Biomedical subjects

J A Finlay

Publications and source records attributed to J A Finlay.

26 records · Page 2Linked to original sources

PubMed1995

Molecular forms of prostate-specific antigen and the human kallikrein gene family: a new era.

Without question, much has been learned about the glycoprotein PSA in recent years. By increasing our understanding of this tumor marker's biochemical and physiologic properties, we will be able to improve its clinical utility. The discovery of the various molecular forms of PSA represents a significant advancement. Knowing the concentration and ratio of these PSA forms will be valuable in deciding which patients require further evaluation with transrectal ultrasound and prostate biopsy and which men can be monitored safely without undergoing further invasive testing. This information will be most valuable in treating the patient with a mildly elevated serum PSA level. Although assays are not yet available to detect specifically hK2, the striking similarities of hK2 to PSA, including selective expression in the prostate, suggest that this marker may also prove useful in prostate cancer management. Indeed, a new era of PSA testing has been entered, and the entire field of prostate cancer will benefit.

Amino Acid Sequence↗

PubMed1995

Outcome prediction in open bite cases.

Some anterior open bites close spontaneously, others do not. It would be advantageous if the orthodontist had some means of predicting the spontaneous outcome in open bite patients. One-hundred-and-twenty-seven patients having open bite were recorded longitudinally for a minimum period of 3 years using cephalometric radiographs. The open bite closed spontaneously in 50 per cent of a prepuberal group aged between 7 and 10 years, in 49 per cent of a puberal group aged 11-14 years, and in 44 per cent of a post-puberal group aged between 14 and 21 years when first seen. Data from cephalometric analysis of the first film in each case was analysed using discriminant function analysis. The analysis correctly predicted the outcome in 88 per cent of the prepuberal group, in 74 per cent of the puberal group, and in 94 per cent of the post-puberal group. The accuracy of the prediction equation was checked in a new sample of 35 subjects with open bite observed over at least 2 years so that the spontaneous outcome was known. The equation correctly predicted the outcome in 79 per cent of prepuberal, in 80 per cent of puberal, and in 100 per cent of post-puberal patients in the second sample.

Adolescent↗

PubMed1994

The Saccharomyces cerevisiae APS1 gene encodes a homolog of the small subunit of the mammalian clathrin AP-1 complex: evidence for functional interaction with clathrin at the Golgi complex.

Clathrin-associated protein (AP) complexes have been implicated in the assembly of clathrin coats and the selectivity of clathrin-mediated protein transport processes. We have identified a yeast gene, APS1, encoding a homolog of the small (referred to herein as sigma) subunits of the mammalian AP-1 complex. Sequence comparisons have shown that Aps1p is more similar to the sigma subunit of the Golgi-localized mammalian AP-1 complex than Aps2p, which is more related to the plasma membrane AP-2 sigma subunit. Like their mammalian counterparts, Aps1p and Aps2p are components of distinct, large (> 200 kDa) complexes and a significant portion of the Aps proteins co-fractionate with clathrin-coated vesicles during gel filtration chromatography. Unexpectedly, even though the evolutionary conservation of AP small subunits is substantial (50% identity between mammalian and yeast proteins), disruptions of APS1 (aps1 delta) and APS2 (aps2 delta), individually or in combination, elicit no detectable mutant phenotypes. These data indicate that the Aps proteins are not absolutely required for clathrin-mediated selective protein transport in cells expressing wild type clathrin. However, aps1 delta accentuated the slow growth and alpha-factor pheromone maturation defect of cells carrying a temperature-sensitive allele of clathrin heavy chain (Chc) (chc1-ts). In contrast, aps1 delta did not influence the effects of chc1-ts on vacuolar protein sorting or receptor-mediated endocytosis. The aps2 delta mutation resulted in a slight effect on chc1-ts cell growth but had no additional effects. The growth defect of cells completely lacking Chc was compounded by aps1 delta but not aps2 delta. These results comprise evidence that Aps1p is involved in a subset of clathrin functions at the Golgi apparatus. The effect of aps1 delta on cells devoid of clathrin function suggests that Aps1p also participates in clathrin-independent processes.

Adaptor Protein Complex 1↗

PubMed1990

Regulation of cellular retinol binding protein type II by 1,25-dihydroxyvitamin D3.

