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Biomedical subjects

J B Matthews

Publications and source records attributed to J B Matthews.

At least 19 recordsLinked to original sources
PubMed1992

The myeloid leukemia cell line HL-60 produces a factor that induces chloride secretion in cultured epithelial cells.

When activated, polymorphonuclear leukocytes (PMNs) produce a small soluble factor, termed neutrophil-derived secretagogue (NDS), that elicits electrogenic Cl- secretion--the transport event responsible for hydration of mucosal surfaces. Work toward purification of this factor has been hampered by variability in activity of PMN-derived NDS. Using a human-derived intestinal epithelial cell line (T84) that serves as a model for studies of the regulation of electrogenic Cl- secretion, we find that the human promyelocytic leukemia cell line HL-60 secrets a factor with NDS-like activity. Buffer conditioned by HL-60 cells (10(7) cells/ml for 1 h), when applied to T84 monolayers grown on permeable supports and analyzed by routine electrophysiological techniques, elicited a short-circuit current (Isc) of 11.7 +/- 1.02 microA/cm2. This short-circuit current was sensitive to bumetanide, an inhibitor of the basolateral Na-K-2Cl cotransporter, and was dependent on the presence of chloride in the assay buffers. Such data indicate that buffer conditioned by HL-60 cells stimulates electrogenic Cl- secretion. Like NDS, the active factor in HL-60-conditioned buffer has a nominal molecular weight of less than 500 and was increased by activation of cells with phorbol ester. 125I and 86Rb efflux assays confirmed that the secretagogue released by stimulated HL-60 cells, similar to PMN-derived NDS, preferentially stimulates opening of Cl- rather than K+ channels in T84 cells. Lastly, release of NDS-like bioactivity increases when HL-60 cells are differentiated toward granulocytes compared to cells differentiated toward monocytes.

Cells, Cultured↗
PubMed1992

Epithelial expression of major histocompatibility complex (MHC) antigens in normal rat salivary and lacrimal glands.

The presence and distribution of MHC class I and class II antigens within these glands of Wistar and Lewis rats was studied using monoclonal antibodies and an indirect immunoperoxidase technique. In rats of both strains and sexes, MHC class 1 antigens were expressed by ductal epithelium in addition to vascular endothelium and other connective tissue elements. Except for a small proportion of secretory cells within lacrimal glands, acini were uniformly negative for class I antigen. MHC class II immune response-associated (Ia) antigens were expressed by stromal dendritic cells in all glands. Glandular expression of Ia was limited to submandibular glands of the two strains. In Lewis rats, staining was detected in some striated and collecting ducts, whereas positive glandular reactivity in Wistar rats was predominantly within the granular-cell tubules. Quantitative histomorphometric studies of Wistar submandibular glands, taken from 2.5-60-week-old male and female animals, demonstrated a close relationship between the extent of glandular Ia reactivity and postnatal granular-cell tubule development. These results indicate that whilst constitutive expression of Ia is a feature of rat submandibular epithelium, the glandular components involved are strain dependent.

Animals↗
PubMed1992

Hypophosphatasia: a family study involving a case diagnosed from gingival crevicular fluid.

Hypophosphatasia is an inherited disorder characterized by defective mineralization of the skeletal and dental structures of the body and deficient liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. There has been a tremendous advance in our knowledge of this condition over the last decade due to the advent of highly specific DNA probes and novel microanalytic techniques. The purpose of this paper is threefold: to review the dental aspects of current literature about this rare condition; to present a case (and family study) that was diagnosed in a 5-yr-old boy from 0.14 microliters of gingival crevicular fluid, using a new ultrasensitive chemiluminescent assay for the enzyme alkaline phosphatase; and to provide strong evidence for an autosomal dominant mode of inheritance.

