The medical records of 263 patients hospitalized between 14 and 28 days in a 405-bed, acute care, community hospital were reviewed before 100 records were obtained with complete data to determine percent recommended body weight (RBW), serum albumin, total lymphocyte count (TLC), and hematocrit on admission and near discharge. Serum albumin and hematocrit were the only indicators that changed significantly during hospitalization, with both decreasing from admission to discharge. Considering the four indicators together, changes in nutritional status of the patients during hospitalization were determined. Eighty three patients were found to be at least at moderate potential for nutritional risk on admission, and 95 were found to be at least at moderate potential for nutritional risk near discharge. No patients who were judged to be potentially at severe nutritional risk on admission improved their nutritional status during hospitalization. Paired comparisons of the four parameters indicated that hematocrit and serum albumin seemed to be measuring changes in potential nutritional status more similarly than any other pair of assessment indicators. Sixty-three of the patients did not receive what was judged to be adequate kilocalories and protein during hospitalization. Twelve of these patients were found to have an increase in potential nutritional risk status. Of the 163 medical records that were reviewed but did not have all indicators recorded, height was most often missing on admission, and weight and serum albumin were most often missing near discharge. / Master of Science

The research investigated the combined effects of protein deficiency (PD) and a gastrointestinal nematode infection, Heligmosomoides bakeri , on immunopathology and nutritional status in BALB/c mice. The acute phase of a primary infection reduced resting metabolic rate, but PD did not. Early challenge infection led to temporary anorexia and cessation of weight gain in both protein-sufficient (PS) and PD mice. / Among PS mice, a challenge dose of 200 L3 caused more active worm expulsion than infection with 100 L3. Both serum monocyte chemotactic protein-5 and gut fluid leakage were positively correlated with worm expulsion whereas numbers of mucosal mast cells, eosinophils, goblet cells and Paneth cells were unaffected by doses. Among PD mice, worm survival was prolonged and no dose-dependent worm expulsion was observed. In addition, a wide range of Th1 inflammatory cytokines including leptin was elevated in infected PD mice suggesting (1) that PD mice are unable to mount the appropriate Th2 inflammation and (2) that infection in PD mice induces a Th1 inflammation that allows continuing persistence of the parasite. / The shift to Th1 inflammatory responses in PD mice may also explain modifications in mineral distributions in tissues. Despite adequate dietary intakes of minerals in both PD and PS mice, serum iron concentrations were lower after H. bakeri challenge infection. Infection also reduced calcium and iron concentrations as well as the Ca/Zn ratio in the spleen. In contrast, PD resulted in increased iron and calcium concentrations as well as increased Ca/Zn ratio in the spleen and Fe/Zn ratio in the liver, but reduced calcium, zinc, copper and sulfur concentrations, and the Cu/Zn ratio in the liver. / Re-feeding PD mice with a PS diet restored parasite expulsion, regardless of whether the PS diet was provided during the primary or challenge infection. Thus, although PD mice have suppressed Th2 responses and elevated Th1 inflammation, their response to the primary infection is sufficient to ensure that parasite expulsion occurs once protein status is restored. / Together, these studies show that the shift toward Th1 inflammation plays a key role in prolonged parasite survival and mineral redistribution in protein deficient, infected mice.

Starvation and protein deficiency increase susceptibility to infec­tions in general and affect the function of various types of cells individually. Saliva contains substances which offer protection to the oral tissues. Its composition and secretion rate may be important in preventing the development of disease, e.g. dental caries. The aim of the present study was to evaluate the effects of starvation and protein deficiency on the secretion and composition of saliva and the effects possibly induced on dental caries. The following results were found. Short-term starvation on a liquid diet reduced the secretion rate and changed the composition of saliva in healthy humans. Chewing during starvation while it did not restore secretion rate, did partially restore the composition. Total protein concentration was not greatly affected by gross mal­nutrition or protein deficiency. A more pronounced effect was observed on individual biologically active proteins. The salivary glands seem not to be prime targets for malnutrition but the rate of biosynthesis of a bacteria aggregating glycoprotein and the activity of salivary peroxidase were significantly reduced by a long-term protein deficien­cy and gross malnutrition respectively in the rat. In humans, short­term starvation on a liquid diet caused an impaired glycosylation of sialic acid to the protein and decreased lysozyme activity. Sialylation was partially restored by chewing. In the rat the establishment of a cariogenic microorganism, S. cricetus (S. mutans) strain E 49 serotype a, was facilitated by protein deficiency. Starvation in both man and the rat produced evident clinical effects. The rate of plaque formation was increased in man and in the rat there was significant increase in caries development induced by a standardi­zed cariogenic challenge. This study shows that nutrition is important for the secretion of saliva and that starvation and protein deficiency increase the cario- genicity of sucrose. / <p>S. 1-49: sammanfattning, s. 51-116: 5 uppsatser</p> / digitalisering@umu

Thesis. 1976. M.S.--Massachusetts Institute of Technology. Dept. of Nutrition and Food Science. / Microfiche copy available in Archives and Science. / Bibliography: leaves 70-78. / by Gwendolyn C. Murphy. / M.S.

