Inborn errors of immunity associated with characteristic phenotypes

Abstract Objectives: The aim of the report is to describe the main immunodeficiencies with syndromic characteristics according to the new classification of Inborn Errors of Immunity. Data source: The data search was centered on the PubMed platform on review studies, meta-analyses, systematic reviews, case reports and a randomized study published in the last 10 years that allowed the characterization of the several immunological defects included in this group. Data synthesis: Immunodeficiencies with syndromic characteristics include 65 immunological defects in 9 subgroups. The diversity of clinical manifestations is observed in each described disease and may appear early or later, with variable severity. Congenital thrombocytopenia, syndromes with DNA repair defect, immuno-osseous dysplasias, thymic defects, Hyper IgE Syndrome, anhidrotic ectodermal dysplasia with immunodeficiency and purine nucleoside phosphorylase deficiency were addressed. Conclusions: Immunological defects can present with very different characteristics; however, the occurrence of infectious processes, autoimmune disorders and progression to malignancy may suggest diagnostic research. In the case of diseases with gene mutations, family history is of utmost importance.

Methylthioadenosine phosphorylase expression in cutaneous squamous cell carcinoma.

The methylthioadenosine phosphorylase (MTAP) gene is a tumour suppressor gene, located on chromosome 9p21, 100 kb telomeric of the p15 and p16 genes, which are often deleted in tumor cells. The role of MTAP protein expression in the genesis of cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity (AI/LOH) in cutaneous SCCs using AI/LOH markers flanking the p15, p16, and MTAP genes and demonstrated reduction in p15 and p16 protein expression in comparison to normal human skin. The present study is a continuation to our previous studies, aimed at determining possible roles played by MTAP protein expression in the genesis of cutaneous SCC. The expression of MTAP protein was detected using immunohistochemical approach in 109 micro array cutaneous SCC and 20 normal human skin tissue samples. The expression of MTAP was not significantly different in the cutaneous SCC cases as compared with normal human skin. This may indicate that MTAP protein expression does not contribute to the genesis of cutaneous SCC.

Research of pH and specific gravity of urine on 3724 healthy children aged from 2 months to 6 years old

Background: Research of pH and specific gravity of urine in healhty children is nessecary in order to evaluate urine in children with neurology. Objectives:This study aims to estimate pH and specific gravity in healthy children aged from 2 months to 6 years old. Subjects and method: 3724 healthy children ( boy: 52,6% and girl: 47.4%) aged from 2 months to 6 years old located in 3 districts: Kien Thuy, Thuy Nguyen, Kien An of Hai Phong were enrolled in the descriptive and cross-sectional study using urianalysis of midstream urine samples in the morning by analyzer Model 101-Teco from USA. The data was collected and analysed bysocial statistic SPSS software. Results: - pH mean in boys was 5.38\xb10.62, in girls: 5.40\xb10.61, and both sexes: 5.39\xb10.62. In general, urine pH decreased according to age groups but there were no sex differences significantly. - Specific gravity mean of healthy boys was 1.018\xb10.007, of girls: 1.018\xb10.006 and both sexes: 1.018\xb10.007. Conclusion: In general, specific gravity increased according to age groups but no sex differences may significantly be found.

