Cerebral Palsy

The luteinizing hormone (LH) plays important roles in vertebrate reproduction. In the present study, we cloned and characterized the zebrafish (Danio rerio) LH<beta> subunit gene structure and promoter region. Analysis of 3.0 kb (LH3.4K~5'UTR) of the LH<beta> subunit proximal promoter region displayed maximal promoter activity in a tilapia ovary cell line (TO2 cells) after treatment with gonadotropin-releasing hormone (GnRH). Transient expression experiments with a 5'-deletion revealed at least 10 regulatory regions in the zebrafish LH<beta> subunit gene. Compared to the molecular mechanisms of other vertebrates, GnRH treatment led to the activation of zebrafish LH<beta> subunit gene transcription in ovary cells. We demonstrated that LH<beta> subunit gene transcription increased with 6 h of treatment with GnRH but was repressed by protein kinase C, mitogen-activated protein kinase, and calcium in the TO2 cell line. To study promoter-specific expression, we constructed an LH<beta> subunit (LH3.4k~5'UTR) promoter region-driven green fluorescent protein (GFP), and the results indicated that LH<beta> promoter-driven GFP transcripts appeared in the pituitary gland. For the gene knockdown study, we targeted knockdown of the LH<beta> subunit gene by two antisense morpholino oligonucleotides that resulted in serious abnormalities and death during zebrafish embryogenesis. These results suggest that the LH plays important roles in reproduction and general embryonic development in zebrafish.

Dengue virus (DV) causes a non-specific febrile illness known as Dengue fever (DF), and a severe life-threatening illness, Dengue hemorrhagic fever/Dengue shock syndrome (DHF/DSS). Hemostatic changes induced by this virus involve three main factors: thrombocytopenia, endothelial cell damage, and significant abnormalities of the coagulation and fibrinolysis systems. The pathogenesis of bleeding in DV infections remains unknown. In this article, we focused on the DV activating endothelial cells and altering the parameters of hemostasis system. The expression of hemostasis-related factors, Thrombomodulin, TF, TFPI, t-PA, and PAI-1, in DV-infected cells were determined by RT-PCR. Flow cytometry analysis and immunofluorescence staining confirmed that the expression levels of TM in the DV-infected HMEC-1 and THP-1 cells were increased. In addition, the purified recombinant domain III of the envelope glycoprotein of DV (EIII) could induce the expression of TM in the HMEC-1 cells and THP-1 cells. The TM expression induced by DV or EIII in the endothelial cells and monocytic cells suggests that the EIII of DV plays an important role in the pathogenesis of DHF/DSS.

With the improvement in survival after breast cancer there has been increasing interest in the long-term effects of radiotherapy, including the development of tumours. Compared with the general population, breast cancer survivors have a 10-50% higher risk of developing a second cancer. Radiotherapy may play a role in the onset of such lesions. We describe here the case of a 68-year-old woman who developed synchronous cutaneous angiosarcoma, melanoma and morphea of the breast skin and the local area, 14 years after radiotherapy for breast carcinoma. Given the risk of post-radiation secondary primaries in breast cancer patients, long-term surveillance is necessary, with particular attention being paid to skin changes in the irradiation field. Radiation-induced morphea is a rare complication in which immunological abnormalities may stimulate malignant transformation. Long-term studies are required to clarify the pathogenesis of these rare associations.

A 64-years-old woman complained of fixed cyanosis and rest pain of the 2nd, 3rd and 4th toes of the right foot, after a sudden onset one month previously to the clinical examination. The diagnosis of “bue toe syndrome” was then made. She was in a post-menopause state, with no hormonal substitution therapy, complaining also of obesity, arterial hypertension and hyperlipidemia, under medication but no laboratory control. Blood tests excluded an hypercoagulable state and the ECG revealed no significant abnormalities. Angio-CT scans and conventional angiography disclosed an atherosclerotic lesion at the femoropopliteal level, with an adherent and floating thrombus in the arterial lumen, causing microemboli to the collateral digital arteries. The complex lesion was removed through a local thromboendarterectomy, followed by a Carrel-DeBakey patch graft angioplasty, using autologous saphenous vein. Post operative course was uneventfull, with an immediate recovery of the clinical picture. Double antiplatelet therapy was advised and an extensive investigation of the possible relationship of this event with an occult malignancy was started, with no conclusive results, until now. The patient was placed in a clinical, laboratory and imagiologic surveillance program and the main features of this entity are emphasized and discussed, according to the data published in the literature on the subject.

