Seasonal variation of eosinophil counts in histologically normal colonic mucosal biopsies.

INTRODUCTION: The eosinophil counts in colonic biopsies are affected by geographical and possibly seasonal variations. This study aims to investigate the significance of seasonal variations of eosinophil counts in histologically normal colonic mucosal biopsies. MATERIALS AND METHODS: This is a retrospective, cross sectional study that included 337 cases of normal colonic biopsies. The number of eosinophils per high power field was counted in the most densely populated area. The eosinophilic counts were compared among genders, age groups, biopsy sites and in various months and seasons. Two tailed T-test was used to compare means and a p value < 0.05 was considered significant. RESULTS: 173 (51%) of cases were from males. The age range was between 18-82 with the mean being 51.7 years (SD= 17.5). 181 (54%) biopsies were from the right colon and 156 (46%) from the left colon. There was a statistically significant difference between eosinophil counts in the right colon (mean 20.2, SD 13.2) and left colon (mean 13.8, SD10.1); p value <0.001. The mean eosinophil counts was highest in autumn (21.1) followed by spring (18.3). The counts in winter and summer were close (15.2 and 15.1 respectively). There was a statistically significant difference between counts in autumn and summer (p=0.013) and between autumn and winter (p=0.008). However, there was no statistically significant differences between autumn and spring counts (p=0.183). When stratified according to site, this pattern of statistical significance was observed in the right colon but not the left colonic mucosal biopsies. CONCLUSION: There are significant seasonal variations of eosinophil counts in normal colonic biopsies which are more pronounced in the right colon. Pathologists and gastroenterologists need to be aware of these variations and to take them into account when determining if a patient has tissue eosinophilia.

Examining the trajectory and predictors of post-concussion sleep quality in children and adolescents.

OBJECTIVES: This study aimed to 1) determine if post-concussion sleep quality of children and adolescents differed from healthy sleep estimates; 2) describe the trajectory of parameters of sleep quality; 3) determine factors that predict sleep quality outcomes; and 4) compare sleep parameter outcomes between asymptomatic and symptomatic participants at 4 weeks post-concussion. METHODS: Nightly actigraphy estimates of sleep in 79 children and adolescents were measured throughout 4 weeks post-concussion. Total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of arousals (NOA), and average arousal length (AAL) were measured. RESULTS: Child and adolescent participants experienced significantly poorer SE and longer WASO duration throughout 4 weeks of recovery and adolescents experienced significantly longer TST. SE significantly improved with time post-injury (p = .047). Older age was associated with longer TST (p = .003) and female sex was associated with longer WASO (p = .025) and AAL duration (p = .044). Week 4 sleep parameter outcomes were not significantly different between asymptomatic and symptomatic participants. CONCLUSIONS: The sleep quality of youth is adversely affected by concussion, particularly in females. Sleep quality appears to improve with time but may require more than 4 weeks to return to normal.

The Systemic Effects of Exercise on Regulators of Muscle and Bone in Girls and Women.

PURPOSE: To assess the systemic effects of an acute bout of moderate-intensity exercise on factors that are known to regulate muscle and bone growth in prepubertal girls and women. METHODS: A total of 12 prepubertal girls (8-10 y) and 12 women (20-30 y) cycled at 60% maximal oxygen uptake for 1 hour followed by 1 hour recovery. Blood samples were collected at rest, mid-exercise, end of exercise, mid-recovery, and end of recovery. Plasma was analyzed for interleukin-6, chemokine ligand 1, fibroblast growth factor-2, total insulin growth factor-1 (IGF-1), and free IGF-1 using enzyme-linked immunosorbent assays assays. RESULTS: Both groups had similar concentrations of systemic factors at baseline with the exception of free IGF-1, which was higher in girls (P = .001). Interleukin-6 response was lower in girls versus women (P = .04), with a difference of +105.1% at end of exercise (P < .001), +113.5% at mid-recovery (P = .001), and +93.2% at end of recovery (P = .02). Girls and women exhibited significant declines in chemokine ligand 1, fibroblast growth factor-2, and total IGF-1 during recovery. CONCLUSION: Compared with women, an acute bout of moderate-intensity exercise in girls elicits a lower inflammatory response, suggesting that other mechanisms may be more important for driving the anabolic effects of exercise on muscle and bone in girls.

