Immunization of mice with Plasmodium TCTP delays establishment of Plasmodium infection.

Translationally controlled tumour protein (TCTP) may play an important role in the establishment or maintenance of parasitemia in a malarial infection. In this study, the potential of TCTP as a malaria vaccine was investigated in two trials. In the initial vaccine trial, Plasmodium falciparum TCTP (PfTCTP) was expressed in Saccharomyces cerevisiae and used to immunize BALB/c mice. Following challenge with Plasmodium yoelii YM, parasitemia was significantly reduced during the early stages of infection. In the second vaccine trial, the TCTP from P. yoelii and P. berghei was expressed in Escherichia coli and used in several mouse malaria models. A significant reduction in parasitemia in the early stages of infection was observed in BALB/c mice challenged with P. yoelii YM. A significantly reduced parasitemia at each day leading up to a delayed and reduced peak parasitemia was also observed in BALB/c mice challenged with the nonlethal Plasmodium chabaudi (P.c.) chabaudi AS. These results suggest that TCTP has an important role for parasite establishment and may be important for pathogenesis.

Cervical metastases of squamous cell carcinoma of the maxilla: a retrospective study of 25 years.

OBJECTIVES: Squamous cell carcinomas (SCCs) of the maxilla are relatively rare; therefore, only little data is available regarding the frequency of cervical metastasis (CM) and therapy strategies. Most authors only undertake clinical observation of the lymph nodes. The aim of this retrospective study was to evaluate the manner of metastasis in SCC of the maxilla. MATERIALS AND METHODS: All patient records from 1987 to 2011 were scanned for SCC of the maxilla. Patients with SCC limited to the maxilla were comprised. The cases were analyzed regarding tumor node metastasis staging system and any special occurrences in the follow-up time such as tumor recurrence, metastasis, and exitus letalis. Classification and staging were performed according to the 2003 UICC system. RESULTS: One hundred thirty-eight patients were comprised of 36 % females and 64 % males (average age, 66 years; women, 71 years; men, 63 years). The average follow-up time was 43 months (range, 0-195). Fifty-eight percent smoked or declared regular consumption of alcohol. About 50 % of the patients had an advanced tumor stage (III-IV). At the time of the primary diagnosis, 38 % of the patients had CM. There is an increased risk for CM occurrence with increasing tumor size and grading and a tumor localized in the postcanine region. Contralateral CM arises frequently in T4 tumors and tumors localized in the postcanine region. CONCLUSION: The data exhibit aggressive regional metastatic behavior of SCC of the maxilla. CLINICAL RELEVANCE: Therefore, surgical treatment of the draining lymphatic system as a primary management strategy is recommended for patients with SCC of the maxilla.

In situ quantification of HER2-protein tyrosine kinase 6 (PTK6) protein-protein complexes in paraffin sections from breast cancer tissues.

BACKGROUND: Protein tyrosine kinase 6 (PTK6; breast tumour kinase) is overexpressed in up to 86% of the invasive breast cancers, and its association with the oncoprotein human epidermal growth factor receptor 2 (HER2) was shown in vitro by co-precipitation. Furthermore, expression of PTK6 in tumours is linked with the expression of HER2. METHOD AND RESULTS: In this study, we used the proximity ligation assay (PLA) technique on formalin-fixed paraffin sections from eighty invasive breast carcinoma tissue specimens to locate PTK6-HER2 protein-protein complexes. Proximity ligation assay signals from protein complexes were assessed quantitatively, and expression levels showed a statistically significant association with tumour size (P=0.015) and course of the cancer disease (P=0.012). CONCLUSION: Protein tyrosine kinase 6 forms protein complexes with HER2 in primary breast cancer tissues, which can be visualised by use of the PLA technique. Human epidermal growth factor receptor 2-PTK6 complexes are of prognostic relevance.

Galactorrhoea of the neck following pectoralis major reconstruction of a pharyngeal defect.

We describe a case of postoperative galactorrhea following the use of a pedicled pectoralis major myocutaneous flap for reconstruction of a pharyngolaryngeal defect in a woman with squamous cell carcinoma. We believe this to be unique in the literature, and an important complication to be reported, due to the similarities in appearance of galactorrhoea and postoperative aerodigestive tract/cutaneous fistula.

A 700-kb physical map of a region of 16q23.2 homozygously deleted in multiple cancers and spanning the common fragile site FRA16D.