BACKGROUND/AIMS: Resting electrocardiogram (ECG) abnormalities have been strongly associated with cardiovascular disease mortality. Little is known, however, about the association between individual components of metabolic syndrome and ECG abnormalities, especially in Asian populations. METHODS: We examined clinical and laboratory data from 31,399 subjects (age 20 to 89 years) who underwent medical check-ups. ECG abnormalities were divided into minor and major abnormalities based on Novacode criteria. Ischemic ECG findings were separately identified and analyzed. RESULTS: The overall prevalence rates of ECG abnormalities were significantly higher in subjects with than in those without metabolic syndrome (p < 0.01). Ischemic ECG was strongly associated with metabolic syndrome in all age groups of both sexes, except for younger women. In multiple logistic regression analysis, metabolic syndrome was independently associated with ischemic ECG (odds ratio, 2.30 [2.04 to 2.62]; p < 0.01), after adjusting for sex, age, smoking, and family history of cardiovascular disease. Of the metabolic syndrome components, hyperglycemia in younger subjects and hypertension in elderly subjects were major factors for ischemic ECG changes, whereas hypertriglyceridemia was not an independent risk factor in any age group. The association between ischemic ECG findings and central obesity was weaker in women than in men. CONCLUSIONS: Metabolic syndrome was strongly associated with ECG abnormalities, especially ischemic ECG findings, in Koreans. The association between each component of metabolic syndrome and ECG abnormalities varied according to age and sex.

There is a complex interplay between sleep, metabolism and the function of the endocrine system. A number of endocrine systems are modulated by either the homeostatic drive to sleep, or by the function of the circadian system. As a result, changes in sleep duration and quality have reciprocal effects on hormone secretion and metabolism. In return, sleep disturbance can result from secondary consequences of abnormal endocrine and metabolic function. Inborn errors of metabolism have been demonstrated to have varying effects. The manifestations of lysosomal storage disorders are primarily dependent on the location of substance deposition; resultant effects include disruption of central respiratory control and changes in airway configuration. Neurologic consequences of these disorders include cases of epileptiform discharges in sleep and case reports of non-narcolepsy associated cataplexy.

Much has been learned about the chromosomal abnormalities of colorectal carcinomas but the cytogenetic relationship between the neoplastic clones present in primary versus metastatic tumour samples remains unclear. We analyse the frequency of abnormalities for 47 chromosome regions using the interphase fluorescence in situ hybridization technique in a group of 48 tumours, including 24 primary colorectal tumours and 24 paired liver metastases. All tumours showed complex karyotypes with numerical/structural abnormalities for seven or more different chromosomes/chromosome regions both in the primary tumours and in their paired metastases. Chromosome 8 was the most frequently altered (22/24 primary tumours), consistently showing del(8p22) and/or gains/amplification of 8q24, followed by abnormalities of the entire chromosome 7 (21/24 primary tumours) and of chromosomes 17p and 20q (20/24 primary tumours). Simultaneous staining for multiple chromosome probes revealed the presence of two or more tumour cell clones in 23/24 cases (46/48 tumour samples). Interestingly, the liver metastases typically contained tumour cell clones similar to those found in the primary tumours, suggesting the absence of selective selection of specific tumour clones. Despite this, additional chromosomal abnormalities were detected in 23/24 metastatic tumours, which preferentially consisted of del(17p13) and gains/amplification of 11q13 and 20q13; moreover, compared to primary tumours, metastases showed an increased number of abnormalities of chromosomes 1p, 7q, 8q, 13q, and 18q, and new chromosomal abnormalities involving chromosomes 6, 10q23, 14q32, 15q22, and 19q13. Owing to the high frequency of numerical abnormalities of the entire chromosome 7 and loss and/or gain/amplification of specific regions of chromosome 8, eg del(8p22) and/or gains/amplification of 8q24 in primary colorectal tumours with associated metastases, it is suggested that their assessment at diagnosis could be of great clinical utility for the identification of colorectal cancer patients at higher risk of developing liver metastases. (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PURPOSE: During spring 2009, a pandemic swine-origin influenza A (H1N1) virus (S-OIV) emerged and spread globally. We describe the chest X-ray and computed tomography (CT) findings of 40 patients with pneumonia due to S-OIV observed in our institution. MATERIAL AND METHODS: Among 534 patients with S-OIV, according to the US Centers for Disease Control and Prevention case definition, seen between June and November 2009, 121 underwent chest X-ray and 40 (median age 44 years, range 16-79) had pneumonia. The initial chest radiographs were evaluated for pattern, distribution and extent of lung abnormalities. Unenhanced chest CT scans were performed in two patients and were reviewed for the same findings. Underlying medical conditions were present in 42% of patients (17/40). RESULTS: Our patients had predominantly mild illness, and pneumonia was observed in 40 individuals (40/121 patients who had chest X-rays, 33%; and 40/534 patients with S-OIV, 7.5%). However, S-OIV can cause severe illness requiring admission to the intensive care unit for advanced mechanical ventilation and extracorporeal life support, including adult respiratory distress syndrome (ARDS) and death. The major radiological abnormalities observed were interstitial changes (60.0%), with (22.0%) or without patchy ground-glass appearance, mostly bilateral, and located in the lower lung zones (7.5%). Extensive disease was seen in 37.5% (15/40), and ARDS was observed in three individuals (0.30%)with underlying medical conditions. Subtle pleural effusion was noted in four patients. CONCLUSIONS: In our series, the most frequent pneumonia patterns observed during S-OIV (H1N1) virus were interstitial changes and patchy ground-glass appearance, mostly bilateral, and located in the lower lung zones. CT, performed in severely ill patients, confirmed the ARDS identified with chest X-rays, better depicting the features and extent of lung abnormalities.