No description available.

Chronic granulomatous disease (CGD) is associated with defective function of the NADPH-oxidase system in conjunction with phagocytic defects which leads to granuloma formation and serious infectious complications. This is often associated with significant morbidity and mortality. The association of defective phagocyte function with other coincidental immune defects is unknown. Defects in innate pathways seen with CGD, including complement systems, and toll-like and dectin receptor pathways, have not been described before. We present the case of a 2-year old male patient hospitalized with recurrent pneumonia, a non-healing skin ulcer, necrotizing lung granulomas, and epididymo-orchitis. Defective neutrophil chemiluminescence was detected by dihydrorhodamine (DHR) testing. Further evaluation demonstrated characteristic molecular mutations of CYBB consistent with CGD. Immune evaluation demonstrated polyclonal hyperglobulinemia, but a greatly reduced mannose binding lectin (MBL) level. Six biallelic polymorphisms in MBL gene and its promoter were analyzed using Light Cycler™ Real-time PCR assay. The LXPA/LYPB haplotype of MBL was detected in our patient; the latter is the defective haplotype associated with low MBL levels. Due to the implications for innate immunity and the protection against bacterial, viral, and fungal infections provided by MBL, a deficiency of this protein may have disastrous consequences on the long term outcomes of CGD. MBL deficiency can also complicate other disorders affecting the immune system, significantly increasing the risk of infection in such patients. Further studies looking at the frequency and implications of MBL deficiency in CGD are needed. © 2012 Bentham Science Publishers.

A deficiência de CD40 Ligante (CD40L) ou síndrome de Hiper-IgM ligada ao X (X-HIGM) é considerada uma imunodeficiência primária combinada de células T e B. O CD40L é expresso na superfície de linfócitos T ativados e interage com o CD40 expresso na superfície de linfócitos B, macrófagos, células dendríticas, células endoteliais e neutrófilos. A interação CD40L-CD40 transmite sinais que induzem ativação, diferenciação e proliferação celular. Nosso objetivo foi analisar as alterações genético-moleculares da molécula CD40L que acometeram indivíduos de 5 famílias brasileiras, ocasionando X-HIGM. Genotipamos 25 indivíduos, sendo 6 pacientes com X-HIGM, 13 parentes relacionados heterozigotos e 6 homozigotos sadios. Dentre os pacientes com X-HIGM dois eram de origem caucasóide e 4 eram mestiços. A idade dos pacientes variou de 2 a 20 anos e o quadro clínico de infecções de repetição teve início em média nos primeiros 4 meses de vida. As principais infecções recorrentes manifestadas pelos pacientes foram pneumonia e otite. O paciente TB apresentou blastomicose, observação original nesta imunodeficiência. A análise genético-molecular foi heterogênea. No paciente TB foi detectado um defeito de splicing levando a deleção do exon 3 (r.345_402del do gene CD40L (CD40LG) no paciente FS uma nova substituição missense g.11856 G>C (c.476 G>C, pW140C), no paciente KC uma substituição nonsense g.11855 G>A (c.475G>A, p. W140X), e nos pacientes CH, FE e VIC uma deleção g. 3074_3077delTAGA, levando a alteração no processamento do RNA. A fenotipagem dos leucócitos demonstrou que a contagem de linfócitos T auxiliares (CD3+CD4+), linfócitos citotóxicos (CD3+CD8+), linfócitos B (CD19+CD40+) e linfócitos T ativados (CD3+CD69+) dos pacientes foram similares aos controles sadios. Contudo, foi observada uma redução significativa nos níveis de expressão de CD40L na superfície de linfócitos CD3+ e CD4+ dos pacientes. A análise dos linfócitos T por microscopia confocal revelou que as células dos homozigotos com expressão residual do CD40L em sua superfície também apresentam redução na densidade da expressão da molécula CD3, sugerindo a necessidade da integridade molecular do CD40L para a expressão normal do CD3. Concluímos que mutações no CD40L que levam à síndrome de X-HIGM são heterogêneas e a análise genético-molecular permitiu um diagnóstico preciso tornando possível o aconselhamento genético e a triagem dos recém-nascidos das famílias avaliadas. / CD40-Ligand (CD40L) deficiency or X linked Hyper-IgM syndrome (X-HIGM) is considered a T and B cell combined primary immunodeficiency. CD40L is expressed on the cell surface of activated T lymphocytes and interacts with CD40, expressed on the surface of B lymphocytes, macrophages, dendritic cells, endothelial cells, and neutrophils. The CD40L-CD40 interaction induces activation, differentiation, and cell proliferation. Our aim was to analyze the molecular-genetic alterations of CD40L molecule affecting individuals of 5 brazilian families, leading to X-HIGM. We genotyped 25 individuals, whom 6 were X-HIGM patients, 13 were heterozygote related patients, and 6 were healthy homozygotes. Within the patients with X-HIGM, two of them were of caucasoid origin and four were mestiços. The patients age ranged from 2 to 20 years and their recurrent infections started in average during their first 4 months of life. The main recurrent infections were pneumonia and otitis. The patient TB presented blastomycosis, a unique observation in this immunodeficiency. The molecular-genetic analysis revealed heterogeneity. TB patient presented a splicing defect causing a deletion of exon 3 (r.345_402del) of CD40L gene (CD40LG). Patient FS presented a new missense mutation g.11856 G>C (c.476 G>C, pW140C). Patient KC presented a nonsense substitution g.11855 G>A (c.475G>A, p. W140X). Patients CH, VIC, and FE presented a deletion g. 3074_3077delTAGA, causing an alteration on RNA processing. The leukocytes fenotyping demonstrated that T helper lymphocytes (CD3+CD4+), T cytotoxic lymphocytes (CD3+CD8+), B lymphocytes (CD19+CD40+), and T activated (CD3+CD69+) cell counts of patients were similar to healthy controls. However it was observed a significant reduction of CD40L expression on cell surface patients CD3+ and CD4+ lymphocytes. The T lymphocyte confocal microscopy analysis revealed that homozygotes with residual expression of CD40L in their surface also presented a reduction on the density of CD3 molecule expression, suggesting the need of molecular integrity of CD40L for normal CD3 expression. We conclude that mutations on CD40L leading to X-HIGM syndrome are heterogeneous and the molecular-genetic analysis allowed a precise diagnosis making possible the genetic counseling and newborn screening of the involved families.

