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R McInnes

Publications and source records attributed to R McInnes.

9 recordsLinked to original sources
PubMed1994

Refining the locus for Best vitelliform macular dystrophy and mutation analysis of the candidate gene ROM1.

Vitelliform macular dystrophy (Best disease) is an autosomal dominant macular dystrophy which shares important clinical features with age-related macular degeneration, the most common cause of legal blindness in the elderly. Unfortunately, our understanding and treatment for this common age-related disorder is limited. Discovery of the gene which causes Best disease has the potential to increase our understanding of the pathogenesis of all types of macular degeneration, including the common age-related form. Best disease has recently been mapped to chromosome 11q13. The photoreceptor-specific protein ROM1 has also been recently mapped to this location, and the ROM1 gene is a candidate gene for Best disease. Using highly polymorphic markers, we have narrowed the genetic region which contains the Best disease gene to the 10-cM region between markers D11S871 and PYGM. Marker D11S956 demonstrated no recombinants with Best disease in three large families and resulted in a lod score of 18.2. In addition, a polymorphism within the ROM1 gene also demonstrated no recombinants and resulted in a lod score of 10.0 in these same three families. We used a combination of SSCP analysis, denaturing gradient gel electrophoresis, and DNA sequencing to screen the entire coding region of the ROM1 gene in 11 different unrelated patients affected with Best disease. No nucleotide changes were found in the coding sequence of any affected patient, indicating that mutations within the coding sequence are unlikely to cause Best disease.

Base Sequence↗
PubMed1991

Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female patients with this disease.

Male dogs with X-linked hereditary nephritis (HN) serve as a model for studying male patients with this disease. In the present study, carrier female dogs were found to resemble female patients in showing a broad range of renal dysfunction. Of 37 carrier female dogs studied, all were healthy up to 5 years of age; however, all had proteinuria develop at 2 to 3 months, and focal segmental glomerulosclerosis (FSGS) was detected after 7 months. After 5 years, 4 of 13 dogs remained healthy and showed mild FSGS on renal biopsy; 4 had mild renal dysfunction develop and their kidneys showed extensive FSGS; 5 died prematurely of renal failure with end-stage kidneys. By immunofluorescence, using antibody to the NC1 domain of collagen type IV, segmental staining of glomerular basement membranes (GBM) was seen in all dogs before 3 to 4 years, and lesions of FSGS were negative. Thereafter, a transition to global staining of GBM was noted and lesions of FSGS became positive. Lens capsule and basement membranes in lung and choroid plexus showed discontinuous staining in two young carrier female dogs and continuous staining in one older carrier female dog. By electron microscopy, multilaminar splitting of some GBM was seen up to 4 years, and thereafter, splitting took on a compressed appearance, with the layers becoming apposed though still detectable. The authors conclude that: 1) carrier female dogs with X-linked HN are mosaics for an abnormality in the NC1 domain of GBM and other basement membranes; 2) FSGS develops in all carrier female dogs in glomerular capillary loops that possess an abnormal NC1 domain, and progresses to a variable extent in different dogs; and 3) the abnormality of NC1 in GBM of carrier female dogs appears to diminish with age, but this does not prevent progression of renal disease. Similar conclusions may apply to females with X-linked HN.

Animals↗
PubMed1989

Abnormalities in the NC1 domain of collagen type IV in GBM in canine hereditary nephritis.

Samoyed hereditary glomerulopathy (SHG) in dogs serves as a model for human X-linked hereditary nephritis (HN). We previously showed that glomerular capillaries of affected males did not stain by immunofluorescence (IF) using serum from a patient with Goodpasture's syndrome. Our goal in the present study was to determine whether the NC1 domain of the collagen type IV molecule, which contains Goodpasture antigen (GPA), could be demonstrated in these dogs, and to assess its immunological reactivity. By SDS-PAGE, NC1 in collagenase digests of glomerular basement membranes (GBM) of unaffected and carrier female dogs in the family with SHG showed 24 kilodalton (kD), 26 kD and 28 kD monomer, and 46 kD and 47 kD dimer components, but the 24 kD monomer was diminished in the affected males. By IF, a rabbit antibody to NCl stained glomerular capillaries of unaffected, affected male, and carrier female dogs. In contrast, a human anti-GBM plasmapheresis fluid (PPF) stained glomerular capillaries of only the unaffected and carrier female dogs. By RIA, both antibodies reacted strongly with NCl in collagenase digests of GBM of the unaffected and carrier female dogs, but showed reduced reactivity with NCl of affected males. By Western blotting, both antibodies bound to dimers and 24 kD and 26 kD monomers of the NCl domain in collagenase digests of GBM of unaffected and carrier female dogs. However, in affected males, the rabbit anti-NCl antibody did not bind to the 24 kD monomer, while the human anti-GBM PPF showed weak binding to the 24 kD and 26 kD monomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Cloning and sequence analysis of cDNA for human argininosuccinate lyase.

Using antibodies specific for argininosuccinate lyase (EC 4.3.2.1), we isolated two cDNA clones by screening a human liver cDNA library constructed in the lambda gt11 expression vector. The identity of these isolates was confirmed by in vitro translation of plasmid-selected mRNA. One of these isolates was used to rescreen the cDNA library and a 1565-base-pair (bp) clone was identified. The entire nucleotide sequence of this clone was determined. An open reading frame was identified which encoded a protein of 463 amino acids with a predicted molecular weight of 51,663. The clone included 115 bp of 5' untranslated sequence and 46 bp of 3' untranslated sequence. A canonical poly(A) addition site was present in the 3' end, 16 bp from the beginning of the poly(A) tract. Comparison of the deduced amino acid sequence of the human enzyme with that of the yeast enzyme revealed a 56% homology, when conservative amino acid changes were taken into consideration. The yeast protein is also 463 amino acids long, with a molecular weight of 51,944. By use of a genomic DNA panel from human-Chinese hamster somatic cell hybrids, the human gene was mapped to chromosome 7. Another hybridizing region, corresponding to a portion of the 5' end of the cDNA, was found on chromosome 22.

Amino Acid Sequence↗
PubMed1981

Observations on the combination of clomiphene citrate-human menopausal gonadotropin-human chorionic gonadotropin in the management of anovulation.

To study the effects of the addition of clomiphene citrate to human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG), 23 cycles of clomiphene citrate-hMG-hCG (CHH) were administered to 10 anovulatory women. Of these 10 women, 5 also received 15 cycles of hMG-hCG (HH). Although there was a significant increase in the ovulation rate in the CHH group (p less than 0.01), there was no difference in the pregnancy rate (p less than 0.05). Patients in the CHH group required significantly less hMG for ovulation induction than the HH group (p less than 0.01). Patients receiving CHH who had low serum levels of follicle-stimulating hormone required significantly more hMG than those with normal values. The luteinizing hormone releasing hormone test may predict those patients who will require less hMG during CHH therapy. The relative safety of the CHH treatment is discussed.

Anovulation↗
PubMed1980

Breast examination does not elevate serum prolactin.

Serum prolactin and cortisol levels were measured in 24 patients entering the Royal Victoria Hospital infertility center both before and after a thorough physical examination that included a pelvic examination and a search for galactorrhea in both breasts. There was no significant change in the levels of prolactin or cortisol in the group as a whole in those with normal prolactin values and those with high basal prolactin values (P less than 0.05). The possible role of stress in the mediation of occasional elevation of basal prolactin values is discussed in relation to the serum cortisol levels.

Adenoma↗