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Any change produced, or feature introduced, in a body after death which is accidentally or physiologically unrelated to the natural state of the body is termed as an artefact. Since artefacts may lead to misinterpretation of post-mortem findings, it is important to rule them out. Artefacts may be produced for a variety of reasons. We present a case report where a young male in his late twenties committed suicide by hanging. He was suffering from haemorrhoids. Because of his posture, there was post-mortem bleeding, which was interpreted by the police as bleeding due to the self-cutting of his veins. Hence, we felt the need to report this case.

The study was conducted to get an overview of the various E.N.T. lesions presenting with proptosis. 50 cases were thoroughly investigated, treated according to the diagnosis and adequately followed up. Based on this data it can be concluded that most of the E.N.T. lesions presenting with proptosis are neoplastic in origin with other chief complaints being epistaxis and nasal obstruction CT scan is a must in the investigation of these conditions and USG of the orbits is an useful non-invasive investigation.

Surveillance of drinking water is essentially a health measure intended to protect the public from water borne diseases. Hydride generator accessory coupled with atomic absorption spectrophotometer was used to analyze arsenic level in 49 ground water samples collected from different areas of Delhi. Arsenic level in ground water samples was in the range of 0.0170 to 0.100 ppm (Mean-0.0431, Standard Deviation-0.0136, Std. error of Mean-0.00194) with minimum concentration at Raney Well No. 7 (0.0170 ppm) and maximum at Kotla Mubarak Pur (0.100 ppm). Arsenic containing sediments and percolation of chemicals into soil as the result of dumping of garbage rich in chemicals into open landfills could be the possible source of arsenic in ground water of Delhi. Extensive survey and continuous monitoring is required to be made to assess the magnitude of problem and earlier intervention.

A 29-year-old male was found dead lying in a pool of blood inside a community toilet locked from inside. The individual is alleged to have committed suicide by cutting his throat with a safety razor blade, which was found at the scene by the investigating police authority. The deceased, as per his relatives, was suffering from depression for the last few days., (Copyright 2004 Elsevier Ireland Ltd.)

Autoerotic asphyxial activity may at times result in unexpected death. Although the majority of deaths that occur during autoerotic asphyxial episodes are accidental, the possibility of suicide must always be entertained. In the case presented here, a 22-year-old married male was found hanging by his neck in his bedroom, which was locked from the inside. He was suspended by a 'lungi' (male wrap-around cloth) from the ceiling fan hook in his room, with his feet touching the ground. He was dressed in a brassiere, panties, and silver anklets. There was no evidence of previous perverse behaviour, and investigation disclosed no evidence of previous autoerotic sexual activity, homosexual behaviour, drug abuse or suicidal ideation.

We report the efficacy of a bimodal immunization regimen that involved priming with naked DNA (multiple doses) followed by a booster with recombinant protein in rhesus monkeys with a chimeric construct containing the N-terminus of thrombospondin-related adhesive protein and the C-terminus of circumsporozoite protein of Plasmodium cynomolgi. The vaccinated animals developed high titer antibodies against the chimeric antigen, the two components of the hybrid and the native proteins of sporozoites. The peripheral blood mononuclear cells isolated from the vaccinated animals had significant in vitro T cell proliferation activity when stimulated with the recombinant chimeric protein. Furthermore, following challenge with 1000 P. cynomolgi sporozoites, the peak and total parasitemia were significantly lower in vaccinated animals than in the control animals.

A 20-year-old girl along with four of her friends, all in their early 20s, met with a fatal accident in the early hours of the day. Their car was hit by a speeding truck at a crossing. All the occupants of the car sustained multiple injuries and died on the spot. The girl was decapitated in the accident. Her head was recovered outside the mangled remains of the vehicle and the rest of the body was extracted from the co-driver's seat of the damaged vehicle.

