Rat and human pancreatic islet cells contain a calcium ion independent phospholipase A2 activity selective for hydrolysis of arachidonate which is stimulated by adenosine triphosphate and is specifically localized to islet beta-cells

The recent demonstration that myocardial Ca(2+)-independent phospholipase A2 exists as a complex of catalytic and regulatory polypeptides that is modulated by ATP has suggested a novel mechanisms through which alterations in glycolytic flux can be coupled to the generation of eicosanoids which facilitate insulin secretion. To determine the potential relevance of this mechanism, we examined the kinetic characteristics, substrate specificities, and cellular locus of phospholipase A2 activity in pancreatic islets. Rat pancreatic islets contain a Ca(2+)-independent phospholipase A2 activity which is optimal at physiologic pH, preferentially hydrolyzes phospholipid substrates containing a vinyl ether linkage at the sn-1 position, and prefers arachidonic acid compared to oleic acid in the sn-2 position. Rat islet Ca(2+)-independent phospholipase A2 activity is inhibited by the mechanism-based inhibitor (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one and is stimulated by ATP. Purification of beta-cells from dispersed pancreatic islet cells by fluorescence-activated cell sorting demonstrated that beta-cells (but not non-beta-cells) contain Ca(2+)-independent, ATP-stimulated phospholipase A2 activity. Remarkably, clonal RIN-m5f insulinoma cells, which possess a defect in glucose-induced insulin secretion, contain a Ca(2+)-independent phospholipase A2 which is not modulated by alterations in ATP concentration. Collectively, these results and those of an accompanying paper [Ramanadham et al. (1993) Biochemistry (following paper in this issue)] implicate Ca(2+)-independent phospholipase A2 as a putative glucose sensor which can couple alterations in glycolytic metabolism to the generation of biologically active eicosanoids and thereby facilitate glucose-induced insulin secretion.     

Amino acid sequence of a four-iron-four-sulphur ferredoxin isolated from Bacillus stearothermophilus

A novel method of RNA fractionation based on a gradual release of the RNA molecules from ribonucleoprotein complexes has been used for the analysis of ribosomal and non-ribosomal complexes of rat liver cytoplasm. Adsorption of native ribonucleoproteins on a Celite column (occuring through only the protein moiety) followed by a consequent dissociation of RNP complexes brought about by various agents results in RNA fractionation in accordance with the tightness of the RNA-protein bonds. The cytoplasmic ribosomal and rapidly labelled non-ribosomal RNA species are separated into several fractions identified as 18S and 28S rRNA's, mRNA and messenger-like RNA. A relatively small fraction (about 10% of the total) of rRNA tenaciously bound to protein has been also revealed.     

Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure

BACKGROUND: This retrospective study assesses the outcomes and patterns of failure in patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site treated with combined surgery and postoperative radiotherapy. METHODS: One hundred thirty-six patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary source were treated postoperatively with radiotherapy at the University of Texas M. D. Anderson Cancer Center between the years 1968 and 1992. Stage distribution was: N1, 31 patients; N2a, 49; N2b, 25; N2c, 3; N3, 18; and Nx, 10. Thirty-nine patients had excisional biopsies only, 64 patients underwent modified neck dissections, and 33 had radical neck dissections. Extracapsular extension was present in 87 cases. Fifty-nine patients had multiple nodes involved. The median duration of follow-up for surviving patients was 8.7 years. RESULTS: Twelve patients, all with extracapsular nodal disease, developed regional relapse. The 5-year actuarial rates of regional relapse in patients with and without extracapsular nodal disease were 16% and 0%, respectively (p = .004). Nine patients (22%) with extracapsular disease and multiple nodes relapsed compared with three patients (7%) with extracapsular disease and a solitary node (p = .02). None of the patients treated with excisional biopsy and radiotherapy relapsed regionally. No statistically significant relationship between dose, treatment duration, time interval between surgery, and the start of radiotherapy and relapse was detected. The 2-, 5-, and 10-year actuarial disease-specific survival rates were 82%, 74%, and 68%, respectively. Fourteen patients developed cancers in head and neck mucosal sites; six of these cancers were located in unirradiated tissues. CONCLUSIONS: Relapse occurred infrequently in patients treated with excisional biopsies and postoperative radiotherapy. Extracapsular extension and multiple nodes were associated with worse regional control and disease-specific survival. These results appear consistent with those expected for patients with advanced neck disease and a known primary site, and the absence of a primary site should not exclude patients from studies aiming to improve outcomes in patients with extensive neck disease from a head and neck squamous cell cancer. We continue to recommend radiation to the necks and pharyngeal axis for patients suspected of having residual microscopic disease following surgery for squamous cell carcinoma metastatic to the neck from an unknown primary site.     