Esquistossomose e desnutrição são graves problemas de saúde pública nos países em desenvolvimento. A esquistossomose provoca uma série de morbidades, que é influenciada, em grande maioria, pela natureza do estímulo à resposta imunológica e ao estado nutricional do hospedeiro. Durante a infecção esquistossomótica, a resposta imune produz citocinas que são liberadas e estimulam a produção de óxido nítrico. Numerosos estudos demonstraram que o estado nutricional e a resposta imune afetam as características fenotípicas dos vermes adultos. No entanto, se o óxido nítrico desempenha um papel neste fenômeno é desconhecido. Neste estudo, os camundongos do tipo selvagem (grupo controle) e camundongos knockout com deficiência na produção de óxido nítrico foram alimentados com uma dieta comercial (UNILAB) ou uma dieta básica regional, dieta com baixa concentração de proteína (7,87%). Por meio de um sistema digital de análise de imagem (Image Pro Plus, USA) e microscopia confocal, estudou-se a morfologia da ventosa oral, tegumento e o sistema reprodutor de vermes machos e fêmeas. Vermes machos e fêmeas recuperados de camundongos desnutridos com deficiência de oxido nítrico mostraram descamação do tegumento. A superfície dorsal de vermes desnutridos machos apresentaram tubérculos irregulares, distribuídos de forma desigual, e escassos. O sistema reprodutivo de vermes fêmeas desnutridas não demonstrou alterações morfológicas. No entanto, os machos deste grupo exibiram menor número de células no processo de diferenciação dentro dos lobos testiculares. Em conclusão, nossos resultados sugerem que a deficiência de produção de óxido nítrico não induz alterações morfológicas em nível do tegumento e do sistema reprodutor de vermes machos. Em contraste, a desnutrição é responsável por tais alterações morfológicas, principalmente no sistema reprodutivo e na ventosa oral. / Schistosomiasis and malnutrition are both serious public health concerns in developing countries. Schistosoma infection causes a range of morbidities, which is influenced to a large extent by the nature of the induced immune response and the nutritional status of the host. During the schistosomiasis infection, the immune response produces cytokines which are released by stimulating production of nitric oxide. Numerous studies have demonstrated that the nutritional status and the immune response affect the phenotypic characteristics of the adult worms. However, whether nitric oxide plays a role is unknown. In this study, wild type mice (control group) and Knockout mice deficient in nitric oxide production either fed a commercial diet (UNILAB) or a regional basic diet with low protein diet (7.87%). By means of a digital system for image analysis (Image Pro Plus, USA) and confocal microscopy, we studied the morphology of the oral sucker, tegument and reproductive system of male and female worms. Malnourished male and female worms showed sloughing of the tegument. The dorsal surface of male malnourished worms presented irregular tubercles, unevenly distributed, and scarce. The reproductive system of female worms malnourished showed no morphological changes. The reproductive system of malnourished female worms did not show morphological changes. However, male worms from this group displayed smaller number of cells in differentiation process within the testicular lobes. In conclusion, our results suggest that the deficiency of nitric oxide does not induce morphological changes at the level of the integument and the reproductive system of male worms. In contrast, malnutrition is responsible by such morphological changes, mainly in the reproductive system and oral sucker.