One of the efficient mode of treatments of chronic hypertension and cardiovascular disorders has been to restrain the formation of angiotensin-II by inhibiting the action of angiotensin-converting enzyme (ACE) on angiotensin-I. A number of ACE inhibitors (ACEIs) have been put to therapeutic use during the last two decades. The efforts continue towards achieving superior molecules or drugs with improved affinities, better bioavailability and thus long duration of action with minimum side effects. The present work evolves around similar objectives. In order to understand the mode of interaction of inhibitors with the active site of the enzyme and subsequently to have lead compounds as possible inhibitors the novel dipeptidomimics and tripeptidomimics have been designed and synthesized using combinatorial chemistry approach. A Focussed library of 10 di- and tri-peptides, eight dipeptidomemics and forty tripeptidomemics was generated. The pharmacophoric heterocyclic moieties and the amino acids have been selected to have affinities with the S1, S1', and S2' subsites of the active site of the enzyme. ACE inhibition studies clearly demonstrated the structural-activity relationships within these classes of peptidomimics. The dipeptidomimics interacted only with S1' and S2' subsites, whereas the tripeptidomemics had additional interaction with S1 subsite, which accounted for their significant ACE inhibition potencies. The in-vitro screening of these peptidomimics have resulted in identification of four promising tripeptidomimics 34[2-benzimidazolepropionyl-Val-Trp], 35[5hydroxytryptophanyl-Val-Trp], 40[2-benzimidazolepropionyl-Ile-Trp] and 45[2-benzimidazolepropionyl-Lys-Trp] with IC50 values in micromolar concentrations.

Although several malaria vaccine candidate antigens have been identified, the most suitable methods for their delivery are still being investigated. In this regard, direct immunization with DNA encoding these vaccine target antigens is an attractive alternative. Here, we have investigated the immune responses to DNA immunization with three major vaccine target antigens: the apical membrane antigen-1 and the 19-kDa C-terminal fragment of merozoite surface protein-1 from the erythrocytic stage, and the thrombospondin-related adhesive protein from the pre-erythrocytic stage of Plasmodium cynomolgi in rhesus monkeys. Antigen-specific antibodies were developed in all the immunized monkeys and peripheral blood mononuclear cells from all immunized monkeys proliferated to different extents upon in vitro stimulation with the corresponding recombinant proteins. The immunized monkeys were challenged with P. cynomolgi sporozoites. All of the immunized animals developed infection but although there was no significant difference between the control and vaccinated animals in terms of pre-patent period, total duration of patency and primary peak parasitemia, the vaccinated animals had significantly lower secondary peak parasitemia than the control animals., (Copyright 2002 Federation of European Microbiological Societies)

The acidic basic repeat antigen (ABRA) of Plasmodium falciparum is localised in the parasitophorous vacuole, and associates with the merozoite surface at the time of schizont rupture. By virtue of its protease-like activity, it is implicated in the process of merozoite invasion and schizont rupture, and therefore, possibly interacts with erythrocyte membrane proteins to execute its function during these events. In this study, using Escherichia coli expressed recombinant fragments of ABRA, we have demonstrated that ABRA interacts with red blood cells through its N-terminus. Out of the four human erythrocyte proteins tested, namely, band 3, glycophorin A and B and spectrin, ABRA showed dose-dependent and saturable binding with the band 3 protein. This binding was lost on chymotrypsin treatment of erythrocytes or their membrane extract. Studies with the deletion constructs of the N-terminus revealed that the binding domain lies in the cysteine-rich N-proximal region of ABRA. In addition to the recombinant fragments, native ABRA derived from the P. falciparum-infected erythrocytes also showed binding to band 3 protein. Sequencing of the cysteine-rich 528 bp region, amplified from fifteen field isolates of P. falciparum, showed that not only the five cysteines of mature ABRA but also the whole sequence is fully conserved, even at the nucleotide level. This sequence conservation of the N-terminus and its role in RBC binding suggests that this region may be crucial for any putative function of ABRA, therefore emphasising its importance as a vaccine/drug target.

Since the legal consequences taking in consideration of Indian evidence Act 1857 of an unwarranted release of confidential information are uncertain and even the consequences may be serious, it is necessary that a physician be most cautious when divulging any information about a patient. Although there are exceptions to the proposition that all confidential information acquired from a patient should be kept secret, the basic rule to remember is that confidential information should not be revealed without obtaining the patient's consent unless law of the land like provision in criminal procedure code of India requires the physician to report the information, to any person or insurance company. Whenever a physician believes it is necessary to reveal a professional secret to protect the welfare of a patient, a third person, or the community, he should exercise caution in the method of disclosure. The following suggestions have been made to guide physicians under these circumstances: 1. Assure yourself that the person informed is sometime entitled to the information, such as the patient's parent or guardian. 2. Do not give information by telephone if you do not recognize the voice of the person making the request. 3. Avoid the use of telegrams or letters to communicate medical information of patient. 4. If you are in doubt about your right to release the information consult your legal council. 5. A person in police custody as an undertrial prisoner has the right not to permit the doctor who has examined him, to disclose the nature of his illness to any person. If a person is convicted, he has no right and the doctor can disclose the result to the authorities. 6. Never release the treatment history without written consent from patient or its legal heirs to any insurance company.

