Infection with an extended-spectrum beta-lactamase-producing strain of Serratia marcescens following tongue reconstruction

We report a case of postsurgical wound infection of polymicrobial etiology caused by Serratia marcescens and Pseudomonas aeruginosa following the use of a radial forearm free flap for oncological tongue reconstruction. S. marcescens was a producer of SHV-12 extended-spectrum beta-lactamase (ESBL). This is the first report from India of this ESBL. S. marcescens and P. aeruginosa were resistant to the empirical perioperative antibiotics administered. Delay in the recognition of the type of infection and in the institution of appropriate therapy resulted in total loss of the free flap.     

Hepatic microsomal cytochrome P450 system during experimental hookworm infection

Experimental infection of golden hamsters with the hookworm, Ancylostoma ceylanicum, caused a profound decline in the hepatic microsomal cytochrome P450 content. Concomitant decrease was also noticed in aminopyrine N-demethylase and benzo[a]pyrene hydroxylase activities. However, aniline hydroxylase activity was only marginally elevated during the infection. Microsomal markers, viz., cytochrome b5, NADH-cytochrome-c reductase, and glucose-6-phosphatase, were not significantly altered. Hepatic tissue exhibited an accumulation of lipids, especially phospholipids, triglycerides, and cholesterol, resulting in fatty necrosis around the central vein region. Isolated hepatic microsomes showed a decrease in phosphatidylcholine content. Impairment in hepatic mixed function oxidase (MFO) activities was further confirmed by prolongation in hexobarbital sleeping time and zoxazolamine-induced paralysis. The hepatic MFO system of A. ceylanicum-infected hamsters responded qualitatively and quantitatively in a manner similar to that of control hamsters, upon stimulation with selective chemical inducers like phenobarbitone and 3-methylcholanthrene. Kinetic and in vitro substrate binding studies revealed that for aminopyrine the substrate affinity and the maximum enzyme activity (Vmax) were decreased, while for aniline the binding affinity was decreased and the binding capacity was enhanced. Results indicate specific/selective impairment of the hepatic microsomal cytochrome P450 system during hookworm infection and may have many practical implications in toxicology and pharmacology.     

Watermelon mosaic virus-Morocco is a distinct potyvirus

Summary The relationship of the Morocco isolate of watermelon mosaic virus (WMV) to WMV 2, soybean mosaic virus (a virus closely related to WMV 2) and the W strain of papaya ringspot virus (PRSV-W), formerly WMV 1, was examined by comparing tryptic peptide profiles using high performance liquid chromatography. The profiles indicated that the coat protein sequence of WMV-Morocco differed substantially from those of the other potyviruses. This conclusion was supported by sequence data from five tryptic peptides from the coat protein of WMV-Morocco, which showed only 61–68% identity to equivalent sequences in PRSV-W, WMV 2 and zucchini yellow mosaic, another potyvirus infecting cucurbits. Based on the above data, and on known correlations between coat protein sequence similarities and potyvirus relationship, it is concluded that WMV-Morocco should be regarded as a distinct potyvirus.     

Trichothiodystrophy type 4 in an Indian family

Trichothiodystrophy, non‐photosensitive type 4 (TTD4), is a rare genetic disorder with an autosomal recessive mode of inheritance. It is characterized by coarse and brittle hair, anomalies of the tissues derived from the neuro‐ectoderm (skin, hair, and nails) and intellectual disability. We herein report two male siblings aged 13 and 16 years with TTD4 and a known homozygous pathogenic variant, c.229del [p.(Arg77Glyfs*76)] in exon 1 of MPLKIP (NM_138701.3). We herein highlight the clinical and molecular findings of the first reported case of TTD4 in probands of Indian ethnicity.     

Mitoxantrone, mitomycin-C, methotrexate combination chemotherapy with radiotherapy and/or surgery in stage III (T4B, NO-2, M0) breast cancer

