Biomedical subjects
K Ghosh
Publications and source records attributed to K Ghosh.
Aberrant CD8 antigen expression in a patient with B chronic lymphocytic leukaemia showing unusual disease progression.
Co-expression of T cell antigens in B-CLL has been well recognized. The commonest T cell antigen known to be expressed in B-CLL is CD5, and recent reports suggest that CD5 expression is associated with good prognosis. Expression of CD8 antigen, however, is much less common with uncertain prognostic significance. We report a case of B-CLL with aberrant CD8 expression, who had unusual disease progression with a fatal outcome.
Removal of cytomegalovirus (CMV) infected leucocytes from CMV seropositive blood units by bedside blood filtration.
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Effects of deletions in the carboxy-terminal hydrophobic region of herpes simplex virus glycoprotein gB on intracellular transport and membrane anchoring.
The gB glycoprotein of herpes simplex virus type 1 is involved in viral entry and fusion and contains a predicted membrane-anchoring sequence of 69 hydrophobic amino acids, which can span the membrane three times, near the carboxy terminus. To define the membrane-anchoring sequence and the role of this hydrophobic stretch, we have constructed deletion mutants of gB-1, lacking one, two, or three predicted membrane-spanning segments within the 69 amino acids. Expression of the wild-type and mutant glycoproteins in COS-1 cells show that mutant glycoproteins lacking segment 3 (amino acids 774 to 795 of the gB-1 protein) were secreted from the cells. Protease digestion and alkaline extraction of microsomes containing labeled mutant proteins further showed that segment 3 was sufficient for stable membrane anchoring of the glycoproteins, indicating that this segment may specify the transmembrane domain of the gB glycoprotein. Also, the mutant glycoproteins containing segment 3 were localized in the nuclear envelop, which is the site of virus budding. Deletion of any of the hydrophobic segments, however, affected the intracellular transport and processing of the mutant glycoproteins. The mutant glycoproteins, although localized in the nuclear envelope, failed to complement the gB-null virus (K082). These results suggest that the carboxy-terminal hydrophobic region contains essential structural determinants of the functional gB glycoprotein.
Haemoglobinopathies in a large hospital in Kuwait.
One year experience of various haemoglobinopathies encountered in a large hospital in Kuwait is presented. During the period under study (1988), 84,341 complete blood counts (CBC's) were performed. Haemoglobin electrophoresis was performed in 1289 of these samples; 261 abnormal results were encountered. Almost all the commonly occurring haemoglobinopathies in the world were seen among Kuwaities, probably as a result of inheritance of different haemoglobinopathy genes from different parts of the world. Indirect evidences suggest that alpha thalassemia may be the commonest haemoglobinopathy in Kuwait; a picture not unlike that of Saudi Arabia which is one of its neighbours.
Phosphorothioate-phosphodiester oligonucleotide co-polymers: assessment for antisense application.
Efforts have been made to reduce the disadvantages associated with the natural oligonucleotides (all-PO) for antisense application by introducing phosphorothioate (PS) linkages into the molecule. A series of such oligodeoxynucleotide copolymers (17-mers) complementary to the coding region of the rabbit beta-globin mRNA, and containing different proportions and arrangements of PO and PS bonds, were synthesized and tested for their protein-binding properties, nuclease stability in vitro, hybridizing ability with the complementary DNA (cDNA), ability to form RNase H-sensitive substrates and antisense activity in cell-free systems. The melting temperatures (Tm) of the co-polymers were reduced by up to 6 degrees C relative to the all-PO oligo, compared to 11 degrees C for the all-PS compound, indicating intermediate hybridizing abilities of the co-polymers. The protein-binding studies with human serum albumin exhibited a linear correlation with the percentage of PS linkage present in the molecule. Nuclease susceptibilities of the co-polymers were also improved, but the number and position of the PS linkages played a significant role in such improvement. Translation inhibition by these oligonucleotides was only found in wheat germ agglutinin (WGA) extract, but not in rabbit reticulocyte lysate (RRL) cell-free system, suggesting the involvement of RNase H in their antisense activities. Provided they have > or = 50% PS linkages, the co-polymers produced almost the same increased inhibition in the WGA system as that of the all-PS oligo. The translation arrest in WGA extract is in good agreement with the in vitro cleavage found for rabbit globin mRNA in the oligo:mRNA duplex by RNase H alone. It is concluded that a copolymer of PO and PS might be preferable to either all-PO or all-PS for antisense applications.
Cell physiology of antisense TGF-beta oligomers in hepatoma cells.
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Magnetism and superconductivity in Sc5-xDyxIr4Si10 alloys.
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Antiferromagnetism in the Dy5Ir4Si10 system.
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Extensive venous thrombosis in a case of Behçet's disease associated with heterozygous protein C deficiency.
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Transient abnormal myelopoiesis in Down's syndrome--are some of them truly leukaemic?
