Postpartum Depression-Identifying Risk and Access to Intervention.

PURPOSE OF REVIEW: As maternal mortality climbs in the USA with mental health conditions driving these preventable deaths, the field of reproductive psychiatry must shift towards identification of women and other birthing individuals at risk and facilitating access. This review brings together recent studies regarding risk of perinatal depression and highlights important comorbidities that place individuals at higher vulnerability to poor perinatal outcomes. RECENT FINDINGS: Recent research suggests that identifying risk for perinatal depression including historical diagnoses of depression, anxiety, trauma, and comorbid substance use and intimate partner violence may move the field to focus on preventive care in peripartum populations. Emerging data shows stark health inequities in racial and ethnic minority populations historically marginalized by the health system and in other vulnerable groups such as LGBTQ+ individuals and those with severe mental illness. Innovative models of care using systems-level approaches can provide opportunities for identification and risk analyses of vulnerable peripartum patients and facilitate access to therapeutic or preventive interventions. Utilizing intergenerational approaches and leveraging multidisciplinary teams that thoughtfully target high-risk women and other birthing individuals could promote significant changes to population-level care in maternal health.

Columbus® computer navigated total knee arthroplasty: Gap balancing versus measured resection.

BACKGROUND: The aim of this study was to compare the medium term functional outcome and patient satisfaction of gap balanced (GB) with measured resection (MR) total knee arthroplasty (TKA) using computer navigation. METHODS: A cohort of 144 consecutive computer navigated TKA were retrospectively identified from an arthroplasty database. Functional assessment using the Oxford Knee Score (OKS) and patient satisfaction were obtained from 113 patients at a mean follow-up of 5.4 (range four to seven) years. There were 44 patients in the GB group and 69 patients in the MR group. RESULTS: The mean OKS for the GB group was 36.9 (SD 9.2) and for the MR was 33.6 (SD 9.8), with a difference of 3.3 (95% CI 0.3 to 6.3) points, which was statistically significant (p=0.01). Linear regression analysis confirmed the independent effect of surgical technique when adjusting for confounding factors and surgeon, with the GB group achieving a greater post-operative OKS (R2=0.39, 3.0 points, 95% CI 1.2 to 4.8, p=0.001). There was a greater rate of patient satisfaction in the GB group (88.6%, n=39/44) compared to the MR group (81.1%, n=56/69), but this was not statistically significant (odds ratio 1.8, 95% CI 0.6 to 5.5, p=0.31). CONCLUSION: Computer navigated Columbus® TKA using a GB technique results in a statistically significantly greater functional outcome but no significant difference in patient satisfaction in the medium term compared to patients undergoing a MR technique.

Cardiovascular response to exercise training in the systemic right ventricle of adults with transposition of the great arteries.

KEY POINTS: Patients with transposition of the great arteries (TGA) and systemic right ventricles have premature congestive heart failure; there is also a growing concern that athletes who perform extraordinary endurance exercise may injure the right ventricle. Therefore we felt it essential to determine whether exercise training might injure a systemic right ventricle which is loaded with every heartbeat. Previous studies have shown that short term exercise training is feasible in TGA patients, but its effect on ventricular function is unclear. We demonstrate that systemic right ventricular function is preserved (and may be improved) in TGA patients with exercise training programmes that are typical of recreational and sports participation, with no evidence of injury on biomarker assessment. Stroke volume reserve during exercise correlates with exercise training response in our TGA patients, identifying this as a marker of a systemic right ventricle (SRV) that may most tolerate (and possibly even be improved by) exercise training. ABSTRACT: We aimed to assess the haemodynamic effects of exercise training in transposition of the great arteries (TGA) patients with systemic right ventricles (SRVs). TGA patients have limited exercise tolerance and early mortality due to systemic (right) ventricular failure. Whether exercise training enhances or injures the SRV is unclear. Fourteen asymptomatic patients (34 ± 10 years) with TGA and SRV were enrolled in a 12 week exercise training programme (moderate and high-intensity workouts). Controls were matched on age, gender, BMI and physical activity. Exercise testing pre- and post- training included: (a) submaximal and peak; (b) prolonged (60 min) submaximal endurance and (c) high-intensity intervals. Oxygen uptake (V̇O2; Douglas bag technique), cardiac output (Q̇c, foreign-gas rebreathing), ventricular function (echocardiography and cardiac MRI) and serum biomarkers were assessed. TGA patients had lower peak V̇O2, Q̇c, and stroke volume (SV), a blunted Q̇c/V̇O2 slope, and diminished SV response to exercise (SV increase from rest: TGA = 15.2%, controls = 68.9%, P < 0.001) compared with controls. After training, TGA patients increased peak V̇O2 by 6 ± 8.5%, similar to controls (interaction P = 0.24). The magnitude of SV reserve on initial testing correlated with Q̇c training response (r = 0.58, P = 0.047), though overall, no change in peak Q̇c was observed. High-sensitivity troponin T (hs-TnT) and N-terminal prohormone of brain naturetic peptide (NT pro-BNP) were low and did not change with acute exercise or after training. Our data show that TGA patients with SRVs in this study safely participated in exercise training and improved peak V̇O2. Neither prolonged submaximal exercise, nor high-intensity intervals, nor short-term exercise training seem to injure the systemic right ventricle.

