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Biomedical subjects

E Park

Publications and source records attributed to E Park.

At least 55 records · Page 3Linked to original sources

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗

Regulation of nitric oxide induced by mycobacterial lipoarabinomannan in murine macrophages: effects of interferon-beta and taurine-chloramine.

We examined the effects of interferon beta (IFN-beta) on the production of liporabinomannan (LAM)-induced nitric oxide (NO) in peritoneal macrophages from low-responder and high-responder (C3H/HeJ and C3H/OuJ) mice. NO was produced in a dose response when induced by lipo-polysaccharide (LPS) or LAM plus interferon gamma (IFN-gamma) or IFN-beta in both high- and low-responder mice. In contrast to IFN-gamma, both high- and low-responder mice failed to induce nitrite production when IFN-beta was added, except at a high concentration of IFN-beta. Tau-Cl (0.5 mM) inhibited NO production about 50% in the high-responder strain when cells were activated with LPS or LAM in combination with either IFN-beta or IFN-gamma, and almost abolished NO production at 1.0 mM. In the low-responder strain, Tau-Cl (0.5 mM) significantly inhibited NO production when cells were activated with IFN-gamma or IFN-beta in addition to LPS or LAM, but did not completely inhibit NO production at 1.0 mM. Tau-Cl appears to play a potent role in regulating inflammatory reaction-induced bacterial or mycobacterial organisms. These data indicate a pivotal role for IFN-gamma and IFN-beta for the production of LPS and LAM initiated NO in peritoneal macrophages from low-responder (C3H/HeJ) mice.

Animals↗

Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtaline (AHTN).

Synthetic musks are present in fine fragrances, cosmetics, soaps and laundry detergents. One of the most important synthetic musks is 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthaline+ ++ (AHTN; annual production: about 1500 metric tons). An increasing number of studies show that AHTN accumulates in surface water and fish and can be detected in human adipose tissue, as well in human milk. In the present report it is shown that a single high dose of AHTN leads to acute hepatic damage in rats, characterized by single cell necrosis, inflammation, swelling of liver parenchymal cells, and the presence of cytoplasmic condensations in the hepatocytes, while at the ultrastructural level disorganization of the rough endoplasmic reticulum and mitochondria as well as focal cytolysis is evident. Furthermore, evidence is presented that AHTN is not genotoxic, does not induce peroxisome proliferation, and does not lead to the induction of drug-metabolizing enzymes as phenobarbital and 3-methylcholanthrene do.

Animals↗

Radiosurgery for brain metastases: is whole brain radiotherapy necessary?

PURPOSE: Because whole brain radiotherapy (WBRT) may cause dementia in long-term survivors, selected patients with brain metastases may benefit from initial treatment with radiosurgery (RS) alone reserving WBRT for salvage as needed. We reviewed results of RS +/- WBRT in patients with newly diagnosed brain metastasis to provide background for a prospective trial. METHODS AND MATERIALS: Patients with single or multiple brain metastases managed initially with RS alone vs. RS + WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively reviewed. The use of upfront WBRT depended on physician preference and referral patterns. Survival, freedom from progression (FFP) endpoints, and brain control allowing for successful salvage therapy were measured from the date of diagnosis of brain metastases. Actuarial curves were estimated using the Kaplan-Meier method. Analyses to adjust for known prognostic factors were performed using the Cox proportional hazards model (CPHM) stratified by primary site. RESULTS: Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival 11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively). Brain FFP (scoring new metastases and/or local failure) was significantly worse for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjustedp = 0.03 and hazard ratio = 0.476). However, brain control allowing for successful salvage of a first failure was not significantly different for RS alone vs. RS + WBRT (62% vs. 73% at 1 year; CPHM adjusted p = 0.56). CONCLUSIONS: The omission of WBRT in the initial management of patients treated with RS for up to 4 brain metastases does not appear to compromise survival or intracranial control allowing for salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in good-prognosis patients with newly diagnosed brain metastases.

Adult↗

Impact of diets with corn oil or olive/sunflower oils on DNA damage in healthy young men.

