Highly selective vagotomy and duodenal ulcers that fail to respond to H2 receptor antagonists

A study was conducted to see whether patients with duodenal ulcers that failed to heal in response to H₂ receptor antagonists had a higher incidence of recurrent ulceration after highly selective vagotomy than patients whose ulcers healed with these drugs. Between 1977 and 1983, 157 patients had a highly selective vagotomy for uncomplicated duodenal ulcer; in 57 patients the ulcer had failed to heal despite treatment with H₂ receptor antagonists (refractory group), 19 patients had developed recurrent ulceration while receiving maintenance treatment, 67 patients had remained healed while taking H₂ receptor antagonists but suffered frequent relapses when treatment was stopped, and 14 patients had not been given these drugs before operation. The overall incidence of recurrent ulceration was 6% after two years and 11% after five years of follow up. In the refractory group, however, the incidence of recurrent ulceration was 18% at two years and 34% after five years, whereas the incidence of recurrence was only 1.5% at two years and 3% after five years in patients whose ulcers had healed with H₂ receptor antagonists. Resistance to H₂ receptor antagonists was not related to preoperative basal or peak acid output but was related to cigarette smoking. Factors associated with recurrent ulceration after highly selective vagotomy were basal acid outputs before and after operation, cigarette smoking, and the surgeon who performed the operation.Duodenal ulcers that fail to respond to H₂ receptor antagonists represent a more severe ulcer diathesis, for which highly selective vagotomy is less effective.     

An interspecific linkage map of mouse chromosome 15 positioned with respect to the centromere

We have used an interspecific backcross between C57BL/6J and Mus spretus to derive a molecular genetic linkage map of chromosome 15 that includes 25 molecular markers and spans 93% of the estimated length of chromosome 15. Using a second interspecific backcross that was analyzed with a centromere-specific marker, we were also able to position our map with respect to the chromosome 15 centromere. This map provides molecular access to many discrete regions on chromosome 15, thus providing a framework for establishing relationships between cloned DNA markers and known mouse mutations and for identifying homologous genes in mice and humans that may be involved in disease.     

Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels.

Changes in intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons were measured using intracellularly injected fura-2. A large component of the [Ca2+]i elevation caused by high frequency stimulation of the Schaffer collaterals was correlated with the Na+ spikes triggered by the excitatory postsynaptic potentials (EPSPs). These spikes were generated in the soma and proximal dendrites and stimulated Ca2+ entry through voltage-gated Ca2+ channels. Suppressing spikes by hyperpolarizing the soma or by injecting QX-314 revealed a smaller nonspike component of Ca2+ entry. A substantial fraction of this component was mediated by the action of the EPSPs on voltage-gated Ca2+ channels, because it persisted in 2-amino-5-phosphonovaleric acid and because it was usually reduced when Ca2+ channel activity was suppressed by hyperpolarization. Ca2+ entry through the N-methyl-D-aspartate receptor channel could not be detected with certainty, perhaps because it was highly localized.     

An evaluation of several adjuvant emulsion regimens for the production of polyclonal antisera in rabbits.

Emulsion adjuvants have been used for production of polyclonal antisera in rabbits (Oryctolagus cunniculi) for decades. Complete Freund's adjuvant has a reputation as a very effective immunoenhancer, but adverse physiological effects, including fever, inflammation and sterile abscess formation, have prompted a search for alternatives to complete Freund's. In this study, we quantitatively compared five adjuvant regimens: (a) a primary inoculation with complete Freund's followed by three boosts with incomplete Freund's; (b) four serial inoculations of incomplete Freund's adjuvant augmented with 6-bromoguanisine; (c) four serial inoculations with RIBI's MPL + TDM + CWS adjuvant emulsion; (d) four serial inoculations with Montanide ISA 50 emulsion; and (e) four serial inoculations with Montanide ISA 70 emulsion. We chose a small (12 amino acid) chain polypeptide coupled to bovine serum albumin as our test antigen. When compared, no system could be seen to be significantly better than a regimen of a primary immunization with complete Freund's adjuvant followed by serial reimmunization with incomplete Freund's adjuvant. The commercially available RIBI adjuvant produced significantly lower antibody levels, while other systems produced essentially equivalent levels. With all five adjuvants, antibody quantities plateaued after the second injection and further immunization did not increase titers significantly. Boost injections did yield greater intradermal tissue reaction than primary inoculations, and intramuscular inoculum volumes of 0.4 cc caused chronic lesions still detectable by the gross necropsy 2 weeks after the final injection.     

Liver transplantation in 100 children: Cambridge and King's College Hospital series.

To review the results of the Addenbrooke''s and King''s College Hospital children''s liver transplantation programme.Retrospective analysis of the first 100 children to receive liver grafts at Addenbrooke''s Hospital, Cambridge, from December 1983 to March 1990.Addenbrooke''s Hospital, Cambridge, and King''s College Hospital, London.153 children assessed for liver transplantation, of whom 22 died before a donor became available and 31 were considered unsuitable. 100 children received grafts, of whom 27 had second grafts.One year actuarial patient survival was 71%, with 57% one year graft survival. In the last two years survival rates had improved considerably, with 86% of patients and 63% of grafts surviving for at least one year. Sixty five children were alive 12 to 86 months after transplantation; 63 were well and leading normal active lives and 56 had entirely normal liver function. Children''s growth and development were essentially normal, with many showing remarkable catch up growth.Liver transplantation offers children with terminal liver disease a high chance of a return to full quality life and normal development. Improved surgical and medical care have progressively improved survival. The timing of transplantation is critical but has been constrained particularly by the availability of donors and resources.     