Adding heat to the live-high train-low altitude model: a practical insight from professional football.

OBJECTIVES: To examine with a parallel group study design the performance and physiological responses to a 14-day off-season 'live high-train low in the heat' training camp in elite football players. METHODS: Seventeen professional Australian Rules Football players participated in outdoor football-specific skills (32 ± 1°C, 11.5 h) and indoor strength (23 ± 1°C, 9.3 h) sessions and slept (12 nights) and cycled indoors (4.3 h) in either normal air (NORM, n=8) or normobaric hypoxia (14 ± 1 h/day, FiO2 15.2-14.3%, corresponding to a simulated altitude of 2500-3000 m, hypoxic (HYP), n=9). They completed the Yo-Yo Intermittent Recovery level 2 (Yo-YoIR2) in temperate conditions (23 ± 1°C, normal air) precamp (Pre) and postcamp (Post). Plasma volume (PV) and haemoglobin mass (Hb(mass)) were measured at similar times and 4 weeks postcamp (4WPost). Sweat sodium concentration ((Na(+))(sweat)) was measured Pre and Post during a heat-response test (44°C). RESULTS: Both groups showed very large improvements in Yo-YoIR2 at Post (+44%; 90% CL 38, 50), with no between-group differences in the changes (-1%; -9, 9). Postcamp, large changes in PV (+5.6%; -1.8, 5.6) and (Na(+))sweat (-29%; -37, -19) were observed in both groups, while Hb(mass) only moderately increased in HYP (+2.6%; 0.5, 4.5). At 4WPost, there was a likely slightly greater increase in Hb(mass) (+4.6%; 0.0, 9.3) and PV (+6%; -5, 18, unclear) in HYP than in NORM. CONCLUSIONS: The combination of heat and hypoxic exposure during sleep/training might offer a promising 'conditioning cocktail' in team sports.

Fungicide Sensitivity of Pythium spp. Associated with Cavity Spot of Carrot in California and Michigan.

The identity of 172 isolates of Pythium spp. from cavity spot lesions on carrot produced in California and Michigan was determined, and their sensitivity to three fungicides was examined. Pythium violae accounted for 85% of California isolates, with P. irregulare, P. dissotocum (the first report as a carrot pathogen in the United States), P. ultimum, and P. sulcatum making the balance. P. sulcatum, P. sylvaticum, and P. intermedium were the most commonly recovered (85%) species in Michigan; others from Michigan included P. intermedium, P. irregulare, and an unclassified strain, M2-05. On fungicide-amended media, 93% of isolates were sensitive to mefenoxam (inhibition of mycelial growth was >60% at 10 µg active ingredient [a.i.]/ml); however, two of five isolates of P. irregulare from California were highly resistant (≤60% inhibition at 100 µg a.i./ml); about half of the isolates of P. intermedium and P. sylvaticum and a single isolate of P. violae were highly or intermediately resistant to mefenoxam (>60% inhibition at 100 µg a.i./ml, or ≤60% inhibition at 10 µg a.i./ml). P. dissotocum, P. irregulare, P. sulcatum, M2-05, and three of seven isolates of P. intermedium were insensitive to fluopicolide (effective concentrations for 50% growth inhibition [EC50] were >50 µg a.i./ml), while P. sylvaticum, P. ultimum, P. violae, and some isolates in P. intermedium were sensitive (EC50 < 1 µg a.i./ml). All isolates were sensitive to zoxamide (EC50 < 1 µg a.i./ml). Sensitivity baselines of P. violae to zoxamide and fluopicolide were established.