Human amnion cells in primary culture respond to glucocorticoids in a characteristic fashion by the increased expression of the inducible prostaglandin endoperoxide H synthase isoenzyme, PGHS-2. Since PGHS-2 induction by agonists generally involves tyrosine kinases, we examined the possibility that the glucocorticoid stimulation of PGHS-2 in the amnion cells is tyrosine kinase dependent. PGHS-2 expression was stimulated in confluent, serum-starved amnion cells with dexamethasone, and the effect of the tyrosine kinase inhibitors herbimycin A and tyrphostins AG126, AG1288, and A1 on enzyme activity induction was determined. All four inhibitors blocked the increase of PGHS activity in a concentration-dependent manner with IC50 values of 0.077 +/- 0.05, 15.38 +/- 5.14, 20.91 +/- 3.1, and 29.77 +/- 8.21 microM, respectively (mean +/- SE, n = 4). Dexamethasone increased (approximately twofold) the tyrosine phosphorylation of 120-, 110-, and 77-kDa proteins in cell extracts, and herbimycin A selectively blocked the phosphorylation of the 110-kDa phosphoprotein. The stimulation of the steady-state level of PGHS-2 mRNA by dexamethasone was also inhibited by herbimycin A. These results suggest that glucocorticoids induce PGHS-2 expression in amnion cells with the involvement of tyrosine kinase(s). The role of tyrosine kinase dependent mechanisms in the control of amnion cell responsiveness to corticosteroids remains to be established.

Purpose: To report a case of brachial plexus injury occurring on the contralateral side in a patient undergoing surgery for acoustic neuroma through translabrynthine approach., Clinical Features: A 51-yr-old woman underwent surgery for acoustic neuroma through translabrynthine approach in the left retroauricular area. She had a short neck with a BMI of 32. Under anesthesia, she was placed in supine position with Sugita pins for head fixation. The head was turned 45 degrees to the right side and the neck was slightly flexed for access to the left retroauricular area, with both arms tucked by the side of the body. Postoperatively, she developed weakness in the right upper extremity comparable with palsy of the upper trunk of the brachial plexus. Hematoma at the right internal jugular vein cannulation site was ruled out by CAT scan and MRI. The only remarkable finding was considerable swelling of the right sternocleidomastoid and scalene muscle group, with some retropharyngeal edema. An EMG confirmed neuropraxia of the upper trunk of brachial plexus. She made a complete recovery of sensory and motor power in the affected limb over the next three months with conservative treatment and physiotherapy., Conclusions: Brachial plexus injury is still seen during anesthesia despite the awareness about its etiology. Malpositioning of the neck during prolonged surgery could lead to compression of scalene muscles and venous drainage impedance. The resultant swelling in the structures surrounding the brachial plexus may result in a severe compression.

Purpose: To compare the insertion time and incidence of catheter damage between skin puncture (SP) and no skin puncture (NP) techniques prior to arterial catheter insertion in patients undergoing neurosurgery., Methods: Patients undergoing surgery for intracranial tumours or cervical spine lesions were randomized to receive either SP or NP prior to arterial catheter insertion. The total insertion time, number of passes made, number of catheters used, method of insertion (direct or transfixation) and whether catheter was inserted with patients awake or anesthetised were recorded. After removal, catheters were examined microscopically for damage., Results: Eighty-two patients, 36 in SP group and 46 in NP group were recruited. Microscopic damage was seen in 36.5% of catheters and there was no difference between the two groups. The mean/median insertion time were 180/62 sec and 205/77 sec for SP and NP respectively (P:NS). The insertion time was shorter for the direct than for the transfixation technique with median of 42 vs 174 sec (P = 0.001)., Conclusion: There are no differences in insertion time or catheter damage between skin puncture and no skin puncture techniques prior to arterial catheter insertion. The practice of skin puncture may be abandoned resulting in decreased risk of needlestick injury.

