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Biomedical subjects

J Lee

Publications and source records attributed to J Lee.

At least 109 records · Page 6Linked to original sources
PubMed2004

Glial cell line-derived neurotrophic factor is essential for neuronal survival in the locus coeruleus-hippocampal noradrenergic pathway.

It has been shown that the noradrenergic (NE) locus coeruleus (LC)-hippocampal pathway plays an important role in learning and memory processing, and that the development of this transmitter pathway is influenced by neurotrophic factors. Although some of these factors have been discovered, the regulatory mechanisms for this developmental event have not been fully elucidated. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor influencing LC-NE neurons. We have utilized a GDNF knockout animal model to explore its function on the LC-NE transmitter system during development, particularly with respect to target innervation. By transplanting various combinations of brainstem (including LC) and hippocampal tissues from wildtype or GDNF knockout fetuses into the brains of adult wildtype mice, we demonstrate that normal postnatal development of brainstem LC-NE neurons is disrupted as a result of the GDNF null mutation. Tyrosine hydroxylase immunohistochemistry revealed that brainstem grafts had markedly reduced number and size of LC neurons in transplants from knockout fetuses. NE fiber innervation into the hippocampal co-transplant from an adjacent brainstem graft was also influenced by the presence of GDNF, with a significantly more robust innervation observed in transplants from wildtype fetuses. The most successful LC/hippocampal co-grafts were generated from fetuses expressing the wildtype GDNF background, whereas the most severely affected transplants were derived from double transplants from null-mutated fetuses. Our data suggest that development of the NE LC-hippocampal pathway is dependent on the presence of GDNF, most likely through a target-derived neurotrophic function.

Animals↗
PubMed2004

Effect of I.C.V. injection of AT4 receptor ligands, NLE1-angiotensin IV and LVV-hemorphin 7, on spatial learning in rats.

Central administration of angiotensin IV (Ang IV) or its analogues enhance performance of rats in passive avoidance and spatial memory paradigms. The purpose of this study was to examine the effect of a single bolus injection of two distinct AT4 ligands, Nle1-Ang IV or LVV-haemorphin-7, on spatial learning in the Barnes circular maze. Mean number of days for rats treated with either Nle1-Ang IV or LVV-haemorphin-7 to achieve learner criterion is significantly reduced compared with controls (P < 0.001 and P < 0.05 respectively). This is due to enhanced ability of the peptide-treated rats to adopt a spatial strategy for finding the escape hatch. In all three measures of learning performance, (1) the number of errors made, (2) the distance travelled and (3) the latency in finding the escape hatch, rats treated with either 100 pmol or 1 nmol of Nle1-Ang IV or 100 pmol LVV-haemorphin-7 performed significantly better than the control groups. As early as the first day of testing, the rats treated with the lower dose of Nle1-Ang IV or LVV-haemorphin-7 made fewer errors (P < 0.01 and P < 0.05 respectively) and travelled shorter distances (P < 0.05 for both groups) than the control animals. The enhanced spatial learning induced by Nle1-Ang IV (100 pmol) was attenuated by the co-administration of the AT4 receptor antagonist, divalinal-Ang IV (10 nmol). Thus, administration of AT4 ligands results in an immediate potentiation of learning, which may be associated with facilitation of synaptic transmission and/or enhancement of acetylcholine release.

Angiotensin II↗
PubMed2004

Changes in expression of T-cell activation-related molecules and cytokines during tolerance induction in an allogeneic skin transplantation murine model.

Bone marrow transplantation after treatment with busulfan and costimulatory blockade with monoclonal antibodies (mAb) cytotoxic T lymphocyte antigen 4 (CTLA4)-Ig and anti-CD154 mAb or two-signal blockade using anti-CD45RB and anti-CD154 mAb are nonmyeloablative treatment regimens for allogeneic transplantation. There may be differences in the mechanisms of donor cell engraftment and reactive cell deletion by which these regimens induce donor-specific tolerance. Therefore, this study was performed to investigate changes in T cells and cytokines during tolerance induction toward allogeneic skin grafts. BALB/c and C57BL/6 mice were used as donors and recipients, respectively. Skin and bone marrow transplantations were performed and busulfan was administered. Three groups were treated with mAb as follows: group 1, anti-CD154 mAb; group 2, anti-CD154 plus anti-CD45RB mAb; and group 3, anti-CD154 mAb plus CTLA4-Ig. The proportions of CD4+ or CD8+ T cells and the expression of CD45RB isoforms on splenocytes were measured using flow cytometry and the production of cytokines by CD4+ T cells using enzyme-linked immunosorbent assay. Group 2 showed a significant reduction in the proportions of CD8+ T cells and CD45RB high isoforms compared with groups 1 and 3. The levels of interleukin (IL)-2 and IL-4 in group 2 were lower and higher than those of groups 1 and 3, respectively. In conclusion, the combined use of anti-CD154 and anti-CD45RB mAb decreases the CD8+ T-cell population and the expression of CD45RB, resulting in a Th2 cytokine profile, which may be a characteristic mechanism leading to donor cell engraftment and reactive cell deletion for donor-specific tolerance.