Automatically Identifying Financial Stress Information from Clinical Notes for Patients with Prostate Cancer.

Background: Financial stress, one of the social determinants, is common among cancer patients because of high out-ofpocket costs for treatment, as well as indirect costs. The National Academy of Medicine (NAM) has advised providers to recognize and discuss cost concerns with patients in order to enhance shared decision-making for treatment and exploration of financial assistant programs. However, financial stress is rarely assessed in clinical practice or research, thus, under-coded and under-documented in clinical practice. Natural language processing (NLP) offers great potential that can automatically extract and process data on financial stress from clinical free text existing in the patient electronic health record (EHR). Methods: We developed and evaluated an NLP approach to identify financial stress from clinical narratives for patients with prostate cancer. Of 4,195 eligible prostate cancer patients, we randomly sampled 3,138 patients (75%) as a training dataset (150,990 documents) to develop a financial stress lexicon and NLP algorithms iteratively. The remaining 1,057 patients (25%) were used as a test dataset (55,516 documents) to evaluate the NLP algorithm performance. The common terms representing financial stress were "financial concerns," "unable to afford," "insurance issue," "unemployed," and "financial assistance." Negations were used to exclude false mentions of financial stress. Results: Applying both pre- and post-negation, the NLP algorithm identified 209 patients (6.0%) from the training sample and 66 patients (6.2%) with 161 notes from the test sample as having documented financial stress. Two independent domain experts manually reviewed all 161 notes with NLP identified positives and randomly selected 161 notes with NLP-identified negatives, the NLP algorithm yielded 0.86 for precision, 1 for recall, and 0.9.2 for F-score. Conclusions: Financial stress information is not commonly documented in the EHR, neither in structured format nor in clinical narratives. However, natural language processing can accurately extract financial stress information from clinical notes when such narrative information is available.

Multiparametric evaluation of preoperative MRI in early stage breast cancer: prognostic impact of peri-tumoral fat.

PURPOSE: Obesity is associated with adverse outcomes in breast cancer patients. Fat-specific cytokines (adipokines) have been proposed as key drivers of breast cancer progression, invasion, and metastasis. We aimed at assessing correlations between peri-tumoral fat, quantified on magnetic resonance imaging (MRI) and pathologic factors potentially impacting therapy recommendations. METHODS: We retrospectively reviewed records of 63 patients with early stage breast cancer who underwent preoperative MRI imaging using appropriately weighted series for breast and tumor contouring. Fat volumes were generated through voxel intensity filtering. The peri-tumoral region was defined as the intersection of a 1-cm spherical extension around the tumor and the breast contour. Peri-tumoral fat was defined as the fraction of a fat content in this volume. Surgical pathology records were used to extract clinical data. Statistical analyses were conducted using Pearson and Spearman correlation coefficients. RESULTS: Among reviewed patients, 45 had T1 tumors (1.22 ± 0.85 cm diameter) and 18 had T2 tumors (2.08 ± 1.06 cm). Axillary lymph nodes were dissected in 31 and positive in 17 patients analyzed. Peri-tumoral fat ratio ranged between 25 and 99 %. Peri-tumoral fat ratio significantly correlated with the nodal-positive ratio of positive axillary lymph nodes (r = 0.532). Peri-tumoral fat ratio demonstrated optimally prominent correlation among obese patients upon body mass index categorical stratification. CONCLUSIONS: In women with early stage breast cancer, peri-tumoral fat correlates positively with the ratio of pathologically involved axillary nodes. This work highlights a novel method for quantitating peri-tumoral fat content. Preoperative breast MRI may be utilized to predict extent of axillary disease.

Circulating Endothelial Progenitor Cells in Youth: Fitness, Physical Activity and Adiposity.

