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Biomedical subjects

P J Lee

Publications and source records attributed to P J Lee.

At least 19 recordsLinked to original sources
PubMed1996

Los Angeles study of residential magnetic fields and childhood brain tumors.

A measurement study of residential magnetic fields and brain tumors in children that was added onto an ongoing case-control interview study in Los Angeles County, California, include 298 children under age 20 years with a primary brain tumor diagnosed from 1984 to 1991 and 298 control children identified by random digit dialing. Magnetic fields were determined for all Los Angeles homes where these 596 children lived from conception to diagnosis (1,131 homes) by mapping and coding the wiring configurations outside the home and by taking a series of exterior spot and profile measurements. In addition, for a subset of subjects (35%; 211 homes) 24-hour measurements were taken in the child's room and one other room. Although measured fields are consistently highest in the highest of the five wire code categories, fields in homes in this category are much lower in Los Angeles than in Denver, where the code originated. Brain tumor risk appears not to relate to measured fields inside (p for trend for child's room = 0.98) or outside (p for trend for front wall = 0.82) the home. An apparent increase in risk among children living at diagnosis in homes with underground wiring appears to be an artifact introduced by using current controls for historical cases because this apparent excess risk disappeared in an analysis restricted to the later years of the study when cases and controls were accrued concurrently. Our study does not show an overall association of pediatric brain tumors with measured fields, with "very high" wiring configurations, or with any of several other potential sources of exposure, such as use of various electrical appliances, but the prevalence of high fields (> 2 mG) and very high fields (> 3 mG) in Los Angeles homes was too low to detect a moderate effect of the magnitude reported in other studies.

Adolescent↗
PubMed1995

Occupations with exposure to electromagnetic fields: a possible risk factor for Alzheimer's disease.

The authors present analyses of data from three independent clinical series and controls indicating an association between working in occupations with probable medium to high exposure to extremely low frequency (< 300 Hz) electromagnetic fields and sporadic Alzheimer's disease. Case-control analyses were carried out using data from patients examined at the following locations: the Department of Neurology, University of Helsinki, Helsinki, Finland, 1982-1985; the Koskela Hospital in Helsinki, 1977-1978; and the University of Southern California site of the Alzheimer's Disease Research Center of Los Angeles and Orange Counties, 1984-1993. The predominant occupations among medium (2-10 mG or > 10 mG intermittently) to high (> 10 mG or > 100 mG intermittently) exposed cases were seamstress, dressmaker, and tailor. The results appear to be independent of education, and the sex-combined odds ratios for the three series are quite homogeneous: 2.9, 3.1, and 3.0. The odds ratio for the three series analyzed together is 3.0 (p < 0.001), with a 95% confidence interval of 1.6-5.4. The odds ratio for women is 3.8 (p < 0.001), with a 95% confidence interval of 1.7-8.6. The most obvious, possibly etiologically relevant exposure is that of electromagnetic fields, which may have biologic plausibility because they may adversely influence calcium homeostasis and/or inappropriately activate immune system cells such as microglial cells, initiating events that result in neuronal degeneration.

Aged↗
PubMed1995

The hepatic glycogen storage diseases--problems beyond childhood.

The introduction of continuous nocturnal enteral glucose feeds and uncooked cornstarch has improved the prognosis for patients with the hepatic glycogen storage diseases. An increasing number of patients are surviving into adulthood in better health, but still at some medical cost. In this review we examine bone mineralization, renal function, hepatic tumours, and vascular endothelial function in GSD I and cardiac function in GSD III. All females over the age of 5 years with GSD I, III, VI and IX had morphologically polycystic ovaries. Thirteen adult GSD I patients have been studied, and been found to have poor bone mineralization and marked renal glomerular and tubular dysfunction. More than half of these patients also had focal hepatic lesions on sonography and yet vascular endothelial function was preserved in the face of hyperlipidaemia. In 12 GSD III patients, one had a focal hepatic lesion and 6 had pronounced left ventricular hypertrophy, although cardiorespiratory function was normal. These data emphasize the multisystem nature of these disorders and highlight the need for careful longterm follow-up.

