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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 91 records · Page 5Linked to original sources

Extracorporeal shock wave lithotripsy for radiolucent stones.

Eleven patients with radiolucent urinary calculi were treated with shock wave lithotripsy. Nine of these patients experienced successful fragmentation of their stones and subsequent spontaneous passage of the calculi fragments. The majority of the stones were composed of uric acid alone or a mixture of uric acid and calcium oxalate. One stone with metabolites of triamterene also fragmented well. Uric acid calculi can be treated successfully with shock wave lithotripsy using adequate visualization by contrast injection.

Adult

Spontaneous rupture of normal spleen: an enigma recalled.

That a normal spleen can rupture spontaneously has long been a point of debate. A definitive case is reported here in an attempt to resolve the issue in its favour. Spleen involved in tropical diseases like malaria, infectious mononucleosis and typhoid fever is prone to rupture spontaneously as well as in cases follow minor trauma. In contrast, normal spleen ruptures almost always following severe trauma, such as road accidents or fall from significant heights. Though cases of spontaneous rupture of normal spleens have appeared off and on in the past, doubt has always surrounded the very existence of such an entity. We are reporting a definitive case of spontaneous rupture of normal spleen. This is only the second case of its kind since 1958 and the first ever from the Indian subcontinent.

Adult

Protection of mouse oesophageal mucosa against gamma rays injury.

The alterations in the oesophageal epithelium were studied in mice after a single whole-body exposure to 7.5 Gy of Co-60 gamma rays in presence or absence of 2-mercaptopropionyl glycine. The epithelium showed an increase in the thickness which reached a maximum on the third day and then decreased gradually up to seventh day after irradiation in the non-drug treated group. In the 2-mercaptopropionyl glycine treated animals the epithelial thickness remained in the normal range except on the day 7 when it was significantly lower than normal. The total cell population registered a steady decline from one to seven days post-irradiation in both groups, but the number of cells was more in the 2-mercaptopropionyl glycine treated group. The number of pycnotic nuclei showed an inverse relationship to the total cell population, it increased continuously up to seven days in both the protected and non-protected groups. However, pycnotic nuclei were significantly lower in the protected group on days 3, 5 and 7 in non-protected group.

Animals

Bone metastases in the patients of carcinoma cervix.

Seventeen of 620 patients (2.7%) of cancer cervix were diagnosed to have bone metastasis (BM). In three bone metastasis were seen at initial presentation; remaining 14 developed BM in 3 to 36 months after the diagnosis of cancer cervix. Backache (8), localised pain (8), in thigh/hip/neck paraparesis (1) were main symptoms. The duration of symptoms ranged from 1 to 4 (median 2.5) months. Lumber spine, pelvic bones and long bones were the commonest site of involvement. The lesions were single in 12 and at multiple sites in five patients. Radiologically the lesions were osteolytic in all except three where Tc99m bone scan showed increased uptake of radionuclide. Palliative radiotherapy resulted in significant symptomatic relief.

Adult

Testing a test.

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Diagnostic Tests, Routine

Posttraumatic hematoma of iliacus muscle with paralysis of the femoral nerve.

One case of traumatic rupture of the iliacus muscle associated with a femoral nerve paralysis is described. The clinical picture was characterized by posttraumatic gradual worsening of pain in the groin, a tender mass in the iliac fossa, flexion deformity of the hip, and femoral nerve paralysis. The review of literature revealed a description of only nine similar cases. Early evacuation of the hematoma is suggested.

Adult

Siderotic cerebral macrophages in the acquired immunodeficiency syndrome.

Excessive hemosiderin-laden perivascular macrophages have been described in the brains of patients with the acquired immunodeficiency syndrome (AIDS) who underwent autopsy; its meaning remains unclear. In the brains of 53 patients with AIDS who consecutively underwent autopsy, we quantified the abnormality, elucidated its relationship to the pathologic features of AIDS, and asked if there was some relationship to endogenous iron storage and transport proteins in brain macrophages and microglia. The number of perivascular siderotic macrophages was significantly increased in patients with AIDS compared with age-matched control subjects. Macrophage siderosis was strongly correlated with the presence of disseminated mycobacterial infection and vacuolar myelopathy at autopsy; a generalized wasting (cachexia) also was related significantly. Many other pathologic abnormalities were not related, including putative human immunodeficiency virus-specific neuropathologic changes such as multinucleated cells and myelin pallor. Activated macrophages and microglial cells in the central nervous system had dense intracytoplasmic accumulation of ferritin (iron storage protein) in AIDS and non-AIDS patients. These results suggest that siderosis of cerebral macrophages is related to an ill-defined nonspecific systemic imbalance associated with the breakdown of abundant stores of endogenous intracellular ferritin. Understanding chronic "secondary" effects of human immunodeficiency virus type 1 infection will become increasingly important as improved survival in patients with AIDS is realized.

