Macrophage/Microglia regulation of astrocytic tenascin: synergistic action of transforming growth factor-beta and basic fibroblast growth factor.

After injury to the CNS, extracellular matrix molecules such as tenascin are upregulated around the injury site and may be involved in inhibition of axon growth. In the present study, astrocytes were investigated to determine which cell types, growth factors, or cytokines are responsible for the injury-induced regulation of tenascin. The addition of activated macrophage- or microglial-conditioned medium increased astrocytic expression of tenascin 2.5-fold, as determined by Northern and Western blot analysis and ELISA. Of the cytokines and growth factors examined, only transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) significantly induced an increase in the production of astrocytic tenascin. Examination of macrophage and microglial supernatants showed the presence of TGF-beta1 but not bFGF; however, the TGF-beta1 concentration in supernatants was lower than that expected to induce an increase in astrocytic tenascin similar to that seen with recombinant TGF-beta1. Western blot analysis of astrocytes showed only the presence of bFGF. Compared with the responses of the individual growth factors, tenascin production by astrocytes was dramatically potentiated when grown in the presence of a combination of both TGF-beta1 and bFGF. A similar synergistic effect was observed after the addition of either TGF-beta1 or bFGF to macrophage-conditioned medium. Northern analysis also showed concomitant increases in TGF-beta1, bFGF, and tenascin after CNS injury to animals 14 d of age or older. These results show that the regulation of astrocytic tenascin is mediated by the synergistic action of TGF-beta1 and bFGF in vitro and after injury in vivo.

Gastric adenocarcinoma: prognostic significance of several pathologic parameters and histologic classifications.

Considerable controversy exists about the value of histologic classifications of gastric adenocarcinoma in the prediction of patient survival. Histologic sections of 75 consecutive gastrectomies were used to compare Lauren and Ming classifications with emphasis on clinical stage, size, location of tumor, desmoplasia, inflammatory reaction, and 5-year survival. Both classifications generally correlated and, when combined, proved helpful in defining certain cases. At surgery, about one third of the total cases of intestinal (INT, Lauren) and expanding (ET, Ming) were in early stages, whereas almost all the diffuse (DT, Lauren) and infiltrative (INF, Ming) types were in late stages. When the Lauren classification was applied to preoperative endoscopic biopsies, a 72% diagnostic correlation with the surgical specimens was found. Followup revealed no survivors of the DT and INF and 12 and 11 survivors of INT and ET, respectively, regardless of stage. Inflammatory response was associated with good prognosis. Desmoplasia and size had no prognostic significance. Tumors of the cardia had worse prognoses than those in the body or antrum. Both Lauren and Ming classifications, and especially the degree of inflammation, were significant in predicting survival. Lauren INT and Ming ET should be declared only when they are the sole or predominant features.

An epithelial and spindle cell breast tumour of myoepithelial origin. An immunohistochemical and ultrastructural study.

An infiltrating epithelial and spindle cell neoplasm developed in the breast of a 63-year-old female. An excisional biopsy was performed. Recurrence with rapid growth due to cyst development eventually resulted in more radical surgery. Interim fine needle aspirations had established its partially cystic nature. The unique microscopic appearance prompted the application of immunohistochemistry and electron microscopy. The tumour cells were found to exhibit characteristics denoting squamous and myoepithelial differentiation. Histopathological features of malignancy were absent. Our findings demonstrate the differentiation potential of breast epithelium. They are in concordance with the results of previous studies which delineate the histochemical and ultrastructural features of myoepithelial and establish the relationship of these cells to squamous metaplasia.

Mucin histochemistry of intestinal metaplasia in Barrett's esophagus.

Histological and histochemical evaluation of 33 biopsies and 8 distal esophagectomy specimens revealed specialized columnar epithelium with intestinal features [intestinal metaplasia (IM)] to be the most common type (91%) of metaplasia in Barrett's esophagus (BE). Junctional epithelium was found in only 3 of the 33 biopsies. The type III subvariety of IM (TIII-M), characterized by the presence of sulfomucins in the non-goblet columnar cells, was found in 58% of all our biopsies and 62% of operative specimens. Six of the 7 cases of epithelial dysplasia were associated with TIII-M; one of them subsequently developed an adenocarcinoma. The transitional epithelium adjacent to adenocarcinomas in the operative specimens also showed TIII-M in five of six cases. Our findings indicate that TIII-M is almost as common in Barrett's-associated carcinoma as in nonneoplastic cases of BE, thereby limiting the usefulness of this histological marker as an indicator of neoplastic change (P = 0.5). On the other hand, TIII-M seems to be significantly associated with mild dysplasia in BE. The value of TIII-M as a prognostic indicator regarding the subsequent development of esophageal carcinoma remains in doubt and could be more precisely assessed by a prospective study.

Education in laboratory management for pathology residents.

In addition to clinical expertise, pathologists are required to have a background in areas of management, administration, and computer operations. During their training, it is imperative that pathology residents have exposure to the subject of modern laboratory management. The authors feel that a rotation in administration is not adequate to give the necessary training but that a formal program is needed to achieve this goal. They have developed a course in laboratory management that uses the available resources of their own department and hospital to meet these needs.