Hypervariations of a protease-encoding gene, PD0218 (pspB), in Xylella fastidiosa strains causing almond leaf scorch and Pierce's disease in California.

Xylella fastidiosa is a gram-negative plant pathogenic bacterium that causes almond leaf scorch disease (ALSD) and Pierce's disease (PD) of grape in many regions of North America and Mexico. Of the two 16S rRNA gene genotypes described in California, A genotype strains cause ALSD only and G genotype strains cause both PD and ALSD. While G genotype strains cause two different diseases, little is known about their genetic variation. In this study, we identified a putative protease locus, PD0218 (pspB), in the genome of X. fastidiosa and evaluated the variation at this locus in X. fastidiosa populations. PD0218 contains tandem repeats of ACDCCA, translated to threonine and proline (TP), upstream of the putative protease conserved domain. Among 116 X. fastidiosa ALSD and PD strains isolated from seven locations in California, tandem repeat numbers (TRNs) varied from 9 to 47, with a total of 30 TRN genotypes, indicating that X. fastidiosa possesses an active mechanism for contracting and expanding tandem repeats at this locus. Significant TRN variation was found among PD strains (mean = 29.9), which could be further divided into two TRN groups: PD-G(small) (mean = 17.3) and PD-G(large) (mean = 44.3). Less variation was found in ALSD strains (mean = 21.7). The variation was even smaller after ALSD strains were subdivided into the A and G genotypes (mean = 13.3, for the G genotype; mean = 27.1, for the A genotype). Genetic variation at the PD0218 locus is potentially useful for sensitive discrimination of X. fastidiosa strains. However, TRN stability, variation range, and correlation to phenotypes should be evaluated in epidemiological applications such as pathotype identification and delineation of pathogen origin.

Clinical significance of elevated alpha-fetoprotein in Alaskan Native patients with chronic hepatitis C.

The clinical significance of elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C virus (HCV) infection is not well defined. We analysed data from a population-based cohort of patients with HCV infection to assess the prevalence of elevated serum AFP, to determine its association with clinical and virologic parameters and with clinical outcomes. We defined a slightly elevated serum AFP level as 8 to <15 and a high-AFP level as > or =15 microg/L. Among 541 HCV-RNA-positive persons, 61 (11%) had a slightly elevated or high AFP at the time of consent. AFP > or =8 microg/L was associated with the older age, aspartate aminotransferase/alanine aminotransferase ratio >1, and higher alkaline phosphatase levels, but not with heavy alcohol use, IV drug use, genotype, viral load or duration of HCV infection. Among 192 persons with an AFP at liver biopsy, 17% had an AFP > or =8 microg/L. The sensitivity/specificity of an AFP level > or =8 in detecting Ishak 3-6 fibrosis was 39%/95%. Among 372 persons with a minimum of four AFP measurements over 6 years, 5% had persistently elevated AFP >8 microg/L, 19% had both elevated and normal AFP measurements, and 76% had persistently normal AFP. Elevated AFP at consent was associated with hepatocellular carcinoma (HCC) and end-stage liver disease. Over 6 years of follow-up, persistently elevated AFP was associated with the development of HCC; no person with AFP persistently <8 microg/mL developed HCC. Serial AFP measurements appear to be useful in identifying persons with advanced fibrosis and help to determine who needs periodic screening with liver ultrasound to detect HCC.

Gender, acculturative stress and Caribbean immigrants' health in the United States of America: an exploratory study.

