The L-isoaspartyl/D-aspartyl protein methyltransferase gene (PCMT1) maps to human chromosome 6q22.3-6q24 and the syntenic region of mouse chromosome 10.

We have mapped the genes for the human and mouse L-isoaspartyl/D-aspartyl protein carboxyl methyltransferase (EC 2.1.1.77) using cDNA probes. We determined that the human gene is present in chromosome 6 by Southern blot analysis of DNA from a panel of mouse-human somatic cell hybrids. In situ hybridization studies allowed us to confirm this identification and further localize the human gene (PCMT1) to the 6q22.3-6q24 region. By analyzing the presence of an EcoRI polymorphism in DNA from backcrosses of C57BL/6J and Mus spretus strains of mice, we localized the mouse gene (Pcmt-1) to chromosome 10, at a position 8.2 +/- 3.5 cM proximal to the Myb locus. This region of the mouse chromosome is homologous to the human 6q24 region.     

ACUTE AND CHRONIC ASTHMA—Treatment with Theophylline in Hydro-Alcoholic Solution: Clinical Evaluation and Pulmonary Function Studies

A flavored solution containing 80 mg. of theophylline and 3 cc. of ethyl alcohol per 15 cc. was given orally to 31 patients with acute asthma to terminate the attack. Thirty patients with moderate to severe chronic asthma were alternated for three or four weeks on daily multiple doses of either the theophylline solution or a placebo.In the acute cases three-second Vital Capacity increased by 33.8 per cent and Maximal Breathing Capacity by 30.2 per cent in one hour after taking 60 cc. to 75 cc. of the theophylline solution. When placebos were given, both measures of lung function declined during the first half hour.Seventy-one and a half per cent of patients with acute cases felt moderate to complete relief of symptoms. In persons with chronic asthma the regular use of the theophylline solution did not change the frequency of asthma in most cases, but it decreased the severity in 59 per cent of cases. The values for three-second Vital Capacity and Maximal Breathing Capacity rose only a little.Gastric irritation was noted in one-third of the chronic cases and one-fourth of the acute cases. This could be reduced by appropriate measures.     

Pathogenic synergy: mixed intra-abdominal infections

In this article we review our researches into the pathogenesis of mixed infections. These may conveniently be divided into in vitro and in vivo studies. In vitro we confirmed that interference with the killing of aerobes by polymorphonuclear leucocytes (PMN’s) is a property of theBacteroides strains tested and appears to depend on competition for opsonins i.e. complement factors. Further studies are in progress to define which complement factors and which bacterial structures are involved. The influence ofB. fragilis on chemotaxis has also been studied. Our preliminary data suggest thatB. fragilis is itself poorly chemotactic and reduces the chemoattractivity ofProteus mirabilis. This observation is surprising when we consider that abscess formation is the hall-mark ofB. fragilis infections and needs clarification. In vivo we have developed a skin infection model in mice which is economical and gives reproducible and quantitative results. In this model we have demonstrated pathogenic synergy betweenEscherichia coli andB. fragilis. Further studies are planned to assess the role of complement and bacterial factors in this in vivo synergy.     

Maternal serum reactivity to species-specific antigens in sheep-goat interspecific pregnancy.

Three models were used to test the hypothesis that interspecific pregnancy failure between the sheep and goat is due to a species-specific, maternal antibody response. Interspecific pregnancies were established in ewes and does, sheep in equilibrium goat chimeric conceptuses produced by injection of ovine blastocysts were transferred to ovine recipients, and ovine and caprine pregnancies were established in interspecific chimeras. Complement-mediated lymphocytotoxic and hemolytic assays were used to monitor onset and titer of antibodies. Sera from 3 of 8 injection-chimera recipients reacted with all caprine peripheral blood lymphocytes (PBL) and red blood cells (RBC) tested (n = 18). Sera from 3 of 6 ewes and 7 of 7 does also were pancytotoxic to PBL of the other species (n greater than or equal to 20). Absorptions with xenogeneic RBC generally removed the reactivity. The data were consistent with responses to species-specific, monomorphic antigens expressed on PBL and RBC, and probably trophoblast. The response preceded or coincided with interspecific pregnancy failure in does, but not in ewes. Accordingly, no xenoreactivity was observed in chimera sera but caprine pregnancies were resorbed (n = 16) and ovine pregnancies developed to term (n = 11). The data did not support the hypothesis that failure of caprine pregnancy in ewes or chimeras is due to a species-specific, maternal antibody response. In contrast, a maternal, cytotoxic antibody response to species-specific antigen(s) may contribute to failure of hybrid or ovine pregnancy in does.     

Virulence ofEscherichia coli strains isolated from urine of patients with acute cystitis and from faeces of healthy women

E. coli strains were isolated from the urine of patients with acute cystitis in general practice and from the faeces of a comparable reference group of healthy individuals. These strains were serotyped and tested for virulence in an experimental mouse model. Of 30 cystitis-strains 18 were virulent, and of 30 faeces-strains 15 were virulent. It is concluded that the cystitis-strains were not more often virulent than the faeces-strains. O antigens commonly found among urinaryE. coli isolates were present in 60% of the cystitis-strains and in 37% of the faeces-strains. K antigens commonly found in urinaryE. coli strains were present in 33% of the cystitis-strains and in 12% of the faeces-strains. Neither the presence of common urinary O-antigens, nor the presence of common urinary K antigens could be associated with virulence of the isolated strains. However, it is suggested that certain O and K antigens (O2, O6, K23) may be associated with virulence for the urinary tract.     

The Terminal Protonephridial Complex of Haplopharynx rostratus (Platyhelminthes,Haplopharyngida)

The terminal protonephridial complex of Haplopharynx rostratus consists of three terminal cells. There are no weirs consisting of ribs connected by a filtration “membrane”, but some cytoplasmic outgrowths into the lumen of the terminal cells. Excretion is by exocytotic vesicles. The terminal cells also contain Golgi complexes and large membrane-bound vacuoles containing electron-dense material. The ciliary bundles (flames) of terminal cells 2 and 3 protrude into the lumen of the centrally located terminal cell I. The complex is surrounded by a sheath containing numerous filaments. The terminal complex of H. rostratus resembles that of the macrostomid Paromalostomum proceracauda, lending support to the view that the two taxa are closely related. © 1998 The Royal Swedish Academy of Sciences. Published by Elsevier Science Ltd. All rights reserved     

Extrapolating Antifungal Animal Data to Humans—Is It Reliable?

This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable. Animal studies have helped identify area under the concentration curve to minimum inhibitory concentration ratio targets for new drugs and formulations such as isavuconazole and delayed-release posaconazole that have translated to successful outcomes in humans. Models have also been influential in the identification of possible combination therapies for the treatment of aspergillosis, such as voriconazole and echinocandins. However, challenges are endured with animal models when it comes to replicating the pharmacokinetics of humans which has been exemplified with the newest itraconazole formulation. Additionally, animal models have displayed a survival benefit with the use of iron chelators and amphotericin for mucormycosis which was not demonstrated in humans. Animal models have been a staple in the development and optimization of antifungal agents. They afford the ability to investigate uncommon diseases, such as invasive fungal infections, that would otherwise take years and many resources to complete. Although there are many benefits of animal models, there are also shortcomings. This is why the reliability of extrapolating data from animal models to humans is often scrutinized.