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K Kett

Publications and source records attributed to K Kett.

At least 19 recordsLinked to original sources
PubMed2003

Oats induced villous atrophy in coeliac disease.

The current trend is to allow coeliac disease (CD) patients to introduce oats to their gluten free diet. We sought further data from the clinical setting with regards to oats consumption by coeliac patients. Several oat products were tested for wheat contamination using a commercial enzyme linked immunoassay (ELISA) kit, and six samples were examined by an ELISA using a cocktail of monoclonal antibodies, mass spectrometry, and western blot analysis. Nineteen adult CD patients on a gluten free diet were challenged with 50 g of oats per day for 12 weeks. Serological testing and gastroduodenoscopy was performed before and after the challenge. Biopsies were scored histologically and levels of mRNA specific for interferon gamma were determined by reverse transcription-polymerase chain reaction analysis. Oats were well tolerated by most patients but several reported initial abdominal discomfort and bloating. One of the patients developed partial villous atrophy and a rash during the first oats challenge. She subsequently improved on an oats free diet but developed subtotal villous atrophy and dramatic dermatitis during a second challenge. Five of the patients showed positive levels of interferon gamma mRNA after challenge. Some concerns therefore remain with respect to the safety of oats for coeliacs.

Adult↗
PubMed2002

Axillary lymph drainage as a prognostic factor of survival in breast cancer.

Axillary lymph node staging is an important prognostic factor in patients with breast cancer. The long-term survival is poor if the number of metastatic axillary lymph nodes exceeds three. With 1-3 metastatic lymph nodes, survival in 30% of the patients is 20 years. The markedly different outcome of these patients with metastatic axillary lymph nodes suggests that other factors likely play a critical role in breast cancer dissemination. In this study, we examined the association of impaired axillary lymph drainage with breast cancer survival. Fifty patients with breast cancer underwent direct breast lymphography before treatment to evaluate the status of ipsilateral axillary lymph nodes and lymph drainage at time of presentation. Twenty-five patients with signs of metastatic disease and/or impaired lymph drainage were followed for 10 years. Seven of 25 patients survived 10 years; 6 are tumor free; and 1 has distant mestastases. The other 18 patients died during the 10 year period. Seventeen of the 18 died from disseminated breast cancer; 1 died of unrelated disease. In the survivors, direct breast lymphography showed normal breast lymph drainage. All patients with distant metastases had obstructed lymph vessels at the time of original diagnosis. These findings suggest that the chance for survival is determined both by the status of axillary lymph drainage as well as the number of metastatic axillary lymph nodes.

Adult↗
PubMed2001

T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase.

Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T cell responses to ingested wheat gliadins. Initial studies used gliadin that had been subjected to non-enzymatic deamidation during pepsin/trypsin digestion to enrich for the gliadin-specific T cells in small intestinal celiac biopsies. These T cells recognized synthetic gliadin peptides only after their deamidation in vitro by purified tissue transglutaminase (tTG). However, as these studies used a deamidated antigen for re-stimulation prior to testing for antigen specificity, this raised the possibility that T cells specific for native epitopes had not been expanded in vitro and had thus been overlooked. To address this possibility and to look for more direct evidence that endogenous tTG mediates deamidation of gluten in the celiac lesions, we have here used a minimally deamidated chymotrypsin-digest of gliadin to challenge biopsies and then investigated the specificity of the T cell lines derived from them. Interestingly, these T cell lines only barely responded to the chymotrypsin-digested gliadins, but efficiently recognized the in vitro tTG-treated variants of the same gliadins. Moreover, the addition of a tTG-inhibitor during the gliadin challenge often resulted in T cell lines with abolished or reduced responses to deamidated gliadin. These data demonstrate that DQ2-restricted T cells within adult celiac lesions predominantly recognize deamidated gliadin epitopes that are formed in situ by endogenous tTG.

Amides↗
PubMed1998

HLA restriction patterns of gliadin- and astrovirus-specific CD4+ T cells isolated in parallel from the small intestine of celiac disease patients.