Given that the health of many immigrants declines after increasing years in their host countries and that there may be gender differences in these experiences, this exploratory study's main objective was twofold: a) assess the relationship between acculturative stress and negative health (ie both mental and physical) and b) determine if there were any gender differences in these stress-health relationships. Gender-stratified analyses were conducted on a sample of 418 (males = 158, females = 260) English-speaking immigrants (the majority of whom were Jamaicans--males = 81%, females = 86%) that lived in the District of Columbia, Virginia, and Maryland (DC Metropolitan Area, United States of America (USA). Mail-order surveys were used to collect the data over a six-month period in 2002. Data for the main independent variable, acculturative stress, were collected using five indices (ie personal problems, group affiliations, adjustment to life in the USA, lonely feelings and feeling socially satisfied). Data for the major dependent variable, health, were collected using four indices (ie symptoms of depression, physical health conditions, the rating of one's health and the feeling of control one had over one's health). After controlling for selected covariates, both males (r = 0.42, p < 0.001) and females (r = 0.19, p < 0.05) reported a positive relationship between personal problems and depression. In other cases, female immigrants, with increasing personal problems, reported more physical health problems (r = 0.20, p < 0.05). Male immigrants who had more group affiliations (r = 0.22, p < 0.05), and who reported more loneliness (r = .26, p < 0.05) had less symptoms of depression. These exploratory results suggest the potential importance of selected variables (eg personal problems and depression) in efforts at improving the health of Caribbean immigrants.

Surface motility of Xylella fastidiosa visualized by oblique illumination.

Stereomicroscopic observations using oblique illuminations revealed the presence of two types of movement trails by Xylella fastidiosa strains (A- and G-genotypes) isolated from almond-leaf scorch samples on the surface of PW and PD3 culture media. The A-genotype strains showed curved motility trails, and the G-genotype strains showed straight motility trails. Haloes were found around some G-genotype colonies due to the excretion of unknown factors and (or) compounds, which might be related to bacterial surface motility.

Gender, acculturative stress and Caribbean immigrants' health in the United States of America: an exploratory study

Given that the health of many immigrants declines after increasing years in their host countries and that there may be gender differences in these experiences, this exploratory study's main objective was twofold: a) assess the relationship between acculturative stress and negative health (ie both mental and physical) and b) determine if there were any gender differences in these stress-health relationships. Gender-stratified analyses were conducted on a sample of 418 (males = 158, females = 260) English-speaking immigrants (the majority of whom were Jamaicans--males = 81%, females = 86%) that lived in the District of Columbia, Virginia, and Maryland (DC Metropolitan Area, United States of America (USA). Mail-order surveys were used to collect the data over a six-month period in 2002. Data for the main independent variable, acculturative stress, were collected using five indices (ie personal problems, group affiliations, adjustment to life in the USA, lonely feelings and feeling socially satisfied). Data for the major dependent variable, health, were collected using four indices (ie symptoms of depression, physical health conditions, the rating of one's health and the feeling of control one had over one's health). After controlling for selected covariates, both males (r = 0.42, p < 0.001) and females (r = 0.19, p < 0.05) reported a positive relationship between personal problems and depression. In other cases, female immigrants, with increasing personal problems, reported more physical health problems (r = 0.20, p < 0.05). Male immigrants who had more group affiliations (r = 0.22, p < 0.05), and who reported more loneliness (r = .26, p < 0.05) had less symptoms of depression. These exploratory results suggest the potential importance of selected variables (eg personal problems and depression) in efforts at improving the health of Caribbean immigrants.

Diagnostic accuracy of a fibrosis serum panel (FIBROSpect II) compared with Knodell and Ishak liver biopsy scores in chronic hepatitis C patients.

Liver biopsy is the primary method of assessing liver injury in hepatitis C patients. FIBROSpect II (FS), a diagnostic panel of three extracellular matrix remodelling markers, may be useful as a noninvasive alternative to this procedure. The purpose of this study was to correlate FS results with liver fibrosis scores to determine if this test is sufficiently accurate to be a viable alternative to liver biopsy. A total of 142 serum specimens were evaluated for fibrosis with FS and were compared with Knodell and Ishak fibrosis scores. FS reports an index score ranging from 0.1 to 1.0, which corresponds to the probability of progressive liver fibrosis. Using a FS index cut-off of 0.42, 50 of 54 patients with Ishak 3-6 were classified as having advanced fibrosis (METAVIR F2-F4) and 58 of 88 patients with Ishak 0-2 as having no/mild fibrosis (METAVIR F0-F1), resulting in a sensitivity of 93%, specificity of 66%, and an overall test accuracy of 76%. With a 38% prevalence of advanced fibrosis, the negative predictive value was 94% and positive predictive value was 63%. A biopsy length of > or = 2 cm was associated with higher concordance between FS results and liver fibrosis scores (P = 0.01). FS was clinically useful in ruling out advanced fibrosis in hepatitis C by identifying patients with mild disease in whom treatment could be deferred. The limitation of this test is its decreased sensitivity and specificity in the middle of the test's reporting range between scores of 0.42 and 0.80.