Circulating endothelial progenitor cells (EPCs) are early markers of cardiovascular impairment. The role of EPCs in youth remains unclear, and is complicated by differences in how cells are identified. This study (1) described EPCs in pre- and late-pubertal males and females, (2) examined their association with fitness, activity and adiposity, and (3) compared EPCs to published cell definitions. 94 participants completed 2 sessions. During the first session, aerobic fitness (Wpeak) and moderate-to-vigorous physical activity (MVPA) were assessed. During the second session, percent body fat (%BF) was determined by DXA, and a fasted blood sample was collected to measure EPCs by flow cytometry. EPCs were identified as CD31(+)CD34(bright)CD45(dim)CD133(+). Samples were reanalyzed and cell counts were compared to 8 previously published EPC definitions. EPCs were similar in pre- and late-pubertal males and females (p>0.05). Neither EPC concentrations nor proportions were correlated with Wpeak (ρ=- 0.04 to-0.06), MVPA (ρ=- 0.09 to - 0.07) or %BF (ρ=0.20 to 0.14). Agreement between cell data analyzed according the different cell definitions ranged from Κ=-0.06 to 0.82. Our findings suggest that EPCs were not associated with fitness, MVPA or adiposity in youth. The overall poor agreement across definitions may be indicative of distinct EPC subpopulations.

Exercise and inflammation in pediatric Crohn's disease.

We examined inflammatory cells, cytokines and growth factors in response to acute bouts of moderate intensity continuous exercise and high intensity intermittent exercise in youth with Crohn's disease and in healthy matched-controls. 15 patients and 15 controls performed 30 min of cycling at 50% of peak mechanical power (PMP) and 6 bouts of 4×15-s of cycling at 100% PMP. Blood was collected at rest, at the mid-point, at the end of exercise and at 30 and 60 min into recovery. In patients with CD, both types of exercise increased immune cells and GH and decreased IGF-I. Moderate intensity exercise induced a greater increase in leukocytes (p<0.05), neutrophils (p<0.05), lymphocytes (p<0.001), monocytes (p<0.05), IL-6 (p<0.05), IL-17 (p<0.05) and GH (p<0.05) and a similar decrease in IGF-I, compared with high intensity exercise. TNF-α did not change significantly with either exercise. Responses in patients were similar compared with controls; however, in patients monocytes remained elevated significantly longer in response to MICE. Youth with Crohn's disease can engage in distinctly different types of exercise without a significant acute exacerbation of inflammation.

Consumo, digestibilidade dos nutrientes e parâmetros ruminais em bovinos alimentados com silagem de capim-mombaça / Intake, digestibilities of the nutrients, and ruminal variables in cattle fed mombaça-grass silage

Avaliaram-se o consumo, a digestibilidade aparente total e parcial dos nutrientes, o pH e a concentração de amônia ruminal em bovinos alimentados com silagem de capim-mombaça e concentrado nas seguintes proporções: 80:20, 65:35, 50:50 e 35:65, com base na matéria seca. Foram utilizados quatro animais Holandês x Zebu, com peso corporal médio inicial de 229kg, canulados no rúmen e abomaso, e distribuídos em quadrado latino 4x4. Os consumos de matéria seca (MS), matéria orgânica (MO), proteína bruta (PB), extrato etéreo (EE) e carboidratos totais (CHOT), expressos em kg/dia, e a digestibilidade parcial dos carboidratos não fibrosos (CNF) apresentaram comportamento linear crescente, com resposta platô nos níveis de concentrado de 54,1; 54,8; 52,9; 62,2; 55,2 e 52,7 por cento. O consumo dos demais nutrientes, exceto da fibra em detergente neutro (FDN), e as digestibilidades aparente total de MS, MO e CNF e a parcial de MO aumentaram linearmente com o incremento do concentrado nas dietas. Não foram encontradas diferenças no consumo e nas digestibilidades aparente total e parcial da FDN. Para concentração de amônia e pH ruminal, observou-se efeito quadrático de tempo de amostragem, com valores máximos de 24,76mg/dL e 6,53 em 2,8 e 3,5 horas após a alimentação, respectivamente.