Celiac disease is a common HLA-DQ2-associated enteropathy caused by an abnormal T-cell-mediated immune response to ingested wheat gliadin proteins. We have previously isolated in situ activated mucosal T cells from celiac disease patients and demonstrated that these T cells were gliadin specific and predominantly DQ2 restricted. In contrast to this, gliadin-specific T cells isolated from peripheral blood display a variable HLA restriction pattern, thereby indicating that the skewed DQ restriction of T cells resident in the celiac lesions could be dictated by a preference for DQ-mediated antigen presentation in the mucosa of CD patients. To address this, we analyzed the HLA restriction of T cells recognizing astrovirus, a common gastroentetitis virus, isolated from intestinal mucosa of six celiac disease patients. As an internal control, gliadin-specific T cells were isolated and analyzed in parallel. The gliadin-specific mucosal T cells were marked in their DQ2 restriction, whereas the parallel astrovirus-specific T cells were predominantly restricted by DR molecules. Our data indicate that the repertoire of T cells present in celiac lesions is determined by the priming antigen(s) and not by a skewing in the expression of functional HLA class II isotypes in the disease affected small intestinal mucosa.

Adult↗
PubMed1997

Urinary steroids at time of surgery in postmenopausal women with breast cancer.

Urinary steroid metabolites were measured by capillary gas chromatography in 22 postmenopausal women with operable breast cancer on day before the tumour excision and in 20 hospitalised control who were before an operation from other cause than cancer. Serum dehydroepiandrosterone-sulphat (DHEAS) and testosterone (T) level were measured by radioimmunassay in the same groups and same time. There was no significant difference in the level of urinary androgen metabolites. Pregnanediol level was significantly lower (P < 0.05) in cancer patients. In the 5 patients with positive axillary nodes the tetrahydrocortisol and alpha-cortolone levels were significantly (P < 0.05) higher than in node negative ones. There was no significant differences in the serum DHEAS and T levels. These results indicate that metabolic changes are existing in postmenopausal patients which may be a cause or a consequence of the disease.

Aged↗
PubMed1997

Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls.

The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cell recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.

Adolescent↗
PubMed1997

Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls.

The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cells recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.

Adult↗
PubMed1997

[Lymph drainage as prognostic factor in breast carcinoma].

Lymph stasis detectable by means of breast lymphography and which developed as a consequence of axillary lymph node metastases has proved to be a valuable factor in the prognosis of breast cancer. As with secondary lymphedema, lymph vessels were found to be dilated, which was regarded as a consequence of tumoral obstruction, and the elevated pressure in these lymph vessels may cause hematogenous spread of the tumors through venous shunts. Significant correlation between preoperative lymphographic findings and the incidence of distant forming 5 years postoperatively was also found, which leads to the conclusion that the distant metastases exist prior to the operation can account for the late tumor recurrence.

Breast Neoplasms↗
PubMed1995

Intestinal B-cell isotype response in relation to local bacterial load: evidence for immunoglobulin A subclass adaptation.

BACKGROUND & AIMS: In experimental animals, the indigenous microbiota modulates mucosal immunity. In humans, such direct evidence is scarce. The aim of this study was to examine the effect of intestinal bacteria on the local immunoglobulin (Ig) response. METHODS: The numbers of IgA-, IgM-, and IgG-producing immunocytes per defined mucosal length unit were determined, and the local IgA subclass response was studied using immunohistochemistry in jejunal segments from adults with bacterial overgrowth and in sterile ileal urinary conduits from children. RESULTS: The ileal bladder mucosa showed atrophy, but the number of immunocytes only tended to be decreased. The jejunal segments with bacterial overgrowth showed minor histological changes; the numbers of IgA and IgG immunocytes were fairly normal, whereas the number of IgM immunocytes was significantly reduced (P < 0.05) (12 cells/U) compared with control mucosa (24 cells/U). The number of IgA2 immunocytes was significantly decreased (P < 0.01) in ileal conduits (7 cells/U or 30% of total IgA) but increased (P < 0.05) in jejunal segments with bacterial overgrowth (42 cells/U or 43% of total IgA) compared with normal ileum (15 cells/U or 40% of total IgA) and jejunum (24 cells/U or 23% of total IgA). CONCLUSIONS: An association exists between bacterial load and IgA subclass production. An increase in IgA2 may enhance mucosal protection and probably reflects immunomodulation caused by lipopolysaccharides.

