Fibronectin/laminin and their receptors in aberrant growth control in FR3T3 cells transformed by Ha-ras oncogene and epidermal growth factor gene

FR3T3 cells transfected with either the Ha-ras oncogene or the epidermal-growth-factor (EGF) gene demonstrate the transformed phenotype as indicated by in vitro and in vivo criteria. We have examined non-transformed FR3T3 cells as well as Ha-ras-oncogene-transformed and EGF-gene-transformed cells for expression of cell surface fibronectin and cell surface laminin. Fibronectin was absent from the surface of the Ha-ras-oncogene-transformed cells but present on both the EGF-gene-transformed cells and the non-transformed FR3T3 cells. Laminin was present on the cell surface in all 3 lines. The lack of surface fibronectin on the Ha-ras-oncogene-transformed cells was associated with reduced fibronectin production as indicated by immunoblotting of whole cell extracts and by ELISA. Concomitantly, there was a significant reduction of fibronectin binding by the Ha-ras-oncogene-transformed cells was compared to their EGF-gene-transformed and non-transformed counterparts. The Ha-ras-oncogene-transformed cells demonstrated reduced cell-substrate adhesiveness relative to the other two cell lines, as indicated by rates of attachment and spreading on plastic culture dishes in the presence of bovine serum albumin. They also demonstrated reduced adhesiveness in response to fibronectin but not laminin. Taken together, our results suggest that aberrant expression of fibronectin/fibronectin receptors is associated with Ha-ras-oncogene-induced transformation. In contrast, transformation by the EGF gene does not appear to involve aberrant expression of fibronectin/fibronectin receptors.     

Immunohistochemical analysis of cyclin A in astrocytic tumours

Cyclins are important regulators of the cell cycle; there is increasing evidence that some cyclins are positively involved in carcinogenesis. Amplification and translocation of the cyclin genes and overexpression of their mRNAs and proteins have been observed in a variety of tumours. We studied cyclin A protein in astrocytic tumours by immunohistochemical analysis. Immunohistochemistry with microwave antigen retrieval was carried out on formalin fixed, paraffin embedded material from 15 glioblastomas (WHO grade IV), 10 anaplastic astrocytomas (WHO grade III), seven diffuse low grade astrocytomas (WHO grade II) and nine pilocytic astrocytomas (WHO grade I) using antibodies against cyclin A and a proliferation marker MIB1. Staining for these antibodies was seen mainly in the tumour cell nuclei; 66% of all cases showing staining for cyclin A and 95% of all cases staining for MIB1. Mean labelling indices (LI) for cyclin A were higher in glioblastoma (mean LI-6.7) and anaplastic astrocytoma (mean LI-5.9) than low grade diffuse astrocytoma (mean LI-1.7) and pilocytic astrocytoma (mean LI −0.12), although there was no clear cut off point between the various tumour types. A good correlation was seen between labelling indices of cyclin A and MIB1 (Pearson correlation coefficient r =0.59, P <0.0001). Cyclin A is variably expressed in astrocytic tumours, either reflecting increased tumour proliferation (cyclin A being an integral component of the cell cycle), an alteration of its gene, protein upregulation or regulation of apoptosis. The genetic basis of expression of cyclin A in astrocytic tumours remains to be determined.     

Antimicrobial properties of methdilazine and its synergism with antibiotics and some chemotherapeutic agents

The antihistamine methdilazine (Md) was found to possess a significantly high antibacterial action when tested against 367 strains of bacteria belonging to both Gram-positive and Gram-negative genera. Different groups of bacteria could be arranged in order of their decreasing sensitivity towards Md as follows: S. aureus, V. cholerae, E. coli and Shigella. The range of minimum inhibitory concentration (micrograms/ml) varied between 25 and 200 in most cases, although few strains were sensitive even at 10 micrograms/ml level of Md. 10 different bacteria sensitive to Md and a number of antibiotics when tested for their interaction with Md on one hand and any of the antibiotics of chemotherapeutic agents on the other, it was found that Md in combination with aminoglycosides and several chemotherapeutics showed enhancement of antibacterial effects resulting in synergism. The chemotherapeutic agents bromodiphenhydramine (Bn), diphenhydramine and methyldopa showed distinct synergism when tested in combination with Md. Determination of the area of inhibition zones for the degree of synergism with Md and streptomycin (Sm) produced statistically significant result (p less than 0.01) in comparison with their individual effect. This could also be corroborated by the fractional inhibitory concentration (FIC) index which was 0.49 for Sm-Md and 0.5 for Bn-Md combinations. The synergism of Sm-Md combination was confirmed by in vivo studies.     

Histomorphological study of adrenal gland in three ophidian species.

Adrenal gland is studied histologically in the common krait, the cobra and the viper. It is comprised largely of cortical tissue with medulla. Chromaffin tissue is spatially distributed on dorsal surface and in the intercortical area of the adrenal gland. Percentage of dorsal chromaffin is higher in the viper and cobra than that of the krait, while that of intercoritcal chromaffin is higher in the krait than that of others. Chromaffin cells are irregular, smaller with densely granulated cytoplasm and larger nuclei than those of interenal gland. Medullary cells are larger in the cobra than those of other snakes. Cytomorphological difference between the dorsal and intercortical chromaffin is marked only in the cobra. Occurrence of larger granules in the dorsal and smaller type in the intercortical chromaffin may be related with noradrenaline and adrenaline secretion respectively. Cortical percent is higher in the krait than that of other snakes. Adrenocortical zonation is found only in the common krait and cobra. Subcapsular zone shows regular cords with radial disposition of columner cells in contrast to the irregular orientation of polygonal cells noted in the central cortex. Differences observed in general morphology and histology of adrenal gland, are possibly due to species difference.     

Management of Vascular Injuries in a Forward Hospital

Background

Management of vascular injuries poses a challenging problem under warlike conditions. Several authorities recommend limb revascularisation only within first 6-8 hours, as the outcome after delayed revascularisation is poor.

Methods

A retrospective analysis of 61 consecutive patients with vascular injury in a forward hospital over a 25- month period was carried out.

Results

Vascular injuries constituted 3.1% of all injuries. The mean injury to treatment delay (lag time) was 11 hours, and 10 patients received treatment after 12 hours. The overall amputation rate was 15%, but only 6.5% for those revascularised within 12 hours and 44% for those undergoing surgery after 12 hours (Chi-square 4.59, p < 0.05). Presence of associated fractures was associated with an adverse outcome (Chi-square 4.24, p < 0.05), as was ligation in comparison to revascularisation (Chi-square 7.86, p < 0.005). Popliteal injuries were associated with a high amputation rate.

Conclusions

Failure to revascularise (ligation of artery), presence of associated fracture, and restoration of circulation beyond 12 hours are associated with a high amputation rate.Key Words: Vascular injuries, trauma, amputation