First Report of Puccinia sorghi on Maize in Oman.

Maize (Zea mays L.) is an important annual forage crop cultivated in the Sultanate of Oman, especially during the summer months. It is used for green fodder and grains and often intercropped in fruit orchards, especially under date palms. In April of 2005, leaf samples showing rust symptoms were collected from Samail, 100 km south of Muscat. Oval-shaped, red-brown pustules covered both sides of the leaves and yielded urediniospores typical of Puccinia sorghi Schwein. Urediniospores were roughly subglobose, measured 23 to 28 × 20 to 25 µm, echinulate, with three or four equitorial germ pores (2). Teliospores (38 to 42 × 16 to 19 µm) were observed, but few in numbers, most probably because of the time of year of collection. Pathogen identity was confirmed by nuclear ribosomal large subunit (28S) and internal transcribed spacer region 2 (ITS-2) DNA analysis (voucher sequence deposited in GenBank, Accession No. DQ345724, voucher specimen deposited in the U.S. National Fungus Collections, BPI 871134). P. sorghi has previously been reported from Yemen and Saudi Arabia (1) but not from Oman. Maize is grown throughout the year in Oman, and pathogen survival probably does not require the presence of the alternate host, nonetheless, Oxalis species are present and current research is attempting to locate and confirm the presence of the aecial stage in Oman. References: (1) CMI Distribution Maps of Plant Diseases. Map No. 279. Ed. 4. CABI, Wallingford, UK, 1978. (2) D. G. White, ed. Compendium of Corn Diseases. The American Phytopathological Society, St Paul, MN, 1999.

First Report of 16S rDNA II Group Phytoplasma on Polygala mascatense, a Weed in Oman.

Polygala mascatense Boiss. (family Polygalaceae) is a common weed found in neglected farms, under date palm trees, and in stony locations throughout the Sultanate of Oman (1). It is a perennial herb approximately 30 to 40 cm tall, has slender branches, is woody at the base, and has linear leaves with purple flowers. Recently (November 2004), in the interior region of Oman (210 km south of Muscat), some polygala plants were found stunted with small leaves, bushy growth, and the floral parts were showing phyllody symptoms. Total genomic DNA extracted from asymptomatic and symptomatic plants with modified cetyltrimethylammoniumbromide (CTAB) buffer method (4) was used as a template for direct polymerase chain reaction (PCR) amplification of phytoplasma 16S rDNA with P1/P7 primers. Direct PCR product was used as template DNA for nested PCR with primers R16F2n/R16R2. DNA from plants infected with alfalfa and lime witches'-broom phytoplasma was used as positive controls, and DNA from healthy plants and water was used as negative controls. Products from nested PCR (1.2 kb) were analyzed by using single endonuclease enzyme digestion (restriction fragment length polymorphism [RFLP]) with Tru9I, HaeIII, HhaI, TaqI, AluI, and RsaI (3). The results showed the presence of a 1.8-kb product amplified with direct PCR and a 1.2-kb product of the nested PCR from infected polygala and the positive controls, whereas no PCR products were observed in the negative controls. The PCR assay confirmed the presence of phytoplasma causing witches'-broom disease in polygala. The RFLP results showed the polygala phyto-plasma to be most similar to the alfalfa phytoplasma, a member of 16SrII group (2). Infected polygala weeds may serve as a reservoir for alfalfa witches'-broom phytoplasma that causes annual losses over $25 million to alfalfa cultivation in Oman (2). A detailed investigation needs to be carried out to establish transmission of phytoplasma from polygala to alfalfa. To our knowledge, this is the first report of phytoplasma infecting polygala weeds in Oman. References: (1) S. A. Ghazanfar. Pages 95-96 in: An Annotated Catalogue of the Vascular Plants in Oman. Scripta Botanica Belgica Meise, National Botanic Garden of Belgium, 1992. (2) A. J. Khan et al. Phytopathology 92:1038, 2002. (3) I. M. Lee et al. Int. J. Syst. Bacteriol. 1153, 1998. (4) M. A. Saghai-Maroof et al. Proc. Natl. Acad. Sci. USA 81:8014, 1984.