hTERT-targeted E. coli purine nucleoside phosphorylase gene/6-methylpurine deoxyribose therapy for pancreatic cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pancreatic cancer is one of the most common tumors and has a 5-year survival for all stages of less than 5%. Most patients with pancreatic cancer are diagnosed at an advanced stage and therefore are not candidates for surgical resection. In recent years, investigation into alternative treatment strategies for this aggressive disease has led to advances in the field of gene therapy for pancreatic cancer. E. coli purine nucleoside phosphorylase/6-methylpurine deoxyribose (ePNP/MePdR) is a suicide gene/prodrug system where PNP enzyme cleaves nontoxic MePdR into cytotoxic membrane-permeable compounds 6-methylpurine (MeP) with high bystander activity. hTERT is expressed in cell lines and tissues for telomerase activity. In this study we examined the efficacy of ePNP under the control of hTERT promoter sequences and assessed the selective killing effects of the ePNP/prodrug MePdR system on pancreatic tumors.</p><p><b>METHODS</b>Recombinant pET-PNP was established. The protein of E. coli PNPase was expressed and an antibody to E. coli PNPase was prepared. Transcriptional activities of hTERT promoter sequences were analyzed using a luciferase reporter gene. A recombinant phTERT-ePNP vector was constructed. The ePNP/MePdR system affects SW1990 human pancreatic cancer cell lines in vitro.</p><p><b>RESULTS</b>The hTERT promoter had high transcriptional activity and conferred specificity on cancer cell lines. The antibody to E. coli PNPase was demonstrated to be specific for the ePNP protein. The MePdR treatment induced a high in vitro cytotoxicity on the sole hTERT-ePNP-producing cell lines and affected SW1990 cells in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>The hTERT promoter control of the ePNP/MePdR system can provide a beneficial anti-tumor treatment in pancreatic cancer cell lines including a good bystander killing effect.</p>

Efectos de la desnutrición proteica y de su recuperación nutricional en el timo de rata / Effects of protein malnutrition and its nutritional recovery in rat thymus

El objetivo de este trabajo fue estudiar el contenido de ADN y la actividad de Adenosina Deaminasa (ADA), Purina Nucleósido Fosforilasa (PNP) y su 5ïNucleotidasa (5ïNT)-enzimas relacionadas con el desarrollo y funcionamiento de los linfocito T- en el timo de ratas con desnutrición proteica leve, moderada y several al destete y la posterior recuperación nutricional. El estrés nutricional causado por la administración desde el destete de dietas carentes de proteínas provocó una disminución del peso del timo, del contenido de DNA y un aumento en la actividad de ADA y PNP sin modificar la actividad de 5ïNT. Este aumento de actividad podría explicarse como un mecanismo para evitar la formación de productos potencialmente tóxicos para los linfocitos T. La administración de la dieta de recuperación fue capaz de revertir los efectos provocados por la desnutrición proteica al destete; no se observaron diferencias significativas en los parámetros estudiados, entre el grupo realimentado y su contro bien nutrido de igual edad. Estos hallazgos avalan la hipótesis relacionada con el equilibrio de nutrientes en la dieta y la evolución del desarrollo celular tímico

Importancia de la dieta sobre el timo de ratas en período de crecimiento / Importance of the diet on the thymus of growing rats

El objetivo de este trabajo fue analizar los efectos provocados por la administración de una dieta con un desequilibrio en el perfil de aminoácidos indispensables sobre el contenido de DNA y la actividad de ADA y PNP en timo de ratas con desnutrición precoz al destete y durante 18 días y la posterior realimentación. Ratas de la cepa Wistar (14-16 crías por madre) recibieron a partir del destete 18 días, luego fueron alimentadas con dieta conteniendo caseína (20 por ciento) de protéina durante 20 días (R). Como control se utilizaron ratas de igual edad que recibierondesde el destete dieta stock de vivero (C). Al finalizar la experiencia se extrajo y pesó el timo, determinándose el contenido de DNA y la actividad de las enzimas ADA y PNP. La administración de proteína de harina de maíz provocó una disminución en el contenido de DNA y aumento en la actividad de ADA y PNP. La realimentación con una dieta que aportaba de proteína de alta calidad y en alta concentración, revirtió dicho efecto

Deficiencia proteica: impacto sobre el timo de ratas en crecimiento / Protein deficiency: effect of thymus of growing rats