BACKGROUND: Plant fats and oils are major sources of mono- and polyunsaturated fatty acids as well as vitamin E, the major fat-soluble antioxidants in human nutrition. Dietary antioxidants are expected to reduce cancer risk by minimizing DNA damage. AIM OF THE STUDY: To compare the effects of gamma-tocopherol rich corn oil and the mixture of the alpha-tocopherol rich olive/sunflower oil on plasma concentration of tocopherols and on the frequency of sister chromatid exchange (SCE), an indicator of DNA damage. METHODS: This study had a double-blind, cross-over design and was conducted in 20 normal healthy non-smoking males aged 19-31 years. Design included a 2-week adjustment period and two 2-week test periods in which diets containing 30% energy as fat including either 80 g of corn oil (CO) (20 mg alpha-tocopherol, 100 mg gamma-tocopherol) or 80 g of olive/ sunflower oil (OSO) (24 mg alpha-tocopherol, 2.4 mg gamma-tocopherol), as the main fat-source, were given. Blood samples for analysis of SCE rate and content of tocopherols were collected at the beginning (T0), after adjustment (T1) and after the test period (T2) in intervals of 2 weeks. RESULTS: After two weeks of the corn oil diet, the plasma concentration of gamma-tocopherol increased but alpha-tocopherol decreased significantly compared to the olive/sunflower oil diet. The concentration of alpha-tocopherol increased (CO: 22.99 +/- 1.11 vs. OSO: 24.40 +/- 1.49 micromol/l) and that of gamma-tocopherol decreased (CO: 4.19 +/- 0.29 vs. OSO: 2.99 +/- 0.25 micromol/l) after the olive/sunflower oil diet. Intake of the corn oil diet was associated with reduced SCE rate and intensity, whereas there was no change in SCE after the olive/sunflower oil diet (CO: 7.66 +/- 0.25 vs. OSO: 8.06 +/- 0.47 mean SCE/cell) CONCLUSIONS: The combination of gamma-tocopherol with alpha-tocopherol in corn oil diet despite the lower alpha-tocopherol equivalents/diene acid equivalents ratio achieved better protection against DNA damage than alpha-tocopherol alone in the olive/sunflower oil diet.

Adult↗

Effects of multivitamin/mineral supplementation, at nutritional doses, on plasma antioxidant status and DNA damage estimated by sister chromatid exchanges in lymphocytes in pregnant women.

The purpose of this study was to evaluate the effect of multivitamin/mineral-supplementation during pregnancy on plasma levels of antioxidants and sister chromatid exchange (SCE) rate--an indicator of damage to DNA. A controlled, semi-randomized, prospective trial was performed comparing the supplement group, who received multivitamin/mineral tablet once daily for 10 weeks, to the control group. Plasma levels of antioxidants and SCE in lymphocytes were measured initially (20 wk gestation) and at the end of the intervention (34 wk gestation). In the control group, SCE rates increased significantly at 34 wk gestation compared to 20 wk gestation, whereas there was no change in the supplement group. Plasma retinol, beta-carotene and ascorbate decreased significantly in the control group. In the supplement group, a significant increase in plasma beta-carotene (55.6%), coenzyme Q10 (40.2%), folic acid (15.9%) and zinc (24.2%) was observed after 10 weeks of supplement. Increased plasma levels of antioxidants in the supplement group could not decrease SCE rates, however, they could prevent an increase in SCE rates which may be induced by reactive oxygen species generated from the enhanced steroid hormones in the last trimester, suggesting that multivitamin/mineral-supplement during pregnancy may prevent DNA damage due to the altered hormonal profile.

Adult↗

Effects of education in dementia assessment: evidence from standardizing the Korean-Dementia Rating Scale.

This study established norms and examined validity and reliability of the recently developed Korean version of the Dementia Rating Scale (K-DRS; Chey, 1998) for the elderly Korean population. The K-DRS was administered to 148 normal elderly Korean people and 20 patients with dementia of the Alzheimer's type (DAT). Norms were developed a priori for two age groups (55-64 and 65-84 years). Education (p < .0001) and age (p < .05) proved significant factors in the performance of the K-DRS, whereas gender did not. Accordingly, norms were further specified into two educational levels (6 years or fewer, and more than 6 years). Education was recognized as an important factor in evaluating dementia in a population with limited education. These implications are significant for dementia studies done in developing countries where educational opportunities have been limited for elderly people. Evidence supporting the validity and reliability of the scale was also found. K-DRS total scores correlated well with diagnostic status (r(pb) = .63) and mental status exam scores (r = .80). Test-retest reliability was .96, and interrater reliability was .99.

Age Factors↗

Correction of areolar depression in postsurgically treated gynecomastic patients.

Nipple-areolar depression after resection for gynecomastia can be avoided by preserving an ample amount of breast tissue and fat under the areola. If a marked depression of the areola occurs, correction can be difficult. Each patient requires an individual assessment, but the principle of rotation of soft tissue under the areolar complex is usually necessary. An effective way to accomplish this is by deepithelialization of a semilunar area inferior to the original subareolar scar, freeing it at its caudal boarder and advancing this deepithelialized flap under the areola and repairing the wound. The technique is simple in design and may be a useful tool in dealing with this difficult problem.