Adamantane↗
PubMed1992

Microfilament-dependent activation of Na+/K+/2Cl- cotransport by cAMP in intestinal epithelial monolayers.

cAMP-mediated stimulation of Cl- secretion in the human intestinal cell line T84 is accompanied by significant remodeling of F-actin, and both the secretory and cytoskeletal responses may be largely ablated by previous cell loading with phalloidin derivatives, reagents that prevent dynamic reordering of microfilaments (1991. J. Clin. Invest. 87:1903-1909). In this study, we examined the effect of phalloidin loading on the cAMP-elicited activity of the individual membrane-associated transport proteins involved in electrogenic Cl- secretion. Efflux of 125I and 86Rb was used to assay forskolin-stimulated Cl- and K+ conductances, respectively, and no inhibitory effect of phalloidin could be detected. Na+/K(+)-ATPase pump activity, assessed as bumetanide-insensitive 86Rb uptake and the ability of monolayers to generate a Na+ absorptive current in response to apical addition of a Na+ ionophore, was not different between control and phalloidin-loaded monolayers. Forskolin was found to stimulate Na+/K+/2Cl- cotransport (bumetanide-sensitive 86Rb uptake) in time-dependent fashion. In the absence of any agonist, cotransporter activity was markedly decreased in phalloidin-loaded monolayers. Furthermore, under phalloidin-loaded conditions, the forskolin-elicited increase in bumetanide-sensitive 86Rb uptake was markedly attenuated. These findings suggest that cAMP-induced activity of Cl- channels, K+ channels, and the Na+/K(+)-ATPase are not influenced by F-actin stabilization. However, cAMP-induced activation of the Na+/K+/2Cl- cotransporter appears to be microfilament-dependent, and ablation of this event is likely to account for the inhibition of cAMP-elicited Cl- secretion seen in the phalloidin-loaded state. Such findings suggest that Na+/K+/2Cl- cotransporter is functionally linked to the cytoskeleton and is a regulated site of cAMP-elicited electrogenic Cl- secretion.

Actin Cytoskeleton↗
PubMed1991

Combined surgical and interventional radiological approach for complex benign biliary tract obstruction.

In patients with complicated high benign biliary strictures surgical technique alone cannot exclude the possibility of recurrent problems, and hepatic atrophy/hypertrophy, portal hypertension and intrahepatic stones may all complicate surgical management. A multidisciplinary approach to these complex cases, which minimizes the need for repeated surgical interventions, has been pursued. Roux-en-Y hepaticojejunostomy was performed and an extended limb of the jejunum brought to the abdominal wall to allow access for later radiological intervention. Over a 30-month period 58 biliary-enteric anastomoses for benign disease were performed. Seventeen of these 58 patients were managed using the combined approach. Ten of these 17 patients had complex postcholecystectomy strictures and seven had strictures resulting from inflammatory disease, hepatic resection or congenital problems. A new classification of results of management of bile duct strictures is proposed. Seven patients were classified as 'excellent', six 'good', two 'fair' and two 'poor'. Results were obtained at a mean follow-up of 16 months and it seems likely that in some patients major surgical reinterventions were avoided.

Adult↗
PubMed1991

Detection of Epstein-Barr virus antigens and DNA in major and minor salivary glands using immunocytochemistry and polymerase chain reaction: possible relationship with Sjogren's syndrome.

This study has investigated the presence of Epstein-Barr virus (EBV) in parotid (n = 12), submandibular (n = 15), and minor salivary glands (n = 25) using immunohistochemical methods for detection of EBV-encoded antigens and the polymerase chain reaction (PCR) for detection of viral DNA. Major salivary glands were from patients without connective tissue disease. Labial glands were from patients with primary Sjogren's syndrome (n = 10), rheumatoid arthritis (n = 8), or from normal individuals (n = 7). None of the glands exhibited specific reactivity for lytic (EA-D, EA-R, VCA) or latent (EBNA-2, LMP) viral antigens. Antibodies to EA-D, when used at 20-50 times their optimal concentration, gave lumenal staining of ducts and acini of all the specimens tested (n = 14), irrespective of the presence (n = 8) or absence (n = 6) of EBV-DNA by PCR. Ductal immunoreactivity for the EBV/C3d (CR2, CD21) receptor was found in 40 per cent of specimens. PCR detected EBV-DNA in 64 per cent submandibular, 46 per cent parotid, and 80 per cent of minor glands. There were no significant differences in the detection of EBV-DNA between specimen/patient groups. Only type A EBV was detected by strain typing PCR. These results indicate that EBV (type A), undetected immunocytochemically, is commonly present at low copy numbers within salivary glands irrespective of a clinical diagnosis of Sjogren's syndrome.

