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J A Warneke

Publications and source records attributed to J A Warneke.

14 recordsLinked to original sources
PubMed2006

Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells.

The eukaryotic initiation factor 3f (eIF3f) is the p47 subunit of the multi-subunit eIF3 complex. eIF3 plays an important role in translation initiation. In the present study, we investigate the biological function of eIF3f in translation and apoptosis in tumor cells. We demonstrated for the first time that eIF3f is downregulated in most human tumors using a cancer profiling array and confirmed by real-time reverse transcription PCR in melanoma and pancreatic cancer. Overexpression of eIF3f inhibits cell proliferation and induces apoptosis in melanoma and pancreatic cancer cells. Silencing of eIF3f protects melanoma cells from apoptosis. We further investigated the biological function of eIF3f. In vitro translation studies indicate that eIF3f is a negative regulator of translation and that the region between amino acids 170 and 248 of eIF3f is required for its translation regulatory function. Ectopic expression of eIF3f inhibits translation and overall cellular protein synthesis. Ribosome profile and ribosomal RNA (rRNA) fragmentation assays revealed that eIF3f reduces ribosomes, which may be associated with rRNA degradation. We propose that eIF3f may play a role in ribosome degradation during apoptosis. These data provide critical insights into the cellular function of eIF3f and in linking translation initiation and apoptosis.

Apoptosis↗
PubMed2003

Investigating sun-damaged skin and actinic keratosis with optical coherence tomography: a pilot study.

Actinic Keratosis (AK) arises from sun-damaged skin and is the first clinical manifestation in the multistep process of skin carcinogenesis to invasive squamous cell carcinoma. Thus, it is an ideal target for chemopreventive efforts. Noninvasive measures of AK severity are needed to assess the efficacy of chemoprevention agents. We performed a pilot study on 20 participants to investigate the OCT appearance of sun-protected skin of the upper inner arm as well as sun-damaged skin and early AKs of the dorsal forearms, and to determine if features or quantitative measures in Optical Coherence Tomography (OCT) images could be used to reliably differentiate between these categories. OCT images of upper inner arm (normal appearing skin) showed skin layers and features (stratum corneum, epidermis, dermis, blood vessels) seen in previous studies; additionally in this participant group the subcutaneous fat layer was usually identified. Sun-damaged skin was characterized by increased signal in the epidermis and rapid attenuation of light. AKs were diverse in appearance but frequently characterized by high surface reflection, the presence of a low-signal band in the stratum corneum, and heterogeneous appearance in the epidermis/dermis. Significant differences were found between skin categories using measures of stratum corneum and epidermal/dermal depths and intensities. The presence of a dark band in the stratum corneum was 79% sensitive and 100% specific for AK. This study indicates that OCT holds promise as a useful technique for identifying and characterizing AKs and monitoring their response to chemoprevention agents.

Adult↗
PubMed2000

Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine.

Alpha-2-(Difluoromethyl)-dl-ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to suppress skin carcinogenesis in murine models after oral or topical administration. We designed a randomized, placebo-controlled study using a topical hydrophilic ointment formulation with or without 10% (w/w) DFMO. Forty-eight participants with moderate-severe actinic keratoses (AKs) on their forearms (i.e., at least 10 well-circumscribed lesions on the lateral surface) completed a 1-month run-in on placebo ointment. Before randomization, all lateral forearm AKs were circled, counted, photographed, and skin biopsies were obtained for DFMO and polyamine levels. Then participants were randomized to receive DFMO ointment on the right versus the left forearm and placebo hydrophilic ointment on the contralateral forearm twice daily for 6 months. DFMO was not detected in the blood of any subject, and there were no systemic toxicities. None of a subsample of 17 placebo forearms had measurable concentrations of DFMO, whereas 13 of the corresponding DFMO-treated forearms had high DFMO skin levels. As compared with placebo, the 6-month DFMO treatment caused a 23.5% reduction in the number of AKs (P = 0.001) as well as significant suppression of AK biopsy spermidine levels (26%; P = 0.04). Seven of the 48 (14.6%) participants experienced severe (2; 4.2%) or moderate (5; 10.4%) inflammatory reactions on their DFMO-treated arms which required dosing modification. Topical DFMO for 6 months can reduce the number of AK lesions and skin spermidine concentrations in high-risk participants and deserves additional study as a skin cancer chemopreventive agent.

Aged↗
PubMed1999

Relationship of p53 mutations to epidermal cell proliferation and apoptosis in human UV-induced skin carcinogenesis.