Adolescent↗
PubMed1995

Gliadin-specific T cell responses in peripheral blood of healthy individuals involve T cells restricted by the coeliac disease associated DQ2 heterodimer.

Coeliac disease (CD) is probably caused by an abnormal immune response towards wheat gliadin in the small intestine. We found that gliadin-specific T cells from the small intestinal mucosa of HLA-DQ2 positive CD patients were almost exclusively restricted by the disease-associated DQ2 molecule. In the peripheral blood of CD patients, a large proportion of gliadin-specific T cells were found to be restricted by DQ molecules, including DQ2, but many were instead restricted by DR or DP molecules of the patient. We have now investigated gliadin-specific T cell responses in peripheral blood from healthy individuals. Four of 20 persons tested had strong in vitro responses and were used as donors for gliadin-specific T cell clones. We found gliadin-specific T cells restricted by the CD-associated DQ2 molecule in peripheral blood for two of these four individuals. It is the presence of such T cells also in the small intestinal mucosa which seems typical of CD.

Antibodies, Monoclonal↗
PubMed1993

[Lymph drainage from the breast to the parasternal lymph nodes].

Breast lymphography revealed linkage between the axillary and parasternal lymph nodes in three out of 55 patients with breast cancer. In all the cases the efferent lymph vessels outlined laterally and, according to Berg's scheme, lymph node groups I, II and III were filled. Lymph vessel responsible for the filling of the parasternal lymph nodes branched from the area of group I lymph nodes. In two out of the 3 cases axillary metastasis was detected in one case, however, the axillary was found unaffected. The lymph vessel linkage observed doesn't seem to support the widely accepted concept, according to which there are only direct efferent lymph vessels running from the breast to the parasternal lymph nodes. This finding also explains why the incidence of parasternal metastases in the breast is higher in the case of tumorous obstruction of the axillary lymph nodes.

Axilla↗
PubMed1992

IgG subclass distribution in serum and rectal mucosa of monozygotic twins with or without inflammatory bowel disease.

Serum samples from 26 monozygotic twin pairs concordant or discordant with regard to inflammatory bowel disease, and rectal biopsies from 42 twins of the same subject group, were examined for IgG subclasses. They were all compared with normal controls. Almost all affected twins were in clinical remission. Paired immunofluorescence staining of the rectal mucosa showed that those with ulcerative colitis had a significantly higher (p < 0.01) proportion of IgG1 producing mucosal immunocytes than normal controls (78.1% v 55.9%). Conversely, the IgG2 cell fraction was significantly reduced (15.9% v 34.6%). Healthy twins from ulcerative colitis pairs tended to show a raised proportion of IgG1 cells and the IgG2 cell fraction was significantly reduced (p < 0.05). In discordant ulcerative colitis twin pairs, no difference appeared in the cellular IgG subclass pattern between healthy and affected twins. Furthermore, the proportion of IgG1 in these healthy and diseased twins showed good correlation (T = 0.867). The results in rectal mucosa of twins with Crohn's disease were widely scattered and affected twins did not differ significantly from normal controls. Healthy twins, however, showed a marginally raised IgG1 cell proportion, but no correlation was seen between the IgG subclass fractions in discordant Crohn's disease twin pairs. The serum concentrations of IgG1 and IgG2 did not differ from normal controls in twins of either category. These results suggested that in ulcerative colitis, the aberrant mucosal production of IgG1 and IgG2 does not depend on active disease, but is apparently at least partially explained by a genetic impact. Conversely, the mucosal IgG subclass pattern in Crohn's disease appears to be determined mainly by exogenous variables.

Adult↗
PubMed1991

Isotype distribution of mucosal IgG-producing cells in patients with various IgG subclass deficiencies.