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A family outbreak of Chlamydia pneumoniae infection.
Chlamydia pneumoniae, a newly described Chlamydia species, has been shown to be a cause of acute respiratory tract infection in both adults and children, but its role in human infection is still under investigation. Here we present a family outbreak of C. pneumoniae infection where three members of a family presented with a 'flu-like illness' and acute upper respiratory tract infection which did not improve despite penicillin or septrin therapy. No history of exposure to birds, pets or animals was obtained. As C. pneumoniae isolation from respiratory secretions is not without difficulty, diagnosis usually relies currently on serum-based tests. In this study C. pneumoniae specific IgM determined by the micro-immunofluorescence test was detected in the three clinical cases. All three cases had an elevated complement-fixing antibody titre to Psittacosis-LGV antigen, which may have suggested psittacosis, if type-specific tests had not been performed. In addition, three other members of the family had C. pneumoniae-specific IgG antibody although specific IgM was absent. These three younger members of the family had been symptomatic in the month preceding symptoms in their older sibling and their parents. All the symptomatic members of the family made a complete recovery on tetracycline therapy.
Surveillance of Mycoplasma pneumoniae infections in Scotland 1986-1991.
Mycoplasma pneumoniae is the second most common cause of community-acquired pneumonia. Infection is found worldwide and epidemics are said to occur in 4-yearly cycles. In Scotland this pattern has been noted since 1982 and, in common with England and Wales as well probably as other parts of Europe, there is a current epidemic which began in the autumn of 1990. The disease has been noted predominantly in children and young adults, with lower respiratory tract infection as the most common manifestation. At present, diagnosis is based on a serological response and various tests are available for detecting both primary infection and reinfection. In view of the present epidemic, initial treatment of respiratory-tract infection, especially in children and young adults, should include adequate cover against Mycoplasma pneumoniae.
A comparison of gag, pol and rev antisense oligodeoxynucleotides as inhibitors of HIV-1.
Sequences from the gag, pol and rev regions of the RF strain of HIV-1 (HIV-1RF) were chosen as targets for antisense phosphorothioate oligodeoxynucleotides (S-oligos). These sequences were the p18/p24 junction in gag, the active site of HIV protease in pol; a sequence from the first exon of the rev gene and S-oligodeoxycytidylic acid controls. Compounds were tested against HIV-1 in both acutely and chronically infected cells. The results show that these phosphorothioate analogues tested in acutely infected cells were active in the 0.1-2 microM range, were dependent on chain length but had no sequence specificity. To study the mechanism of action, the time of addition of S-oligos to acutely infected cells was delayed for up to 48 h post-infection. It was found that antiviral activity was lost when compounds were added to the cultures later than 10 h post-infection. With chronically infected cells only the antisense rev sequence showed activity at 30 microM and neither of the gag or pol antisense sequences has a significant effect on HIV replication at 50 microM. These results are consistent with previous in vitro studies which demonstrate that antisense S-oligodeoxynucleotides have several modes of action.
Translation inhibition by phosphorothioate oligodeoxynucleotides in cell-free systems.
A detailed comparison was made of the concentration dependence of translation inhibition by phosphorothioate and phosphodiester oligodeoxynucleotides of the same anti-beta-globin sequence in cell-free systems using beta-globin mRNA and unrelated mRNAs as controls. The results confirm that at low concentrations the phosphorothioate oligomer is more potent as an antisense compound, while at higher concentration (greater than 4 microM) it exhibits more nonspecific inhibition than the phosphodiester oligomer for RNase H-mediated translation inhibition.
Antisense oligonucleotides: inhibition of liver cell proliferation and in vivo disposition.
As oligomers inhibited hepatoma growth in vitro. These cells have oligomer-specific binding sites. The oligomers were taken up by liver and have potential for hepatic growth modulation in intact animals.
Critical behavior in the dielectric properties of random self-similar composites.
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Studies on the mechanism of synthesis and release of the procoagulant activity from leukaemic cells.
The synthesis and release of procoagulant activity (PCA) from leukaemic leucocytes was studied in an in vitro culture system stimulated by endotoxin. Puromycin, actinomycin-D, vinblastine, colchicine, dibutyryl cyclic AMP and ouabain were added to the culture system to study some of the metabolic processes of these cells in relation to synthesis and release of PCA. It was found that production of PCA is an active process and depends on new protein synthesis. The release of PCA from cells can be inhibited by vinblastine, an inhibitor of microfilament and microtubules in the cell. The optimal release of PCA occurs at pH 7.2-7.4 at 37 degrees C and is not inhibited by the ATPase inhibitor ouabain. Dibutyryl cyclic AMP inhibits the release/synthesis of PCA. Gram negative septicaemia and endotoxinaemia are capable of increased production and release of PCA from leukaemic cells and could contribute to the coagulation failure seen in this disease.