Animals↗
PubMed2004

Overexpression of LIM kinase 1 renders resistance to apoptosis in PC12 cells by inhibition of caspase activation.

LIM kinases (LIMKs) regulate actin polymerization by phosphorylating cofilin and are predominantly expressed in neural tissue. In this study, the effect of LIMK1 overexpression in PC12 cell apoptosis was investigated. PC12 cells overexpressing the wild-type LIMK1 were more resistant to serum-withdrawal-induced cell death and the level of caspase 3 activation in these cells was lower than in the control PC12 cells or than in the PC12 cells expressing a mutant LIMK1 lacking the kinase domain. The inhibition of JNK activation was observed in the PC12 cells overexpressing the wild-type LIMK1 after serum withdrawal. These results suggest that the LIMK1 might allow resistance to apoptosis in PC12 cells by inhibiting JNK activation.

Actin Cytoskeleton↗
PubMed2004

Copper oxide needles administered during early pregnancy improves the copper status of ewes and their lambs.

AIM: To determine the effect of copper oxide (CuO) needles administered orally to ewes in early pregnancy on the copper (Cu) status of ewes throughout gestation and lactation, and of their lambs from birth to weaning. METHODS: In mid-April, after mating, 12 twin-bearing ewes were given an oral capsule containing 5 g CuO needles while 12 others served as untreated controls. Changes in Cu status were monitored by determining serum and liver Cu concentrations on Days 1, 62, 117, 153, 185 and 216 in the ewes, and at 1, 36, 68 and 99 days of age for lambs. Pasture herbage samples were collected at about 60-day intervals for Cu, molybdenum (Mo), iron (Fe) and sulphur (S) determinations. RESULTS: Copper status of the ewe flock was adequate, as initial mean serum and liver Cu concentrations were 15 micromol/L and 1,060 micromol/kg fresh tissue, respectively. The CuO needles did not affect serum Cu concentrations of the ewes or their lambs. Mean serum Cu concentration of all lambs at birth was about half that of ewes (8 vs 17 micromol/L), regardless of Cu supplementation, and not until at least 68 days of age was it similar to the dams'. Liver Cu concentrations of lambs at birth were also lower than that of the ewes (380 vs 640 micromol/kg fresh tissue among the controls), but changed little over time. CuO treatment increased liver Cu concentration in ewes for at least 185 days and in lambs for 36 days (p<0.05). Among untreated ewes, there was a seasonal decline in mean liver Cu concentrations, which were highest in autumn and lowest in early spring (1,060 vs 370 micromol/kg fresh tissue). The mean pasture mineral concentrations were Cu 5.7, Mo 0.48, Fe 194 and S 2,900 mg/kg dry matter (DM). CONCLUSIONS: CuO needles administered to ewes in early pregnancy increased their Cu status through gestation and early lactation, and the Cu status of their lambs for 36 days from birth. Serum Cu concentration was not affected by treatment but a marked rise was observed in all lambs between birth and 10 weeks of age. CLINICAL RELEVANCE: Copper deficiency in young lambs may be conveniently and effectively prevented by treating ewes with CuO needles during early pregnancy. The serum Cu concentration in lambs <8 weeks old may not reflect the Cu status of the flock.

Journal Article↗
PubMed2004

Adding nutritional value to meat and milk from pasture-fed livestock.

