The South Asian Origins of the Global Network to Eradicate Blindness: WHO, NGOs, and Decentralization.

The global network to eradicate blindness emerged out of the work of Western and South Asian professionals to eradicate smallpox which was endemic in South Asia. The history of the emergence of the global network to eradicate blindness demonstrates a shift from vertical command and control public health programs directed by the WHO, to the decentralized public health services originating in non-profit, non-governmental organizations and coordinated by the WHO. The WHO constitution started with a federal regionalist structure that encouraged collaboration and coordination with NGOs. In South Asia in particular, epidemiologists and general medical practitioners moved from eradicating smallpox through the WHO to creating their own domestic and international NGOs based in various countries with a mission to control blindness in South Asia and Africa. In 1975, pushed by the WHO Director General, these new NGOs in turn joined with individual ophthalmologists and existing blind member associations to form the International Agency for the Prevention of Blindness. Thus, the WHO was shaped by, and shaping, international NGOs such as the IAPB. The IAPB pushed for the formation of the WHO Prevention of Blindness program. This was the earliest example of how the IAPB facilitates bottom-up agenda-setting in the WHO. In 1980, when the WHO officially closed the smallpox program, the Prevention of Blindness program first received independent funding. Presently, the IAPB acts as a decentralized arm of the WHO.

Cloning and sequence analysis of a putative transcription factor (MTF1) gene from Mucor circinelloides.

We describe here the fortuitous cloning of a putative transcription factor gene (MTF1) from the dimorphic fungus Mucor circinelloides. Sequence analysis of MTF1 revealed an open reading frame (ORF) of 1059 nucleotides encoding a protein of M(r) 39601. The deduced amino acid sequence from the ORF imparts two glutamine-rich stretches which are homologous to a number of transcription factors characterized previously from various organisms. A Southern blot analysis of Mucor genomic DNA digested with different restriction endonucleases and probed with the 1.9 kb EcoR1 fragment of the putative transcription factor gene shows a single copy number of the the gene. Northern analysis during morphogenetic changes in Mucor suggested constitutive expression of the gene.

The carboxypeptidase Y-encoding gene from Candida albicans and its transcription during yeast-to-hyphae conversion.

We have cloned and sequenced the gene (CPY1) encoding the carboxypeptidase Y (CPY) of Candida albicans. The gene contains an open reading frame comprising 542 amino acids (aa) with an M(r) of 61,104. The aa sequence shows 74% identity to the mature CPY aa sequence from Saccharomyces cerevisiae. The putative pre (signal) and pro sequences at the N terminus of the C. albicans protein, however, show significant divergence from the corresponding prepro sequence of the S. cerevisiae protein. Southern analysis of C. albicans genomic DNA suggested the presence of only one CPY-encoding gene. Northern analysis during yeast-to-hyphae conversion suggested that the CPY1 gene is transiently down-regulated on a transcriptional level during the early events of this developmental switch.

Purification and characterization of a developmentally regulated carboxypeptidase from Mucor racemosus.

A developmentally regulated carboxypeptidase was purified from hyphae of the dimorphic fungus Mucor racemosus. The enzyme, designated carboxypeptidase 3 (CP3), has been purified greater than 900-fold to homogeneity and characterized. The carboxypeptidase migrated as a single electrophoretic band in isoelectric focusing polyacrylamide gel electrophoresis (PAGE), with an isoelectric point of pH 4.4. The apparent molecular mass of the native enzyme was estimated by gel filtration to be 52 kDa. Sodium dodecyl sulfate (SDS)-PAGE under nonreducing conditions revealed the presence of a single polypeptide of 51 kDa. SDS-PAGE of CP3 reacted with 2-mercaptoethanol revealed the presence of two polypeptides of 31 and 18 kDa, indicating a dimer structure (alpha 1 beta 1) of the enzyme with disulfide-linked subunits. By using [1,3-3H]diisopropylfluorophosphate as an active-site labeling reagent, it was determined that the catalytic site resides on the small subunit of the carboxypeptidase. With N-carboben zoxy-L-phenylalanyl-L-leucine (N-CBZ-Phe-Leu) as the substrate, the Km, kcat, and Vmax values were 1.7 x 10(-4) M, 490 s-1, and 588 mumol of Leu released per min per mg of protein, respectively. CP3 was determined to be a serine protease, since its catalytic activity was blocked by the serine protease inhibitors diisopropylfluorophosphate, phenylmethylsulfonyl fluoride, and 3,4-dichloroi Socoumarin (DCI). The enzyme was strongly inhibited by the mercurial compound p-chloromercuribenzoate. The carboxypeptidase readily hydrolyzed peptides with aliphatic or aromatic side chains, whereas most of the peptides which contained glycine in the penultimate position did not serve as substrates for the enzyme. Although CP3 activity was undetectable in Mucor yeast cells, antisera revealed the presence of the enzyme in the yeast form of the fungus. The partial amino acid sequence of the carboxypeptidase was determined.

Pain relief for outpatient colonoscopy: a comparison of alfentanil with fentanyl.

Alfentanil was used as an adjuvant to midazolam for analgesia in thirty outpatients undergoing colonoscopy. A similar group of thirty outpatients received fentanyl. The operating conditions and recovery times of the two groups were compared. Alfentanil usage resulted in better operating conditions. Recovery time was similar. Patient acceptance was high. No patient suffered respiratory depression during or after the procedure.

Peptide transport in Candida albicans.

The tripeptide L-methionyl-L-methionyl-L-[METHYL-14C]methionine was taken up into Candida albicans by a saturable system with a pH optimum of 3.5, a temperature optimum of 37 degrees C and an apparent Km of 3.3 x 10(-5) M. Metabolic inhibitors such as sodium azide and dinitrophenol completely prevented uptake. Neither methionine nor dimethionine effectively competed with trimethionine uptake. (Leu)3, Gly-Met-Gly, acetyl-(Met)3, D-Met-L-Met-L-Met and Met-Met-Ile effectively competed with (Met)3 uptake, whereas (Lys)3, L-Met-L-Met-D-Met, D-Met-D-Met-D-Met, (Met)3 methyl ester and (Ala)3 did not. Trimethionine was rapidly hydrolysed by a peptidase after entry into the cell.

Postoperative pulmonary function. A comparison of ventilation with nitrogen or nitrous oxide during anaesthesia.

Arterial blood-gases and lung volumes were measured in 48 patients before and after upper abdominal surgery. There was no significant difference between the results of 25 patients ventilated with oxygen and nitrogen during anaesthesia compared with a comparable group which received oxygen and nitrous oxide.

Respiratory effects of extradural nerve block in the postoperative period.

The effects of continuous extradural block in the postoperative period on arterial hypoxaemia are discussed. Comparing two matched groups of patients following upper abdominal surgery, one receiving continuous extradural analgesia and one narcotic analgesia, there were small but statistically insignificant improvements in PaO2 in the former group. It was concluded that abdominal muscle spasm is not an important cause of postoperative arterial hypoxaemia.