Adult↗
PubMed1995

Bone mineralisation in type 1 glycogen storage disease.

UNLABELLED: Radial bone mineral content (BMC) was measured using single photon absorptiometry in 11 prepubertal children, aged 3.4-12.6 years, with glycogen storage disease type 1 (GSD-1), 2 of whom were receiving granulocyte colony stimulating factor (G-CSF) therapy for chronic neutropenia. Patients were short (median height SD score -1.35, range -3.74 to -0.27), and had reduced BMC Z scores (median 1.79, range -6.35 to +0.27) and radial bone width Z scores (median -0.72, range -2.00 to +0.68). Those receiving G-CSF did not differ significantly from the rest of the group. Generally dietary calcium intake was low and urinary calcium excretion increased. Urinary lactate excretion was high but did not correlate with BMC Z scores. Factors regulating bone metabolism (parathyroid hormone and 25-hydroxy vitamin D concentrations) and markers of bone formation (osteocalcin and skeletal alkaline phosphatase) were not increased implying that there was no compensation for increased bone resorption. CONCLUSION: Patients with GSD-1 may be at increased risk of fracture in later life and require close attention to metabolic control and calcium balance.

Absorptiometry, Photon↗
PubMed1995

The prevalence of polycystic ovaries in the hepatic glycogen storage diseases: its association with hyperinsulinism.

OBJECTIVE: There has been much debate concerning the relative contribution of insulin resistance to the development of polycystic ovaries (PCO). We therefore aimed to assess ovarian morphology and insulin/androgen status in females with the hepatic glycogen storage diseases types Ia (GSD-Ia) and III (GSD-III), disorders associated with abnormalities of insulin secretion. DESIGN: A cross-sectional study of ovarian ultrasonography, oral glucose tolerance tests (oGTTs) and single measurements of gonadotrophins and androgens were performed. PATIENTS: Twenty-seven patients were evaluated: 13 with GSD-Ia, median age 11.2 years (range, 3.3-26.7) and 14 with GSD-III, aged 13.2 years (4.2-31.3). None had clinical signs of hyperandrogenism and only two of the 13 adults (15%) had menstrual irregularities. They were compared to 9 normal adult female controls, aged 21-28 years. MEASUREMENTS: Ovarian morphology and volume were measured. Blood glucose and plasma insulin concentrations were measured at the beginning and end of a 2-hour oGTT. Single measures of LH, FSH, testosterone, dehydroepiandrosterone sulphate, androstenedione, IGF-I and SHBG were made on samples taken at the beginning of the oGTT. RESULTS: In both GSD-Ia and III, all those older than 4.8 years of age had a polycystic ovarian appearance. Pre-pubertal GSD-Ia patients had lower basal and 2-hour blood glucose and plasma insulin concentrations than pre-pubertal GSD-III patients. In adults with GSD-Ia and GSD-III, although basal and 2-hour blood glucose concentrations did not differ, both basal and 2-hour plasma insulin concentrations were significantly higher than controls. Serum gonadotrophins, androgens, IGF-I and SHBG were mostly normal. CONCLUSIONS: A polycystic ovarian appearance is a common finding in patients with glycogen storage disease even before puberty. In GSD-III and adults with GSD-Ia, this ovarian appearance was associated with hyperinsulinism, suggesting an aetiological link, but this was not the case in pre-pubertal children with GDS-Ia. Inborn errors of carbohydrate metabolism may act as useful models for examining control mechanisms of ovarian physiology and development.

Adolescent↗
PubMed1995

Spinal meningiomas in women in Los Angeles County: investigation of an etiological hypothesis.