Amendment effects on soil test phosphorus.

Applications of animal manures have increased soil test P values in many parts of the USA and thus increased the risk that soil P will be transferred to surface water and decrease water quality. To continue farming these areas, landowners need tools to reduce the risk of P losses. A field experiment was conducted near Kurten, TX, on a Zulch fine sandy loam (thermic Udertic Paleustalfs) with Bray-1 P values exceeding 3000 mg P kg(-1) soil (dry wt.) in the A(p) horizon to evaluate the effectiveness of soil amendments for reducing soil test P values. Soils were amended annually from 1999 to 2001 with 1.5 and 5.0 Mg gypsum ha(-1), 1.4 Mg alum ha(-1), or 24.4 Mg ha(-1) of waste paper product high in Al alone or in combination with 1.5 Mg gypsum ha(-1) and/or 1.4 Mg alum ha(-1). These treatments supplied a maximum of 225 and 1163 kg ha(-1) yr(-1) of Al and Ca, respectively. Soil Bray-1 P and dissolved reactive P levels were monitored from 1999 to 2004. None of the soil amendment treatments affected Bray-1 P values. Only annual additions of 5.0 Mg gypsum ha(-1) from 1999 to 2001 significantly reduced soil dissolved reactive P. Dissolved reactive P levels reached minimal levels after two applications of 5.0 Mg gypsum ha(-1) but increased in 2003 and 2004. These results indicate that soil dissolved reactive P levels can be reduced if sufficient amounts of gypsum were added to supply Ca in amounts similar to the soil test P values.

Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases.

BACKGROUND: The role of palliative resection of the primary tumour in patients who present with metastatic colorectal cancer is unclear. AIMS: This study compared the incidence of major intestinal complications in such patients who received chemotherapy treatment with or without prior palliative resection of the primary tumour. PATIENTS: The incidence of intestinal obstruction, perforation, fistula formation, and gastrointestinal haemorrhage, and the requirement for abdominal radiotherapy in patients with metastatic colorectal cancer treated at a single institution over a 10 year period was determined. RESULTS: Eighty two patients received initial treatment with chemotherapy without resection of the primary tumour (unresected group) and 280 patients had undergone prior resection (resected group). In the unresected group, the incidence of peritonitis, fistula formation, and intestinal haemorrhage was 2.4% (95% confidence interval (CI) 0.3-8.5%), 3.7% (95% CI 0.8-10.3%), and 3.7% (95% CI 0.8-10.3%), respectively, and was not significantly different from the resected group. Intestinal obstruction affected 13.4% (95% CI 6.9-22.7%) of patients in the unresected group and 13.2% (95% CI 9.2-17.2%) of patients in the resected group. More patients in the unresected group required >/=3 blood transfusions (14.6% v 7.5%; p=0.048) and abdominal radiotherapy (18.3% v 9.6%; p=0.03) than the resected group. CONCLUSIONS: The incidence of major intestinal complications in patients with unresected colorectal cancer and synchronous metastases who receive initial treatment with chemotherapy is low. Chemotherapy may be successfully used as initial treatment for such patients with no increased risk of most major intestinal complications compared with patients who have undergone initial resection of the primary tumour.

Loss of MHC class II inducibility in hyperplastic tissue in Rb-defective mice.

Retinoblastoma gene (Rb) defects occur frequently in human tumors. Studies of Rb-defective human tumor cell lines and Rb-/- murine embryonic fibroblasts demonstrate that Rb is required for interferon-gamma (IFN-gamma) induced major histocompatibility complex (MHC) class II expression. MHC class II expressing tumors generate anti-tumor immune responses associated with tumor-specific infiltrating lymphocytes. The role of Rb in IFN-gamma induced MHC class II expression on an endogenous tumor was examined by immunohistochemical staining for IAbeta and Rb on tissues from Rb+/- mice. MHC class II IAbeta is not induced by IFN-gamma in Rb-deficient neoplastic cells, but remains inducible in related normal tissue.

