BACKGROUND AND OBJECTIVES: The transplantation of human umbilical cord blood cells (hUCBCs) has been shown to attenuate the unregulated activation of microglia in a rat model of cerebral palsy (CP). To investigate whether hUCBCs transplantation is also anti-inflammatory in humans, we performed a clinical trial in patients with CP. METHODS AND RESULTS: Allogeneic or autologous hUCBCs and erythropoietin (EPO) were intravenously injected into human patients with CP (mean age of approximately 38 weeks), and patients were analyzed for their motor function and social behavior. Blood samples were tested for cytokine levels. The most surprising finding in the study was that the cytokine levels were dependent on the donor cell source (allogeneic or autologous). Interestingly, the allogeneic treatment group demonstrated significantly decreased levels of pro-inflammatory factors, such as IL-1alpha, IL-6, TNF-beta, and RANTES, and showed a statistically significant improvement in motor and social behavior compared to the autologous treatment group. CONCLUSIONS: Given that inflammation plays a pivotal role in CP, our results suggest that allogeneic hUCBCs therapy may be an appropriate strategy for CP treatment. In addition, prior to transplantation, a detailed analysis of the amount of proinflammatory cytokines in cord blood may be needed to avoid exacerbating inflammatory responses.
Animals ; Cerebral Palsy ; Chemokine CCL5 ; Cytokines ; Erythropoietin ; Fetal Blood ; Humans ; Inflammation ; Interleukin-6 ; Lymphotoxin-alpha ; Microglia ; Rats ; Social Behavior ; Tissue Donors ; Transplants ; Umbilical Cord

The resistance to recombinant human erythropoietin (r-HuEPO) in patients with chronic renal failure can develop in conditions such as iron deficiency, chronic bleeding, or chronic inflammatory disease. Recently, there have been several case reports of pure red cell aplasia due to antibody production to r-HuEPO in chronic hemodialysis patients. A 59-year old female undergoing chronic hemodialysis responded well to r-HuEPO for 6 years. But, a rapidly progressive anemia was then noted which was unresponsive to maximal doses of r-HuEPO and the patient became transfusion-dependent. Bone marrow examination showed absence of red cell precursors. A detailed search for the cause of this pure red cell aplasia was unrevealing. We conclude that although very rare, pure red cell aplasia should be considered in evaluating chronic hemodialysis patients with erythropoietin-resistant anemia.
Anemia* ; Antibody Formation ; Bone Marrow Examination ; Erythropoietin ; Female ; Hemorrhage ; Humans ; Iron ; Kidney Failure, Chronic ; Middle Aged ; Red-Cell Aplasia, Pure* ; Renal Dialysis*

OBJECTIVE: We found previously that interferon regulatory factor (Irf)-1 is a germinal vesicle (GV)-selective gene that highly expressed in GV as compared to metaphase II oocytes. To our knowledge, the function of Irf-1 in oocytes has yet to be examined. The present study was conducted to determine the relationship between retinoic acid (RA) and RA-mediated expression of Irf-1 and the mouse oocyte maturation. METHODS: Immature cumulus-oocyte-complexes (COCs) were collected from 17-day-old female mice and cultured in vitro for 16 hours in the presence of varying concentrations of RA (0-10 microM). Rate of oocyte maturation and activation was measured. Gene expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and cytokine secretion in the medium was measured by Bio-Plex analysis. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: The rates of oocyte maturation to metaphase II and oocyte activation increased significantly with RA treatment (10 nM-1 microM). With 100 nM RA treatment, lowest level of Irf-1 mRNA and cumulus cell's apoptosis was found. Among 23 cytokines measured by Bio-Plex system, the substantial changes in secretion of tumor necrosis factor-alpha, macrophage inflammatory protein-1beta, eotaxin and interleukin-12 (p40) from COCs in response to RA were detected. CONCLUSION: We concluded that the maturation of oocytes and Irf-1 expression are negatively correlated, and RA enhances the developmental competence of mouse immature oocytes in vitro by suppressing apoptosis of cumulus cells. Using a mouse model, results of the present study provide insights into improved culture conditions for in vitro oocyte maturation and relevant cytokine production and secretion in assisted reproductive technology.
Animals ; Apoptosis ; Cumulus Cells ; Cytokines ; DNA Nucleotidylexotransferase ; Female ; Gene Expression ; Humans ; In Vitro Oocyte Maturation Techniques ; Interferon Regulatory Factor-1 ; Interferons ; Interleukin-12 ; Macrophages ; Mental Competency ; Metaphase ; Mice ; Oocytes ; Reproductive Techniques, Assisted ; RNA, Messenger ; Tretinoin ; Tumor Necrosis Factor-alpha