Epidemic of echovirus 19 in the north-east of England.

We report the first large-scale outbreak of echovirus 19 infection. It occurred in the north-east of England during the summer and autumn of 1974. The virus was isolated from 268 patients in the region. The infection spread from the urban to more rural areas, reaching a peak in mid-August. Males were affected more often than females in the ratio 1-6:1. Half of the patients were under eight years of age, relatively few were over 35 years. Aseptic meningitis and upper respiratory infections were the commonest presentations, though a wide range of other diseases occurred including gastroenteritis, myalgia, pericarditis, undifferentiated pyrexia, rashes and a syndrome analagous to bacteraemic shock. There was no evidence that the pattern or severity of the disease changed during the outbreak. Infants under the age of six months were more seriously affected than older children and adults. All patients except one made an uneventful recovery. Of the routine tissue culture cells HEp2 and HeLa were by far the most satisfactory for virus isolation.

Bactericidal activity of metronidazole against Bacteroides fragilis.

Metronidazole was found to be active against Bacteroides fragilis strains isolated from human lesions. The minimal inhibitory concentrations (MIC) were from 0.16 to 2.5 mug/ml and the minimal bactericidal concentrations (MBC) were from 0.16 to 2.5 mug/ml; usually the MIC and MBC figures were equivalent. These levels are easily attainable in the serum following normal therapeutic doses. The drug is not toxic and side effects are rare and it would therefore seem highly suitable for treating Bacteroides infections and also may be considered prophylactically in certain situations that are described.

The effect of carbon dioxide on the sensitivity of Bacteroides fragilis to certain antibiotics in vitro.

The effect of 10% carbon dioxide on the sensitivity to four antibiotics of 10 strains of Bacteroides fragilis was studied. The minimum inhibitory concentrations of erythromycin and lincomycin hydrochloride for these strains were four to 32 times higher, when grown in hydrogen plus 10% carbon dioxide, than the values obtained when the strains were grown in pure hydrogen. A similar effect was obtained by growing the strains in hydrogen on an acid medium. Except for Haemophilus influenzae and Clostridium tertium the sensitivity to erythromycin and lincomycin hydrochloride of other species of bacteria examined was not affected by the atmosphere in which the tests were carried out. 7-Chlorolincomycin and rifamycin B diethylamide, to which the strains of B. fragilis were uniformly sensitive, were not significantly affected by additional carbon dioxide. The possible mechanisms underlying this phenomenon and its clinical implications are discussed, and a case report describing the successful use of erythromycin in the treatment of a cerebral abscess due to B. fragilis is presented. In a recent study in this laboratory of the sensitivity to antibiotics of B. fragilis the majority of strains were found to be inhibited by 0.15 mug/ml of erythromycin and by 0.55 mug/ml of lincomycin hydrochloride (Ingham, Selkon, Codd, and Hale, 1968). After this work had been completed hydrogen plus 10% carbon dioxide was substituted for pure hydrogen in the anaerobic technique. Strains of B. fragilis isolated on routine culture now appeared to be relatively resistant to erythromycin and lincomycin hydrochloride when their sensitivity was examined by the disc diffusion method. A more detailed investigation of this phenomenon was carried out, the results of which are reported here. The opportunity was also taken to examine the susceptibility of B. fragilis to two new antibiotics, namely, 7-chlorolincomycin and rifamycin B diethylamide.

A study in vitro of the sensitivity to antibiotics of Bacteroides fragilis.

During a two-year period of observation Bacteroides species were isolated from specimens of pus and vaginal swabs from 115 patients in this hospital. Thirty-five representative strains proved on examination to be Bacteroides fragilis. Minimal inhibitory and minimal bactericidal concentrations of six antibiotics for these strains were determined. All strains were resistant to streptomycin, neomycin, and polymyxin, slightly sensitive to penicillin and ampicillin, and fully sensitive to tetracycline, chloramphenicol, erythromycin, and lincomycin. The minimum bactericidal concentrations of chloramphenicol, erythromycin, and lincomycin were two to four times the minimal inhibitory concentrations. Tetracycline failed to exert any consistent bactericidal effect.The treatment of patients with infections caused by B. fragilis is discussed in the light of the findings in vitro.

The relationship and significance of the mantoux and lepromin reactions in leprosy

1- Tuberculin (Mantoux) and lepromin (Dharmendra) tests have been carried out among leprosy patients and normal and tuberculous controls in Malaya and Singapore. 2- Leprosy patients were found to have a much lower positive Mantoux rate than the normal population, although this difference was more marked in children than in adults. In Singapore, the figure among adults with leprosy approached that of the normal population. 3- Children with leprosy were found to respond to BCG vaccination, giving a Mantoux conversion rate very little lower than that found in normal children. 4- It is suggested that leprosy infects a selected population, consisting of Mantoux negatives. That is, tuberculosis infection may give some protection against leprosy. On the other hand, evidence is produced which demonstrates that tuberculosis is readily superimposed on existing leprosy. 5- The conversion to a Mantoux positive state appears to be the essential feature, not the positive lepromin response, that may result from such vaccination. This latter response, it is suggested, is nonspecific.