Acquired Immunodeficiency Syndrome

A novel method for the isolation of nematode larvae using pluronic F-68-treated cellulose strips.

A new method is described for the isolation of cultured nematode larvae. This allows effective separation of larvae from fecal contamination, exsheathed larvae from cast sheaths, and viable larvae from nonviable larvae. The method involves the use of cellulose strips and has been assessed using larvae from 2 hookworm species, Necator americanus and Ancylostoma ceylanicum. Pretreatment of the cellulose strips with 1.0% (w/v) of the nonionic surfactant, Pluronic F-68, significantly increased larval recovery of both species.

Ancylostoma

Transcriptional activity of rel family proteins.

Our studies originally demonstrated that the v-rel oncoprotein repressed gene expression in chicken lymphoid cells, while it activated transcription in rodent fibroblasts. Here we report that the c-rel protein can activate expression of genes linked to kappa B motifs when low levels of endogenous kappa B-binding activity are present. In contrast v-rel, and to a lesser extent c-rel, inhibit NF-kappa B-mediated activation of the human immunodeficiency virus long terminal repeat (HIV LTR) in phorbol ester-stimulated HeLa cells. Competition assays show that v-rel competitively inhibits both NF-kappa B and c-rel-mediated transcriptional activation. Analysis of mutant HIV LTR-chloramphenicol acetyltransferase (CAT) constructs in which all Sp1 or both NF-kappa B elements have been deleted shows that NF-kappa B motifs are required for rel-mediated effects on gene expression. Transforming v-rel mutants compete efficiently with phorbol ester-activated kappa B factors, whereas a transformation-defective mutant of v-rel is impaired in this activity. Taken together, these results strengthen the hypothesis that v-rel functions as a dominant interfering member of rel family proteins. These results also suggest that the ability of v- and c-rel to activate or repress gene expression in specific cells may result from their capacity to compete with endogenous rel family proteins whose expression and/or activity are cell-specific.

Base Sequence

Molecular evolution of the urate oxidase-encoding gene in hominoid primates: nonsense mutations.

Nucleotide sequences of portions of second and fifth exons of urate oxidase encoding gene (UOX) of chimpanzee, gorilla, orangutan, rhesus monkey and squirrel monkey obtained following amplification by polymerase chain reaction have been compared with corresponding sequences of human, baboon and rat UOX. Two or more nonsense mutations are found in the coding regions of this UOX gene thus far analyzed in human, chimpanzee, gorilla and orangutan, but not in the baboon, rhesus monkey and squirrel monkey. Of these nonsense mutations, the stop codon at amino acid position 33 is constant in the human and the three great apes suggesting that this may be the original mutation responsible for the inactivation of the UOX gene during hominoid evolution.

Amino Acid Sequence

Conserved chromatin structure in c-myc 5'flanking DNA after viral transduction.

The role of local sequence information in establishing the chromatin structure of the human c-myc upstream region (MUR) was investigated. Adeno-associated virus (AAV)-mediated gene transduction was used to introduce an additional unrearranged copy of the 2.4 kb HindIII-XhoI fragment of the MUR into a novel location in the genome in each of two cloned HeLa cell lines. The AAV-based rep- cap- viral vector SKMA used to transduce the MUR retained only 1.4 kb (24%) of the AAV genome and could accommodate inserts as large as 2.4 kb. SKMA was capable of infecting HeLa cells and integrating into the host genome at single copy number. Integration may have occurred at a preferred site in the HeLa genome, but this site was apparently distinct from the previously identified preferred AAV integration site on human chromosome 19. Indirect end-labelling was used to map DNase I and micrococcal nuclease (MNase) cleavage sites over the transduced c-myc sequences and the endogenous c-myc loci in infected HeLa cells. A similarly ordered chromatin domain, extending 5' from c-myc promoter P0, was found to exist at the transduced c-myc locus in each clone. The position and relative sensitivity of 13 MNase cleavage sites and five DNase I hypersensitive sites, originally identified at the endogenous MUR in non-transduced cells, were shown to be conserved when this DNA was moved to a new chromosome site. A conserved DNase I hypersensitive site also was mapped to the region between the left AAV terminal repeat and AAV promoter P5. These results suggest that the information required to establish the particular chromatin structure of the MUR resides within the local DNA sequence of that region.