Human skin is continually subjected to UV-irradiation with the p53 gene playing a pivotal role in repair of UV-induced DNA damage and apoptosis. Consequently, p53 alterations are early events in human UV-induced skin carcinogenesis. We studied 13 squamous cell carcinomas (SCC), 16 actinic keratoses (AK), 13 samples adjacent to an AK (chronically sun-damaged), and 14 normal-appearing skin samples for p53 mutation, p53 immunostaining (IHC), apoptosis (in situ TUNEL and morphology), and proliferation (PCNA). The frequency of p53 mutation increased from 14% in normal skin, to 38.5% in sun-damaged skin, 63% in AK, and 54% in SCC. p53 IHC increased similarly. Apoptosis (TUNEL) increased from 0.06 +/- 0.02%, to 0.1 +/- 0.2, 0.3 +/- 0.3, and 0.4 +/- 0.3 in normal skin, sun-damaged skin, AK, and SCC, respectively. Apoptosis was strongly correlated with proliferation (i.e., TUNEL and PCNA, r = 0.7, P < 0.0001), and proliferation was significantly increased in the progression from normal skin to SCC. Bax was significantly increased in SCC compared to AK. These data imply that apoptosis in samples with a high frequency of p53 mutation may not necessarily be p53-dependent. We suggest that there is a mechanism for apoptosis in response to increased cellular proliferation that is p53-independent.

Aged↗
PubMed1995

Aspiration pneumonia following surgically placed feeding tubes.

BACKGROUND: The enteral route is preferred in surgical patients requiring nutritional support; however, controversy surrounds the choice of location of feeding tube placement. Although jejunostomy has been commonly accepted as superior to gastrostomy for long-term nutritional support because of an assumed lower risk of aspiration pneumonia, recent studies suggest that reevaluation of common practices of surgical tube placement is warranted. PATIENTS AND METHODS: We conducted a retrospective chart review of gastrostomy and jejunostomy procedures from 1986 to 1993. Demographic information and complications related to the procedure were reviewed. Aspiration pneumonia was defined as respiratory symptoms, leukocytosis, and infiltrate on chest radiograph. RESULTS: Sixty-nine gastrostomies and 86 jejunostomies were performed during the study period. Six patients were diagnosed with aspiration pneumonia; 2 cases of which occurred with jejunostomy and 4 cases occurred with gastrostomy (P = not significant). CONCLUSIONS: There was no difference in rates of pulmonary aspiration or other complications between gastrostomy and jejunostomy. We suggest that when a surgically placed feeding tube is required, the determination of appropriate procedure be based on clinical factors such as the technical difficulty of the operation or long-term feeding goals.

Enteral Nutrition↗
PubMed1995

Abdominal wall hernias in patients with abdominal aortic aneurysmal versus aortoiliac occlusive disease.

BACKGROUND: This study was undertaken to determine the incidence of ventral incisional hernias (VIHs) and inguinal hernias (IHs) in patients with abdominal aortic aneurysmal (AAA) versus those with aortoiliac occlusive disease (AIOD). PATIENTS AND METHODS: The medical records of 193 patients (128 with AAA and 65 with AIOD) who had undergone elective aortic reconstruction were reviewed to determine the number and location of abdominal wall hernias (AWHs). RESULTS: Forty-one AWHs (28 IHs and 13 VIHs) were detected in patients with AAA compared to 13 (11 IHs and 2 VIHs) in patients with AIOD. There was a significantly greater incidence of VIHs in patients with AAA versus patients with AIOD (10% versus 3%, P < 0.05) and recurrent AWHs (28% versus 19%, P < 0.01), but not of IHs (22% versus 17%). CONCLUSION: Patients with AAA have a higher incidence of VIHs and recurrent AWHs--without a corresponding increase in patient-related risk factors--than patients without aneurysm, suggesting that as yet unidentified etiologic factors may contribute to the development of AWHs in these patients.

Aorta, Abdominal↗
PubMed1994

Stereotactic fine-needle aspiration cytology of nonpalpable breast lesions: an analysis of 258 consecutive aspirates.

BACKGROUND: The role of stereotactic fine-needle aspiration cytology (SFNAC) in the diagnosis of nonpalpable breast lesions is poorly defined. PATIENTS AND METHODS: Data were prospectively collected from 225 consecutive patients with nonpalpable breast lesions who had aspiration cytology followed by immediate surgical excision. RESULTS: Between 1988 and 1993, 258 such procedures were performed. The results of 84 (33%) were interpreted as benign, 84 (33%) as atypical, 28 (11%) as suspicious for malignancy, and 49 (19%) as malignant. In all, 88 (34%) surgical specimens were malignant. SFNAC had an 80% sensitivity, a 96% specificity, a 91% positive predictive value, and an 89% negative predictive value. There were 18 false-negative and 7 false-positive aspirates. CONCLUSIONS: SFNAC for diagnosing nonpalpable breast lesions is moderately sensitive and highly specific, and has a high positive and negative predictive value. In conjunction with mammography and clinical assessment, the procedure is useful for determining which patients with nonpalpable breast lesions may require surgical biopsy.