Adult↗
PubMed1991

MHC antigen expression in human oral squamous carcinoma cell lines.

This study quantified the constitutive and interferon-gamma (IFN-gamma) stimulated expression of MHC class I (HLA-ABC and beta 2 microglobulin) and class II antigens (HLA-DR, -DP, -DQ) on normal and malignant oral keratinocytes using radioimmunoassay and immunocytochemical techniques. Normal keratinocytes and three of four malignant cell lines (H103, H157, H314) expressed MHC class I antigens constitutively; IFN-gamma increased MHC class I expression with significant changes in normals, H157 and H314. Normal keratinocytes expressed significantly more constitutive MHC class I antigens than H103 and H157 and significantly more IFN-gamma stimulated MHC class I antigens than H103, H157 and H314. MHC class II antigens predominantly were not expressed constitutively on normals, H103 and H157 but, in H314, HLA-DR, -DP and -DQ antigens were demonstrated on 35, 11 and 5 per cent of cells, respectively, and resulted in a non-coordinated pattern of expression (HLA-DR greater than -DP = -DQ). IFN-gamma induced HLA-DR on normals, H103 and H157, whilst HLA-DP and -DQ remained undetectable. In H314, IFN-gamma enhanced HLA-DR, -DP and -DQ (significant increase of HLA-DQ) but the interrelationship between these antigens was maintained (HLA-DR greater than -DP = -DQ). Normal keratinocytes expressed significantly more IFN-gamma stimulated HLA-DR than H103 and H157 but significantly less HLA-DR than H314 under similar experimental conditions. One oral malignant cell line (H191) did not express MHC class I and MHC class II antigens either constitutively or in response to IFN-gamma. The results demonstrate aberrant patterns of MHC expression (absence, enhanced, diminished) in the different malignant oral keratinocyte cell lines.

Carcinoma, Squamous Cell↗
PubMed1991

Primed and naive helper T cells in labial glands from patients with Sjogren's syndrome.

This study has investigated the presence and distribution of B cells, T cells and T-cell subsets within labial glands of patients with primary Sjogren's syndrome (n = 9) and secondary Sjogren's syndrome associated with rheumatoid arthritis (n = 8) using a sequential double immunoperoxidase technique and true colour image analysis. The composition of the inflammatory infiltrates was similar in glands from both patient groups. B cells were normally present within large foci with few detected in diffuse infiltrates such that the ratio of T:B cells in foci (2.4:1) was significantly lower than in diffuse infiltrates (7.3:1; P less than 0.001). In all infiltrates helper T cells (CD8-, CD3+) predominated over suppressor/cytotoxic cells (CD8+, CD3+; 2.7:1). Analysis of primed (CD45RA-, CD45RO+) and naive (CD45RA+, CD45RO-) CD8- T cells showed that the ratio of the primed to naive subset was significantly higher in focal (4.2:1) compared to diffuse (1.5:1; P less than 0.001) areas of lymphoid infiltration. These results indicate that the focal lymphocytic infiltrates characteristic of Sjogren's syndrome contain B cells associated with a T-cell population consisting predominantly of primed CD8- helper T cells. This latter population may be responsible for upregulating glandular B-cell activity in Sjogren's syndrome.

Antigens, CD↗
PubMed1991

Differentiation of malignant oral rat keratinocytes reflects changes in EGF and TGF-beta receptor expression but not growth factor dependence.