A synthetic chimeric peptide of Met-enkephalin and FMRFamide (YGGFMKKKFMRFa), based on MERF was synthesized. This peptide was tested for possible antinociceptive effects using the tail flick test in mice. The effect of the chimeric peptide on morphine antinociception and development of tolerance to the antinociceptive action of morphine was also investigated. The chimeric peptide produced significant, dose-dependent antinociception (40, 60 and 90 mg/kg) in the tail flick test. Pretreatment with naloxone (5 mg/kg, IP) significantly attenuated the antinociceptive effect induced by the chimeric peptide (90 mg/kg, IP), indicating involvement of an opioidergic mechanism. In combination experiments with morphine, the antinociceptive dose of the chimeric peptide (60 mg/kg, IP) potentiated morphine (7 mg/kg, IP) antinociception. A low dose of the chimeric peptide (10 mg/kg, IP), that did not produce significant antinociception on its own, also potentiated morphine antinociception. In the tolerance studies, male albino mice received twice daily injections of morphine (20 mg/kg, IP) followed by either saline (0.1 ml) or chimeric peptide (80 mg/kg, IP) for a period of 4 days. A control group received twice daily injections of saline (0.1 ml) for the same period. When tested on Day 5, tolerance to antinociceptive action of morphine (15 mg/kg, IP) was evidenced by decreased response in chronic morphine plus saline treated mice compared to control group. Concurrent administration of chimeric peptide (80 mg/kg, IP) with morphine significantly attenuated the development of tolerance to the antinociceptive action of morphine. The preliminary results of this study demonstrate that peripherally administered chimeric peptide can produce dose dependent, naloxone reversible, antinociception; potentiate morphine antinociception and attenuate morphine tolerance, indicating a possible role of these type of amphiactive sequences in antinociception and its modulation. These chimeric peptides may also prove to be useful tools for further ascertaining the role of FMRFa family of peptides in mechanisms leading to opiate tolerance and dependence.

Prostaglandin H2 synthase (PGHS)-1 and PGHS-2 expression was examined in primary cultures of human amnion cells, an in vitro model of amnion tissue. Epidermal growth factor (EGF), the protein kinase C (PKC) activating phorbol ester TPA, and the protein phosphatase inhibitor, okadaic acid (OA), stimulated PGHS activity and the level of PGHS-2 mRNA, but did not affect the level of PGHS-1 mRNA. In situ hybridization suggested that the same population of cells responded to EGF, TPA and OA. Okadaic acid promoted PGHS activity independently of PKC. EGF stimulated the activity of extracellular signal-regulated protein kinase (Erk) and N-terminal c-Jun kinase (Jnk). OA increased Jnk activity but had no effect on Erk activity, while TPA had no influence on either Erk or Jnk activity. PD098059, a selective inhibitor of the Erk-activating kinase MEK, blocked the stimulation of PGHS expression by EGF, but did not decrease stimulation in response to OA. Herbimycin A, a tyrosine kinase inhibitor, suppressed the stimulation of PGHS activity and PGHS-2 mRNA abundance by all three stimulants, and blocked signalling via the Erk and Jnk mitogen-activated protein kinase pathways. Thus, growth factor stimulation, PKC activation and protein phosphatase inhibition induced the expression of PGHS-2 in primary amnion cells by distinct regulatory mechanisms involving tyrosine kinase(s). Tyrosine kinase inhibitors may constitute a new category of PGHS-2 inhibitors that act by blocking the expression of the enzyme., (Copyright 1998 Elsevier Science B.V.)

