Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets

Platelets stimulated with thrombin release an inhibitor of plasminogen activator (PAI), which has been shown previously to be neutralized by activated protein C (APC). The requirements for optimal neutralization of PAI activity were investigated. The releasate of gel-filtered human platelets stimulated with thrombin served as a source of PAI. When 6 X 10(8) platelets/mL were incubated with thrombin (1 IU/mL), the releasate contained 18 to 26 ng/mL PAI as determined by incubation of the releasate with urokinase and measurement of residual urokinase activity on plasminogen (S2251). Preincubation of PAI with up to 4 micrograms/mL APC for two hours yielded less than 20% neutralization of PAI activity. In the presence of protein S, phospholipid, and Ca2+, neutralization of PAI activity was time-dependent with 50% neutralization occurring in two hours with 1 microgram/mL APC. The cofactor effects of protein S and phospholipid were concentration- dependent with half-maximal acceleration at approximately 3 micrograms/mL protein S and 10 micrograms/mL phospholipid when the experiments were performed at 1 microgram/mL APC. Diisopropylfluorophosphate-inactivated APC, gla-domainless APC, and thrombin-cleaved protein S had no effect on PAI activity, indicating requirement for preservation of the APC active site and of the Ca2+ binding ability of both APC and protein S. These results suggest coordinate binding of APC and protein S onto phospholipid membrane as a prerequisite for optimal expression of PAI neutralized by APC.     

Nutritional care and candidates for small bowel transplantation

Twenty two children were evaluated for small bowel transplantation between 1989 and 1994. Eight were unfit for transplantation and died within three months; a raised plasma bilirubin concentration (> 200 mumol/l) predicted death from liver failure within six months (p = 0.0001). The 11 children who were not managed by a multidisciplinary nutritional care team were less well nourished at referral, had more complications with intravenous feeding catheters, and greater early mortality while awaiting transplantation (p < 0.05). It is recommended that children with chronic intestinal failure be referred for assessment early, before liver dysfunction is established.     

New method for determining faecal fat excretion in infancy

Collecting complete, timed stool samples for the estimation of faecal fat from infants wearing nappies is difficult. A gravimetric method has been adapted by applying a chloroform/methanol homophasic solvent system to extract lipids from whole soiled nappies. In a study of 22 collections in six infants, no stools were lost and the recovery of lipids was 96%, with results similar to a reference titrimetric method. In addition to total fat, individual lipids were measured using gas-liquid chromatography. The method simplifies stool collection and analysis, is aesthetically more acceptable, and leads to reduced microbial hazards. It also allows the detailed study of excreted lipid species enabling the coefficient of absorption of dietary lipids of various chain lengths to be determined individually.     

O6-methylguanine-DNA methyltransferase activity in human buccal mucosal tissue and cell cultures. Complex mixtures related to habitual use of tobacco and betel quid inhibit the activity in vitro

Extracts prepared from tissue specimens of normal, non-tumourous human buccal mucosa, and cultured buccal epithelial cells and fibroblasts, exhibited O6-methylguanine-DNA methyltransferase (MGMT) activity by catalysing the repair of the premutagenic O6-methylguanine lesion in isolated DNA with rates of 0.2 to 0.3 pmol/mg protein. An SV40 T antigen-immortalized buccal epithelial cell line termed SVpgC2a and a buccal squamous carcinoma line termed SqCC/Y1, both of which lack normal tumour suppressor gene p53 function, exhibited about 50 and 10% of the MGMT activity of normal cells, respectively. The normal, experimentally transformed and tumourous buccal cell types showed MGMT mRNA levels which correlated with their respective levels of MGMT activity. Exposure of buccal cell cultures to various organic or water- based extracts of products related to the use of tobacco and betel quid, decreased both cell survival (measured by reduction of tetrazolium dye) and MGMT activity (measured subsequently to the exposures in cellular extracts). Organic extracts of bidi smoke condensate and betel leaf showed higher potency than those of tobacco and snuff. An aqueous snuff extract also decreased both parameters, whereas an aqueous areca nut extract was without effect. The well- established sulph-hydryl-reactive agent Hg2+, a corrosion product of dental amalgam, served as a positive control and decreased MGMT activity following treatment of cells within a range of 1-10 microM. Taken together, significant MGMT activities were demonstrated in buccal tissue specimens and in the major buccal mucosal cell types in vitro. Lower than normal MGMT activity in two transformed buccal epithelial cell lines correlated with decreased MGMT mRNA and lack of functional p53. Finally, in vitro experiments suggested the potential inhibition of buccal mucosal MGMT activity by complex mixtures present in the saliva of tobacco and betel nut chewers.      