A series of 3 studies explored the hypothesis that the preponderance of spinal meningiomas among postmenopausal women relates to their higher prevalence of spinal osteoporosis: (a) medical records showed that meningiomas in women, unlike other spinal tumors, usually arise in the mid thoracic spine where osteoporotic vertebral fractures predominate; (b) radiographic evidence of osteoporosis was seen commonly with meningiomas but not with other spinal tumors; and (c) age-adjusted multivariate analysis of data from an interview study of 81 women with spinal meningioma and 155 random digit dial controls showed 6 factors related to risk. Four factors were protective: (a) current use (at diagnosis) of estrogen replacement therapy [odds ratio (OR) = 0.2; 95% confidence interval (CI) = 0.1-0.6]; (b) past use of oral contraceptives (P trend < 0.01); (c) past participation in sports (OR = 0.5; CI = 0.2-0.9); and (d) premenopausal status (OR = 0.2; CI = 0.1-0.7). Risk increased among women who had ever smoked cigarettes (OR = 1.7; CI = 0.9-3.1) or had a history of high dose radiography (> 500 mrad exposure to active marrow/examination; includes upper or lower gastrointestinal series and/or cardiac angiography; OR = 2.9, and CI = 1.6-5.3), although no association was seen with prior radiotherapy. Other results that did not support the hypothesis include findings that cases and controls were similar in mean body weight and in the proportion who had postmenopausal fractures or height loss. In conclusion, these studies lend some support to our hypothesis, but other known meningioma risk factors such as ionizing radiation also appear important.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Epizootic of low-virulence hepatotropic murine hepatitis virus in a nude mice breeding colony in Taiwan.

A natural outbreak of mouse hepatitis virus infection developed in a breeding colony of nude mice in Taiwan. The outbreak was unique in that morbidity was high in both adult and suckling mice, but only sucklings died. In contrast, all suckling heterozygous (nu/+) mice survived, and no lesions were found in adult female heterozygous (nu/+) mice. Adult male nude mice had chronic, active, necrotizing hepatitis with syncytial giant cells, but no lesions were detected in other tissues. Immunohistochemistry with anti-A59 and anti-JHM serum revealed mouse hepatitis virus antigen in the liver of infected adult and suckling nude mice, although less intensively in the kidney of adult nude mice. Suckling BALB/c mice inoculated with filtrates of the liver of adult nude mice developed hepatitis similar to that in the naturally infected nude mice. Virus was isolated by inoculating cell-free liver filtrate from infected adult nude mice onto 3T3 cells. Electron microscopy of purified virus revealed 100-nm-diameter enveloped particles with characteristic petal-shaped surface projections. We conclude that the outbreak was caused by a weakly virulent, highly hepatotropic murine hepatitis virus.

Animals↗
PubMed1994

Hyperlipidaemia does not impair vascular endothelial function in glycogen storage disease type 1a.

Patients with glycogen storage disease type 1 (GSD-1) often have marked hyperlipidaemia with abnormal lipoprotein profiles. This metabolic abnormality improves, but is not fully corrected, with dietary therapy and therefore these patients may be at high risk for the development of atherosclerosis. Endothelial dysfunction is an early event in atherogenesis and can be detected in children and young adults at high risk. We studied endothelial function, using a non-invasive ultrasonographic method, in the brachial arteries of 6 adult GSD-1a patients (aged 23-33 years) with mean cholesterol of 7.9 mmol/l (range 4.7 to 14.6) and mean triglycerides of 9.1 mmol/l (range 4.1 to 21.3), and 12 age- and sex-matched normolipidaemic controls. Flow-mediated (endothelium-dependent) dilation was similar in patients and controls (8.2% vs. 10.5%; P = 0.20). Although the patient numbers are small, these results are consistent with the surprising lack of clinically evident atherosclerosis in GSD-1. The reasons these patients appear less susceptible to the damaging arterial effects of hyperlipidaemia are unknown. These results may have implications for others with secondary hyperlipidaemias.

