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Biomedical subjects

B Ramachandran

Publications and source records attributed to B Ramachandran.

23 records · Page 2Linked to original sources
PubMed1990

Structural and functional comparison of the genes for human platelet factor 4 and PF4alt.

Platelet factor 4 (PF4) is a 70 amino acid heparin-binding protein released from the alpha-granules of activated platelets. Its exact biologic function is not known, although PF4 is a member of a multigene family involved in chemotaxis, coagulation, inflammation, and cell growth. We previously cloned the cDNA for human PF4 from a human erythroleukemic (HEL) cell expression library. We now report the isolation and sequence determination of the gene for human PF4. This gene contains three exons and spans approximately 1,000 basepairs (bp). Concurrently, we have cloned a highly homologous gene that we have called PF4alt. We show that PF4 and PF4alt are non-allelic genes: the human PF4 gene is encoded on a 10 kilobasepairs (kb) EcoRI fragment, and its DNA sequence agrees with protein and cDNA data for PF4, while PF4alt is encoded in a polymorphic 3 or 5 kb EcoRI fragment. Compared with PF4, this gene has 14% DNA and 38% amino acid divergence in the signal peptide region, and 2.6% DNA and 4.3% amino acid divergence in the coding region of the mature protein. PF4alt contains three amino acid substitutions (P58----L, K66----E, and L67----H) near the C-terminus, in a region known to be critical for PF4 function. Primer extension studies show the 5'-untranslated region of PF4 is 73 bp long. A TATA box is present 30 bp 5' to the transcription start site. A 90 bp stretch of pyrimidines (including 53 consecutive thymidine residues) begins at -227 bp and is analogous to a similar region of 30 residues 5' to the rodent PF4 gene. This pyrimidine-rich region is absent from the PF4alt gene; however, DNA homology exists between the two human genes in the 5'- and 3'-flanking regions and extends for over 3.6 kb. Alternating purine/pyrimidine tracts occur both 5' and 3' to PF4 and PF4alt but do not define the endpoints of the gene duplication, which extend beyond these sequences at least at the 5' end. Northern blot analysis using gene-specific oligonucleotides and platelet RNA showed an 800 or 900 nucleotide (n) message for PF4 and PF4alt, respectively. Northern blot and primer extension studies show that steady-state platelet PF4 mRNA levels are approximately one magnitude greater than PF4alt mRNA levels. Thus, these studies demonstrate that PF4alt mRNA is expressed in platelets. Whether PF4alt protein is expressed remains to be determined, and the nature of its biologic function needs to be studied.(ABSTRACT TRUNCATED AT 400 WORDS)

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Hypoglycemic effect of macrocyclic binuclear oxovanadium (IV) complex on streptozotocin-induced diabetic rats.

Though vanadium complexes mimic the action of insulin, owing to their toxicity, research is still in progress for a new vanadium complex with maximum efficacy at low concentration and without any side effects. A novel macrocyclic binuclear oxovanadium complex was synthesized, its composition and structure were confirmed by spectral studies and its efficacy was studied in streptozotocin-induced diabetic rats over a period of 30 days. The oral administration of the complex normalizes the blood glucose level in the diabetic rats and also maintains normoglycemia after a glucose load. The biochemical studies revealed that the complex is not toxic to the system. The nontoxic nature of this complex may be due to the presence of the vanadyl ions in an intact form. The study highlights the nontoxic and hypoglycemic effects of the new macrocyclic binuclear oxovanadium complex.

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