Results of primary surgery with or without locoregional radiotherapy (LRRT) are poor in stage III (T4b, NO-2, M0) breast cancer. Combination of mitoxantrone, mitomycin-c and methotrexate (MMM) has been reported to be as efficacious as doxorubicin based protocols with advantages of reduced nausea, vomiting, alopecia and cardiotoxicity. We tested MMM chemotherapy with LRRT and surgery in locally advanced breast cancer (LABC) with a view to assess response, survival, breast conservation, cost and toxicity. Fifty two previously untreated patients were given Mitoxantrone: 8 mg/m sq by infusion on days 1 and 21, Mitomycin-C: 8 mg/m sq by infusion on day 1 and Methotrexate: 35 mg/m sq i.v. on days 1 and 21. Cycles were repeated every 42 days. After 3 cycles LRRT was given if lump reduced to less than 2 cms. Otherwise patients were subjected to modified radical mastectomy (MRM) or radical mastectomy (RM). Following this 3 more cycles of chemotherapy were given. Patients with soft tissue, skin or heavy nodal involvement also received LRRT. Tamoxifen 20 mg daily was prescribed at the end of chemotherapy to postmenopausal patients. Complete/partial responses were seen in 5 and 26 patients, respectively after chemotherapy giving an overall response of 59.5%. Twenty four patients each had LRRT and MRM/RM. Responses could be significantly enhanced by LRRT/and or surgery. Nineteen out of 25 relapses were at distant sites. Breast conservation was achieved in 24/52 (46%) patients. Three year disease free and overall survival was 54% and 65%, respectively. There was 1 toxic death. Severe prolonged myelosuppresion was seen in those who also received LRRT. Mucositis, alopecia, nausea and vomiting were minor problems. Overall, combination was less expensive than doxorubicin based protocols.     

Coat protein of potyviruses 7. Amino acid sequence of peanut stripe virus

Summary The amino acid sequence of the 287-residue coat protein of peanut stripe virus (PStV) was determined from the sequences of overlapping peptide fragments. Results indicated that the amino terminus was blocked by an acetyl group, as has previously been found for the coat protein of Johnsongrass mosaic potyvirus. Comparison of the PStV sequence with coat proteins of 20 distinct potyviruses gave sequence identities of 47–57%, except for zucchini yellow mosaic virus (ZYMV), passionfruit woodiness virus (PWV), and the related strains watermelon mosaic virus 2 (WMV 2) and soybean mosaic virus-N, which showed sequence identities of 70–76%. Several amino acid residues which were common to the core sequences of these coat proteins were at positions previously found to be invariant among potyvirus coat proteins. The degree of these similarities suggests that although PStV, WMV 2, ZYMV, and PWV are distinct potyviruses, they share a common ancestor in their evolutionary development.     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Transcription from the gene encoding the herpesvirus entry receptor nectin-1 (HveC) in nervous tissue of adult mouse

Hepatitis C virus core protein, in addition to being a component of the viral capsid, has a number of regulatory functions. Here we showed two bodies of evidence indicating that a fraction of the core protein species is a substrate of the ubiquitin (Ub)-proteasome pathway of targeted proteolysis. First, the core protein processing the C-terminal hydrophobic region is metabolically unstable, and incubation with a proteasome inhibitor led to a significant accumulation of the protein. Second, an in vivo ubiquitylation assay indicates conjugation of multi-Ub chain to the unstable core protein. In contrast, a stable form of core protein, p21, is also able to be ubiquitylated, but it links to a single or only a few Ub moiety. Therefore, processing event(s) at the C-terminal hydrophobic domain of HCV core protein may affect the ubiquitylation pathway, particularly the efficiency of the multi-Ub chain assembly, resulting in stable, matured core proteins.     

Pathological changes in broiler chickens fed ochratoxin A and inoculated with Escherichia coli.

A study was conducted to evaluate the effects of ochratoxin A (OA) on Escherichia coli-challenged broiler chickens. One hundred and eighty-four one-day-old broiler chicks were divided into two groups of 92 chicks each, with one group fed a control mash diet and the other fed a mash diet containing 2 parts/10(6) OA. On day 14, each group was further subdivided into two groups with one group inoculated with E. coli O78 (1 x 10(7) colony-forming units/0.5 ml) by the intraperitoneal route, whereas the other group was not inoculated with E. coli. Four birds from each group were sacrificed at 1, 2, 3, 5, 7, 10, 14 and 21 days post-inoculation to record pathological changes in the liver, kidneys, heart, lungs, bursa, spleen and thymus. E. coli infection induced perihepatitis and pericarditis in the liver and heart, respectively, in chickens infected with E. coli alone or in OA-fed birds from 1 day post-infection (DPI) onwards. At 1 DPI, a thin fibrin layer covered the liver and heart; however, at subsequent days, the layer became thicker. E. coli infection did not produce appreciable changes in the kidneys, bursa or thymus. However, there was congestion of the lungs along with mononuclear cell infiltration. Ochratoxin feeding induced changes from 10 DPI onwards in chicks fed OA alone and those infected with E. coli. The changes in kidneys included swollen proximal convoluted tubules, degeneration of tubular epithelium and interstitial nephritis. Degenerative changes and mononuclear cell infiltration were recorded in the liver. There was atrophy of the lymphoid organs along with depletion of lymphocytes. Gross and histopathological changes were more severe in chickens fed OA and inoculated with E. coli than the chickens fed OA alone or those infected with E. coli, indicating combined action of these two.