Association between Short Maternal Height and Low Birth Weight: a Hospital-based Study in Japan

Anthropometry measurements, such as height and weight, have recently been used to predict poorer birth outcomes. However, the relationship between maternal height and birth outcomes remains unclear. We examined the effect of shorter maternal height on low birth weight (LBW) among 17,150 pairs of Japanese mothers and newborns. Data for this analysis were collected from newborns who were delivered at a large hospital in Japan. Maternal height was the exposure variable, and LBW and admission to the neonatal intensive care unit were the outcome variables. Logistic regression models were used to estimate the associations. The shortest maternal height quartile (131.0–151.9 cm) was related to LBW (OR 1.91 [95% CI 1.64, 2.22]). The groups with the second (152.0–157.9 cm) and the third shortest maternal height quartiles (158.0–160.9 cm) were also related to LBW. A P trend with one quartile change also showed a significant relationship. The relationship between maternal height and NICU admission disappeared when the statistical model was adjusted for LBW. A newborn’s small size was one factor in the relationship between shorter maternal height and NICU admission. In developed countries, shorter mothers provide a useful prenatal target to anticipate and plan for LBW newborns and NICU admission.     

COMPUTERISATION : NEED OF THE HOUR

Medical branches at formation headquarter and certain hospitals have taken into use Personal Computers (PCs) for data entry. Military Hospital Secunderabad has been progressing Project DHANWANTARI which is an on line medical information system. The type of network is host based to be developed into a Local Area Network (LAN). This article deals with concept of area networks and future scenario pertaining to computerisation of Armed Forces Medical Services (AFMS) hospitals.KEY WORDS: Armed Forces Medical Services, Local area network, Training     

Macrophage origin of Reed-Sternberg cells: an immunohistochemical study

In an immunohistochemical study of 26 biopsies from 24 patients with Hodgkin's disease a granular staining pattern for alpha-1-antitrypsin (α₁AT) and alpha-1-antichymotrypsin (α₁ACT) was seen in Reed-Sternberg (RS) cells and mononuclear Hodgkin's (H) cells in over half the cases. The pattern of staining for these antiproteases seen in RS and H cells has previously only been observed in normal and malignant cells of the monocyte/macrophage lineage within the lymphoreticular system. A faintly granular evenly distributed staining for IgG was found in viable RS and H cells. This staining was associated with a similar distribution of both light chains but not J chain, suggesting that the immunoglobulin had not been synthesised by these cells but had been taken up from the extracellular environment. It is suggested that this uptake is an active process occurring in viable RS and H cells, possibly via Fcγ receptors and further supports an origin from cells of the monocyte/macrophage lineage. IgA, IgD, albumin, fibrinogen, C1q, C4 and C3 were present in some cells, IgM was more rarely found and lysozyme was absent. The fact that cells staining for these serum proteins generally showed signs of degeneration and that the extent of staining correlated with the molecular weight, but not serum concentration, of the protein suggests that they are passively acquired by dead or dying cells and thus represent a separate phenomenon from IgG uptake. The function of IgG uptake and accumulation by RS cells and the α₁AT and α₁ACT markers may prove of use in identifying the macrophage subtype from which these cells are derived.     

Attitudes and treatment outcome of breast conservation therapy for stage I & II breast cancer using peroperative iridium‐192 implant boost to the tumour bed

Breast conservation therapy for early breast cancer is an established but grossly under‐utilized treatment option in India for various reasons. Breast conservation therapy was offered to 200 suitable breast cancer patients between June 1993 and June 1998. Fifty‐one patients (25%) opted for breast conservation and the remaining preferred mastectomy. In patients agreeing to conservation therapy, surgery was performed first along with peroperative implantation of iridium‐192 to deliver a boost. Whole breast irradiation of 45 Gy was delivered 3–4 weeks after the boost. Cosmesis was assessed at the end of 6 months from completion of therapy. The main reason for refusal of breast conservation therapy was fear of recurrence in the remaining breast (60%). There were no locoregional failures in our study at a median follow up of 42 months; one patient experienced a systemic relapse. Cosmesis was good to excellent in 80% of patients. Breast conservation therapy using peroperative iridium‐192 implant provides excellent locoregional disease control and cosmesis. The results of our study indicate that patient preference for mastectomy is an important reason for the under‐utilization of breast conservation therapy in India.