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.     

Selected chromosome counts of the Czechoslovak flora I

Chromosome numbers of the following nine taxa of the Czechoslovak flora are given:Atriplex rosea L.,Cardamine resedifolia L.,Groenlandia densa (L.)Fourr.,Isoëtes lacustris L.,Lysimachia nemorum L.,Parnassia palustris L.,Phelipanche caesia (Rchb.) Soják,Rumex patientia L. subsp.patientia andSymphytum officinale L. s. str. A new chromosome number of 2n=80 is reported forRumex patientia L. subsp.patientia. Chromosome numbers of another five taxa are first reported from Czechoslovakia. Each of the ascertained chromosome counts is discussed with respect to hitherto known reports.     

Rat liver lowMr phosphotyrosine protein phosphatase isoenzymes: Purification and amino acid sequences

Two lowM _r phosphotyrosine protein phosphatases have been isolated from rat liver. The enzymes were previously known as lowM _r acid phosphatases, but several recent studies have demonstrated that this family of enzymes possesses specific phosphotyrosine protein phosphatase activity. We determined the complete amino acid sequences of the two isoenzymes and named them AcP1 and AcP2. Both consist of 157 amino acid residues, are acetylated at the NH₂-terminus, and have His as the COOH-terminus. The molecular weights calculated from the sequences are 18,062 for AcP1 and 17,848 for AcP2. They are homologous except in the 40–73 zone, where about 50% of residues are different. This fact suggests that the two isoenzymes are produced by an alternative splicing mechanism. There is no homology between these two isoenzymes and the receptor-like phosphotyrosine protein phosphatases LAR, CD45, human placenta PTPase 1B, and rat brain PTPase-1. AcP1 and AcP2 are also distinct from rat liver PTPase-1 and PTPase-2, since these last enzymes have higher molecular weights. AcP1 differs from AcP2 with respect to (1) substrate affinity and (2) its sensitivity to activators and inhibitors, thus suggesting a their different physiological function.     

Guanine nucleotide- and muscarinic agonist-dependent phosphoinositide metabolism in synaptoneurosomes from cerebral cortex of immature rats

Guanine nucleotide-, neurotransmitter-, and fluoride-stimulated accumulation of [³H]inositol phosphates ([³H]InsPs) was measured in [³H]inositol-labeled synaptoneurosomes from cerebral cortex of immature (7-day-old) and adult rats, in order to clarify the role of GTP-binding proteins (G-proteins) in modulating phosphoinositide (PtdIns) metabolism during brain development. GTP(S) [Guanosine 5-O-(3-thio)triphosphate] time- and concentration-dependently stimulated PtdIns hydrolysis. Its effect was potentiated by full (carbachol, metacholine) and partial (oxotremorine) cholinergic agonists through activation of muscarinic receptors. The presence of deoxycholate was required to demonstrate agonist protentiation of the guanine nucleotide effect. The response to GTP(S) was higher in adult than in immature rats, while the effect of cholinergic agonists was similar at the two ages examined. At both ages, histamine potentiated the effect of GTP(S), while norepinephrine was ineffective. At both ages, guanosine 5-O-(2-thio)diphosphate [GDP(S)] and pertussis toxin significantly decreased GTP(S)-induced [³H]InsPs formation. The phorbol ester phorbol 12-myristate 13-acetate (PMA), on the other hand, did not inhibit the guanine nucleotide response in synaptoneurosomes from immature rats. NaF mimicked the action of GTP(S) in stimulating PtdIns hydrolysis. Its effect was not affected by carbachol and was highly synergistic with that of AlCl₃, according to the concept that fluoroaluminate (AlF₄ ^–) is the active stimulatory species. No quantitative differences were found in the response to these salts between immature and adult animals. These results provide evidence that, in both the immature and adult rat brain, neuroreceptor activation is coupled to PtdIns hydrolysis through modulatory G-proteins.     

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.     

Recognition of HLA-B27 by mouse cytotoxic T-cell clones: a transgenic mouse

As a basis for the characterization of mouse T cells involved in the recognition of xenogeneic HLA molecules, a panel of HLA-B27-reactive cytotoxic T-cell clones was generated upon stimulation by cells from HLA-B27-transgenic mice. The HLA-B27-induced T-cell response was found to comprise two categories of clones: some recognizing HLA-B27 independent of H-2 molecules expressed by the target cells (unrestricted clones), others recognizing HLA-B27 in an H-2 restricted manner. The unrestricted clones exhibited diverse specificities, as judged from their various cross-reactivities with other xenogeneic (HLA) or allogeneic (H-2) molecules. In addition, although most of the unrestricted clones were able to react with both mouse and human HLA-B27-transgenic mice. The HLA-B27 induced T-cell which reacted only with HLA-B27-positive mouse, and not human cells. These findings illustrate that both H-2-restricted and unrestricted T cells with diverse species contribute to HLA-B27-xenorecognition.     

Principles of environmental physics

Book Review

Principles of environmental physicsJ.L. Monteith and M.H. Unsworth Second edition. London: Edward Arnold, 1990. xii + 291 pages. £30.00 (hardback), £14.95 (paperback). ISBN 0-7131-2931-X     

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.