...O distance is 3.023 (3) A in this intermolecular interaction.

Organosilicon Compounds↗
PubMed1989

EEG asymmetries may be affected by cranial and brain parenchymal asymmetries.

The plagiocephaly index, an index that reflects an underlying anatomic asymmetry of the brain, was assessed in ten schizophrenic patients and its values were correlated with the lateral distribution of quantitatively evaluated EEG. The correlations between the index and alpha power at F7 were significant, positive for frontal asymmetry (frontal bulging) and negative for occipital flattening. We then studied ten normal subjects in an attempt to illuminate the contribution of several cephalic and cranial variables to the imbalance of alpha-afterdischarges (AD) of VEP recorded at O1-O2. The asymmetry index of AD was computed and correlated with asymmetries of CT-derived measures of occipital bone thickness, occipital lobe width, mastoid area, and sulcal asymmetry (the asymmetry of intraparietal sulcus location from the longitudinal fissure). With the exception of the sulcal variable all measures significantly covaried with alpha AD. These findings caution that it may be important to determine cranial and brain parenchymal asymmetries where brain laterality is pertinent to studies of EEG.

Adolescent↗
PubMed1988

Orientation of the cruciate ligament in the sagittal plane. A method of predicting its length-change with flexion.

We have studied the kinematics of the knee in the sagittal plane, using a four-bar linkage as model, and assuming that a "neutral fibre" in each ligament remains isometric throughout flexion. We devised a computer program to calculate the distance separating any pair of points, one on each bone, for various cruciate attachments at various angles of flexion. The parameters for the linkage in four cadaveric knees were obtained by marking the centre of attachment of the cruciate ligaments with tacks and taking lateral radiographs. The movements of the bones were then calculated, in the computer model, for various attachments of "replacement" ligament fibres, the distance between the attachment sites being plotted against the angle of flexion. It was then possible to define zones around the isometric attachment points within which changes in length would be predictable. Our results show that the position of the femoral sites of attachment of both anterior and posterior cruciate replacement was more critical than that of the tibial attachments.

Adult↗