Bilateral asymmetric deficiency of the pectoralis major muscle

We observed a rare, bilateral congenital deficiency of the pectoralis major muscle in a 72-year-old female cadaver in our gross anatomy dissection laboratory. The outward appearance of the anterior thoracic wall, which included well-developed breasts, revealed no obvious abnormalities. Upon dissection, the following features were observed: 1) on the left side, the sternal portion of the sternocostal head of the pectoralis major muscle was absent, the costal portion of the sternocostal head and the clavicular head were both well developed, a normal pectoralis minor was present, and the deltoid and subclavius muscles were not hypertrophied as is often the case when the pectoralis major muscle is deficient; 2) on the right side, the entire pectoralis major muscle was absent and the pectoralis minor, deltoid, and coracobrachialis muscles were infiltrated with connective tissue and fat; and 3) on both sides, the lateral pectoral nerves were absent and the medial pectoral nerves were present. The absence of the lateral pectoral nerves suggests that the deficiencies in the pectoralis major muscles are congenital malformations resulting from a developmental failure of the embryonic muscles rather than a sequel to polio or Poland's syndrome.     

Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63

Waanders E, Venselaar H, te Morsche RHM, de Koning DB, Kamath PS, Torres VE, Somlo S, Drenth JPH. Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63. Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein structure and function. We screened 464 subjects including 76 probands by direct sequencing or conformation‐sensitive capillary electrophoresis. We analyzed the effects of all known and novel mutations using a combination of splice site recognition, evolutionary conservation, secondary and tertiary structure predictions, Poly Phen , and p Mut and sift . We identified a total of 26 novel mutations in PRKCSH (n = 14) and SEC63 (n = 12), including four splice site mutations, eight insertions/ deletions, six non‐sense mutations, and eight missense mutations. Out of 48 PCLD mutations, 13 were predicted to affect splicing. Most mutations were located in highly conserved regions and homology modeling for two domains of Sec63p showed severe effects of the residue substitutions. In conclusion, we identified 26 novel mutations associated with PCLD and we provide in silico analysis in order to delineate the role of these mutations.     

The combination of plasmid interleukin-12 with a single DNA vaccine is more effective than Mycobacterium bovis (bacille Calmette-Guèrin) in protecting against systemic Mycobacterim avium infection

Sub‐unit vaccines utilizing purified mycobacterial proteins or DNA vaccines induce partial protection against mycobacterial infections. For example, immunization with DNA vaccines expressing the gene for the immunodominant 35 000 MW protein, common to Mycobacterium avium and Mycobacterium leprae but absent from the Mycobacterium tuberculosis complex, conferred significant protection against infection with either virulent M. avium or M. leprae in mice. However, the level of protection was equivalent to that obtained with the viable, attenuated vaccine, Mycobacterium bovis, bacille Calmette–Guèrin (BCG). The cytokine, interleukin (IL)‐12, is essential for priming naïve CD4⁺ T lymphocytes to differentiate into interferon‐γ (IFN‐γ)‐secreting T cells. We have used a novel self‐splicing vector expressing both chains of murine IL‐12 to determine if plasmid IL‐12 would increase the efficacy of a vaccine expressing the M. avium 35 000 MW protein (DNA‐Av35). Co‐immunization with p2AIL‐12 and DNA‐Av35 led to a significant increase in the number of antigen‐specific IFN‐γ secreting cells and total amount of IFN‐γ released, but a concomitant fall in the antibody response to the 35 000 MW protein. This pattern of response was associated with enhanced clearance of M. avium from the liver and spleen of coimmunized mice, and was significantly more effective than BCG or DNA‐Av35. alone. Following M. avium challenge there was significant increase in the expansion of the 35 000 MW antigen‐reactive T cells in the coimmunized mice. Therefore, plasmid‐delivered IL‐12 acts as an effective adjuvant to increase the protective efficacy of a single DNA vaccine against M. avium infection above that achieved by BCG, and this strategy may improve the efficacy of subunit vaccines against M. leprae and M. tuberculosis.     

The juice of fresh leaves of <Emphasis Type="Italic">Catharanthus roseus</Emphasis> Linn. reduces blood glucose in normal and alloxan diabetic rabbits

Background  

The leaf juice or water decoction of Catharanthus roseus L. (Apocyanaceae) is used as a folk medicine for the treatment of diabetes all over the world. In the present investigation, the leaf juice of C. roseus has been evaluated for its hypoglycemic activity in normal and alloxan-induced diabetic rabbits.     

Optimization of Cultural Conditions for Protease Production by a Fungal Species

Studies were carried out on a paddy soil fungal isolate identified to be a strain of Aspergillus niger from Manipal. The parameters that largely impact enzyme production viz., fermentation time, impeller speed, pH, temperature and nutrient supplements were studied. Optimization of production parameters for production of protease was done by the single-parameter mode. Casein served as substrate and proteolytic activity was estimated using Folin-Ciocalteau method at 660 nm. A maximum yield of 71.3 mg tyrosine/g casein substrate was produced in 96 h on a soluble starch medium at pH 4 in shake flask experiments. Production was carried out on a 3-liter fermenter and 40.7 mg of tyrosine was liberated/g of substrate. The enzyme was extracted with 50% ammonium sulfate and sodium dodecyl sulfate-Polyacrylamide gel electrophoresis showed two bands having mw 45.7 kDa and 38.5 kDa, respectively. The enzyme activity was found to be 147.84 U/ml.     