This study examined the characteristics of keratinocytes from 4-nitroquinoline N-oxide-treated rat oral epithelium that formed well differentiated carcinomas or spindle cell tumours when transplanted s.c. to athymic mice. Small polygonal-type cells in early culture passage gave rise to xenografts that were well differentiated carcinomas with keratin positivity and a differential reactivity with two anti-vimentin antibodies (positive Vim Dako, negative Vim 3B4). Progressive culture of the polygonal cells resulted in cells of a more stellate-like morphology which, when transplanted, formed spindle cell tumours that were keratin negative and vimentin positive (Vim Dako and Vim 3B4). The staining pattern of the xenografts was similar to that of the cultured cell derivatives. By contrast to normal oral keratinocytes which were stimulated by epidermal growth factor (EGF), the parental and xenograft-derived cells were markedly less responsive and at times refractory to EGF. Low affinity EGF receptors characterized normal keratinocytes whilst parental and xenograft-derived cells from well differentiated carcinomas and spindle cell tumours expressed diminished numbers of low and high affinity and high affinity EGF receptors respectively. Normal keratinocytes and parental tumour cells were inhibited by transforming growth factor (TGF-beta) whereas xenograft-derived cell lines from both well differentiated carcinomas and spindle cell tumours were refractory to TGF-beta. TGF-beta receptors were predominantly of high affinity although xenograft-derived cells, particularly from spindle cell tumours, expressed increased numbers of receptors which were of lower affinity. The results indicate that spindle cell tumours are a variant of well differentiated carcinomas and express an aberrant pattern of differentiation. Resistance to EGF-induced stimulation and TGF-beta-induced inhibition appears not to be an integral part of the tumour phenotype but the pattern of EGF and TGF-beta receptor expression closely follows the degree of tumour differentiation.

Animals↗
PubMed1991

Review article: stomach wars--a mucosal defense initiative.

A model is presented which attempts to unify many of the processes identified in recent years as contributing to the maintenance of mucosal integrity in the stomach. Two concepts, namely acid disposal and rapid repair of superficial injury, are highlighted as being of particular physiological significance. The mechanisms involved in protection of the normal mucosa against luminal aggressors (e.g. acid/pepsin, ethanol, aspirin) must be distinguished from the factors which influence the healing of a pre-existent ulcer. In this context, the relatively neglected topic of wound healing in the gastric mucosa is considered, and the implications for current therapeutic strategies and for the discovery of new anti-ulcer drugs are explored.

Animals↗
PubMed1991

Expression of rheumatoid factor associated cross-reactive idiotopes by glandular B cells in Sjögren's syndrome.

B cell expression of the germline gene-encoded, kappa IIIb-associated, rheumatoid factor (RF) cross-reactive idiotope (CRI) 17-109 and three VHI associated RF CRIs (G6, G8, H1) was investigated immunocytochemically in labial salivary glands from nine patients with primary and six with secondary Sjögren's syndrome, and in inflamed submandibular salivary glands from 10 patients with no history of connective tissue disease. Expression of CRIs by B cell infiltrates in labial glands from patients with primary and secondary Sjögren's syndrome were similar. Lymphoid infiltrates of labial glands from Sjögren's syndrome patients contained a higher proportion of kappa III+ cells reactive for the kappa IIIb-associated 17-109 idiotope (P less than 0.01) and larger G6 (P less than 0.02) and H1 (P less than 0.01) positive B cell populations than those within inflamed submandibular salivary glands. Furthermore, in labial glands there was a significant correlation between numbers of 17-109 and G6 idiotope reactive cells (r = 0.61; P less than 0.02), reflecting the known association between these H and L chain CRIs in RF IgM paraproteins. These results indicate that B cells bearing both VKIII and VHI-associated CRI are increased in the glandular infiltrates in Sjögren's syndrome and support the idea that this condition is associated with proliferation of immature B cell clones retaining germ-line V genes.