Intake; total and partial digestibilities of nutrients; and ruminal pH and ammonia concentration were evaluated in beef cattle fed Mombaça-grass silage and concentrate at the following proportions: 80:20, 65:35, 50:50, and 35:65, in the dry matter basis. Four Holstein x Zebu steers, with average live weight of 229kg, fitted with ruminal and abomasal canullae, were used. The animals were allotted in a 4x4 latin square design. The intakes of dry matter (DM), organic matter (OM), crude protein (CP), ether extract (EE), and total carbohydrates (kg/day), as well the partials digestibilities of non fibrous carbohydrates (NFC) increased linearly with plateau at the concentrate levels of 54.1, 54.8, 52.9, 62.2, 55.2, and 52.7 percent. The intakes of others nutrients, except neutral detergent fiber (NDF), and the total apparent digestibilities of DM, OM, and NFC and the partial digestibility of OM increased linearly as the concentrate levels in the diets increased. No differences were found on the intake and the total and partial apparent digestibilities of NDF. The ruminal pH and ammonia concentration presented a quadratic affect in relation to the time of sampling, with maximum register at 2.8 and 3.5 hours after feeding, respectively, corresponding to pH 6.53 and 24.76mg/dL of ammonia.

Reproducibility of computer-assisted joint alignment measurement in OA knee radiographs.

OBJECTIVES: (1) To investigate the reproducibility of computer-assisted measurements of knee alignment angle (KA) from digitized radiographs of osteoarthritis (OA) participants requiring total knee arthroplasty (TKA) and (2) to determine whether landmark choice affects the precision of KA measurements on radiographs. METHODS: Using a custom algorithm, femoral, central, and tibial measurement-guiding rules were interactively placed on digitized posteroanterior fixed-flexion knee radiographs by mouse control and positioned according to different anatomic landmarks. The angle subtended by lines connecting these guiding rules was measured by three readers to assess interobserver, intraobserver and experience-inexperience reproducibility. Test-retest reproducibility was evaluated with duplicate radiographs from a healthy cohort. Reproducibility was assessed using root-mean square coefficients of variation (RMSCV%). The Bland-Altman method was performed on data obtained from varying anatomic landmarks (confidence interval, CI= 95%). RESULTS: From 16 healthy and 30 TKA participants, reproducibility analyses revealed a high degree of intraobserver (n=38, RMSCV=0.56%), interobserver (n=38, RMSCV=0.72%), test-retest (n=16, RMSCV=0.87%) and experience-inexperience (n=38, RMSCV=0.73%) reproducibility with variances below 1%. Varying the orientation of tibial and femoral rules according to anatomic landmarks produced a difference that exceeded an a priori limit of agreement of -1.11 degrees to +1.67 degrees. CONCLUSION: Our custom-designed software provides a robust method for measuring KAs within digitized knee radiographs. Although test-retest analyses were only performed in a healthy cohort, we anticipate a similar degree of reproducibility in an OA sample. A standardized set of anatomic landmarks employed for KA measurement is recommended since arbitrary selection of landmarks resulted in imprecise KA measurement even with a computer-assisted technique.

Prediçäo da composiçäo química do sorgo pela técnica de espectroscopia de reflectância no infravermelho próximo / Prediction of sorghum chemical composition by near infrared spectroscopy technique

Determinou-se a composiçäo química do sorgo pela espectroscopia de reflectância no infravermelho próximo (NIRS), comparando-a com os dados obtidos pelas análises convencionais de laboratório. Foram utilizadas 132 amostras de quatro variedades de sorgo: AG212 (porte alto), AG 2002 (porte alto), AG 2005 (duplo propósito) e AG 213 (porte alto). Com o intuito de se obter uma curva ampla, todas as amostras foram agrupadas compondo uma curva denominada sorgo in natura. As variáveis avaliadas foram carboidratos solúveis (CHO sol), fibra detergente neutro (FDN), fibra detergente ácido (FDA), proteína bruta (PB), matéria seca (MS) e digestibilidade in vitro da matéria seca (DIVMS). Utilizou-se o tratamento de absorbância e foram encontrados os seguintes coeficientes de determinaçäo ( por cento): CHO sol = 98,7, FDN = 96,4, FDA = 98,1, PB = 99,5, MS = 95,8 e DIVMS = 93,1. A calibraçäo foi boa (baixo erro de calibraçäo e alto coeficiente de determinaçäo) para o tratamento de absorbância.

Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.