Defective transforming growth factor beta signaling pathway in head and neck squamous cell carcinoma as evidenced by the lack of expression of activated Smad2.

PURPOSE: Transforming growth factor beta (TGF-beta) regulates cell growth and differentiation, in normal squamous epithelium, via specific TGF-beta receptors and intracellular signaling molecules (Smads). We have previously observed that TGF-beta type II receptor (TbetaR-II) expression decreases in squamous cell carcinomas as tumors become less differentiated and more biologically aggressive. However, a small fraction of tumors remain TbetaR-II positive. In this article, we examine the integrity of the other members of the TGF-beta-signaling machinery, the Smad proteins. EXPERIMENTAL DESIGN: Thirteen archived head and neck squamous cell carcinomas were selected from the files of the Pathology Department of the H. Lee Moffitt Cancer Center. Protein immunoexpression was quantitated by image analysis in the context of histopathological parameters. Mutation analysis of the MADR2/Smad2 gene was also performed. RESULTS: In both TbetaR-II-positive and TbetaR-II-negative tumors, expression of the non-TGF-beta-specific Smads (4, 6, and 7) was variable, whereas expression of the pathway-specific Smad2 was lost in 38% of the tumors. Expression of the activated, phosphorylated form of this molecule, Smad2-P, was lost in approximately 70% of the tumors. No abnormal mRNA expression and no mutations in the MADR2/Smad2 gene were observed. CONCLUSIONS: These results suggest that multiple defects in TGF-beta signaling, both at the receptor and postreceptor level, may play a role in the oncogenesis of head and neck squamous cell carcinoma.

Mapping maize sequences to chromosomes using oat-maize chromosome addition materials.

Oat- (Avena sativa) maize (Zea mays) chromosome additions are produced by crossing maize and oat. During early embryo development maize chromosomes are preferentially eliminated, and oat plants are often recovered that retain a single maize chromosome. Each of the 10 maize chromosomes recently has been isolated as a separate oat-maize addition. We describe here the mapping of 400 maize sequences to chromosomes using polymerase chain reaction and DNA from the oat-maize addition material. Fifty of the sequences were from cloned markers that had been previously mapped by linkage analysis, and our results were consistent with those obtained using Southern-blot analysis. Previously unmapped expressed sequence tags and sequence tagged sites (350) were mapped to chromosomes. Maize gene sequences and expression data are rapidly being accumulated. Coupling this information with positional information from high throughput mapping programs provides plant biologists powerful tools for identifying candidate genes of interest.

A complete set of maize individual chromosome additions to the oat genome.

All 10 chromosomes of maize (Zea mays, 2n = 2x = 20) were recovered as single additions to the haploid complement of oat (Avena sativa, 2n = 6x = 42) among F(1) plants generated from crosses involving three different lines of maize to eight different lines of oat. In vitro rescue culture of more than 4,300 immature F(1) embryos resulted in a germination frequency of 11% with recovery of 379 F(1) plantlets (8.7%) of moderately vigorous growth. Some F(1) plants were sectored with distinct chromosome constitutions among tillers of the same plant and also between root and shoot cells. Meiotic restitution facilitated development of un-reduced gametes in the F(1). Self-pollination of these partially fertile F(1) plants resulted in disomic additions (2n = 6x + 2 = 44) for maize chromosomes 1, 2, 3, 4, 6, 7, and 9. Maize chromosome 8 was recovered as a monosomic addition (2n = 6x + 1 = 43). Monosomic additions for maize chromosomes 5 and 10 to a haploid complement of oat (n = 3x + 1 = 22) were recovered several times among the F(1) plants. Although partially fertile, these chromosome 5 and 10 addition plants have not yet transmitted the added maize chromosome to F(2) offspring. We discuss the development and general utility of this set of oat-maize addition lines as a novel tool for maize genomics and genetics.

A SNP resource for human chromosome 22: extracting dense clusters of SNPs from the genomic sequence.

The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR-RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]