B-Lymphocytes↗
PubMed1991

Biliary stricture following hepatic resection.

Anatomic distortion and displacement of hilar structures due to liver lobe atrophy and hypertrophy occasionally complicates the surgical approach for biliary stricture repair. Benign biliary stricture following hepatic resection deserves special consideration in this regard because the inevitable hypertrophy of the residual liver causes marked rotation and displacement of the hepatic hilum that if not anticipated may render exposure for repair difficult and dangerous. Three patients with biliary stricture after hepatectomy illustrate the influence of hepatic regeneration on attempts at subsequent stricture repair. Following left hepatectomy, hypertrophy of the right and caudate lobes causes an anteromedial rotation and displacement of the portal structures. After right hepatectomy, the rotation is posterolateral, and a thoracoabdominal approach may be necessary for adequate exposure. Radiographs obtained in the standard anteroposterior projection may be deceptive, and lateral views are recommended to aid in operative planning.

Adult↗
PubMed1990

Management of the Mirizzi syndrome and the surgical implications of cholecystcholedochal fistula.

Several methods of handling the residual choledochal defects encountered during operation for type II Mirizzi syndrome have been described. Early experience with eight patients treated by a variety of procedures including direct suture and flap techniques led to disappointingly high morbidity and mortality rates. Since 1986 a standardized surgical approach has been used in four patients without complications or mortality. Essential to management are preoperative diagnosis by ultrasonography and endoscopic retrograde cholangiopancreatography and classification of the Mirizzi syndrome into two types as proposed by McSherry. Mirizzi type I consists of an extrinsic compression of the hepatic duct by a calculus impacted in the cystic duct or in Hartmann's pouch. This is treated by cholecystectomy with or without common bile duct exploration. In the more difficult Mirizzi type II, the stone has eroded into the hepatic duct causing a cholecystcholedochal fistula. This is treated by partial cholecystectomy and a cholecystcholedochoduodenostomy. This management strategy prevents inadvertent bile duct injury and has yielded satisfactory results.

Aged↗
PubMed1990

The behaviour of human oral squamous cell carcinoma in cell culture.

This study examined the initial behaviour of 48 human oral squamous cell carcinomas (SCC) in cell culture. The early outcome of these cultures (contamination, absence of cell growth, epithelial cell senescence/fibroblast overgrowth, extended keratinocyte growth) did not reflect the clinical characteristics of the tumours of origin. Four new human oral SCC cell lines were characterized more extensively. Each cell line was immortal, 3T3-independent, and expressed low degrees of anchorage independence (CFE less than 4 per cent). Two of the four cell lines were tumorigenic in athymic mice. All of the cell lines expressed keratin intermediate filaments and two showed weak co-expression of vimentin. A wide range of keratins were expressed by the tumour xenografts; cornified keratins (K1, K10) were only expressed in the absence of K19 and vimentin, and vice versa. The nuclear:cytoplasmic ratio and the degree of serum independence correlated with each other and with the STNMP clinical grading of the tumours of origin.

Adult↗
PubMed1990

An immunocytochemical study of keratin reactivity during rat odontogenesis.

The cytokeratin distribution in the developing rat enamel organ from day 15 of gestation through to 11 days post partum was examined immunohistochemically using a panel of monoclonal antibodies. A temporo-spatial programme of keratin expression was observed during odontogenesis and positive reactivity of the enamel organ was seen with the pan keratin antibodies CK1 (clone LP34 - reacts with a number of keratins including 6 and 18) and AE1-3 (reacts with most acidic and basic keratins). No reactivity was observed in the enamel organ with the other antibodies examined (Ks 8.12 [reacts with keratins 13 and 16], Ks 8.60 [reacts with keratins 10 and 11) and MCA157 [reacts with rat liver antigen]), although these antibodies did stain other epithelial tissues. This study supports the view that the epithelial cells of the enamel organ synthesize a tissue-specific subset of keratins which are related to the differentiation of the cells.

Animals↗