Adult↗
PubMed1994

Contraindications and complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is a commonly performed procedure for the removal of symptomatic gallstones. Compared with open cholecystectomy, laparoscopic cholecystectomy is associated with less postoperative pain, earlier discharge from the hospital and a more rapid recovery. However, there are specific contraindications to the procedure, including empyema of the gallbladder, gangrenous cholecystitis, coagulopathy, portal hypertension and peritonitis. Complications from laparoscopic cholecystectomy include common duct injury, bleeding, bile leakage and wound infection. An understanding of these issues allows the family physician to more appropriately select patients for laparoscopic removal of the gallbladder.

Cholecystectomy, Laparoscopic↗
PubMed1992

Resection of lung metastases from soft-tissue sarcomas. A multivariate analysis.

From 1970 through 1986, 78 patients underwent 162 thoracotomies for removal of lung metastases from soft-tissue sarcomas. A multivariate analysis showed that the presence of a local recurrence, an incomplete pulmonary resection, and a shorter disease-free interval were poor prognostic factors. Patients who underwent multiple thoracotomies survived longer from the time of initial thoracotomy. The histologic type of sarcoma and the number of metastases resected showed no statistical significance. The median survival of the 61 patients who had a complete resection was 21 months. Patients with five or fewer metastases resected had an overall 5-year survival of 22% compared with 21% for patients who had six or more metastases resected. However, patients with five or fewer metastases showed a trend toward a higher 10-year disease-free survival. A complete resection of pulmonary metastases from soft-tissue sarcoma can prolong survival even if multiple metastases are present, although patients with fewer metastases may have a longer disease-free survival.

Adolescent↗
PubMed1989

Subhepatic appendicitis.

Intestinal malrotation is a developmental anomaly that occasionally causes an unusual array of symptoms in adults. The delay in diagnosis that is common in patients with malrotation frequently results in a ruptured appendix. Appendicitis should be considered when characteristic signs and symptoms are present, even if the location of abdominal pain is atypical.

Abscess↗
PubMed1987

Role of surgical treatment in the management of complications of the gastrointestinal tract in patients with leukemia.

The clinical course of patients with leukemia, specifically after treatment, is complicated by opportunistic infections, often derived from the gastrointestinal tract. Four hundred and thirty-eight patients with leukemia were treated at the Arizona Health Sciences Center from 1976 to 1985. Fifty-five (13 per cent) had 60 major gastrointestinal complications develop. Thirty-seven were treated medically with a mortality rate of 51 per cent, while 18 who were treated surgically had a 17 per cent mortality rate. These infections usually occur during induction or consolidation chemotherapy. Positive blood cultures and white blood cell counts of less than 2,500 per millimeter are a frequent occurrence. The most common complications of the gastrointestinal tract are enterocolitis, perirectal sepsis and bleeding. Because of the combined defects in phagocytosis (neutropenia), antibody production and cell mediated immunity, opportunistic infections (such as viral, fungal, parasitic or bacterial) are frequent and often lethal, despite routine antibiotic coverage. A protocol to identify a subset of patients with septic leukemia who may require emergency surgical treatment is vital since death in this group is most commonly from undiagnosed sepsis or progression of hematologic defects. This protocol should include repeated physical examinations, daily roentgenograms of the abdomen, liberal use of endoscopy, contrast roentgenography and computed tomography (CT) or ultrasound. Extensive surgical procedures can be safely carried out in patients with leukemia. The diagnosis of leukemia should not be a deterrent to emergency surgical exploration.

Adolescent↗
PubMed1984

The mechanism of hepatoprotection by epsilon aminocaproic acid and putrescine.

Hepatic neutral serine proteases (including plasminogen activator) and ornithine decarboxylase (ODC) are induced by the hepatotoxin galactosamine (GALN). We examined the hepatoprotection conferred by epsilon-aminocaproic acid (EACA), a fibrinolytic inhibitor, putrescine (PUTR), the polyamine generated from ornithine by ODC, and alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC. GALN, 450 mg/kg, was administered intraperitoneally to Wistar-Lewis rats (group I). Groups II, III, and IV were also given EACA (80 mg/kg), PUTR (0.3 mmol/kg), or DFMO (0.3 mmol/kg), respectively, 1 hour before and 3, 7, and 12 hours after GALN. Rats were killed 2 hours after an intraperitoneal dose of 3H-thymidine was administered, 30 or 45 hours after GALN. EACA and PUTR were effective protectants against necrosis as judged by enzymes and histologic findings. Neither increased thymidine incorporation above the levels seen with GALN only. DFMO offered no protection even though thymidine incorporation at 45 hours was increased. Both EACA and PUTR, which have similar chemical structures, possessed significant antiprotease activity in vitro, suggesting that they act by inhibiting toxin-induced neutral serine protease activity and not by accelerating regeneration.

Aminocaproates↗