We have identified a >600-kb region at 16q23.2 that is homozygously deleted from malignant ovarian ascites using representational difference analysis. Overlapping homozygous deletions were also observed in the colon carcinoma cell line HCT116 and a xenograft established from the small cell lung cancer cell line WX330. This region coincides with that described previously by others as showing loss of heterozygosity in prostate and breast cancers (C. Li et al., Genes Chromosomes Cancer, 24: 175-182, 1999; A. Latil et al., Cancer Res., 57: 1058-1062, 1997; K. Driouch et al., Genes Chromosomes Cancer, 19: 185-191, 1997; A. Iida et al., Br. J. Cancer, 75: 264-267, 1997). In addition, the minimally deleted region spans the common fragile site FRA16D. We have constructed a 700-kb physical map encompassing the deleted region. By fluorescence in situ hybridization of aphidicolin-induced metaphase chromosomes, we have preliminary data to suggest that P1-derived bacterial artificial chromosome clones from the contig lie on both sides of FRA16D. This is confirmed by extensive fluorescence in situ hybridization analysis of the region reported in the accompanying article (M. Mangelsdorf et al., Cancer Res., 60: 1683-1689, 2000) and is consistent with an involvement of this common fragile site in the loss of 16q23.2 material in various cancer types. The minimally deleted region of approximately 210 kb has been characterized using our own markers and public domain markers. Eleven distinct expressed sequences mapped to the region, providing a basis for identifying the predicted tumor suppressor gene in this region.

Identification of a region of frequent loss of heterozygosity at 11q24 in colorectal cancer.

Loss of heterozygosity (LOH) at 11q23-qter occurs frequently in ovarian and other cancers, but for colorectal cancer, the evidence is conflicting. Seven polymorphic loci were analyzed between D11S897 and D11S969 in 50 colorectal tumors. Two distinct LOH regions were detected, suggesting possible sites for tumor-suppressor genes involved in colorectal neoplasia: a large centromeric region between D11S897 and D11S925, and a telomeric 4.9-Mb region between D11S912 and D11S969. There was no correlation with clinicopathological features. This analysis describes a region of LOH in the region 11q23.3-24.3 for the first time in colorectal cancer and provides complementary evidence for the ongoing effort to identify the gene(s) involved.

Definition and refinement of a region of loss of heterozygosity at 11q23.3-q24.3 in epithelial ovarian cancer associated with poor prognosis.

Previous cytogenetic and loss of heterozygosity (LOH) data suggest that disruption of chromosome 11q23-qter occurs frequently in epithelial ovarian cancer and is associated with an adverse clinicopathological phenotype. Ten polymorphic microsatellite repeat loci were analyzed by PCR from the 11q22-q25 region between D11S35 and D11S968 in 40 ovarian tumors (including 31 epithelial ovarian cancers). Two distinct regions of loss were detected, suggesting possible sites for genes involved in epithelial ovarian neoplasia: a large centromeric region between D11S35 and D11S933 (11q22-q23.3) and a telomeric 8.5-Mb region lying between D11S934 and D11S1320 (11q23.3-24.3) not previously defined. LOH of the latter region but not the former one was significantly associated with poor survival, despite all tumors in this study having LOH somewhere on chromosome 11. This analysis provides a starting point for positional cloning.

WWOX mRNA expression profile in epithelial ovarian cancer supports the role of WWOX variant 1 as a tumour suppressor, although the role of variant 4 remains unclear.

WWOX is a candidate tumour suppressor gene that exhibits LOH or homozygous deletion in several tumour types. As well as the predominant full-length transcript (variant 1) there also exist alternatively spliced transcripts found previously only in malignant tissue. It has been suggested that proteins encoded by these variants may interfere with normal WWOX function in a dominant negative fashion. The most prevalent alternate transcript demonstrated in ovarian cancer is variant 4, which lacks exons 6-8. Here, we report the first comparison of the mRNA expression of WWOX variants 1 and 4 in human ovarian tumours and normal ovaries, and correlate expression with clinical data. We demonstrate significantly lower WWOX variant 1 expression in tumours than in normal ovaries. This reduction was not associated with any specific clinical subgroup. Variant 4 was expressed at low levels, and significantly associated with high grade and advanced stage ovarian cancer. Furthermore, tumours co-expressing variant 4 and relatively high levels of variant 1 showed significantly worse survival than tumours expressing variant 1 alone. However, variant 4 was also frequently identified in non-malignant ovarian tissue. These results support the role of WWOX variant 1 as a suppressor of ovarian tumourigenesis, but the role of variant 4 remains speculative.

