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Biomedical subjects

M Ui

Publications and source records attributed to M Ui.

366 records · Page 21Linked to original sources

Functional reconstitution of purified muscarinic receptors and inhibitory guanine nucleotide regulatory protein.

Muscarinic receptors trigger several different responses including an increase in concentration of cyclic GMP, a decrease in cyclic AMP concentration, breakdown of polyphosphoinositides and changes in ion permeability. It is not yet clear whether these reactions occur sequentially or independently and which directly coupled to the muscarinic receptor. Several lines of evidence indicate that muscarinic receptors in many, if not all, cell types are coupled to the inhibitory guanine nucleotide regulatory protein (Ni or Gi) of adenylate cyclase. To provide direct evidence for this coupling, we have reconstituted muscarinic receptors purified from porcine brain with Ni purified from rat brain in a phospholipid vesicle. Here, we report that the GTPase activity of Ni is stimulated by carbachol. This action is blocked by the simultaneous addition of atropine and is not observed when the Ni protein is ADP-ribosylated. We conclude that one function of the muscarinic receptor is the activation of Ni.

Adenosine Diphosphate Ribose↗

Plasma guanosine 3',5'-monophosphate responses to the cold pressor test in patients with vibration disease.

Plasma cyclic guanosine 3',5'-monophosphate (cyclic GMP) levels were determined during the cold pressor test (CPT) in 10 normal volunteers and 39 patients with vibration disease. The CPT caused no significant increase in plasma cyclic GMP in the controls. There was a sharp rise in plasma cyclic GMP during and after the CPT in patients with vibration disease. This increase was suppressed by simultaneous injection of phentolamine or atropine. In patients who had been treated with kallidinogenase or nicametate citrate for 3-6 months, the CPT caused no significant increase in plasma cyclic GMP. In 1 patient the plasma cyclic GMP was suppressed by dihydroergotamine. From these findings it is very likely that cholinergic or alpha-adrenergic receptor responses are enhanced in patients with vibration disease.

Adult↗

Protective immunity of gene-deleted SHIVs having an HIV-1 Env against challenge infection with a gene-intact SHIV.

We constructed three simian-human immunodeficiency viruses (SHIVs) lacking regulatory gene(s) and analyzed their induction of protective immunity against challenge infection with gene-intact SHIV in rhesus macaques. Inoculation of SHIV-dn lacking nef and SHIV-drn lacking nef and vpr induced transient viremia, while that of SHIV-dxrn lacking nef, vpr, and vpx induced no viremia. The SHIVs with fewer deletions were more effective in inducing neutralizing antibodies and cytotoxic T lymphocyte responses. When these macaques were challenged with parental gene-intact SHIV-NM-3rN, all the SHIV-dn-vaccinated macaques and two of the four SHIV-drn-vaccinated macaques showed complete resistance. The other two SHIV-drn-vaccinated macaques and all SHIV-dxrn-vaccinated macaques did not show complete resistance, but they did show suppression of replication of the challenge virus. These results suggested that as more genes were deleted, protective immunity was decreased.

AIDS Vaccines↗