SNP array mapping of chromosome 20p deletions: Genotypes,phenotypes, and copy number variation

The use of array technology to define chromosome deletions and duplications is bringing us closer to establishing a genotype/phenotype map of genomic copy number alterations. We studied 21 patients and five relatives with deletions of the short arm of chromosome 20 using the Illumina HumanHap550 SNP array to: 1) more accurately determine the deletion sizes; 2) identify and compare breakpoints; 3) establish genotype/phenotype correlations; and 4) investigate the use of the HumanHap550 platform for analysis of chromosome deletions. Deletions ranged from 95 kb to 14.62 Mb, and all of the breakpoints were unique. Eleven patients had deletions between 95 kb and 4 Mb and these individuals had normal development, with no anomalies outside of those associated with Alagille syndrome (AGS). The proximal and distal boundaries of these 11 deletions constitute a 5.4‐Mb region, and we propose that haploinsufficiency for only 1 of the 12 genes in this region causes phenotypic abnormalities. This defines the JAG1‐associated critical region, in which deletions do not confer findings other than those associated with AGS. The other 10 patients had deletions between 3.28 Mb and 14.62 Mb, which extended outside the critical region, and, notably, all of these patients had developmental delay. This group had other findings such as autism, scoliosis, and bifid uvula. We identified 47 additional polymorphic genome‐wide copy number variants (>20 SNPs), with 0 to 5 variants called per patient. Deletions of the short arm of chromosome 20 are associated with relatively mild and limited clinical anomalies. The use of SNP arrays provides accurate high‐resolution definition of genomic abnormalities. Hum Mutat 0,1–8, 2008. © 2008 Wiley‐Liss, Inc.     

Two-Dimensional Echocardiographic Findings of Pulmonary Valve Cyst Secondary to Pulmonary Valvuloplasty

Real time two-dimensional transthoracic and transesophageal echocardiography demonstrated a mobile echolucent mass attached to the pulmonary valve in a 25-year-old adult, 20 years following balloon pulmonary valvuloplasty. The mass was surgically excised and pathology showed it to be a cyst.     

Ixabepilone in combination with capecitabine and as monotherapy for treatment of advanced breast cancer refractory to previous chemotherapies

PURPOSE: To describe the considerations leading to marketing approval of ixabepilone in combination with capecitabine and as monotherapy for the treatment of advanced breast cancer that is refractory to other chemotherapies. EXPERIMENTAL DESIGN: Data from one randomized multicenter trial comparing combination therapy with ixabepilone and capecitabine to capecitabine alone were analyzed for support of the combination therapy indication. For monotherapy, a single-arm trial of ixabepilone was analyzed. Supporting data came from an additional single-arm combination therapy study and two single-arm monotherapy studies. RESULTS: In patients with metastatic or locally advanced breast cancer who had disease progression on or following an anthracycline and a taxane, ixabepilone plus capecitabine showed an improvement in progression-free survival compared with capecitabine alone {median progression-free survival, 5.7 [95% confidence interval (95% CI), 4.8-6.7] versus 4.1 (95% CI, 3.1-4.3) months, stratified log-rank P < 0.0001; hazard ratio, 0.69 (95% CI, 0.58-0.83)}. As monotherapy for patients who had disease progression on or following an anthracycline, a taxane, and capecitabine, ixabepilone as monotherapy showed a 12% objective response rate by independent blinded review and 18% by investigator assessment. The major toxicities from ixabepilone therapy were peripheral neuropathy and myelosuppression, particularly neutropenia. CONCLUSIONS: On October 16, 2007, the Food and Drug Administration approved ixabepilone for injection in combination with capecitabine or as monotherapy for the treatment of patients with advanced breast cancer who have experienced disease progression on previous chemotherapies.     

Differentiation of typhoid fever from fulminant hepatic failure in patients presenting with jaundice and encephalopathy

OBJECTIVE: To determine the clinical and laboratory features that allow the early diagnosis of typhoid fever in patients who present with jaundice and encephalopathy. PATIENTS AND METHODS: This 12-month prospective study, conducted in Bangalore, India, between 1990 and 1991, evaluated the clinical and laboratory features of all patients (N=47) who presented with encephalopathy within 8 weeks of onset of jaundice. Ciprofloxacin and dexamethasone were used to treat 11 patients diagnosed on blood culture as having typhoid fever. The other 36 patients were presumed to have fulminant hepatic failure with a viral cause and were treated with supportive measures (bioartificial liver support and transplantation were not available). RESULTS: In patients with jaundice and encephalopathy, a liver span of greater than 9 cm on physical examination, thrombocytopenia, elevated alkaline phosphatase level, aspartate aminotransferase level greater than alanine aminotransferase level, and only mild prolongation of the prothrombin time suggested a diagnosis of typhoid fever. All 11 patients diagnosed as having typhoid fever had an excellent response to treatment with ciprofloxacin and dexamethasone with no mortality and with normalization of the liver test results in 2 weeks. On the other hand, 30 of the 36 patients with nontyphoid fulminant hepatic failure died. CONCLUSIONS: In patients presenting with jaundice and encephalopathy, physical examination and simple laboratory tests can help make an early diagnosis of typhoid fever. We believe that patients with a presumptive diagnosis of typhoid fever should be treated with ciprofloxacin and dexamethasone, even before the results of blood cultures are available.     

Retinoic acid nuclear receptors and tumor promotion: decreased expression of retinoic acid nuclear receptors by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate

During studies to determine the mechanism of tumor promotionby 12-O-tetradecanoylphorbol-13-acetate (TPA), we found thatTPA downregulates mouse epidermal retinoic acid nuclear receptors(RAR), a superfamily of nuclear steroid/thyrold receptors implicatedin mediating effects of retinoic acid (RA). Application of TPAto mouse skin decreased the binding of [³H]RA to RAR from mouseepidermal nuclear extracts. In this experiment, 20 nmol of TPAwas applied to mouse skin and 3.5 h later binding of [³H]RAto RAR was analyzed by chromatography on a size-exclusion column.TPA treatment resulted in an