Staple meat and milk provide excellent nutrition, but when traditional foods and ingredients are tailored to meet the particular nutritional or lifestyle demands of a population they become even more attractive and valuable. These foods can be considered as delivery systems for health-promoting nutrients. Nutritional improvement of meat and milk can be achieved several ways, preferably by making desirable changes on-farm to directly improve the food without subsequent manipulations. Scope for these changes is limited by animal homeostasis, but alternatives may be less desirable. Methods in vivo that suit typical pastoral farming practice and can complement the solving of animal health and production problems include: selection of traits or phenotypes; specialty diets; long-acting parenteral supplements; and modification of ruminal microflora. Successful techniques to increase the concentration of calcium, selenium, iodine and iron in milk or meat are described. Manipulations to change composition are only one part of bringing tailored foods to market. Commercial realisation of these new products needs the initiative and collaboration of scientists, veterinarians, growers and producers responding to market pull. The uptake of future biotechnologies to capture more value inside the farm gate will also be required if the pastoral industry in New Zealand is to sustain a global competitive advantage.

Journal Article↗
PubMed2004

Pigment-lightening effect of N,N'-dilinoleylcystamine on human melanoma cells.

BACKGROUND: Cystamine and linoleic acid have been reported to reduce melanin synthesis in vitro and in vivo. N,N'-dilinoleylcystamine (DLC) is a compound of cystamine and linoleic acid connected by an ester bond. OBJECTIVES: To investigate the effects of DLC on melanin synthesis using cultured human melanoma cells. METHODS: Levels of total melanin, eumelanin and phaeomelanin, tyrosinase protein and tyrosinase activity in situ were measured in HM3KO melanoma cells. Changes in degree of pigmentation were quantified by image analysis and compared with absorbance values. Tyrosinase from HM3KO cells was used to measure the direct effect of DLC on DOPA and DOPAchrome production. RESULTS: At concentrations of 1.4-14 micromol L-1, DLC reduced the pigmentation of HM3KO melanoma cells but did not affect cell growth. The visual decrease in pigmentation produced by DLC was more dramatic than the decrease in total melanin content as measured by absorbance at 500 nm. DLC treatment decreased eumelanin synthesis and increased phaeomelanin synthesis in HM3KO melanoma cells. An in situ tyrosinase assay showed that DLC inhibited tyrosinase activity, as well as the level of tyrosinase protein. CONCLUSIONS: These results suggest that DLC has pigment-lightening effects on HM3KO melanoma cells, produced by reducing the level of eumelanin while increasing the level of phaeomelanin.

Blotting, Western↗
PubMed2004

Serum adiponectin concentrations predict the developments of type 2 diabetes and the metabolic syndrome in elderly Koreans.

OBJECTIVE: To determine whether low serum adiponectin concentrations are able to predict the future developments of type 2 diabetes and the metabolic syndrome using the National Cholesterol Education Programme (NCEP) criteria. We also investigated the stability of adiponectin levels and the relationships between baseline adiponectin levels and changes in the parameters related to the metabolic syndrome over a period of 3 years. PATIENTS AND MEASUREMENTS: This prospective cohort study included 372 elderly Koreans who participate in the SWS (South-West Seoul) study, which was conducted in 1999 and 2002 in Seoul, Korea. Fasting and postchallenge 2-h plasma glucose, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid profiles and serum adiponectin data obtained in 1999 and 2002 were examined. RESULTS: The within-person variation between 1999 and 2002 of serum adiponectin was not significant (P = 0.61). Serum adiponectin was closely correlated with the risks factors of cardiovascular disease (CVD), that is negatively with BMI, WHR, blood pressure, triglyceride and blood glucose levels, and positively with high density lipoprotein (HDL)-cholesterol levels. Subjects with the metabolic syndrome showed lower serum adiponectin concentrations than those without the metabolic syndrome (P < 0.0001). Baseline adiponectin levels were found to be correlated with subsequent changes in WHR, low density lipoprotein (LDL)-cholesterol, fasting and postload 2-h glucose over the 3-year period, after adjusting for baseline values. Multiple logistic regression analysis showed that lower baseline serum adiponectin concentrations were significantly associated with the developments of type 2 diabetes and the metabolic syndrome after adjusting for age, sex, obesity, history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), hypertension and dyslipidaemia. CONCLUSIONS: Reduced concentrations of adiponectin were found to be independently associated with increased risk of both type 2 diabetes and the metabolic syndrome in elderly Koreans.

Adiponectin↗
PubMed2004

Association of the oestrogen receptor alpha gene polymorphisms with disease onset in systemic lupus erythematosus.