Diagnostic accuracy of gray scale ultrasongraphy for the jaundiced patient. A report of 275 cases.

This study of cholestatic jaundice suggests that gray scale ultrasonography should precede invasive techniques or surgery. The failure of ultrasound to demonstrate dilated ducts suggests intrahepatic cholestasis. Display of liver parenchyma by ultrasound provided the correct diagnosis of diffuse liver disease in 61% of the cases. Observation of a dilated biliary tree allowed differentiation between intrahepatic and extrahepatic obstruction, with an accuracy of 96.4%. One false positive (0.7%) occurred, and most false negatives were due to gallstones producing intermittent obstruction owing to a ball-valve effect. Observations of normal biliary canaliculi suggest that physiological distention of intrahepatic biliary vessels does not occur. Long-standing obstruction of biliary tree may result in permanent distention despite surgical relief, predisposing the patient to recurrent ascending cholangitis. This stresses the need for early diagnosis and prompt relief of extrahepatic biliary obstruction.

Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial.

OBJECTIVES: Parenchymal involvement of intraventricular hemorrhage (IVH) is a major risk factor for neurodevelopmental handicap in very low birth weight neonates. Previous trials have suggested that indomethacin would lower the incidence and severity of IVH in very low birth weight neonates. METHODS: We enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would lower the incidence and severity of IVH. Serial cranial ultrasound examinations and echocardiographs were performed. RESULTS: There were no differences in the birth weight, gestational age, sex, Apgar scores, and percent of neonates treated with surfactant between the indomethacin and placebo groups. Within the first 5 days, 25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4 IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin-treated neonates and 29 control neonates died (P = .08); there was a difference favoring indomethacin with respect to survival time (P = .06). Eighty-six percent of all neonates had a patent ductus arteriosus on the first postnatal day; indomethacin was associated with significant ductal closure by the fifth day of life (P < .001). There were no differences in adverse events attributed to indomethacin between the two treatment groups. CONCLUSIONS: Low-dose prophylactic indomethacin significantly lowers the incidence and severity of IVH, particularly the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus arteriosus and is not associated with significant adverse drug events in very low birth weight neonates.

Physical parameters affecting the visibility of small ventricular septal defects using two-dimensional echocardiography.

We report a study showing that two-dimensional echocardiography is capable of visualizing a ventricular septal defect as small as 3 mm. The physical parameters which determine the visibility of an aperture in the myocardium include the presence of anterior refractile tissue, the amount of ultrasound beam focusing and range over which this occurs, the angle of incidence of the ultrasound beam on the septum, and the number of lines of information per degree of sector sweep. These factors are illustrated by in vitro tests. The influence of operator controllable variables in two-dimensional sector scanning echocardiography is discussed.

New criteria for the diagnosis of gestational trophoblastic disease.

The purpose of the study was to test the hypothesis of whether the combined use of ultrasound and human chorionic gonadotropin (hCG) determinations could increase the diagnostic accuracy of sonography in the diagnosis of hydatidiform mole. The criteria used were the absence of fetal heart movement by ultrasound when the hCG level was above 82,350 mIU/mL and the presence of an hCG level in excess of 2 SD above the mean for the biometrically derived gestational age for suspected partial moles. The threshold of 82,350 mIU/mL was derived by probit analysis of the hCG serum levels of a population of normal intrauterine pregnancies prospectively examined to determine the level of hCG at which fetal heart activity would be visible by sonography. The diagnostic accuracy of these criteria was compared with the preoperative sonographic examination in 36 hydatidiform moles. When sonography was used alone, 15 of 36 cases (41.6%) did not have a definitive diagnosis on the first examination. The combination of hCG and ultrasound would have correctly identified 32 of the 36 cases (88.8%). This improvement was statistically significant (P less than .005).

Grey-scale ultrasonography in the differential diagnosis of jaundice.

One hundred fifty patients with cholestatic jaundice were studied prospectively by grey-scale ultrasonography. All patients had a diagnosis established by subsequent biopsy, autopsy, or surgery. Using the presence or absence of a dilated biliary tree as the criterion, the intrahepatic or extrahepatic nature of the jaundice was correctly differentiated in 145 of 150 patients, an accuracy of 97%. All 64 of the patients with intrahepatic jaundice were correctly identified. Five of the 86 remaining patients, each of whom had gallstones, were misdiagnosed. In eighty-two patients (54.7%), the specific etiology was diagnosed. Ultrasound is an accurate method for the evaluation of jaundice and would appear to have a definite value as a screening procedure before proceeding to more invasive studies.