Previously we purified and sequenced an 18-kDa chick duodenal protein that was modulated by 1,25-dihydroxyvitamin D3. The N-terminus of this protein has striking sequence homology to cellular retinol binding protein type II (CRBP II). Furthermore, this purified chick protein binds retinol. Antibodies have now been generated to the chick protein and used for immunoblot analysis to demonstrate that the chick protein has molecular weight, tissue distribution, and subcellular localization similar to rat CRBP II. These antibodies also cross-reacted with rat CRBP II. Antibodies to rat CRBP II cross-react with the chick protein. Northern analysis using a cDNA probe for rat CRBP II showed a single 860 base pair mRNA in both chick and rat intestinal RNA preparations. These results demonstrate that the 1,25-dihydroxyvitamin D3 modulated protein in chick embryonic organ culture is chick CRBP II. Pulse-chase experiments in chick embryonic duodenal organ culture strongly suggest that 1,25-dihydroxyvitamin D3 markedly decreases the synthesis of CRBP II, while not changing the degradation rate. The concentration of 1,25-dihydroxyvitamin D3 required for the decrease in CRBP II synthesis is approximately that required to stimulate calcium uptake into embryonic chick duodenal organ cultures.

Animals↗

PubMed1988

Purification and properties of an 18-kilodalton, 1,25-dihydroxyvitamin D3 modulated protein from embryonic chick intestine.

An 18,000-dalton protein (pI = 5.1) shown previously to be modulated by 1,25-dihydroxyvitamin D3 was purified to allow its further characterization. This protein from embryonic chick intestine was shown to comigrate during two-dimensional electrophoresis with an abundant protein from the intestine of 4-week-old chickens. The protein was purified from 4-week chick intestine and analyzed for amino acid composition, and 28 amino acids of its N-terminal sequence were determined. The N-terminal amino acid sequence had significant homology to cellular retinol binding protein II, an intestinal protein that has been recently sequenced. The purified 18-kilodalton protein was shown to bind retinol by fluorescence spectrophotometry. This 18-kilodalton protein is dramatically changed by 1,25-dihydroxyvitamin D3 in the chick embryonic organ culture system. Therefore, further study of it may lead to a better understanding of vitamin A and D interaction and how 1,25-dihydroxyvitamin D3 acts through proteins to stimulate intestinal calcium and phosphate transport.

Amino Acid Sequence↗

PubMed1987

Retrospective conversion: a survey of UNYOC/MLA members.

The Upstate New York and Ontario MLA surveyed its members to determine which libraries are conducting retrospective conversion projects and their reasons and methods. All academic and medical school libraries that responded are converting, but only 16 of 39 hospital libraries and 14 of 23 other libraries have such plans. The majority of respondents intend to do the work themselves instead of contracting with a vendor. They highly recommend that a written plan be drawn up before proceeding with retrospective conversion.

Attitude↗

PubMedDate not supplied

Identification of human glandular kallikrein hK2 from LNCaP cells.

Based on studies indicating that human glandular kallikrein (hK2) mRNA is present in the prostate, we prepared a monoclonal antibody to a synthetic peptide corresponding to the 41-56 region of hK2 to try to identify the hK2 protein. Although prostate-specific antigen (PSA) and hK2 share 80% homology, the 41-56 amino acid sequence of hK2 is only 50% homologous with PSA. A monoclonal antibody, HK1A523, was identified that demonstrates high specificity for hK2. In western blot analysis, the antibody has a 1,000-fold greater sensitivity for the detection of hK2 than for PSA. The antibody was used to probe spent media from the prostate carcinoma cell line, LNCaP. An immunoreactive species was N-terminally sequenced and identified as mature hK2. HK1A523 was also utilized to probe prostate tumor cytosols and seminal fluid where putative forms of hK2 were also identified. The hK2 protein therefore is expressed and secreted from prostate carcinoma cells.

Antibodies, Monoclonal↗

PubMedDate not supplied

Detection of human glandular kallikrein, hK2, as its precursor form and in complex with protease inhibitors in prostate carcinoma serum.

Forms of human glandular kallikrein (kK2) in prostate carcinoma serum were identified using monoclonal antibodies specific for hK2 and prohK2. Recombinant mammalian hK2, prohK2, and prostate = specific antigen (PSA) were utilized to confirm the specificity of monoclonal antibodies for hK2 and the lack of reactivity with PSA. In prostate cancer patient sera containing high levels of hK2 (>100 ng/ml), hK2 exists as a complex with alpha1-antichymotrypsin with a molecular weight of 90 kDa. The kallikrein also exists as a 32-kDa free form, which includes the precursor pro form of hK2. The relative amount of complex and free hK2 varied, but in most sera examined the 32-kDa form predominated. Recombinant hK2 readily formed complexes with alpha2-macroglobulin when the two proteins were incubated together as well as when hK2 was spiked into female serum.

Antibodies, Monoclonal↗