We have previously demonstrated that epidermal growth factor (EGF), colony stimulating factor-1 (CSF-I), and granulocyte-monocyte colony stimulating factor (GMCSF) stimulate, while transforming growth factor beta 1 (TGF beta 1) inhibits, cytotrophoblast differentiation. To identify genes mediating EGF induced differentiation, we constructed a subtracted cDNA library between undifferentiated cytotrophoblast and differentiating cytotrophoblast. We identified six novel genes and four known syncytial products alpha-human chorionic gonadotrophin (alpha hCG) pregnancy-specific beta 1-glycoprotein, 3 beta-hydroxysteroid dehydrogenase, and plasminogen activator inhibitor type 1 whose mRNAs increased during differentiation. Ten other genes were identified whose mRNAs increased during differentiation. Five of these (keratin 19, calcreticulin, heat shock protein 27, serum and glucocorticoid-regulated kinase and adrenomedullin) were not previously reported to be expressed in placenta. Five other genes known to be expressed in placenta were identified. keratin 8, fibronectin, mitochondrial ATP synthase, 1119, and cytosolic copper-zinc superoxide dismutase (SOD-1). Several of these genes may have regulatory functions in trophoblast differentiation.

We have produced monoclonal antibodies (MAbs) which react with a minor and the major coat proteins of filamentous phage M13 and have characterised them by combining the techniques of enzyme-linked immunosorbent assay (ELISA) and Western blotting. These coat proteins are the minor coat protein, gIIIp, the product of gene III and the major coat protein, gVIIIp, the product of gene VIII. Both gIIIp and gVIIIp are important in the context of 'phage display' of foreign peptides/proteins as fusions to these proteins. The anti-gIIIp MAbs were able to detect native gIIIp as well as the fusion proteins comprising foreign proteins and gIIIp in ELISA and on Western blot, indicating their utility for studying the expression of foreign proteins in phage display. Similarly anti-gVIIIp MAbs detected gVIIIp both in ELISA and on Western blot. In an 'affinity capture phage ELISA', phages that were captured by virtue of the interaction between the foreign protein (ligand fused to the gIIIp and displayed on the phage surface) and the immobilised counterpart (receptor), could be easily detected using anti-gVIIIp MAbs. Considering the potential of 'phage display' technology in protein engineering, these antibodies should find wide applications.

Formation of the human placenta requires a subset of cytotrophoblast stem cells to acquire an invasive phenotype. We examined the effect on cytotrophoblast invasiveness of growth factors that control the differentiation of other cells. Exogenous TGF-beta 1, PDGF-AA, PDGF-BB, and TNF-alpha affected neither cell morphology nor the rate of cytotrophoblast invasion in vitro. In contrast, addition of EGF to first trimester cytotrophoblast cultures produced dramatic changes in morphology and a severalfold increase in invasive capacity. The effects of EGF on later gestation cytotrophoblasts, whose invasive capacity is diminished, were much less pronounced. Next we investigated whether cytotrophoblasts themselves produce ligands that interact with the EGF receptor. A radioimmunoassay and a radioreceptor assay failed to detect EGF receptor ligands in cytotrophoblast-conditioned medium. Likewise, by RT-PCR cytotrophoblasts expressed neither EGF nor TGF-alpha mRNA. In contrast, EGF receptor mRNA was expressed and its protein levels remained constant during the experiment. Immunolocalization using F(ab') fragments of an anti-human EGF antibody failed to detect this growth factor in the chorionic villus. We conclude that maternal ligands that interact with the EGF receptor could play an important role by up-regulating trophoblast invasion, particularly during the early stages of pregnancy.

A cytogenetic survey was conducted on personnel exposed to petroleum exhaust fumes (vapour and smoke at automobile workshops). The incidence of chromosomal aberrations (CAs) in this population was evaluated. A total of 1.15 +/- 0.22 aberrations were encountered in the exposed group as compared with 0.47 +/- 0.12 aberrations in the age matched controls. The increase in CAs in the exposed group was highly significant (P < 0.01, test of variance). A strongly positive correlation between increasing exposure duration and a higher incidence of CAs was apparent. No stratification for a higher incidence of CAs on the basis of smoking and/or alcoholic habits could be made in the exposed group.