Esquistossomose e desnutrição são graves problemas de saúde pública nos países em desenvolvimento. A esquistossomose provoca uma série de morbidades, que é influenciada, em grande maioria, pela natureza do estímulo à resposta imunológica e ao estado nutricional do hospedeiro. Durante a infecção esquistossomótica, a resposta imune produz citocinas que são liberadas e estimulam a produção de óxido nítrico. Numerosos estudos demonstraram que o estado nutricional e a resposta imune afetam as características fenotípicas dos vermes adultos. No entanto, se o óxido nítrico desempenha um papel neste fenômeno é desconhecido. Neste estudo, os camundongos do tipo selvagem (grupo controle) e camundongos knockout com deficiência na produção de óxido nítrico foram alimentados com uma dieta comercial (UNILAB) ou uma dieta básica regional, dieta com baixa concentração de proteína (7,87%). Por meio de um sistema digital de análise de imagem (Image Pro Plus, USA) e microscopia confocal, estudou-se a morfologia da ventosa oral, tegumento e o sistema reprodutor de vermes machos e fêmeas. Vermes machos e fêmeas recuperados de camundongos desnutridos com deficiência de oxido nítrico mostraram descamação do tegumento. A superfície dorsal de vermes desnutridos machos apresentaram tubérculos irregulares, distribuídos de forma desigual, e escassos. O sistema reprodutivo de vermes fêmeas desnutridas não demonstrou alterações morfológicas. No entanto, os machos deste grupo exibiram menor número de células no processo de diferenciação dentro dos lobos testiculares. Em conclusão, nossos resultados sugerem que a deficiência de produção de óxido nítrico não induz alterações morfológicas em nível do tegumento e do sistema reprodutor de vermes machos. Em contraste, a desnutrição é responsável por tais alterações morfológicas, principalmente no sistema reprodutivo e na ventosa oral. / Schistosomiasis and malnutrition are both serious public health concerns in developing countries. Schistosoma infection causes a range of morbidities, which is influenced to a large extent by the nature of the induced immune response and the nutritional status of the host. During the schistosomiasis infection, the immune response produces cytokines which are released by stimulating production of nitric oxide. Numerous studies have demonstrated that the nutritional status and the immune response affect the phenotypic characteristics of the adult worms. However, whether nitric oxide plays a role is unknown. In this study, wild type mice (control group) and Knockout mice deficient in nitric oxide production either fed a commercial diet (UNILAB) or a regional basic diet with low protein diet (7.87%). By means of a digital system for image analysis (Image Pro Plus, USA) and confocal microscopy, we studied the morphology of the oral sucker, tegument and reproductive system of male and female worms. Malnourished male and female worms showed sloughing of the tegument. The dorsal surface of male malnourished worms presented irregular tubercles, unevenly distributed, and scarce. The reproductive system of female worms malnourished showed no morphological changes. The reproductive system of malnourished female worms did not show morphological changes. However, male worms from this group displayed smaller number of cells in differentiation process within the testicular lobes. In conclusion, our results suggest that the deficiency of nitric oxide does not induce morphological changes at the level of the integument and the reproductive system of male worms. In contrast, malnutrition is responsible by such morphological changes, mainly in the reproductive system and oral sucker.