Se analiza las consecuencias provocadas por desequilibrios nutricionales sobre el contenido de DNA y la actividad de las enzimas ADA y PNP en timo de ratas en crecimientos. Ratas Wistar al destete fueron alimentadas con: 1- dieta libre de proteínas hasta asemejar cuadros de malnutrición proteica leve, moderada y severa; 2- dieta conteniendo harina de maíz en baja concentración (6,5 por ciento). La subnutrición durante la lactancia se obtuvo duplicando la camada (12-14 crías por madre). Como controles se utilizaron ratas bien nutridas de igual edad, que desde el destete recibieron dieta stock. Al finalizar la experiencia, se les extrajo el timo (Pt)(mg). Se determinó DNA (mg/órgano), el número de núcleos, el tamaño celular- Pt(mg)/No. de Núcleos- y la actividad de las enzimas ADA y PNP (umol de ácido úrico x 10 - 1/P)(P=Pt(mg) /P corporal 0.75). Los resultados muestran que tanto la subnutrición durante la lactancia, como la malnutrición proteica al destete y la administración de dieta de baja calidad, afectan la proliferación celular en el timo, Sólo la carencia de proteína o su baja calidad, aumenta la actividad de ADA y PNP

Purine Nucleoside Phosphorylase Activities in Sera and Lymphocytes of Peripheral Blood from Patients with Allergic Contact Dermatitis and Drug Eruption / 대한피부과학회지

The present study was designed to measure the activity of purine nucleosiae phosphorylase(PNPase) in sera and lymphocytes af peripheral blood from patients with allergie contact dermstitis and drug eruption since PNPase activities are known to be decreased in cell-mediated immune deficieney diseases. The PNPase activities in sera and lymphocytes of normal subjects were (7.2 +1.05) * 105 unit/L of sera and (1.85+0.38) unit/102 lymphocytes, respectively. In allergic contact dermatitis, the PNPase activities in sera and lymphocytes of patients were (3.9+0.78) *105 unit/L of aera and (0.69+0.23) uoit/102 lymphocyteis, which were signifieantly lower than those of normal subjects. There were no differences in PNPase activities of sera and lymphocytes between drug eruption patients and normal subjects. From these results, it is suggested that the lowered PNPase aetivity in allergie contact dermatitis might be associated with abnormal lymphocytes differentiation or activation or some other unknown mechanism, since lowered PNPase activity in allergic contact dermatitis is in contrast to the generally accepted concept that enhanced status of CMI in ACD will lead to the increase in PWPase activity.

Purine Nucleoside Phosphorylase Activities in Sera , Erythrocytes and Lymphocytes of Blood from Patients with Various Dermatoses / 대한피부과학회지

The present study was designed to measure the activity of purine nucleoside phosphorylalse (PNPase) in sera, erythrocytes and lymphocytes of blood from patients with various dermatoses as it's activities are known to be decreased in cell-mediated immune deficiency diseases. The PNPase activities in sera, erythrocytes and lymphocytes of normal subjects were (3. 9+1. 03) x 104 unit/L, 5.04+1. 06 unit/107rbc, l. 74+0. 35 unit/103 lymphocytes respectively. In urticaria, leukocytoclastic vasculitis and purpura, there were no differences in PNPase antivities between patients groups and normal subjects. In atopic dermatitis, there were no differences in PNPase activities of sera and erythrocytes between patients group and normal subjects. But, lymphocyte PNPase activities of atopic patients were lowered than those of normal subjects(1.41 +0. 52 unit/10 lymphocytes). In tuberculoid leprosy, there were no differences in lymphocyte PNPase activities between patients group and normal subjects. But, the PNPase activities in sera and erythrocytes of patients group were lowered than those of normal subjects (3. 20. 76) x 104 unit/L, 3. 8n+1.96 unit/107rbc). The PNPase activities in sera((l. 87+/-0. 62) x 104 unit/L), erythrocytes(2. 08+0. 98 unit/107rbc) and lymphocytes (0.51+0. 26 unit/103 lymphocytes) of lepromatous leprosy patients were significantly lowered than those of normal subjects.