The subclass distribution of IgG-producing immunocytes was examined by immunohistochemistry in nasal and rectal mucosa of infection-prone patients with untreated IgG subclass deficiencies. Biopsy specimens from the two sites were obtained in 18 clinically and serologically well-characterized adult subjects; only a nasal or rectal sample was available from nine similar patients. Chronic lung disease was common in the patient groups with selective serum IgG1 deficiency and combined IgG1 and IgG3 deficiency, whereas the other categories of patients had mainly upper airway and other mild infections. Serum IgG2 or IgG3 deficiency was usually expressed also at the cellular level in rectal mucosa, and the proportion of rectal IgG1 cells was significantly correlated with the IgG1 level (r = 0.90, P less than 0.001). Likewise, there tended to be a decreased expression of the actual subclass at the cellular level in nasal mucosa of patients with serum IgG1 or IgG2 deficiency. Conversely, the median nasal proportion of IgG3 cells was remarkably unaffected by a deficiency of this subclass in serum and rectal mucosa. Interestingly, these patients rather tended to have raised IgG3 and reduced IgG2 cell proportions in their nasal mucosa, although this apparent local IgG3 compensation was nevertheless strongly correlated with the serum IgG3 level (r = 0.87, P less than 0.002). These disparities may reflect different antigenic and mitogenic exposure of the two tissue sites; for example, a persistent protein bombardment of the nasal mucosa that could conceivably override locally a B cell maturation defect. The possible clinical consequences of such variable mucosal expression of IgG subclass deficiencies remain to be studied.

Adult↗
PubMed1990

[Ultrasonic diagnosis and treatment of a rare form of isolated gallbladder injury].

A rare form of traumatic cholecystitis revealing a suffusion in the wall of the gallbladder with stones is reviewed by the authors. An isolated occurrence as such injuries is extremely rare. The possibilities and accuracy of preoperative ultrasonic diagnosis are discussed in diseases of the gallbladder. Similar reports in the literature of last ten years have not been found, therefore aim of the present report is to call attention to the disease which if left without treatment can be fatal. According to the authors an operative treatment is of vital importance in such cases.

Aged↗
PubMed1990

Secretory immunity in celiac disease: cellular expression of immunoglobulin A subclass and joining chain.

Two-color immunofluorescence staining in situ demonstrated increased proportions of immunoglobulin A2 subclass-producing cells in jejunal mucosa from adult patients with untreated (47%, P less than 0.01) or treated (37%, P less than 0.05) celiac disease compared with controls (28%). Costaining was also performed for joining chain, which is a key factor in the epithelial transport of secretory antibodies; its expression by immunoglobulin A2 cells was only marginally reduced in untreated patients (96%) compared with treated patients and controls (98%). Also, immunoglobulin A1 cells showed similar joining chain positivity (89%) in all three groups. Considering the expanded total jejunal immunoglobulin A-cell population and the subclass-associated joining chain expression, it could be calculated that the potential of immunoglobulin A2 cells for contribution to secretory immunity was increased 3.9 times in untreated (P less than 0.01) and 1.8 times in treated (P less than 0.05) patients and that of immunoglobulin A1 cells was increased 1.7 times in untreated (P less than 0.05) but remained unaltered in treated patients. The estimated relative contributions of locally produced immunoglobulin A2 to secretory immunoglobulin A would thus be 51% and 37% in the two patient categories, respectively, compared with 31% in the controls. These data suggested enhanced secretory immunity in celiac disease and might reflect a protective, possibly antimicrobial, immune response. It could not be excluded, however, that increased generation of secretory immunoglobulin A at the same time contributes to the gluten-induced pathogenesis of celiac disease.

Adult↗
PubMed1989

[Candida species produce IgA proteases--an important biological property].

IgA-specific microbial proteases possess the ability to reduce the protective effects of secretory IgA antibodies. The fact that fungi such as Candida produce both IgA1-and IgA2-specific proteases has not been acknowledged in articles and discussions concerning the chronic Candida syndrome. Therefore a short survey of these interesting proteases is presented, along with hypotheses concerning alterations IgA fragments may induce in immunoregulation and uptake of antigens from the gut.

Candida↗