A deficiência de CD40 Ligante (CD40L) ou síndrome de Hiper-IgM ligada ao X (X-HIGM) é considerada uma imunodeficiência primária combinada de células T e B. O CD40L é expresso na superfície de linfócitos T ativados e interage com o CD40 expresso na superfície de linfócitos B, macrófagos, células dendríticas, células endoteliais e neutrófilos. A interação CD40L-CD40 transmite sinais que induzem ativação, diferenciação e proliferação celular. Nosso objetivo foi analisar as alterações genético-moleculares da molécula CD40L que acometeram indivíduos de 5 famílias brasileiras, ocasionando X-HIGM. Genotipamos 25 indivíduos, sendo 6 pacientes com X-HIGM, 13 parentes relacionados heterozigotos e 6 homozigotos sadios. Dentre os pacientes com X-HIGM dois eram de origem caucasóide e 4 eram mestiços. A idade dos pacientes variou de 2 a 20 anos e o quadro clínico de infecções de repetição teve início em média nos primeiros 4 meses de vida. As principais infecções recorrentes manifestadas pelos pacientes foram pneumonia e otite. O paciente TB apresentou blastomicose, observação original nesta imunodeficiência. A análise genético-molecular foi heterogênea. No paciente TB foi detectado um defeito de splicing levando a deleção do exon 3 (r.345_402del do gene CD40L (CD40LG) no paciente FS uma nova substituição missense g.11856 G>C (c.476 G>C, pW140C), no paciente KC uma substituição nonsense g.11855 G>A (c.475G>A, p. W140X), e nos pacientes CH, FE e VIC uma deleção g. 3074_3077delTAGA, levando a alteração no processamento do RNA. A fenotipagem dos leucócitos demonstrou que a contagem de linfócitos T auxiliares (CD3+CD4+), linfócitos citotóxicos (CD3+CD8+), linfócitos B (CD19+CD40+) e linfócitos T ativados (CD3+CD69+) dos pacientes foram similares aos controles sadios. Contudo, foi observada uma redução significativa nos níveis de expressão de CD40L na superfície de linfócitos CD3+ e CD4+ dos pacientes. A análise dos linfócitos T por microscopia confocal revelou que as células dos homozigotos com expressão residual do CD40L em sua superfície também apresentam redução na densidade da expressão da molécula CD3, sugerindo a necessidade da integridade molecular do CD40L para a expressão normal do CD3. Concluímos que mutações no CD40L que levam à síndrome de X-HIGM são heterogêneas e a análise genético-molecular permitiu um diagnóstico preciso tornando possível o aconselhamento genético e a triagem dos recém-nascidos das famílias avaliadas. / CD40-Ligand (CD40L) deficiency or X linked Hyper-IgM syndrome (X-HIGM) is considered a T and B cell combined primary immunodeficiency. CD40L is expressed on the cell surface of activated T lymphocytes and interacts with CD40, expressed on the surface of B lymphocytes, macrophages, dendritic cells, endothelial cells, and neutrophils. The CD40L-CD40 interaction induces activation, differentiation, and cell proliferation. Our aim was to analyze the molecular-genetic alterations of CD40L molecule affecting individuals of 5 brazilian families, leading to X-HIGM. We genotyped 25 individuals, whom 6 were X-HIGM patients, 13 were heterozygote related patients, and 6 were healthy homozygotes. Within the patients with X-HIGM, two of them were of caucasoid origin and four were mestiços. The patients age ranged from 2 to 20 years and their recurrent infections started in average during their first 4 months of life. The main recurrent infections were pneumonia and otitis. The patient TB presented blastomycosis, a unique observation in this immunodeficiency. The molecular-genetic analysis revealed heterogeneity. TB patient presented a splicing defect causing a deletion of exon 3 (r.345_402del) of CD40L gene (CD40LG). Patient FS presented a new missense mutation g.11856 G>C (c.476 G>C, pW140C). Patient KC presented a nonsense substitution g.11855 G>A (c.475G>A, p. W140X). Patients CH, VIC, and FE presented a deletion g. 3074_3077delTAGA, causing an alteration on RNA processing. The leukocytes fenotyping demonstrated that T helper lymphocytes (CD3+CD4+), T cytotoxic lymphocytes (CD3+CD8+), B lymphocytes (CD19+CD40+), and T activated (CD3+CD69+) cell counts of patients were similar to healthy controls. However it was observed a significant reduction of CD40L expression on cell surface patients CD3+ and CD4+ lymphocytes. The T lymphocyte confocal microscopy analysis revealed that homozygotes with residual expression of CD40L in their surface also presented a reduction on the density of CD3 molecule expression, suggesting the need of molecular integrity of CD40L for normal CD3 expression. We conclude that mutations on CD40L leading to X-HIGM syndrome are heterogeneous and the molecular-genetic analysis allowed a precise diagnosis making possible the genetic counseling and newborn screening of the involved families.