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Biomedical subjects

J B Matthews

Publications and source records attributed to J B Matthews.

At least 163 records · Page 9Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Current and future drugs for acid-peptic disease: a plethora of opinions on possible mechanisms of action.

Sixty-seven invited participants involved in the development, evaluation, and use of therapies for acid-peptic disorders participated in a meeting to discuss the scientific basis for healing actions of ulcer drugs and the prospects for future developments ("Realities of Mucosal Protection in the Upper Gastrointestinal Tract," Lausanne, Switzerland, November 8-10, 1987). Eighty-one key statements were prepared and subsequently analyzed on the basis of a voting system. Of the 45 statements that dealt with existing therapies, only 3 statements showed positive consensus (agreement of two-thirds or more of voters) about mechanisms of ulcer healing. Participants agreed that both (1) hydrogen/potassium adenosine triphosphatase inhibitors and (2) histamine H2 antagonists healed ulcers solely by acid inhibition, and (3) that sucralfate works by topical action. Substantial uncertainty about the mechanisms by which bismuth compounds and antacids heal ulcers was noted as well as their wide range of effects. The mechanism of ulcer healing by prostaglandins and the clinical relevance of antiulcer effects of drugs demonstrated in acute studies with animals were also controversial. There was greater agreement among participants about unexplored drug effects that might produce ulcer healing. Of the 36 such mechanisms surveyed, the most support went to therapies aimed at enhancement of mucosal blood flow, epithelial restitution, and mucosal alkaline secretion or inhibition of luminal pepsin activity. The diversity of opinions among participants suggests a high level of empiricism in the development of ulcer healing drugs apart from those that inhibit acid secretion. This empiricism probably arises from inadequate understanding of processes of mucosal injury and repair.

Drug Design↗

Hepatic abscess after biliary tract procedures.

Seven patients with hepatic abscess that developed after prior operation upon the biliary tract were treated during a two year period. In contrast with the fulminant clinical presentation of hepatic abscess usually associated with acute obstructive suppurative cholangitis, the presentation of hepatic abscess after prior biliary tract procedures was surprisingly indolent; several patients had been treated with oral antibiotics for several weeks or months with the presumptive diagnosis of nonsuppurative cholangitis. Thorough investigation of the entire biliary tree was necessary to identify associated biliary disease, which included biliary-enteric anastomotic stricture, intrahepatic stricture, excluded sectoral bile duct from iatrogenic injury and reflux of abnormally contaminated intestinal contents. Extensive reconstructions of the biliary tract were performed upon three patients. Recurrence of the abscess occurred once after percutaneous and once after surgical drainage and was managed by drainage of the associated excluded sectoral bile duct or fistulojejunostomy. Operative drainage of hepatic abscess after prior biliary operation may be preferable to percutaneous techniques to provide definitive surgical management of associated pathologic findings of the biliary tract.

Adolescent↗

[Etiology, diagnosis and treatment of hepatic abscesses after biliary tract surgery].

The majority of hepatic abscesses of biliary tract origin are the result of suppurative or non suppurative cholangitis, caused either by common duct stones, inflammatory stricture or malignancies. We report our experience of 7 consecutive liver abscesses after biliary tract surgery, treated in our surgical unit over a 2-year period, there were 6 females and 1 male with an age of 41 to 83 years. Hepatic abscess after biliary surgery developed from 10 days to 14 months postoperatively. Two patients underwent primary surgical drainage and remained clinically well 6 months and 2 years postoperatively. Five patients initially had percutaneous drainage and 4 of them subsequently underwent operative drainage; one patient declined any further operative treatment after percutaneous drainage and died 8 days later from continuing sepsis. Multiple factors may account for the development of both cholangitis and hepatic abscess following biliary tract procedures. Radiologic investigation should not only focus on the abscess itself but must also identify underlying biliary pathology. Our experience suggests that a surgical approach may be preferable to percutaneous techniques as it allows appropriate management of the associated biliary pathology.

Adult↗

The technique of papilloduodenectomy.

Papilloduodenectomy consists of precise and wide resection of the papilla of Vater, performed by stepwise incision of the posterior duodenal wall around the papilla, with sequential hemostasis followed by suture placement between the duodenal wall and bile duct. The end results after completion of the resection assures fixation of the biliary and pancreatic duct to the posterior wall of the duodenum, which minimizes the risk of biliary or pancreatic leakage. Results of local excision of the papilla of Vater for periampullary tumors appear satisfactory and this procedure may be particularly indicated for older or higher risk patients. Pancreaticoduodenectomy should probably remain the procedure of choice for reasonably fit patients with established malignant disease.

Adenocarcinoma↗

Resectability of large focal liver lesions.

Despite modern imaging techniques evaluation of the resectability of large focal liver lesions is often difficult or impossible until the time of operation. Based on experience with 54 primary or secondary focal liver tumours, a simple morphological classification has been found to be reasonably predictive of resectability. All tumours were classified before operation using computed tomography, ultrasound and angiography; 38 patients underwent laparotomy. Dependent, 'hanging' tumours (n = 7) were resected in six cases, expansively growing 'pushing' tumours (n = 19) were resected in 18 cases, and infiltrating, 'invasive' tumours (n = 17) were not resected because of involvement with major vascular structures. Eleven small tumours (less than 5 cm) were not classifiable by this system. This simple classification may be a useful clinical concept in preoperative assessment of resectability of focal liver lesions. Hanging tumours should always be resected, and large expansile tumours are generally resectable despite their size. Invasive tumours can only be resected in exceptional cases.