Bone tumors of the coracoid process of the scapula

Bone tumors of the coracoid process of the scapula are rare, and diagnosis and treatment often are delayed. The records of 18 patients with bone tumors of the coracoid process were reviewed. Histologic types included eight cases of ordinary chondrosarcoma, three cases of dedifferentiated chondrosarcoma, two cases of osteoid osteoma, and one case each of osteosarcoma, plasmacytoma, lymphoma, giant cell tumor, and aneurysmal bone cyst. All 18 patients had shoulder pain, and eight of them had been treated with steroid injections for nonneoplastic conditions. Radiologically, chondrosarcoma did not always show clear cortical destruction, and one giant cell tumor had features mimicking those of chondrosarcoma. Five patients (three with dedifferentiated chondrosarcoma, one with chondrosarcoma, one with plasmacytoma) died of disease. The coracoid process was the site with a markedly high proportion of chondrosarcomas. Bone tumors of the coracoid process may be difficult to detect on plain radiographs. In the patient with persistent shoulder pain unresponsive to the selected treatment, additional imaging studies should be considered to eliminate the possibility of a bone lesion.     

Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia

BACKGROUND: Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. PURPOSE: This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. METHODS: Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.     

Peripheral nerve regeneration: the effects of postoperative irradiation

Our purpose is to review recent data and provide a clinical opinion on the use of antibiotics to prevent preterm birth or related maternal-neonatal complications. A literature review and a synthesis of opinion are provided. During prenatal care, standard practices should be applied regarding Neisseria gonorrhoeae, Chlamydia trachomatis, and bacteriuria. In addition, screen for and treat bacterial vaginosis in patients at high risk for preterm birth but do not treat Ureaplasma urealyticum or group B streptococci genital colonization. With preterm labor and intact membranes, standard practices should be applied regarding group B streptococci prophylaxis. Do not give antibiotics routinely to prolong pregnancy, but in patients with bacterial vaginosis and Trichomonas vaginalis specific treatment should be given. With preterm premature rupture of membranes, standard practices should be applied regarding group B streptococci prophylaxis, but additional antibiotics should also be given to prolong pregnancies at 24 to 32 weeks' gestation. Reported adverse effects have been few to date. However, increased diligence is needed for resistant organisms. In selected clinical settings antibiotic therapy is now indicated to prolong pregnancy and prevent maternal-neonatal complications associated with preterm birth.     

Outcome of hypertension management in Asian Americans

BACKGROUND: Ethnic and/or racial differences in drug response to antihypertensive agents have been recognized, yet the prescribing practices and the information on efficacy of various agents rely mainly on the response of whites to drugs. OBJECTIVES: To assess the management of hypertension in Asian Americans and to compare it with an age- and sex-matched group of white patients with hypertension. METHODS: The patients' medical records were used as the primary source of information for the data collection. The observational period was a 12-month window and included 200 patients of Asian origin with hypertension and 196 white patients with hypertension whose medical records were randomly selected. RESULTS: The study describes the pattern of use of antihypertensive agents and the differences in response to antihypertensive agents between Asian Americans and whites. The preferred antihypertensive agents in both Asian and white patients included monotherapy with either calcium channel blockers or angiotensin-converting enzyme inhibitors. However, medication changes, dose reduction, and the experience of side effects were all significantly more frequently recorded in Asian patients than in white patients (P < .001, P < .008, and P < .002, respectively). CONCLUSIONS: These findings are supportive of some previous reports on ethnic differences in drug response to antihypertensive agents. The findings also point to the need for further prospective studies on the outcome of hypertension management in Asian American patients.     

Radiofrequency volumetric tissue reduction for treatment of turbinate hypertrophy: a pilot study

BACKGROUND: Apoptosis maintains cell homeostasis. Altered apoptosis is involved in carcinogenesis. It was our aim to investigate whether reflux esophagitis may alter apoptosis in the esophageal mucosa and whether antireflux surgery may restore normal apoptosis. METHODS: Apoptosis was studied preoperatively and postoperatively in esophageal biopsies of 39 patients with various grades of reflux esophagitis and in Barrett's mucosa using the TUNEL method. Biopsies were also taken from lesions of the squamous epithelium adjacent to the Barrett's mucosa. RESULTS: Apoptosis increased with the severity of esophagitis. Apoptosis was low in Barrett's epithelium. Squamous epithelium adjacent to Barrett's mucosa showed increased apoptosis. After surgery apoptosis decreased in squamous epithelium, and it remained low in Barrett's epithelium. CONCLUSIONS: Apoptosis in reflux esophagitis may be protective against increased proliferation. Low apoptosis following antireflux surgery indicates that surgery is effective to prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barrett's may promote carcinogenesis. This may not change following surgery.