Congenital adrenal hyperplasia (CAH) refers to a family of monogenic inherited disorders of adrenal steroidogenesis most often caused by enzyme 21-hydroxylase deficiency (21-OHD). In the classic forms of CAH (simple virilizing and salt wasting), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Prenatal treatment of CAH with dexamethasone has been successfully used for over a decade. This article serves as an update on 532 pregnancies prenatally diagnosed using amniocentesis or chorionic villus sampling between 1978 and 2001 at New York Presbyterian Hospital-Weill Medical College of Cornell University. Of the 532 pregnancies, 281 were prenatally treated for CAH due to the risk of 21-hydroxylase deficiency. Follow-up telephone interviews with mothers, genetic counselors, endocrinologists, pediatricians, and obstetricians were performed in all cases. Of the pregnancies evaluated, 116 babies were affected with classic 21-OHD. Of these, 61 were female, 49 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 9 wk gestation (in proper doses) was effective in reducing virilization. There were no statistical differences in the symptoms during pregnancy between mothers treated with dexamethasone and those not treated with dexamethasone, except for weight gain, edema, and striae, which were greater in the treated group. No significant or enduring side-effects were noted in the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight from untreated, unaffected newborns. Based on our experience, prenatal diagnosis and proper prenatal treatment of 21-OHD are effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity, genital surgery, and possible sex misassignment.

Congenital adrenal hyperplasia: update on prenatal diagnosis and treatment.

The diagnostic term congenital adrenal hyperplasia (CAH) applies to a family of inherited disorders of steroidogenesis caused by an abnormality in one of the five enzymatic steps necessary in the conversion of cholesterol to cortisol. The enzyme defects are translated as autosomal recessive traits, with the enzyme deficient in more than 90% of CAH cases being 21-hydroxylase. In the classical forms of CAH (simple virilizing and salt wasting), owing to 21-hydroxylase deficiency (21-OHD), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Non-classical 21-OHD (NC21OHD) refers to the condition in which partial deficiencies of 21-hydroxylation produce less extreme hyperandrogenemia and milder symptoms. Females do not demonstrate genital ambiguity at birth. The gene for adrenal 21-hydroxylase, CYP21, is located on chromosome 6p in the area of HLA genes. Specific mutations may be correlated with a given degree of enzymatic compromise and the clinical form of 21-OHD. NC21OHD patients are predicted to have mild mutations on both alleles or one severe and one mild mutation of the 21-OH locus (compound heterozygote). In most cases the mutation groups represent one diagnosis (e.g., Del/Del with SW CAH), however we have found several non-correlations of genotype to phenotype. Non-classical and classical patients were found within the same mutation group. Phenotypic variability within each mutation group has important implications for prenatal diagnosis and treatment. Prenatal treatment of 21-OHD with dexamethasone has been utilized for a decade. An algorithm has been developed for prenatal diagnosis and treatment, which, when followed closely, has been safe for both the mother and the fetus, and has been effective in preventing ambiguous genitalia in the affected female newborn. This is an instance of an inborn metabolic error successfully treated prenatally. Since 1986, prenatal diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) has been carried out in 403 pregnancies in The New York Hospital Cornell Medical Center. In 280, diagnoses were made by amniocentesis, while 123 were diagnosed using chorionic villus sampling. Of the 403 pregnancies evaluated, 84 babies were affected with classical 21-OHD. Of these, 52 were females, 36 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 10 weeks of gestation (23 affected female fetuses) was effective in reducing virilization. Thirteen cases had affected female sibs (Prader stages 1-4); 6 of these fetuses were born with entirely normal female genitalia, while 6 were significantly less virilized (Prader stages 1-2) than their sibs, and one was Prader stage 3. Eight newborns had male sibs: 4 were born with normal genitalia, 3 were Prader stages 1-2, and 3 were born Prader stages 3-4. No significant or enduring side effects were noted in either the mothers or the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight, length, or head circumference from untreated, unaffected newborns. Based on our experience, proper prenatal diagnosis and treatment of 21-OHD is effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity of genital surgery, sex misassignment, and gender confusion.

Facilitating physician referrals on the World Wide Web: representation and appropriate utilization of clinical expertise.