AIMS/HYPOTHESIS: Microvascular dysfunction is associated with end-organ damage. Macular oedema is an important component of diabetic retinopathy. Macular thickness can be accurately quantified by optical coherence tomography (OCT), enabling accurate assessment of the macular prior to clinically apparent abnormalities. We investigated whether macular (fovea) thickness in non-diabetic individuals is related to the microvascular variables controlling fluid filtration across a blood vessel wall, in particular capillary pressure and the microvascular filtration capacity (Kf). METHODS: We recruited 50 non-diabetic individuals (25 men, 25 women; age range: 26-78 years; BMI range: 20-46 kg/m(2)). Fovea thickness was assessed by OCT. Microvascular assessments included: finger nailfold capillary pressure; Kf; microvascular structural assessments, i.e. skin vasodilatory capacity, minimum vascular resistance (MVR) and microvascular distensibility; and endothelial function. RESULTS: At 214.6 (19.9) microm (mean [SD]), fovea thickness was within normal range. Capillary pressure, adjusted for BMI, was associated with fovea thickness (standardised beta 0.573, p = 0.006, linear regression). Fovea thickness was not associated with Kf, microvascular structural assessments or endothelial function. Capillary pressure was still associated with fovea thickness when adjusted for microvascular variables (Kf, vasodilatory capacity, MVR, microvascular distensibility or endothelial function), or for risk factors for diabetes (systemic blood pressure, insulin sensitivity, inflammation, glycaemic status and lipids) and age. CONCLUSIONS/INTERPRETATION: Capillary pressure, a key determinant of movement of fluid across a blood vessel wall, is associated with fovea thickness in non-diabetic individuals. This suggests that with regard to potential preventative or therapeutic targets, attention should be directed at the mechanisms determining retinal microvascular pressure.

BACKGROUND: This work evaluates pregnancy and infant loss in 1,069 vehicle-treated cynomolgus monkeys from 78 embryo-fetal development (EFD) studies and 14 pre-postnatal development (PPND) studies accrued during 1981-2007. METHODS: Losses were analysed by survival function and hazard ratio using logistic regression for influence of year, study type (e.g., dose duration), and test item route of administration (ig, im, iv, sc). RESULTS: Neither study type nor route of dosing affected pregnancy outcome. Losses were higher pre-1990 (104 losses/347 pregnancies) compared to 1990 onwards (94 losses/722 pregnancies). Losses were greatest before gestation day 50 and at parturition. Using post-1989 data, Monte-Carlo simulations of pregnancy outcomes were created. The power associated with the comparison of vehicle survival curves and simulated adverse survival curves was examined. This showed that EFD studies with initial vehicle group sizes of 16 and 20 have an 80% probability of having 13 and 16 ongoing pregnancies at gestational day 100, respectively. For PPND studies with initial vehicle group sizes of 16, 20, or 28, there is an 80% likelihood of having 9, 11, or 16 infants at day 7 post-partum, respectively. A PPND study initiated with group size 20 could detect a threefold increase of test item-related pregnancy or infant loss. CONCLUSIONS: For designing and managing primate developmental toxicity studies, this type of analysis provides an objective tool to facilitate decisions either by supplementing groups with additional pregnant animals or stopping a group because an adverse effect on offspring survival has already been adequately revealed. Birth Defects Res (Part B) 89:175-187, 2010.(c) 2010 Wiley-Liss, Inc.