Objective: The null hypothesis is that partial hydatidiform moles have normal differentiated function (human chorionic gonadotropin and human placental lactogen secretion) in response to epidermal growth factor and 8-bromo-cyclic adenosine monophosphate., Study Design: Two complete moles, 10 partial hydatidiform moles, and 19 normal first-trimester placentas in monolayer culture were exposed to 10 ng/ml epidermal growth factor, 1 mmol/L 8-bromo-cyclic adenosine monophosphate plus 1 mmol/L theophylline, or control. Human chorionic gonadotropin and human placental lactogen secretion was measured. Frequency of response to stimuli was compared by chi 2 analysis, and hormone secretion was compared by analysis of variance., Results: Partial moles demonstrated reduced frequencies of response of human chorionic gonadotropin and human placental lactogen to epidermal growth factor (partial moles 2/8 and 2/8, respectively; normal placentas 16/19 and 7/18, respectively; p less than 0.025) and of human chorionic gonadotropin to 8-bromo-cyclic adenosine monophosphate (partial moles 3/5, normal placentas 13/16; p less than 0.005)., Conclusion: Partial hydatidiform moles demonstrate impaired human chorionic gonadotropin and human placental lactogen secretory responsiveness to epidermal growth factor and cyclic nucleotides in comparison with normal first-trimester trophoblast.

Cytogenetic investigations were carried out on 50 workers exposed to stone dust in a stone crusher industry and on 25 control subjects never exposed to such dust. The frequency of chromosomal aberrations and sister chromatid exchanges in exposed individuals was significantly higher than that in controls (P less than 0.01). The cytogenetic indices demonstrated a clear dependence on the working environment. The effect of smoking and/or alcoholic habits coupled with exposure to stone dust has also been investigated. The results indicate that the mutagenic risk in the working environment is probably associated with silica dust in the area.

Previously, no inhibitors of placental differentiation have been described. In this study, we determined the effect of transforming growth factor beta 1 (TGF beta 1) on cytotrophoblast differentiation. Monolayer cultures of pure cytotrophoblasts were exposed to 0.001-10 ng/ml TGF beta 1 with and without the presence of 10 ng/ml epidermal growth factor (EGF), an inducer of placental differentiation. Over 7 days of culture, in 11 separate experiments, phase contrast microscopy demonstrated marked inhibition of EGF-induced syncytial formation by TGF beta 1. Basal human (h)CG and h-placental lactogen (PL) release were reduced compared to control by fractions of 0.75 (TGF beta 1/control) and 0.54, respectively. EGF alone induced fractional (EGF/control) increases in hCG and hPL release of 2.46 and 2.68, respectively. However, this stimulation was significantly inhibited by 10 ng/ml TGF beta 1. Dose-response studies showed that maximal TGF beta 1 inhibition of EGF-stimulated hormone secretion occurred at 0.1 ng/ml or more TGF beta 1. Partial differentiation (syncytium formation) occurred despite the presence of TGF beta 1, suggesting a portion of cytotrophoblasts were committed to differentiation at the time of culture. We conclude that TGF beta 1 acts as a major inhibitor of trophoblast differentiation and concomitant peptide hormone secretion.

The leukemia-associated antigen CD9 is present on a variety of normal cells, with apparent variable expression on normal human fibroblasts. In this study, we demonstrate by immunoperoxidase staining and direct binding studies that the CD9 antigen is uniformly expressed on normal human fibroblasts grown from first trimester and term placenta, embryonic fetal fibroblasts, and from human adult and fetal skin fibroblasts. Higher CD9 expression was present on fetal cells. CD9 antigen was not present on trophoblast. Over 99% of fibroblasts could be absorbed onto antibody to the CD9 antigen conjugated to magnetic beads. By applying this selective immunoadsorption of fibroblasts to term placental cytotrophoblast preparations, we demonstrated that fibroblast contamination could be nearly completely eliminated. This is a novel technique for purifying primary trophoblast cultures and may have wider applicability in cell culture of other cell types.

To determine mechanisms of endocrine dysfunction in patients with testicular cancer, we performed static and dynamic testing of the hypothalamic-pituitary-testicular axis and testicular exocrine function in 13 patients and 11 normal control subjects, as well as in vitro studies of tumor tissue and remaining adjacent "normal" testicular tissue in the 13 patients. In tumor tissue, we demonstrated (a) elevated concentrations of total serum estradiol and serum estradiol not bound to sex hormone-binding globulin, (b) impaired spermatogenesis and sperm motility, and (c) blocking of multiple enzymes necessary for steroidogenesis. The data were consistent with a paracrine-endocrine mechanism in which tumor-produced human chorionic gonadotropin stimulates production of estradiol by "normal" testicular tissue but not tumor tissue, and the high estradiol levels then result in impaired spermatogenesis.