Gynecomastia↗

Apoptosis may be either suppressed or enhanced with strategic combinations of antineoplastic drugs or anti-IgM.

A variety of drugs have been used to treat B-lymphocyte neoplasms, including both cell cycle-specific (CCS) and non-cell-cycle-specific drugs. Although the therapy for such cancers is complex and can include both types of drugs, the efficacy of these drugs in inducing cell death remains unclear. In this paper we have concentrated on specific CCS drugs and have examined their ability to induce programmed cell death (apoptosis) in Burkitt's lymphoma cell lines derived from patients. The CCS drugs chosen were hydroxyurea and aphidicolin (active in late G1, early S phase), the topoisomerase poisons camptothecin and etoposide (S, early G2 phase) and vincristine and Taxol (late G2, M phase). These choices allow comparison of two drugs with differing modes of action for each of the various phases of the cell cycle. Our results indicate that the variation in apoptosis between drugs that act at the same phase of the cell cycle is negligible. Both S/G2 and G2/M blockers are very potent at inducing apoptosis whereas G1/S blockers are ineffective in the induction of apoptosis. In addition, marked kinetic variations in the rate of apoptosis induction were observed, etoposide and camptothecin being more rapid in their action than the other agents. The order of effectiveness in inducing apoptosis on a kinetic basis was S/G2 agents >> G2/M agents >> G1/S agents. In this study we have also found that growth inhibition was induced by all the CCS agents chosen and by anti-IgM in various Burkitt's lymphoma lines. Furthermore c-myc was down-regulated under similar conditions. Since apoptosis was only selectively induced by some of the CCS agents, it implies c-myc expression is associated with growth regulation and c-myc down-regulation is an insufficient condition for the induction of apoptosis. In addition, cotreatments using the CCS and other agents revealed the following: Cotreatment using two CCS drugs which act at the same stage in the cell cycle showed either no change or only additivity to the effects seen with either agent alone. However, cotreatment with CCS drugs showed that an inhibitory effect is found between G1/S and G2/M drugs or S/G2 and G2/M drugs. No effect was found between G1/S and S/G2 drugs. Anti-IgM, which by itself was capable of inducing apoptosis, was observed to augment apoptosis induced by very low concentrations of G2/M-acting drugs but it has little effect on G1/S or the S/G2 drugs. The inhibitory effect of anti-CD40 or TNF-alpha on anti-IgM-induced apoptosis did not carry over to an effect on apoptosis induction by the CCS agents. Thus specific combinations of agents may lead to either enhancement, inhibition, or no interactive effect on apoptosis.

Antibodies, Anti-Idiotypic↗

Taurine chloramine inhibits production of nitric oxide and prostaglandin E2 in activated C6 glioma cells by suppressing inducible nitric oxide synthase and cyclooxygenase-2 expression.

Taurine prevents tissue damage in various models of inflammation through a mechanism postulated to involve taurine monochloramine (Tau-Cl). Tau-Cl is formed through the action of a halide-dependent myeloperoxidase system associated with polymorphonuclear leukocytes (PMN), eosinophils, and basophils. Production of nitric oxide (NO), PGE2, and other proinflammatory mediators by activated macrophages is inhibited by Tau-Cl. Since glial cells may be activated to produce NO, PGE2 and other proinflammatory mediators, similar to macrophages, we examined the effects of Tau-Cl on the production of NO and PGE2 by rat C6 glioma cells. C6 cells were seeded to grow over 2-3 days to approximately 90% confluency before exposure to various concentrations of Tau-Cl in HBSS for 2 h (37 degreesC, 5% CO2). The HBSS was replaced, after washing the cells, with DMEM containing 4% fetal calf serum and activators (LPS, 10 microgram/ml; rat rIFN-gamma, 50 U/ml; and human rTNF-alpha, 50 ng/ml). Media content of NO2- and PGE2 was measured 48 h after activation and cell lysates were subjected to SDS-PAGE followed by Western blot analyses to determine the relative expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. Media accumulation of NO2- and PGE2 was inhibited by Tau-Cl in a concentration dependent manner and this was accompanied by decreased amounts of iNOS and COX-2 proteins in cell lysates. Additional experiments determined the effects of Tau-Cl on the kinetics of iNOS and COX-2 mRNA expression. Expression of iNOS mRNA was markedly inhibited in activated C6 cells that were previously exposed to Tau-Cl and this persisted for at least 24 h. In contrast, inhibition of COX-2 mRNA expression was only transiently reduced in Tau-Cl exposed cells during the first 4 h of activation and was relatively unimpaired thereafter (8-24 h). These results suggest that Tau-Cl inhibits the transcriptional expression of the iNOS gene but inhibits expression of COX-2 protein by post-transcriptional mechanisms.