Adult↗
PubMed1992

Use of helper-free retroviral vector to direct a high expression of porcine growth hormone in mouse fibroblast cells.

A retroviral vector has been employed to express the cDNA coding for porcine growth hormone (pGH) in the mouse fibroblast cell NIH 3T3 in large quantity. In this study, a single gene vector which contained no selectable marker was used. We have coinfected NIH 3T3 cells with pGH retrovirus and Neo(r) retrovirus to obtain a stable, high-expression clone. Using a superinfection strategy, we further increased the copy number of proviral DNA in the host chromosome, thus increasing the pGH secretion from 22 to 55 micrograms/10(6) cells/24 h. The recombinant pGH produced from mouse fibroblast cells was heterogeneous at the N-terminus, which mimicked the situation with bovine growth hormone either from natural sources or from recombinant products derived from mouse fibroblasts. This technology is useful for many biologically important genes to be stably transduced by retroviral vector into mammalian cells and highly expressed.

3T3 Cells↗
PubMed1991

Use of recombinant DNA derived human relaxin to probe the structure of the native protein.

This report describes the physical, chemical, and biological characterization of recombinant human relaxin (rhRlx) used as a probe to establish the disulfide pairing in native human relaxin. This strategy is necessary since native human relaxin is only available in the nanogram range. The relaxin molecule is composed of two nonidentical peptide chains, an A-chain 24 amino acids in length and a B-chain of 29 amino acids, linked by two disulfide bridges with an additional disulfide linkage in the A-chain. Native relaxin isolated from human corpora lutea was compared to rhRlx by reversed-phase chromatography, partial sequence analysis, mass spectroscopy, and bioassay. The potency of rhRlx was established by its ability to stimulate cAMP from primary human uterine endometrial cells. Native relaxin isolated from human corpora lutea was equipotent to chemically synthesized relaxin, which in turn was equipotent to rhRlx. A tryptic map was developed for rhRlx to confirm the complete amino acid sequence and assignment of the disulfide bonds. The three disulfide bonds (CysA10-CysA15, CysA11-CysB11, and CysA24-CysB23) were assigned by mass spectrometric analysis of the tryptic peptides and by comparison to chemically synthesized peptides disulfide linked in the two most probable configurations. In addition, the observed amino acid composition and sequence of rhRlx was in agreement with that predicted from the cDNA sequence with the exception that the A-chain amino terminal was pyroglutamic acid. The migration of rhRlx upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis was consistent with a monomeric structure, and the identity of the band was demonstrated by immunoblotting.

Amino Acid Sequence↗
PubMed1986

Human prostate-specific antigen: structural and functional similarity with serine proteases.

The complete amino acid sequence of the prostate-specific antigen (PA) from human seminal plasma has been determined from analyses of the peptides generated by cyanogen bromide, hydroxylamine, endoproteinases Arg-C and Lys-C. The single polypeptide chain of PA contains 240-amino acid residues and has a calculated Mr of 26,496. An N-linked carbohydrate side chain is predicted at asparagine-45, and O-linked carbohydrate side chains are possibly attached to serine-69, threonine-70, and serine-71. The primary structure of PA shows a high degree of sequence homology with other serine proteases of the kallikrein family. The active site residues of histidine, aspartic acid, and serine comprising the charge-relay system of typical serine proteases were found in similar positions in PA (histidine-41, aspartic acid-96, and serine-192). At pH 7.8, PA hydrolyzed insulin A and B chains, recombinant interleukin 2, and--to a lesser extent--gelatin, myoglobin, ovalbumin, and fibrinogen. The cleavage sites of these proteins by PA were chemically analyzed as the alpha-carboxyl side of some hydrophobic residues, tyrosine, leucine, valine, and phenylalanine, and of basic residues histidine, lysine, and arginine. The chymotrypsin-like activity of PA exhibited with the chromogenic substrate N-succinyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanine p-nitroanilide yielded a specific activity of 9.21 microM per min per mg of PA and Km and kcat values of 15.3 mM and 0.075s-1, respectively. "Trypsin-like" activity of PA was also detected with N alpha-benzoyl-DL-arginine p-nitroanilide and gave a specific activity of 1.98 microM per min per mg of PA. Protease inhibitors such as phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate, L-1-tosylamido-2-phenylethyl chloromethyl ketone, aprotinin, leupeptin, soybean trypsin inhibitor as well as Zn2+ and spermidine were effective inhibitors of PA enzymatic activity.