In highly integrated and increasingly complex health care systems, the identification and proper utilization of clinical staff expertise are key factors for efficiently delivering high quality patient care. To achieve these capabilities on an enterprise-wide scale, we have embarked on a multi-phased project to develop World Wide Web (WWW)-based physician referral capabilities for two large teaching hospitals. Currently, users may search for information concerning the education, training, board certifications, and self-designated clinical interests of staff members. Address, phone number, email address, and a photo are also presented. Our experience indicates that institutional changes are required to successfully deploy and maintain online physician referral services and that accurate and equitable representation of clinical expertise and the incorporation of referral guidelines require an incremental introduction of a carefully planned program that addresses the needs of clinicians, administrators, and health care policy-makers.

Representation of clinical practice guidelines through an interactive World-Wide-Web interface.

The widespread utility of clinical practice guidelines is greatly dependent on the ease with which they can be accessed, used, and applied. Because it supports hyperlinking and is widely accessible, the World-Wide Web is a medium that is well suited for browsing through guidelines. We have developed a process for implementing algorithmic guidelines into a graphical format that allows the user to browse these guidelines in an interactive fashion. The guidelines we used were already in or could be transformed to an algorithmic format that lends itself well to analysis with decision table techniques, which in turn permits a fairly straightforward conversion into a graphical representation. The results of this process allow a user to browse a particular guideline algorithm and to visualize the traversed parts of the algorithm by flowcharts. Our first experiences with this method of representing a few sample clinical practice guidelines have been encouraging, and we hope to extend this method to other guidelines.

Genetic analysis of 11 beta-hydroxysteroid dehydrogenase.

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the Type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11 beta-OHSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the short-chain dehydrogenase family. Using site-directed mutagenesis, it was demonstrated that the amino terminus and two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11 beta-OHSD deficiency, did not reveal any mutations in the HSD11 gene. This disorder may involve an additional enzyme with 11 beta-OHSD activity or possibly another cortisol metabolizing enzyme.

The representation of time in clinical patient simulations.

Simulated clinical scenarios are generally compressed in time to enhance educational effectiveness and to minimize testing time. Designers should consider how to best control potential sources of distortion in the perception of time and how to best communicate the passage of time to the user.

Transcripts originating in intron 1 of the HSD11 (11 beta-hydroxysteroid dehydrogenase) gene encode a truncated polypeptide that is enzymatically inactive.

There is evidence for the presence in the kidney of more than one isoform of 11 beta-hydroxysteroid dehydrogenase (11HSD), an enzyme that interconverts cortisol and cortisone (in rodents, corticosterone and 11-dehydrocorticosterone). A specific isoform might arise from transcripts in the kidney that are known to originate in intron 1; translation from these transcripts is predicted to initiate at the codon that in the full-length rat enzyme encodes Met27. Alignment of the full-length rat and human 11HSD sequences with other members of the short chain dehydrogenase family suggests that initiation of translation at Met27 might yield a functional enzyme, since the amino-termini of most of these enzymes occur at equivalent positions. We confirmed that short transcripts are found in the kidney and are detectable at lower levels in the liver and lung. In vitro transcription and translation of short cDNA demonstrated that the AUG encoding Met27 is indeed a functional initiation codon. However, Chinese hamster ovary cells transfected with short cDNA in the pCMV4 vector expressed apparently low levels of the corresponding truncated polypeptide and had no 11HSD activity. Thus, the functional significance of transcripts originating in intron 1 is unclear.

Tyr-179 and Lys-183 are essential for enzymatic activity of 11 beta-hydroxysteroid dehydrogenase.

Tyr-179 and Lys-183 are likely to be functionally important residues in 11 beta-hydroxysteroid dehydrogenase, as these amino acids are absolutely conserved in all members of the "short chain dehydrogenase" family. We modified these residues by site-directed mutagenesis of rat cDNA and transfected these constructs into CHO cells. A highly but not absolutely conserved residue, Asp-110, was also studied. Mutation of Tyr-179 to Phe or Ser completely abolished enzymatic activity (interconversion of corticosterone and 11-dehydrocorticosterone), as did Lys-183-->Arg. Asp-110-->Asn affected activity only mildly. Tyr-179 and Lys-183 may be directly involved in the catalytic function of this class of enzymes.