Animals↗

Evaluation of urinary IL-1alpha and IL-1beta in gravid females and patients with bacterial cystitis and microscopic hematuria.

OBJECTIVES: to determine IL-1alpha and IL-1beta levels in patients with bacterial cystitis, microscopic hematuria, and gravid females relative to a control group of normal subjects. METHODS: enzyme immunoassays were used to measure concomitantly urinary IL-1alpha and IL-1beta in clean catch urine samples from normal subjects (n = 31) and study patients (n = 46). All normal subjects and patients underwent urinalysis, urine culture, and urine creatinine level determination. Since the IL-1alpha assay was developed for serum, the utility of the assay for urine specimens was unknown. The key parameters of urine collection, processing and sample storage for IL-1alpha were evaluated in detail. RESULTS: mean values +/- SEM (pg/mg) for IL-1alpha/ Cr and IL-1beta/Cr were control group (0.25 +/- 0.10 and 0.17 +/- 0.06), bacterial cystitis (9.97 +/- 1.15 and 42.45 +/- 1.86), and microscopic hematuria (2.81 +/- 0.65 and 2.82 +/- 0.70). Differences in cytokine levels between the control group and patients with either bacterial cystitis or microscopic hematuria were statistically significant for both IL-1alpha/Cr (P < 0.026; P < 0.007, respectively) and IL-1beta /Cr (P < 0.0004; P < 0.014, respectively). IL-1beta/Cr correlates better with pyuria than IL-1alpha/ Cr (P = 0.02 vs P = 0.44). In gravid females, only IL-1alpha was significantly elevated relative to non-pregnant females (IL-1beta elevation approached statistical significance). Gravid females with positive urine cultures could not be distinguished from those with negative cultures based on either interleukin (P > 0.05). CONCLUSIONS: Significant elevations of IL-1alpha and IL-1beta occur in patients with bacterial cystitis and microscopic hematuria. Correlation between pyuria and cytokine elevation was stronger for IL-1beta than for IL-1alpha. Changes in IL-1alpha may reflect changes in the bladder epithelium rather than in the inflammatory leukocytes. The ability of IL-1alpha and IL-1beta to serve as markers for bacterial cystitis in gravid females is diminished due to high basal levels during pregnancy.

Bacterial Infections↗

Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: the diabetes in early pregnancy study.

Previous studies indicate that fasting plasma glucose decreases during gestation, but the timing and extent are not consistent from study to study. We had an opportunity to examine this question in the normal pregnancy cohort of women studied in the Diabetes in Early Pregnancy Study. Subjects were monitored to identify pregnancy by human chorionic gonadotropin testing, enrolled within 21 days of conception, and screened to rule out gestational diabetes at the juncture of the second and third trimesters. All subjects were instructed to fast overnight for 10 to 12 hours. Three hundred sixty-one women were studied between 6 and 12 weeks of gestation. A median decrease in plasma glucose of 2 mg/dL was observed between weeks 6 and 10 (P=.007). In a smaller group of subjects evaluated through the third trimester, little further glucose reduction was observed. A reduction in glycosylated hemoglobin levels between 10 and 20 weeks (P=.002) followed the earlier reduction in first trimester glucose levels. Analysis by body mass index (BMI) showed a smaller first trimester reduction with increasing BMI, and none among severely obese women (BMI > 29.9 kg/m2). The decline in fasting plasma glucose in pregnancy begins early in the first trimester, well before fetal glucose requirements can contribute to the decline in the glucose level. Thereafter, plasma glucose levels decrease little. These results suggest that in the setting in which this study was performed (an overnight fast) maternal physiologic adjustments account for a reduction in plasma glucose early in the first trimester of pregnancy, and possibly even later in gestation as well.

Adult↗

Interfacial characterization of plasma-spray coated calcium phosphate on Ti-6Al-4V.