Amino Acid Sequence↗
PubMed1985

Family involvement and metabolic control of childhood diabetes.

To investigate the association between the family environment and metabolic control of childhood diabetes 20 diabetic children aged between 4 and 12 years with same-sex healthy siblings and two cohabiting parents were selected. The parents were interviewed separately and completed questionnaires about their own and their spouse's involvement and shared activities with both children, diabetic management, and knowledge of and attitudes towards diabetes. They also completed the Moos Family Environment Scale (FES) which yields ten sub-scales relating to different aspects of family functioning as did 20 sets of parents with age- and sex-matched healthy children, who also completed questionnaires concerning their involvement and shared activities with their children. There were no differences between the families of diabetics and of controls in the extent to which either parent was involved with their children or in the attention each child received. Fathers of diabetic children differed from controls in their use of punishment and diabetic families were less achievement oriented. The degree of metabolic control (HbA1 assessment at three-monthly intervals) was related to parental involvement with the non-diabetic child and to some aspects of the FES including parental incongruence. These differences in family functioning suggest useful directions for possible intervention programmes.

Attitude to Health↗
PubMed1984

Iron-induced changes in rat liver isoferritins.

The effects of single and of multiple iron injection on the distribution of isoferritins was studied in rat liver with the aid of 14C-labelling either after or before iron treatment. Several effects of iron can be seen. Analysis of protein and labelling patterns show that it not only produces a disproportionate increase in the more-basic isoferritins, but may, in sufficient dose, actually lead to a decrease in the more-acidic isoferritins. Use of iron injection after radioactivity shows that it must give rise to post-assembly changes causing acidic isoferritins to become more basic. With a moderate iron dose this change is relatively slow, taking several hours, and seems to occur in addition to a differential stimulation of the synthesis of the more-basic isoferritins. With higher iron dosage the post-assembly changes may be so rapid that it is difficult to distinguish them from a switch in the pattern of synthesis.

Animals↗
PubMed1984

Functional studies on rat-liver isoferritins.

Rat-liver and horse-spleen isoferritins were obtained by preparative isoelectric focussing and several of these were fractionated further by sucrose density gradient centrifugation. H- and L-subunit compositions were also measured. Isoferritins were found to have neither a fixed iron content nor a unique subunit composition. In both species within a single isoferritin a small increase in the percentage of H subunit paralleled increasing iron content. Although in horse-spleen ferritin a similar correlation was found over the isoferritin profile as a whole, this was not generally true of rat-liver isoferritins, since iron distributions varied with the iron status of the animals. Rates of iron incorporation into isoapoferritins were measured in vitro and the distribution of 59Fe among rat liver isoferritins was measured at various times after injection of 59Fe. The data do not support the proposal that, in rat liver, L-rich isoferritins are the preferred iron-storage form.

Animals↗
PubMed1984

The effect of iron on ferritin turnover in rat liver.

It has previously been reported that in rat liver the rates of synthesis and degradation of ferritin labelled with [14C]leucine or arginine are dependent on the iron status of the rats. It has also been concluded that isoferritins differ markedly in their rates of turnover. Here we provide experimental evidence which shows that the rate of degradation of rat liver ferritin (labelled by injection of [14C]bicarbonate to minimise problems of reutilisation) is unaltered by repeated iron injection, although ferritin synthesis is stimulated. Our data also strongly suggest that the proposed differential degradation of isoferritins is improbable.

Animals↗