In 17-30% of subjects, at least one kidney is supplied by more than one artery arising from the aorta. Subjects with multiple renal arteries have been reported to suffer more frequently from hypertension, But the precise association between hypertension and multiple renal arteries was not yet defined. A 20- year old woman presented clinical manifestations of renovascular hypertension. Basal renin activity was elevated, and time-activity curves showed delayed peak time at captopril renal scan. Angiography showed multiple renal arteries with 2 right and left 3 arteries. There was neither stenosis nor inflammation. We strated angiotensin-receptor blocker, calcium channel blocker, and beta-blocker. The patient currently remains normotensive in an outpatient unit. In general, accessory renal arteries are narrower and longer than main artery. As a results, the renal segments supplied by accessory vessels might have lower levels of blood pressure than the remainder of the parenchyma, thereby increasing the renin secretion. So hypertension associated with multiple renal arteries might be involved in renin-angiotensin-aldosterone system activation.
Angiography ; Aorta ; Arteries ; Blood Pressure ; Calcium Channels ; Captopril ; Constriction, Pathologic ; Female ; Humans ; Hypertension ; Hypertension, Renovascular* ; Inflammation ; Kidney ; Outpatients ; Renal Artery* ; Renin ; Renin-Angiotensin System

BACKGROUND: The glucose transporters (GLUTs) exhibit different tissue-specific expression. This study aimed to investigate the types of GLUTs expressed in human granulosa cells (GCs) obtained from women with polycystic ovary syndrome (PCOS) and their relationship with insulin resistance (IR) and the outcomes of in vitro maturation (IVM) of immature oocytes. METHODS: Expression of GLUTs was evaluated in GCs from women with PCOS with or without IR. Thirty-six women with PCOS undergoing an IVM program were included. Differential gene expression between the insulin sensitive (IS) and IR group was measured by reverse transcription polymerase chain reaction. RESULTS: Expression of GLUTs 1, 3, 5, 8, and 13 was constitutive, whereas expression of GLUTs 2 and 7 was not observed in human GCs. The remaining GLUTs, 4, 6, 9, 10, 11, and 12, were differentially expressed among patients according to metabolic status, such as insulin sensitivity. A higher number of GCs from patients with IR (92%) expressed GLUT6 than GCs from IS PCOS patients (46.3%). Logistic regression showed that expression of GLUTs 9, 11, and 12 correlates with rates of IVM at 48 hours, fertilization, and implantation, respectively. CONCLUSION: This is the first report describing the expression pattern of all 13 members of the GLUT family in human GCs. Results of the present study suggest that patients' insulin sensitivity regulates GLUT expression in GCs in PCOS patients, and this may control oocyte quality for IVM and subsequent processes such as fertilization and implantation in patients taking part in an in vitro fertilization program.
Female ; Fertilization ; Fertilization in Vitro ; Gene Expression ; Glucose Transport Proteins, Facilitative ; Glucose* ; Granulosa Cells* ; Humans ; Insulin ; Insulin Resistance ; Logistic Models ; Oocytes* ; Polycystic Ovary Syndrome* ; Polymerase Chain Reaction ; Reverse Transcription

Sclerosing peritonitis is a rare but fatal complication of peritoneal dialysis (PD). Management of sclerosing peritonitis includes cessation of PD, total parenteral nutrition, and surgery. Recently, a few reports have indicated immunosuppression might be beneficial in sclerosing peritonitis. In these reports, all of patients had the combination therapy of steroid and immunosuppressant. A 37-year old man develped sclerosing peritonitis 3 months after switching from PD to hemodialysis because of uncontrolled peritonitis. An abdominal computed tomography (CT) scan demonstrated massive ascites with multilocuated fluid collection and extensive enhancement of the peritoneum. A peritoneal biopsy showed proliferation of fibrous collagenous tissue with infiltration of lymphocytes. We started corticosteroid for one month. A follow-up CT scan showed complete resolution with absence of peritoneum thickness and fluid collection 16 months after corticosteroid therapy. The patient currently remains free of symptoms in an outpatient hemodialysis unit. To our knowledge, this is the first case of sclerosing peritonitis successfully treated with corticosteroid therapy alone in Korea.
Adult ; Ascites ; Biopsy ; Collagen ; Follow-Up Studies ; Humans ; Immunosuppression ; Korea ; Lymphocytes ; Outpatients ; Parenteral Nutrition, Total ; Peritoneal Dialysis ; Peritoneum ; Peritonitis* ; Renal Dialysis ; Tomography, X-Ray Computed