Serum haptoglobin, transferrin and albumin were studied electrophoretically in 50 patients with carcinoma of breast and in 50 normal healthy women. Results on haptoglobin show a preponderance of products of gene Hp1 (0.26) in patients as compared to controls (0.14). No variation was observed at the transferrin locus in either sample. The most notable finding was the detection of four cases of alloalbuminaemia (8%) in breast cancer Patients. The high incidence of alloalbuminaemia prompted us to extend our observations further. For this purpose sera from 41 patients was collected. One more case of alloalbuminaemia of the fast type was detected. However, in contrast to our first series of patients, quite high incidence (12.2%) of transferrin variants was recorded in this sample. Family studies were conducted on all the patients with protein anomalies.

Soluble polymers of rat (or human) albumin and alpha-1,4-glucosidase are prepared using the cross-linking agent glutaraldehyde. The resulting polymer has an average molecular weight of 800 000 indicating an average composition of 12 albumin molecules for each enzyme molecule. Compared with an equivalent amount of free enzyme, the enzyme-albumin polymer has an increased resistance to heat denaturation (half-life of 15 h compared with 1 h for free enzyme at 37 degrees C) and to proteolysis by trypsin (half-life of 180 min compared with 10 min). The high degree of resistance to bioinactivation of the enzyme-albumin polymer is discussed in relation to requirements for enzyme replacement therapy in a range of metabolic diseases including type II glycogenosis (Pompe's disease) where alpha-1,4-glucosidase is the defective enzyme.

Chemically cross-linking alpha-1,4-glucosidase, homologous albumin and antibody (immunoglobulin G, IgG) molecules raised against isolated rat hepatocytes yields an active and stable soluble enzyme-polymer complex of mol.wt. approx. 10(6). After intravenous injection, the 125I-labelled complex is seen to be preferentially associated with hepatocytes when compared with labelled free alpha-1,4-glucosidase, enzyme-albumin polymers without IgG or polymer linked to a non-specific IgG molecule, all of which are associated to a much larger extent with the Kupffer cells. The procedure offers several advantages for targeting of enzymes to specific tissues and cells and for the possible lowering of hepatocyte glycogen content in Type II glycogenesis (Pompe's disease).

Human trophoblast differentiates by the fusion of cytotrophoblasts to form syncytiotrophoblast. To determine factors controlling this process, the effects of epidermal growth factor (EGF) on trophoblast differentiation were studied using long term serum-free culture of isolated trophoblast. Only trophoblast was present in the cultures, as demonstrated by positive immunoperoxidase staining with beta hCG, cytokeratin, and trophoblast-specific H315 monoclonal antisera and by the absence of contaminating endothelial cells, fibroblasts, and macrophages, as shown by negative staining with vimentin and OKM1 monoclonal antisera. EGF induced large sustained increases in hCG and human placental lactogen (hPL) secretion in a dose-dependent manner. The minimum effective dose was 0.1 ng/mL, and the maximum effective dose was 1 ng/mL. Light and electron microscopic studies showed EGF-induced differentiation of cytotrophoblast to form syncytiotrophoblast. DNA content and cell number did not change during the process. The formation of syncytia thus probably accounted for the increase in hCG and hPL secretion. We conclude that EGF causes morphological differentiation, but not cell proliferation, of trophoblasts, and the differentiation results in increased hCG and hPL secretion from the syncytia.

Serum albumin, ceruloplasmin, transferrin and haptoglobin were studied in 50 patients with both toxic and non-toxic forms of goitre. Albumin was monomorphic in all cases and its amount was substantially lower than normal in two patients. Ceruloplasmin was both qualitatively and quantitatively normal in all patients. No genetic variants of transferrin were encountered but 22% of the patients had this protein, at levels barely detectable by electrophoretic means. Such cases of hypotransferrinaemia occurred oftener in patients with the toxic form of goitre than in those with the non-toxic one. The distribution of haptoglobin types in patients was much the same as in the control blood donors. However, the patients had a greater incidence of ahaptoglobinaemia.

Two cases of liposarcoma of the jaws were reported. These appear to be the first cases of their kind in the literature. Pathological and clinical features were discussed. Early diagnosis and radical treatment after accurate histological typing were stressed.