Microstructural characterization was performed on plasma-spray coated calcium phosphate and its interface with Ti-6Al-4V using scanning and transmission electron microscopy. The amorphous calcium phosphate phase was found near the coating/substrate interface, usually in between the crystalline hydroxyapatite grains and the Ti-6Al-4V substrate. The presence of the amorphous calcium phosphate and the channels extending from the interface to the coating surface was attributed to the low interfacial bond strength in a physiological environment. There was an indication of titanium diffusing into the amorphous regions. However, no reaction phases were found between the coating and the Ti-6Al-4V substrate. In the coating area remote from the interface, no intergranular amorphous calcium phosphate phase was observed. The microstructure of the Ti-6Al-4V substrate near the interface was observed to be affected by heat generated during plasma spraying.

Journal Article↗

Urinary IL-6 is elevated in patients with urolithiasis.

PURPOSE: To evaluate the possible role of cytokines interleukin (IL)-1beta, IL-1alpha and IL-6 in patients with urolithiasis. MATERIALS AND METHODS: Fifty-six patients currently with stone disease, 63 patients with bacterial cystitis, and 66 normal individuals were evaluated for urinary IL-1alpha, IL-1beta and IL-6. Clean catch urine samples were obtained and evaluated for cytokine levels using enzyme immunoassays for the respective cytokines. Statistical analysis of the results was carried out using the Kruskal-Wallis test followed by Newman-Keuls test and the chi-squared test. RESULTS: The patients with stone disease had significant elevations in IL-6 (p value< 10(-7)) relative to normal subjects. The levels of IL-6 in stone patients were lower than those of patients with bacterial cystitis. Neither IL-1beta nor IL-1alpha was elevated in stone patients relative to normals. By contrast, bacterial cystitis patients showed significant elevations in all three cytokines relative to normal subjects. Chi-squared analysis confirmed that stone patients had elevated IL-6 without elevation in either IL-1alpha or IL-1beta relative to normal subjects. CONCLUSIONS: Stone patients show significant elevations in IL-6 without marked increases in either IL-1beta or alpha relative to normal subjects. This elevation in IL-6 is not from infection as is seen in bacterial cystitis subjects. The elevation in IL-6 may be useful in the understanding of the pathogenesis of urolithiasis or as a potential marker for stone disease and we are currently investigating these possibilities.

Cystitis↗

Activity-controlled circadian base rate.

The current pacing rates are clustered around a fixed base rate since pacemaker patients are usually sedentary, resting, or sleeping most of the time. This fixed base rate is either too low for daytime hemodynamic support or too high for nighttime rest and recovery. Multiple Holter studies involving normal individuals have suggested that the resting base rate fluctuates during the course of the day. The circadian base rate (CBR) algorithm was designed to provide patients with a circadian change in paced resting rate and a normal rate distribution. The CBR algorithm, using a sophisticated accelerometer sensor, was developed and tested using the downloaded activity data from patients implanted with Trilogy DR+ pacemakers. Twenty-five patients (19 men, 6 women, age 72 +/- 9 years) were studied. Trilogy DR+ is able to record the detailed sensor and system behavior data for a week. During outpatient visits, the pacemaker was interrogated and the data accumulated in the pacemaker memory were downloaded. The CBR algorithm was applied to the activity variance histogram to calculate the base rate and to construct its histogram. The base rates in the CBR histogram are generally below 100 ppm with a distribution that mimics the natural sinus rate distribution of normal subjects. The CBR algorithm provides the highest daytime rates for hemodynamic support and the lowest nighttime rates for cardiac recovery, with a smoothly changing base rate modeling the normal circadian variation in heart rate.

Aged↗

The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development.

OBJECTIVE: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS: We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-332) pregnant women. RESULTS: Levels of beta-OHB in diabetic women were 2.5-fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. beta-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birth weight (P = 0.004-0.02), even after adjusting for maternal glucose levels. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels. CONCLUSIONS: The lst trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown.

3-Hydroxybutyric Acid↗

Production and characterization of fusion proteins containing transferrin and nerve growth factor.

To explore the ability to use genetic fusions of transferrin as a carrier for brain targeting and delivery, a series of fusion proteins containing both human nerve growth factor (NGF) and human transferrin was produced in mammalian cells. A protein in which the hinge region from human IgG3 joined the carboxyl terminus of NGF and the amino terminus of transferrin formed a covalent homodimer, bound human transferrin receptor, and retained full NGF in PC12 cells. In contrast, proteins in which polypeptide dimerization was not induced or in which NGF was fused through its amino terminus had greatly reduced NGF activity. The ability to maintain both biologically active NGF and transferrin as part of a fusion protein may offer a novel way to deliver NGF and other neurotrophic factors to the central nervous system.

Blood-Brain Barrier↗