OBJECTIVE: To evaluate the genetic influence of PvuII and XbaI polymorphisms of oestrogen receptor alpha (ORalpha) in patients with systemic lupus erythematosus (SLE) in Korea. METHODS: Genomic DNA from 268 female controls and 137 female SLE patients (41 childhood onset and 96 adult onset) were analysed using PvuII and XbaI restriction fragment length polymorphism. Comparison of the frequencies of alleles and genotypes was made in control and patient groups and in childhood onset and adult onset SLE subgroups. RESULTS: Although the Pp genotype occurred more often in SLE patients than in controls (p(c) = 0.017), ORalpha genotype distributions of adult onset SLE did not differ significantly from controls. The PP, Pp, and xx genotypes occurred less often in childhood onset SLE (p(c) = 0.0045, 0.0498, and 0.0255, respectively) than in controls. Additionally, the PP genotype was less common in childhood onset than in adult onset SLE (p(c) = 0.016). SLE patients with the PP genotypes were older at disease onset than those with the other genotypes (p = 0.001). Patients with the Xx genotype had an earlier onset of SLE than those with the xx genotype (p = 0.025). The frequency of the combined ppXx genotype was greater in childhood onset SLE than in controls (p(c) = 0.0009) or adult onset SLE (p(c) = 0.027). The same trend was supported by subgroup analyses according to age at menarche and logistic multivariate analyses. CONCLUSIONS: ORalpha polymorphisms are significantly associated with the age at disease onset in Koreans with SLE.

Adolescent↗
PubMed2004

Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations.

BACKGROUND: Previous guidelines recommend doubling the daily dose of maintenance inhaled corticosteroid to treat or prevent progression of exacerbations of asthma. METHODS: Over a 6 month period a cohort of patients were evaluated prospectively and randomised in a double blind controlled trial to treatment with either a continued maintenance dose (MD) of inhaled corticosteroid or doubling the dose (DD) at the time of an exacerbation. RESULTS: A total of 290 patients were randomised (33% male) and 98 (DD, n = 46) experienced evaluable asthma exacerbations during the study period. Mean (SD) baseline characteristics at randomisation (age 33.5 (14.0) years; forced expiratory volume in 1 second (FEV(1)) 2.8 (0.7) l; peak expiratory flow (PEF) 422.9 (110.5) l/min) were similar in both groups. In the DD group 41% of patients were considered treatment failures because they either required systemic steroids (n = 12), had an unscheduled visit to a physician (n = 1), or their asthma did not return to baseline (n = 6). This did not differ from the MD group in which 40% were treatment failures (n = 9, 0, and 12, respectively; p = 0.94). CONCLUSIONS: In patients who regularly take an inhaled corticosteroid, doubling the maintenance dose may not affect the pattern of the exacerbation.

Adolescent↗
PubMed2004

Home care artificial heart monitoring system via internet.

The availability of a remote management system, which provides both physiological-related information about the patient and device-related information about the implanted device, would be helpful during in vivo experiments or clinical trials involving artificial heart implantation. In order to be able to monitor the course of the in vivo experiment continuously regardless of the patient's location, an internet-based remote monitoring system was developed, which can monitor physiological-related information such as pressure (AoP, LAP, RAP, PAP) and flow data, as well as device-related information such as current, direction and pump operating conditions. The home care artificial heart monitoring system which we developed consists of four main components, which are the transcutaneous information transmission system (TITS), local monitoring station (LMS), data server station (DSS), and client monitoring station (CMS). The device-related information and physiological-related information can be transmitted in real time from a patient in a remote non-clinical environment to the specialist situated in a clinic depending on the current capabilities and availability of the internet. The local monitoring station situated at the remote site is composed of a data acquisition and preprocessing unit connected to a computer via its RS-232 port, and which communicate using a Java-based client-server architecture. The remote monitoring system so developed was used during an in vivo experiment of the artificial heart implantation for 2 months and performed successfully according to design specifications.

Animals↗
PubMed2004

Factors affecting clinical outcome of patients who undergo transcatheter arterial embolisation in splenic injury.

