Sequence analysis of the gene encoding the Chlamydia pneumoniae DnaK protein homolog.

The antigen-coding region of a 4.2-kb PstI fragment of Chlamydia pneumoniae (pLC3), which encodes a 75-kDa immunoreactive protein recognized during human C. pneumoniae infection, was localized to a 2.0-kb EcoRI fragment. This subclone expressed an immunoreactive fusion protein of ca. 82 kDa. Nucleotide sequence analysis of the C. pneumoniae gene revealed that it consisted of a 1,980-base open reading frame with an inferred 71,550-Da protein of 660 amino acids. Putative Escherichia coli-like promoters and a ribosomal binding site were located in the 5' upstream region, and an 11-base dyad forming a stable stem-loop structure following two in-frame stop codons was identified. The C. pneumoniae 75-kDa protein is a member of the hsp70 family of heat shock proteins and has 87% amino acid similarity with the Chlamydia trachomatis protein.     

Characterization of angiotensin peptides in plasma of anephric man.

Recent evidence suggests that a considerable proportion of plasma angiotensin is generated not in blood but in peripheral tissues. Through the measurement of angiotensin peptides and renin in the plasma of 11 anephric subjects, we have investigated whether kidney-derived renin, or some other tissue mechanism for angiotensin generation, is the major determinant of plasma angiotensin. Particular care was taken to prevent inadvertent activation of inactive renin and possible generation, conversion and metabolism of angiotensin peptides during processing of blood samples. Initial experiments revealed that plasma from anephric subjects contains high amounts of material which interferes in radioimmunoassays for angiotensin, even after high-performance liquid chromatography (HPLC). Therefore, in order to obtain an unambiguous identification of angiotensin peptides, a dual HPLC method was developed in which angiotensin peptides were first separated by HPLC, then acetylated and run again on HPLC before radioimmunoassay for angiotensin I and II (detection limits, 0.25 and 0.2 fmol/ml, respectively). The levels of angiotensin I and II were 1.2 +/- 1.6 and 0.7 +/- 0.5 fmol/ml (mean +/- s.d., n = 9-10), respectively, being 6% of levels in normal subjects, and were consistent with the active renin levels (1.8 +/- 1.7 muIU/ml, n = 11) which were 7% of levels in normal subjects. Artefactual activation of prorenin and angiotensin generation during sample processing were excluded as significant causes of the low levels of active renin and angiotensin I and II in anephric plasma. These data indicate that kidney-derived renin is the major determinant of angiotensin levels in normal human plasma. However, the present demonstration of low levels of active renin and angiotensin I and II in plasma of anephric subjects provides unequivocal evidence for a functional extrarenal renin-angiotensin system in man.     

Polyethylene Glycol Precipitates of Serum Contain a Large Proportion of Uncomplexed Immunoglobulins and C3

High pressure liquid chromatography (HPLC) was used to fractionate redissolved polyethylene glycol (PEG) precipitates isolated from the sera of normal volunteers and from patients with IgA nephropathy (IgAN) and systemic lupus erythematosus (SLE), 2 diseases characterized by elevated levels of circulating immune complexes. The individual fractions were analyzed by solid phase ELISA for IgA, IgM, C3, IgG, and complexes of IgG-IgA and IgG-C3. Although PEG precipitates were enriched for high molecular weight IgA and IgG (presumably bound within CIC), significant amounts of IgM, unbound IgG and C3 were also present. The quantities of the PEG-precipitable proteins did not correlate with their serum concentrations. IgG-IgA and IgG-C3 complexes were found in all precipitates examined, but the levels of complexes were higher in both patient groups. These results indicate that PEG precipitates a considerable quantity of proteins not bound in immune complexes. There appeared to be greater protein precipitation from sera of the patient groups compared to the amount precipitated from the normal sera. These results suggest that an understanding of the mechanism of PEG precipitation may be important in defining abnormalities in IgAN, SLE and perhaps other diseases characterized by elevated levels of CIC. In addition, the possibility of undetected CIC in PEG precipitable material must be considered.     

Meningiomas presenting with paranasal sinus involvement

Extracranial paranasal spread of meningiomas is uncommon. We describe the management of four cases, all of which first presented to an oto-rhino-laryngologist for an opinion. We suggest that greater use of modern imaging techniques could lead to earlier diagnosis. The natural history of extracranial spread is relatively benign but the management of regrowth of residual disease is difficult. We therefore suggest radical surgery in the first instance provided that the patients general health and configuration of the tumour allow.     

INFANTILE MYOFIBROMATOSIS WITH HEMANGIOPERICYTOMA-LIKE FEATURES OF THE TONGUE: A Case Study Including Ultrastructure

We report a case of an infantile myofibromatosis with hemangiopericytoma-like features arising in the tongue of a 5-month-old female infant. Many authors now classify neoplasms as infantile myofibromatosis that were previously called infantile hemangiopericytoma. The ultrastructural features of our tumor illustrate its biphasic nature and provide a possible explanation for its histogenesis. Infantile myofibromatosis, including those diagnosed as infantile hemangiopericytomas, rarely arise in any intraoral location. Despite the generally good prognosis associated with these neoplasms, complete surgical excision is recommended to avoid recurrences.     

Loss of Heterozygosity at the α-Inhibin Locus on Chromosome 2q Is Not a Feature of Human Granulosa Cell Tumors

The α-inhibin gene has been shown in knockout mouse models to be a suppressor of granulosa tumorigenesis in the mouse. To determine if α-inhibin has the same function in humans, we have assessed the frequency of loss of heterozygosity (LOH) of the α-inhibin gene locus on chromosome 2q in 17 human granulosa cell tumors and 36 epithelial ovarian cancers. LOH was detected in 12 of 36 (33.3%) epithelial tumors but in only 1 of 17 (6%) granulosa cell tumors. These data suggest that in contrast to the suggestions from the mouse model α-inhibin does not function as a granulosa cell tumor suppressor gene in the human. Furthermore, analysis of the TP53 gene in the granulosa cell tumors failed to detect either LOH or point mutations, indicating that they have a developmental pathway distinct from that of epithelial ovarian tumors.     

Long-acting dihydropyridine calcium antagonists. 1. 2-Alkoxymethyl derivatives incorporating basic substituents

A series of dihydropyridines substituted at the 2-position by basic side chains are described and their potencies as calcium antagonists listed. One compound, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5- methoxycarbonyl-6-methyl-1,4-dihydropyridine (17, amlodipine) was found to be comparable in potency to nifedipine and to have an elimination half-life of 30 h in dogs. Oral bioavailability approached 100%, and hemodynamic responses were gradual in onset and long-lasting in effect. The two enantiomers have been prepared, and the bulk of the activity was found to reside with the (-) isomer, 18. X-ray crystallographic studies, carried out on a close analogue of 17, suggest the existence of a weak hydrogen bond between the side-chain oxygen and the proton on the ring nitrogen.