Humans↗

Epithelial dendritic cells and connective tissue macrophages in oral carcinogenesis and the effects of systemic Corynebacterium parvum.

Epithelial dendritic cells (EDC) and connective tissue macrophages were examined during the induction and growth of oral squamous cell carcinomas in Sprague-Dawley rats treated with the carcinogen 4-nitroquinoline N-oxide (4NQO) and the immune potentiator Corynebacterium parvum. Splenomegaly was induced in all animals receiving C. parvum. Acetone-fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (MRC OX-6) and macrophage subpopulations (ED1, ED2, ED3). EDC were predominantly Ia+, ED1-, ED2- and ED3-. The lamina propria contained Ia+, ED1+ and ED2+ cells; ED3-reactive cells were rare. ED2+ cells predominated in the interstitial connective tissue of deeper muscle. In the non-invasive tissues, the number of positive cells (Ia+EDC and connective tissue Ia+, ED1+ and ED3+ cells) increased significantly throughout the experimental period (0-9 months), were significantly more prevalent in the test tissues (4NQO, 4NQO + C.parvum, C.parvum) compared to untreated controls and, at 9 months, the carcinogen-treated rats (4NQO, 4NQO + C.parvum) had significantly more Ia+ EDC and connective tissue Ia+ cells than C.parvum controls. Irrespective of the marker under study, there were no significant differences between rats treated with 4NQO or 4NQO + C.parvum at any time during the experimental period. Similarly, intra-epithelial Ia+ and ED1+ cells increased significantly throughout the experimental period in all test groups compared to untreated controls, but no significant differences were evident between carcinogen-treated animals (4NQO, 4NQO + C.parvum) and C.parvum controls. Significant positive correlations between connective tissue Ia+ and ED1+ cells and also intra-epithelial Ia+ and ED1+ cells were present in all experimental groups; connective tissue ED2+ and ED3+ cell numbers did not correlate with any of the other phenotypes and intra-epithelial ED2+ and ED3+ cells were rare/absent. Palatal and/or lingual tumours developed in 80% of carcinogen-treated rats by 9 months and the tumour incidence was similar in rats treated with either 4NQO or 4NQO + C.parvum. There were no significant differences in the number of Ia+ EDC between the infiltrating and the non-invasive overlying epithelium of the lingual carcinomas and the non-invasive lingual epithelium treated with either 4NQO or 4NQO + C.parvum.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Nitroquinoline-1-oxide↗

Epithelial cell markers and proliferating cells in odontogenic jaw cysts.

The expression of keratins, CEA, EMA, and rat liver antigen (RLA) and the presence of Ki67+ proliferating cells were studied in the epithelial linings of 50 odontogenic cysts using an indirect immunoperoxidase method on acetone-fixed frozen sections. All cysts were positive with monoclonal antibodies of broad keratin specificity (CK1, AE1-3), and between 40 and 100 per cent of epithelial cells expressed keratins 13 and 19. Keratins 7, 8, and 18 were rarely expressed although surface cells in areas of mucous metaplasia often expressed keratins 7 and 18. Expression of keratin 10/11 was related to the presence of a well-ordered epithelial lining and was detected in isolated cells in 4/32 non-keratinizing cysts and in the upper suprabasal cell layers of 17/18 keratocysts. Although CEA, EMA, and RLA were detected in the epithelium of all specimens, the pattern of expression of CEA and EMA differed between cyst types. Ki67+ proliferating cells were most prevalent in keratocyst epithelia, where they were usually found within lower suprabasal layers which were negative or weakly positive for keratins 10/11 and 13. These results indicate differences in keratin, CEA, and EMA expression between cyst types which appear to be dependent on epithelial differentiation/structure rather than cyst type or histogenesis. Although these differences may not be of diagnostic significance, the consistent expression of both keratins 13 and 19 may provide a useful marker of odontogenic epithelium in general.

Antigens, Neoplasm↗

The relationship between epithelial Ia expression and the inflammatory cell infiltrate during experimental oral carcinogenesis.

The development of oral epithelial expression of Ia antigens and its relationship to the presence of IL-2r+ (CD25+) cells was investigated in rats treated with the water soluble carcinogen 4-nitroquinoline-N-oxide (4NQO). Acetone fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (I-A & I-E) and IL-2 receptor. After 4 weeks 4NQO treatment all rats expressed oral epithelial Ia but thereafter (2-9 months) expression was present in only 20-40% of animals. Epithelial expression of Ia by histologically normal, dysplastic and neoplastic epithelium was always associated with the presence of an underlying inflammatory cell infiltrate containing CD25+ cells. Overall there were significantly more CD25+ cells in tissue specimens containing Ia+ epithelium compared with Ia- epithelium. Furthermore, during the first 4 weeks of carcinogen treatment, a significant positive correlation was found between the CD25+ cell density and occurrence of focal epithelial Ia expression. These results, together with analysis of the T cell, NK cell, macrophage and B cell content of the infiltrates induced by 4NQO, suggest that the CD25+ cells represent activated T cells. Thus, our results in this experimental model are consistent with the idea that epithelial expression of Ia is the result of production of IFN-gamma by locally activated T cells.

4-Nitroquinoline-1-oxide↗