PURPOSE: Loss of cholinergic neurons in the hippocampus is a hallmark of many dementias. Administration of stem cells as a therapeutic intervention for patients is under active investigation, but the optimal stem cell type and transplantation modality has not yet been established. In this study, we studied the therapeutic effects of human placenta-derived mesenchymal stem cells (pMSCs) in dementia rat model using either intracerebroventricular (ICV) or intravenous (IV) injections and analyzed their mechanisms of therapeutic action. MATERIALS AND METHODS: Dementia modeling was established by intraventricular injection of 192 IgG-saporin, which causes lesion of cholinergic neurons. Sixty-five male Sprague-Dawley rats were divided into five groups: control, lesion, lesion+ICV injection of pMSCs, lesion+IV injection of pMSCs, and lesion+donepezil. Rats were subjected to the Morris water maze and subsequent immunostaining analyses. RESULTS: Both ICV and IV pMSC administrations allowed significant cognitive recovery compared to the lesioned rats. Acetylcholinesterase activity was significantly rescued in the hippocampus of rats injected with pMSCs post-lesion. Choline acetyltransferase did not co-localize with pMSCs, showing that pMSCs did not directly differentiate into cholinergic cells. Number of microglial cells increased in lesioned rats and significantly decreased back to normal levels with pMSC injection. CONCLUSION: Our results suggest that ICV and IV injections of pMSCs facilitate the recovery of cholinergic neuronal populations and cognitive behavior. This recovery likely occurs through paracrine effects that resemble microglia function rather than direct differentiation of injected pMSCs into cholinergic neurons.
Acetylcholinesterase ; Animals ; Choline O-Acetyltransferase ; Cholinergic Neurons ; Dementia* ; Hippocampus ; Humans ; Injections, Intraventricular ; Male ; Mesenchymal Stromal Cells* ; Methods* ; Microglia ; Models, Animal* ; Negotiating* ; Placenta ; Rats* ; Rats, Sprague-Dawley ; Stem Cells* ; Therapeutic Uses ; Water

Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient’s parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.

BACKGROUND AND OBJECTIVES: The presence of leukocytosis in patients with acute myocardial infarction (AMI) has been reported to be related to the extent of MI and with the prognosis. However, whether the leukocytosis itself is a cause or result of the myocardial injury has not been determined. The relationship between the leukocyte count and the extent of myocardial injury was investigated in patients with AMI that had undergone reperfusion therapy. SUBJECTS AND METHODS: Patients with AMI that had undergone thrombolysis (n=60) or primary PCI (n=36) were included. The initial leukocyte counts were analyzed with regard to the peak and initial CK-MB levels. The relationship between leukocytosis and the time elapsed from the onset of symptoms, infarct related coronary arteries and the proximity of the lesions were also investigated. RESULTS: In both groups, the initial leukocyte count did not show a significant relationship with the initial CK-MB level or the time elapsed from symptoms onset, which could be an indication of the extent of early myocardial injury. Furthermore, no significant relationship was shown with the infarct related coronary artery or proximity of the lesion. However, a relationship was shown with the maximum CK-MB level, which could be an indication of the extent of myocardial injury following reperfusion therapy in both groups (p<0.01). CONCLUSION: This study suggests that the initial leukocyte count in patients with AMI might is an important prognostic factor that determines the extent of myocardial injury following reperfusion therapy, rather than being a simple indicator of the extent of early myocardial injury.
Coronary Vessels ; Humans ; Leukocyte Count* ; Leukocytes* ; Leukocytosis ; Myocardial Infarction* ; Myocardial Reperfusion ; Prognosis ; Reperfusion*