Ultrasound and false normal oral cholecystogram.

Although oral cholecystography is a highly accurate investigation for the diagnosis of gallbladder disease, false normal examinations do occur. In other patients, the presence of jaundice, nausea, or vomiting may preclude oral cholecystography. When there is clinical suspicion of gallbladder disease with a normal or equivocal oral cholecystogram, ultrasound examination is a highly accurate alternative imaging procedure. We describe in this article three patients with apparently normal oral cholecystography who were found to have obvious gallstones on ultrasound examination and at surgery. The relative accuracy of these diagnostic procedures is reviewed and their place in the diagnosis of biliary tract disease is discussed.

Ultrasonic evaluation of hepatic and splenic trauma.

Blunt abdominal trauma comprises a major portion of surgical emergencies. These patients require imaging modalities that are rapid and accurate. In two patients with upper abdominal trauma, gray scale ultrasound was successfully used both for initial diagnosis and for monitoring the postoperative course.

The effect of thiol-active compounds and sterols on the membrane-associated hemolysin of Mycoplasma pulmonis.

Previous studies had shown that Mycoplasma pulmonis contained a bovine serum albumin-dependent, membrane-associated hemolysin. Biochemical analyses were performed to further characterize this activity. The membrane-associated hemolytic activity could be activated by dithiothreitol and beta-mercaptoethanol, and inactivated by oxidizing compounds, a sulfhydryl inhibitor and heat treatment. Cholesterol and other sterols were inhibitory in a stereo-specific manner, but they did not interfere with adherence of M. pulmonis to red blood cells. These results indicated that once attached, the M. pulmonis hemolysin recognized cholesterol in the opposing membrane leading to red cell lysis. Because of the unique location of this toxin and its sensitivity to cholesterol, the mycoplasma membrane hemolysins may belong to a unique class of bacterial toxins.

Urography in preoperative evaluation of abdominal aortic aneurysms.

Ultrasound is a commonly used and accurate method to diagnose abdominal aortic aneurysms. A case of abdominal aortic aneurysm, diagnosed by ultrasound, which at surgery was found to have an overlying horseshoe kidney with multiple renal vessels is reported. The clot surrounding the aneurysm most likely prevented demonstration of the isthmus of the horseshoe kidney by echography. Since preservation of renal blood supply is crucial, urography should routinely be performed prior to surgery to discover such anomalies.

Gray scale ultrasound in identification of lymphoma complicating lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is a necrotizing vasculitis involving multiple organs which may be associated with lymphomatous transformation. A case of lymphomatoid granulomatosis is presented in which gray scale ultrasound identified lymphomatous transformation involving the right kidney and retroperitoneum, thus preventing unnecessary surgery. Ultrasound is a valuable modality for identifying and characterizing abdominal masses in patients at risk for neoplastic disease.

Gray scale ultrasonography, computerized tomography, and nephrotomography in evaluation of polycystic kidney and liver disease.

A comparison of gray scale ultrasonography and computerized axial tomography in adults with known adult-type polycystic disease and of ultrasonography and high-dose nephrotomography in their progeny is being conducted. Although all three modalities have proved capable of demonstrating cysts of the kidney and liver, ultrasound has been the most consistent in identifying these lesions. Ultrasound is valuable in diagnosing polycystic disease in adult with large, poorly functioning kidneys; in addition, since cysts could be identified by ultrasound in children who had normal nephrotograms, it provides a safe and useful method of obtaining information for genetic counseling.

Transvaginal ultrasonography for the diagnosis of ectopic pregnancy.

The transvaginal (TVU) and transabdominal (TAU) ultrasound approaches were compared in their ability to identify by direct visualization the adnexal mass of ectopic pregnancy. There were 22 patients who had a surgically proven ectopic pregnancy. The TAU approach identified the adnexal mass in 50% and the TVU approach in 91% of the patients (P less than 0.01). Below both previously reported threshold titers for the expected TAU intrauterine sac visualization, at 6500 mIU and 3600 mIU, respectively, the TVU approach allowed the identification of significantly more ectopic adnexal masses than the TAU approach. The results of the present study demonstrate the increased efficacy of TVU over TAU in the direct identification of the adnexal mass associated with ectopic gestation.