Biomedical subjects

P Ong

Publications and source records attributed to P Ong.

At least 19 recordsLinked to original sources

PubMed2002

Depression: reduced number of granule cells in the hippocampus of female, but not male, rats due to prenatal restraint stress.

It has been hypothesized that decreased neurogenesis in the dentate gyrus may be involved in mediating depressive disorders, which are 1.5-3 times more frequent in women than in men. Additionally, prenatal stress may increase the risk of developing depression in adulthood. However, the interrelations between prenatal stress and the development of depression in adulthood, preferentially in females, are not understood. Here, we subjected pregnant rats to a single 20-min period of restraint stress on day 18 after mating. When the offspring were 75 days of age, the numbers of granule cells and pyramidal cells (area CA1-3) in the hippocampus were analyzed with the optical fractionator. The Cavalieri's principle was applied to analyze the volumes of both granule cell layer and pyramidal cell layer in the hippocampus. Prenatally stressed females, but not males, had reduced numbers of hippocampal granule cells compared to their non-prenatally stressed counterparts. This is the first report of a sex-specific difference concerning the reduction of the number of hippocampal granule cells due to prenatal stress. In humans, prenatal stress may induce cell loss in the granule cells of the hippocampus preferentially in females compared to males, and this may be a sex-specific predisposing factor for the development of depression in adulthood.

Animals↗

PubMed2000

Cytogenetic analysis of invasive breast cancer: a study of 27 Asian patients.

Tumor cytogenetic analysis from 27 patients with breast cancer diagnosed at the Singapore General Hospital revealed complex karyotypic aberrations in 12 cases. The study group comprised 25 women and 2 men, ranging in age from 33 to 78 years (median 52 years). Ethnic distribution consisted of 22 Chinese, 3 Malaysian, and 2 Indian patients. Pathologic assessment disclosed 24 invasive ductal, 2 invasive mucinous, and 1 mixed invasive mucinous and ductal carcinomas. Histologic grading showed 3 grade 1, 10 grade 2, and 12 grade 3 tumors; 2 cancers were not graded, because they had been subjected to prior chemotherapy. Tumor sizes ranged from 1.5 to 10 cm (median 3 cm). Eleven cases were axillary node negative, whereas the remaining 16 node-positive cancers affected as many as 3 nodes in 8 cases and 4 or more nodes in another 8. Twenty cases demonstrated estrogen-receptor positivity, and 8 cases progesterone-receptor positivity. The spectrum of cytogenetic abnormalities involved chromosomes 1, 3, 6, 7, 8, 11, 16, and 17 and ranged from gains and deletions of both long and short arms, trisomy, monosomy, and other rearrangements. There was a trend toward the presence of karyotypic abnormalities in tumors of higher grade.

Adenocarcinoma↗

PubMed1998

Molecular genetics of cystinuria: mutation analysis of SLC3A1 and evidence for another gene in type I (silent) phenotype.

BACKGROUND: Cystinuria is a hereditary disorder that affects luminal transport of cystine and dibasic amino acids in kidney and small intestine. Three subtypes have been defined on the basis of urinary excretion of cystine in obligate heterozygotes. Mutations in the SLC3A1 gene have been associated with the Type I phenotype. METHODS: We investigated 20 cystinuria patients from Quebec (8 Type I/I, 9 Type I/III and 3 Type II/N) for mutations in SLC3A1. DNA was studied by Southern blotting and by the single strand conformation polymorphism (SSCP) protocol to identify mutations. Expression of mutations in Xenopus oocytes was performed to confirm the effect of missense mutations on cystine uptake. RESULTS: Six novel mutations (2 large deletions, a 2 bp deletion and 3 single bp substitutions) were identified on the Type I allele. Four missense mutations (T216M, S217R, R270L and I618M) were expressed in vitro; the first three changes significantly decreased uptake. CONCLUSIONS: Combined with our previous work, we have identified 15/16 mutations in SLC3A1 on Type I alleles in the eight Type I/I patients, but only one SLC3A1 mutation on the nine Type I alleles of the Type I/III patients. Therefore, we propose that the Type I phenotype could be caused by mutations in other, as yet unidentified cystinuria genes.

Amino Acid Transport Systems, Basic↗

PubMed1998

Cystinuria subtype and the risk of nephrolithiasis.

BACKGROUND: Cystinuria patients may be classified into several subgroups based on the urinary phenotype of heterozygotes. However, the relative risk for nephrolithiasis and the prevalence of SLC3A1 mutations in these subgroups are unknown. METHODS: Urinary cystine excretion, age at onset of nephrolithiasis and nature of SLC3A1 mutations were assessed prospectively in 23 cystinuria patients identified primarily through the Quebec Newborn Screening Program. Probands were classified as to cystinuria subtype on the basis of parental urinary cystine excretion. RESULTS: For classical Type I/I cystinuria, both parents excrete cystine in the normal range and probands carry two mutations of the SLC3A1 gene in nearly every case. Between ages 1 to 7 years, mean cystine excretion was high (4566 +/- 480 microns cystine/g creatinine) and exceeded the theoretic threshold for solubility on 70% of visits. Four of eight Type I/I patients began forming stones in the first decade. Type I/III patients (N = 12) excreted less cystine (1544 +/- 163 mumol cystine/g creatinine), exceeded the threshold of urinary cystine solubility less frequently (22% of visits) and had no nephrolithiasis in the first decade; one formed a stone at age 16 years. Only one SLC3A1 mutation was identified in this group. Two Type II/N cystinuria children were identified. In these families, the same level of relatively high excretion (> 600 mumol cystine/g creatinine) was noted in two or three generations, but no SLC3A1 mutations were identified. CONCLUSIONS: Classical recessive Type I/I cystinuria is genetically and phenotypically distinct from the other subtypes (Type I/III and Type II/N) identified in our population.

Adolescent↗

PubMed1996

Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype.

The activity of a damage-specific DNA-binding protein (DDB) is absent from a subset, Ddb-, of cell strains from patients with xeroderma pigmentosum group E (XP-E). DDB is a heterodimer of 127-kDa and 48-kDa subunits. We have now identified single-base mutations in the gene of the 48-kDa subunit in cells from the three known Ddb- individuals, but not in XP-E strains that have the activity. An A --> G transition causes a K244E change in XP82TO and a G --> A transition causes an R273H change in XP2RO and XP3RO. No mutations were found in the cDNA of the 127-kDa subunit. Overexpression of p48 in insect cells greatly increases DDB activity in the cells, especially if p127 is jointly overexpressed. These results demonstrate that p48 is required for DNA binding activity, but at the same time necessitate further definition of the genetic basis of XP group E.

Animals↗

PubMed1993