Recombination aneusomy of chromosome 5 associated with multiple severe congenital malformations

A male infant is described in whom congenital anomalies were recognized prenatally by ultrasound examination. The infant was delivered following spontaneous labor and died approximately 15 min after birth. An autopsy revealed major anomalies in the central nervous system (holoprosencephaly with premaxillary agenesis), the gastrointestinal system (esophageal atresia) and the heart (tetralogy of Fallot). Chromosomal studies revealed recombinant chromosome 5 [46,XY, rec(5), dup q, inv(5)(p15q32)], resulting in partial trisomy 5q and partial monosomy 5p. Cytogenetic investigation of the family revealed a pericentric inversion of chromosome 5 in the father and paternal grandmother, 46,XY (and XX, respectively,) inv(5)(p15q32). The congenital anomalies in this infant are more extensive and severe than previously reported in cases of recombination aneusomy involving chromosome 5.     

Highly Polymorphic Domains of the Human Serum Amyloid A (SAA) Gene GSAA1

The DNA of the human serum amyloid A (SAA) gene GSAA1 contains several repetitive regions within its introns. We have studied length variations at one such region in the 2nd intron by selective amplification using the polymerase chain reaction (PCR) and defined oligonucleotide primers. The lengths of the repetitive regions frequently differ between individual chromosomes and can be transmitted as Mendelian markers, making them useful for genetic linkage analysis.     

Heart rate reactivity and heart period variability throughout the first year after heart transplantation

Heart rate reactivity to mental stress is substantially blunted early after heart transplantation, suggesting that the loss of neural modulation limits the cardiovascular response to mental stress. We tested whether reactivity to mental stress recovers during the first year after heart transplantation. Hemodynamic and respiratory responses to mental arithmetic challenge were studied in 20 heart transplant recipients 3, 6, and 12 months after surgery. A normal comparison group was studied at equivalent intervals. Heart rate reactivity to mental arithmetic was significantly reduced in the cardiac transplant group compared to the normal subjects. This effect persisted up to 1 year after transplantation. Heart period variability in the heart transplant recipients was minimal in all three-test sessions. The findings suggest that no functional reinnervation or other compensatory adaptation occurs up to 1 year after heart transplantation.     

Studies of Antibody to Herpes Simplex Virus Fcγ-Binding Protein gE in Patients with Rheumatoid Arthritis, Juvenile Rheumatoid Arthritis and Normal Controls

IgG antibody to gE, the Fc gamma-binding herpes simplex 1 (HSV-1) viral glycoprotein, was studied in 49 rheumatoid arthritis (RA) patients and 43 normal controls. Antibody to gD, another important HSV-1 antigen, was assayed in parallel. No difference between RA patients and normal controls was found in levels of anti-gE antibody measured by reactivity of IgG F(ab')2 fragments reacting with gE coated to ELISA plates. No difference in anti-gD antibody was recorded between normals and patients with RA. Levels of IgG anti-IgE antibody did not correlate with quantitative elevations of serum rheumatoid factor (RF) in RA patients. When IgG anti-gE and anti-gD were assayed in 20 patients with juvenile rheumatoid arthritis and 22 children controls, no significant differences were noted. However, when individual RFs from patients with RA were tested for reactivity against a panel of affinity-isolated F(ab')2 antibodies to gE, some evidence for individual autospecificity was obtained. Four of 20 monoclonal IgM RFs produced from RA patients' B cells showed marked elevations of reactivity with some RA patients' F(ab')2 antibodies to gE. All four of the monoclonal RFs showing this specificity were derived from RA synovial tissue B cells. These findings may provide support for the concept that some RFs in patients with RA show individual specificity for internal image determinants of IgG antibodies to viral Fc gamma-binding proteins.     

Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway

Myotubular myopathy (MTM1) is an X-linked disease, characterized by severe neonatal hypotonia and generalized muscle weakness, with pathological features suggesting an impairment in maturation of muscle fibres. The MTM1 gene encodes a protein (myotubularin) with a phosphotyrosine phosphatase consensus. It defines a family of at least nine genes in man, including the antiphosphatase hMTMR5/Sbf1 and hMTMR2, recently found mutated in a recessive form of Charcot-Marie-Tooth disease. Myotubularin shows a dual specificity protein phosphatase activity in vitro. We have performed an in vivo test of tyrosine phosphatase activity in Schizosaccharomyces pombe, indicating that myotubularin does not have a broad specificity tyrosine phosphatase activity. Expression of active human myotubularin inhibited growth of S.pombe and induced a vacuolar phenotype similar to that of mutants of the vacuolar protein sorting (VPS) pathway and notably of mutants of VPS34, a phosphatidylinositol 3-kinase (PI3K). In S.pombe cells deleted for the endogenous MTM homologous gene, expression of human myotubularin decreased the level of phosphatidylinositol 3-phosphate (PI3P). We have created a substrate trap mutant which shows relocalization to plasma membrane projections (spikes) in HeLa cells and was inactive in the S.pombe assay. This mutant, but not the wild-type or a phosphatase site mutant, was able to immunoprecipitate a VPS34 kinase activity. Wild-type myotubularin was also able to directly dephosphorylate PI3P and PI4P in vitro. Myotubularin may thus decrease PI3P levels by down-regulating PI3K activity and by directly degrading PI3P.     

Production of specific anti-rat 5-HT1A receptor antibodies in rabbits injected with a synthetic peptide

Polyclonal antibodies were raised by the repeated injection of rabbits with a synthetic peptide corresponding to a highly selective portion (amino acid residues 243 to 268) of the amino acid sequence of the rat 5-HT1A receptor. The anti-peptide antiserum allowed the immunoprecipitation of 5-HT1A receptors but not of other 5-HT1 sites solubilized from rat hippocampal membranes. Immunoautoradiographic labelling of rat brain sections with the anti-peptide antiserum was superimposed with the autoradiographic distribution of 5-HT1A sites labelled by the selective radioligand [3H]8-OH-DPAT.