Adenoviruses, Human

Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type-2.

Pretreatment of HT-1080 fibrosarcoma cells with tumor necrosis factor (TNF) induced resistance to the cytolytic activity of this cytokine in combination with cycloheximide. This resistance correlated with the synthesis of plasminogen activator inhibitor type-2 (PAI-2). HT-1080 cells were transfected with a PAI-2 expression vector in both sense and antisense orientation. The resistance to TNF-mediated cytolysis of transfected cell clones was correlated with the level of PAI-2 expression. Cells expressing antisense PAI-2 RNA showed reduced expression of PAI-2 and increased sensitivity to TNF-mediated cytolysis. Cells expressing constitutively PAI-2 were treated with TNF and cycloheximide to select cells with increased resistance to cytolysis and enhanced PAI-2 expression. PAI-2 gradually disappeared during a treatment with TNF and cycloheximide. This finding suggested that PAI-2 formed a complex with a target proteinase, which could be involved in mediating the cytolytic activity of TNF.

Blotting, Northern

Evidence for domain organization within the 61-kDa calmodulin-dependent cyclic nucleotide phosphodiesterase from bovine brain.

The complete amino acid sequence of the 61-kDa calmodulin-dependent, cyclic nucleotide phosphodiesterase (CaM-PDE) from bovine brain has been determined. The native protein is a homodimer of N alpha-acetylated, 529-residue polypeptide chains, each of which has a calculated molecular weight of 60,755. The structural organization of this CaM-PDE has been investigated with use of limited proteolysis and synthetic peptide analogues. A site capable of interacting with CaM has been identified, and the position of the catalytic domain has been mapped. A fully active, CaM-independent fragment (Mr = 36,000), produced by limited tryptic cleavage in the absence of CaM, represents a functional catalytic domain. N-Terminal sequence and size indicate that this 36-kDa fragment is comprised of residues 136 to approximately 450 of the CaM-PDE. This catalytic domain encompasses a approximately 250 residue sequence that is conserved among PDE isozymes of diverse size, phylogeny, and function. CaM-PDE and its PDE homologues comprise a unique family of proteins, each having a catalytic domain that evolved from a common progenitor. A search of the sequence for potential CaM-binding sites revealed only one 15-residue segment with both a net positive charge and the ability to form an amphiphilic alpha-helix. Peptide analogues that include this amphiphilic segment were synthesized. Each was found to inhibit the CaM-dependent activation of the enzyme and to bind directly to CaM with high affinity in a calcium-dependent manner. This site is among the sequences cleaved from a 45-kDa chymotryptic fragment that has the complete catalytic domain but no longer binds CaM. These results indicate that residues located between position 23 and 41 of the native enzyme contribute significantly to the binding of CaM although the involvement of residues from additional sites is not excluded.

3',5'-Cyclic-AMP Phosphodiesterases

Amino acid sequence of nitrite reductase: a copper protein from Achromobacter cycloclastes.

The amino acid sequence of the copper-containing nitrite reductase (EC 1.7.99.3) from Achromobacter cycloclastes strain IAM 1013 has been determined by using peptides derived from digestion with Achromobacter protease I (Lys), Staphylococcus aureus V8 protease (Glu), cyanogen bromide, and BNPS-skatole in acetic acid. The subunit contains 340 amino acids. The identity of the first seven amino acids is tentative. The sequence has been instrumental in the X-ray structure determination of this molecule; in conjunction with the X-ray structure, ligands to a type I copper atom and a type II copper atom (one of each per subunit) have been identified. Comparison of the sequence to those of multi-copper oxidases such as ascorbate oxidase, laccase, and ceruloplasmin [Messerschmidt, A., & Huber, R. (1990) Eur. J. Biochem. 187, 341-352] reveals that each of two domains seen in the X-ray structure is similar to the oxidases and also to the small blue copper-containing proteins such as plastocyanin. The combination of sequence and structural similarity to ascorbate oxidase and sequence similarity to ceruloplasmin leads to a plausible model for the domain structure of ceruloplasmin.

Alcaligenes