Transcatheter arterial embolisation (TAE) offers a less invasive approach to traditional laparotomy for the management of bleeding in the context of blunt splenic injury. This is a retrospective review study to identify clinical factors associated with clinical outcome of the patients who underwent this procedure. Of 65 patients with splenic injuries at our institution, 26 patients underwent TAE for management of bleeding. The following factors were assessed to determine their relationship to procedure outcomes: American Association for the Surgery of Trauma (AAST) grade, complications, age, shock index, injury severity score (ISS), haemoglobin (Hb), haematocrit (Ht), prothrombin time (PT), activated partial thromboplastin time (APTT), systolic blood pressure (BP), BP changes during TAE, blood transfused before TAE and timing of TAE. The overall good clinical outcome rate was 73.1% (19/26). Of the factors we assessed, absence of concomitant pelvic injury, higher Hb, higher Ht, higher BP, greater increases in BP during TAE and a decreased requirement for blood transfusions before TAE were associated with good clinical outcome of the patients who underwent TAE in splenic injury.

Adolescent↗
PubMed2004

Evidence that angiotensin II enhances apomorphine-induced jaw movements via AT1 receptors in the ventrolateral striatum: studies by magnet-sensing system in freely moving rats.

The role of angiotensin AT(1) receptors in the ventrolateral striatum in modulating apomorphine-induced jaw movements was studied using a magnet-sensing system combined with an intracerebral drug microinjection technique in freely moving rats. Bilateral injections of angiotensin II (1 and 2 micro g/0.2 micro l in each side) into the ventrolateral striatum, which alone did not significantly elicit jaw movements, dose-dependently enhanced apomorphine (1 mg/kg i.v.)-induced repetitive jaw movements. The enhancement of apomorphine-induced jaw movements by angiotensin II (2 micro g) was dose-dependently antagonized by the angiotensin AT(1) receptor antagonist losartan (15 and 30 mg/kg i.p.), given 3 h before, while losartan (30 mg/kg i.p.) alone did not significantly affect the apomorphine (1 mg/kg)-induced jaw movements. These results indicate that angiotensin II enhances apomorphine-induced jaw movements via stimulation of angiotensin AT(1) receptors located in the ventrolateral striatum.

Angiotensin II↗
PubMed2004

Capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer.

The selection of chemotherapeutic regimens is challenging for metastatic breast cancer (MBC) patients whose diseases have failed to respond to anthracyline and taxane. Capecitabine has advantages of oral administration and favorable toxicity profiles. This study was conducted to evaluate the efficacy of capecitabine and to identify the subgroup of patients who would potentially have benefit from capecitabine monotherapy in patients with anthracycline- and taxane-pretreated MBC. Female patients with MBC who had been previously treated with anthracycline and taxane received oral capecitabine 2500 mg/m(2) divided in two doses daily for 2 wk with 1-wk rest period. Between September, 1999, and December, 2002, a total of 38 patients were enrolled. Among the 36 evaluable patients, one patient achieved a complete response (CR), 9 patients had partial responses (PRs), and 13 patients had stable diseases (SDs). Response rate was 26% [95% confidence interval (CI), 12-40%] and the tumor control rate (TCR, CR+PR+SD) was 61% (95% CI, 45-77%). The median follow-up duration was 27.8 mo. The median duration of response was 8.9 mo, the median time to progression was 4.6 mo, and the median overall survival was 18.1 mo. The major toxicities were hand-foot syndrome, diarrhea, and emesis. There was no treatment-related death. The predictors of better overall survival were positivity of hormone receptor, disease-free survival longer than 1 yr, non-refractoriness to anthracycline, and fewer number (<or= 3) of involved organs. Capecitabine monotherapy is effective and well tolerated for MBC patients who had previously been treated with anthracycline and taxane. The TCR could predict overall survival as well as the objective response in this study, suggesting a possible role of TCR as a surrogate marker for survival in MBC patients on salvage chemotherapy. The patients who have relatively slow growing tumor and less tumor burden could have benefit from capecitabine monotherapy following anthracycline- and taxane-based chemotherapy.

Administration, Oral↗
PubMed2004

The associations between plasma adiponectin, ghrelin levels and cardiovascular risk factors.