Animal models for human craniofacial malformations.

Holoprosencephaly malformations, of which the fetal alcohol syndrome appears to be a mild form, can result from medial anterior neural plate deficiencies as demonstrated in an ethanol treated animal model. These malformations are associated with more medial positioning of the nasal placodes and resulting underdevelopment or absence of the medial nasal prominences (MNPs) and their derivatives. Malformations seen in the human retinoic acid syndrome (RAS) can be produced by administration of the drug 13-cis-retinoic acid in animals. Primary effects on neural crest cells account for most of these RAS malformations. Many of the malformations seen in the RAS are similar to those of hemifacial microsomia, suggesting similar neural crest involvement. Excessive cell death, apparently limited to trigeminal ganglion neuroblasts of placodal origin, follows 13-cis retinoic acid administration at the time of ganglion formation and leads to malformations virtually identical to those of the Treacher Collins syndrome (TCS). Secondary effects on neural crest cells in the area of the ganglion appear to be responsible for the TCS malformations. Malformations of the DiGeorge Syndrome are similar to those of the RAS and can be produced in mice by ethanol administration or by "knocking out" a homeobox gene (box 1.5). Human and animal studies indicate that cleft lips of multifactorial etiology may be generically susceptible because of small MNP)s or other MNP developmental alterations, such as those found in A/J mice, that make prominence contact more difficult. Experimental maternal hypoxia in mice indicates that cigarette smoking may increase the incidence of cleft lip by interfering with morphogenetic movements. Other human cleft lips may result from the action of a single major gene coding for TGF-alpha variants. A study with mouse palatal shelves in culture and other information suggest that a fusion problem may be involved.     

Microbially Mediated Mn(II) Oxidation in an Oligotrophic Arctic Lake

Rates of oxidation of Mn(II) were measured by an in situ incubation technique in the water column of Toolik Lake, Alaska. Measured rates were lower than those observed in other aquatic systems but were sufficient to oxidize all Mn(II) in the lake within a 3-month period. Measured rates compared favorably with rates estimated from a previous study of the geochemical cycling of Mn in Toolik Lake. The Mn(II) oxidation was largely microbially mediated, as indicated by inhibition of oxidation rates by sodium azide. Azide had been previously demonstrated to be a suitable microbial poison for studying Mn(II) oxidation in seawater. This study demonstrates that azide is also a suitable poison for freshwaters and that it inhibits microbial but not abiotic oxidation of Mn(II). Manganese(II) oxidation rates were similar during cold, under-ice conditions in early spring and during warmer summer conditions. This observation suggests that Mn(II) concentration, rather than temperature or oxygen concentration, is the most important factor regulating Mn(II) oxidation rates in Toolik Lake.     

Platelet-activating factor induces glycogen degradation in fetal rabbit lung in utero

The role of platelet-activating factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in initiating glycogen breakdown in the fetal rabbit lung was assessed by intraperitoneal administration of this potent ether-linked glycerophospholipid. Forty-five min after in utero injection of PAF (2.5 X 10(-7) mol), fetal pulmonary and hepatic glycogen concentrations were reduced from 326 to 256 and from 9.8 to 6.6 micrograms of glycogen/mg protein, respectively. Glycolytic activity was similarly increased as judged by an elevation of lactate (2-fold) in lung, liver, and plasma upon PAF injection. These actions of PAF were dose- and time-dependent. The glycogenolytic response did not occur when an equimolar dose of the inactive enantiomer, D-PAF was injected. Pretreatment of the fetus with a specific PAF receptor antagonist, SRI-63-441, prevented the PAF response. We have previously demonstrated (Hoffman, D. R., Truong, C. T., and Johnston, J. M. (1986) Biochim. Biophys. Acta 879, 88-96) that PAF biosynthesis and PAF concentrations increase significantly on day 24 of fetal rabbit lung development. A concurrent decrease in pulmonary glycogen concentration at this point of gestation is potentially reflective of the PAF-induced action. Thus, these observations would suggest a role for PAF in the normal physiology of fetal lung maturation.     

Genealogy of Principal Strains of the Yeast Genetic Stock Center

We have constructed a genealogy of strain S288C, from which many of the mutant and segregant strains currently used in studies on the genetics and molecular biology of Saccharomyces cerevisiae have been derived. We have determined that its six progenitor strains were EM93, EM126, NRRL YB-210 and the three baking strains Yeast Foam, FLD and LK. We have estimated that approximately 88% of the gene pool of S288C is contributed by strain EM93. The principal ancestral genotypes were those of segregant strains EM93-1C and EM93-3B, initially distributed by C. C. Lindegren to several laboratories. We have analyzed an isolate of a lyophilized culture of strain EM93 and determined its genotype as MATa/MATα SUC2/SUC2 GAL2/gal2 MAL/MAL mel/mel CUP1/cup1 FLO1/flo1. Strain EM93 is therefore the probable origin of genes SUC2, gal2, CUP1 and flo1 of S288C. We give details of the current availability of several of the progenitor strains and propose that this genealogy should be of assistance in elucidating the origins of several types of genetic and molecular heterogeneities in Saccharomyces.