OBJECTIVE: Ghrelin is a recently discovered peptide, which is produced primarily in the stomach. This orexigenic peptide participates not only in the induction of mealtime hunger but also in long-term body weight regulation and energy homeostasis. Adiponectin is a protein secreted by adipocytes, and has been proposed to mediate obesity-related insulin resistance. Moreover, concentrations of adiponectin are reduced in individuals with obesity, insulin resistance and cardiovascular disease. However, human data are sparse about the direct relationship between adiponectin, ghrelin and cardiovascular risk factors including insulin resistance. DESIGN: Three hundred and thirty-eight elderly Korean women (mean age+/-s.d., 72.3+/-5.5 years) were included in the present study. METHODS: Plasma ghrelin and adiponectin levels were measured by RIA. Anthropometric measurements were taken and a 75 g oral glucose tolerance test performed. Fasting insulin and lipid profile were measured and insulin resistance was determined using the homeostasis model assessment insulin resistance index (HOMA-R) and the quantitative insulin sensitivity check index. RESULTS: Plasma adiponectin levels were negatively correlated with central obesity indices such as waist circumference (r=-0.27, P<0.001) and waist-to-hip ratio (WHR) (r=-0.32, P<0.001), and with insulin resistance indices such as fasting insulin (r=-0.17, P=0.004) and HOMA-R (r=-0.13, P=0.035). Plasma ghrelin levels were negatively correlated with WHR (r=-0.12, P=0.03), but plasma adiponectin and ghrelin levels were not correlated (r=0.03, P=0.66). Multiple regression analysis showed that adiponectin was associated with WHR, fasting insulin and fasting glucose levels. When ghrelin was used as a dependent variable, only WHR remained in the final fitted model. CONCLUSION: Fasting plasma adiponectin and ghrelin levels were found to be associated with central obesity or insulin resistance. However, plasma adiponectin and ghrelin concentrations were not associated with each other in elderly Korean women.

Adiponectin↗
PubMed2004

Gamma-glutamyl transpeptidase inhibition suppresses milk protein synthesis in isolated ovine mammary cells.

The membrane spanning enzyme gamma-glutamyl transpeptidase (gamma-GT; EC 2.3.2.2) catalyses the breakdown of the tripeptide glutathione and uses free amino acids (AA) to form gamma-glutamyl transpeptidase (GT) AA that become transported into cells and converted back into free AA. gamma-Glutamyl transpeptidase activity has been shown to be important for mammary AA uptake in rodent systems, and while gamma-GT activity is high in lactating bovine mammary tissue, the role of this enzyme in milk protein synthesis of the ruminant has not been defined. The present study shows that gamma-GT activity in the ovine mammary gland, like that of rodents, increases during pregnancy and peaks early in lactation. Acivicin, a well-known inhibitor of gamma-GT, decreased gamma-GT activity in acini isolated from the ovine mammary gland and did not have secondary toxicity effects on cell viability or the uptake of radiolabeled amino-isobutyric acid. Isolated ovine acini were incubated in the presence of radiolabeled leucine, and incorporation of label into secreted protein increased during incubation. Incubation of acini with acivicin decreased milk protein secretion by 75%, indicating that gamma-GT plays an important role in milk protein production in the ruminant. Acivicin did not inhibit secretion of specific caseins but caused a global decrease in individual proteins suggesting that gamma-GT may be responsible for providing a complement of AA for milk protein synthesis.

Animals↗
PubMed2004

Familial risk of allergic rhinitis and atopic dermatitis among Chinese families in Singapore.

INTRODUCTION: This study aims to determine the familial risk of atopic dermatitis (AD) and allergic rhinitis (AR) in Chinese children. MATERIALS AND METHODS: A cross-sectional study was conducted in a housing estate in Singapore. Data was collected using an interviewer-administered questionnaire. Participants included 257 Chinese families. Prevalence rate ratios (PRRs) and 95% confidence interval (CI) were calculated. RESULTS: For AD in all children, an increasing trend was found with PRRs of 1.9 (95% CI, 0.3 to 11.8) and 1.5 (95% CI, 0.4 to 5.5) for only father and only mother affected, respectively, to 2.3 (95% CI, 0.4 to 13.7) for both parents affected. In AR, a PRR of 2.7 (95% CI, 1.8 to 3.9) and 2.2 (95% CI, 1.5 to 3.2) for only father and only mother affected, respectively, and 4.5 (95% CI, 3.3 to 6.1) for both affected was found. The PRR (2.2; 95% CI, 1.4 to 3.7) of the first child developing AR when paternal or maternal history was positive was similar. This rose to 3.4 (95% CI, 2.2 to 5.1) when both parents also had AR. The PRR of the second child developing AR was 3.9 (95% CI, 1.7 to 8.9) when the first child alone was positive for AR and 7.0 (95% CI, 3.5 to 13.9) when both parents and the eldest child had AR. CONCLUSION: A positive family history increases the risk of developing AD and AR with increasing risk dependent on number of relatives affected. The second child's risk of AR is also associated with AR in the first child, suggesting mechanisms of incomplete penetrance.

China↗