Using polymerase chain reaction to human papillomavirus in oral and pharyngolaryngeal carcinomas

Purpose: Increasingly, evidence has shown that human papillomavirus (HPV) plays a role in the induction of certain carcinomas. The presence of HPV sequences in 56 previously untreated oral and pharyngolaryngeal carcinomas was examined by the polymerase chain reaction (PCR).Materials and Methods: After DNA extraction, samples underwent 40 replication cycles with specific oligonucleotide primers corresponding to sequences from the E6 open-reading frame of HPV-6b, HPV-16, and HPV-18. To determine the E6 genomic integration, positive samples were processed with specific primers for the corresponding HPV L1 genes. Genomic HPV DNA cloned into PBR 322 was used as positive control.Results: HPV E6 DNA of the 6b and 16 types was detected in 14 patients (25%). The L1 gene was not present.Conclusion: Detected HPV E6 DNA might be integrated into the cell genome in the positive cases as indicated by the absence of the L1 gene-coding for the viral capside. Histological and clinical parameters, such as tumor location, degree of differentiation, stage, recurrence, and survival rates, were unrelated to the presence of HPV.     

Kaposi's sarcoma tumor cells preferentially express Bcl-xL.

Several recently identified proteins such as Bcl-2 and Bcl-x have been found to regulate programmed cell death (i.e., apoptosis). In this report, we examined the levels of expression of proteins that can either prevent apoptosis (i.e., Bcl-2 or the long form of Bcl-x, designated Bcl-x1) or promote apoptosis (i.e., Bax or the short form of Bcl-x, designated Bcl-xs) in proliferating benign and malignant endothelial cells (ECs). In normal skin with quiescent ECs, no detection by immunohistochemical staining was observed for Bcl-xL, Bcl-xs, or Bcl-2. However, in diseased skin samples that feature a prominent angiogenic response such as in psoriasis or pyogenic granulomas, the proliferating ECs markedly overexpressed Bcl-xL, with little to no Bcl-2. In an acquired-immune-deficiency-syndrome-related neoplasm, Kaposi's sarcoma, the spindle-shaped tumor cells also overexpressed Bcl-xL compared with Bcl-2. These in vivo studies were extended in vitro using cultured ECs and Kaposi's sarcoma tumor cells that were examined by flow cytometry and immunoblot analysis. Both cultured ECs and Kaposi's sarcoma tumor cells express significantly higher levels of Bcl-xL than Bcl-2. Such overexpression of cell survival gene products may contribute to prolonging the longevity of EC-derived cells in several different benign and neoplastic skin disorders that are characterized by a prominent angiogenic tissue response.     

Trimethoprim-sulfamethoxazole versus pentamidine for Pneumocystis carinii pneumonia in AIDS patients: results of a large prospective randomized treatment trial.

OBJECTIVE: To compare the clinical efficacy and safety of trimethoprim-sulfamethoxazole (TMP-SMX) with pentamidine in the therapy of Pneumocystis carinii pneumonia (PCP) in patients with AIDS. PATIENTS, PARTICIPANTS: TMP-SMX (TMP, 20 mg/kg/day plus SMX, 100 mg/kg/day) was compared with pentamidine (4 mg/kg/day), both administered intravenously for 21 days in a prospective randomized treatment trial of 163 patients diagnosed with PCP between November 1984 and May 1988. RESULTS: Ninety-two evaluable patients received TMP-SMX as initial therapy; 68 received pentamidine. Failure to complete therapy was common. Of those receiving TMP-SMX, 39 (42%) required change in therapy because of failure to respond, and an additional 31 (34%) because of drug toxicity. This compared with 27 (40%; P = 0.733) and 17 (25%; P = 0.235), respectively, in the pentamidine-treated group. The overall survival rates were similar in the two groups, 62 out of 92 (67%) initially administered TMP-SMX versus 50 out of 68 (74%) initially administered pentamidine (P = 0.402). The survival rates for patients requiring a change in therapy because of failure to respond was 46% (18 out of 39) for the TMP-SMX group compared with 56% (15 out of 27) for the pentamidine group. When a change in therapy was made because of toxicity, survival rates were 97% (30 out of 31) for those receiving TMP-SMX versus 94% (16 out of 17) for those receiving pentamidine. CONCLUSION: TMP-SMX and pentamidine are of equivalent efficacy as initial therapies for PCP in patients with AIDS.     

Angiotensin II receptor expression and inhibition in the chronically hypoxic rat lung.

1. Angiotensin II (AII) binding density and the effect of chronic AII receptor blockade were examined in the rat model of hypoxia-induced pulmonary hypertension. 2. [125I]-[Sar1,Ile2]AII binding capacity was increased in lung membranes from rats exposed to hypoxia (10% fractional inspired O2) for 7 days compared to normal rats (Bmax 108 +/- 12 vs 77 +/- 3 fmol mg-1 protein; P < 0.05), with no significant change in dissociation constant. Competition with specific AII receptor subtype antagonists demonstrated that AT1 is the predominant subtype in both normal and hypoxic lung. 3. Rats treated intravenously with the AT1 antagonist, GR138950C, 1 mg kg-1 day-1 rather than saline alone during 7 days of exposure to hypoxia developed less pulmonary hypertension (pulmonary arterial pressure: 21.3 +/- 1.7 vs 28.3 +/- 1.1 mmHg; P < 0.05), right ventricular hypertrophy (right/left ventricle weight ratio: 0.35 +/- 0.01 vs 0.45 +/- 0.01; P < 0.05) and pulmonary artery remodelling (abundance of thick-walled pulmonary vessels: 9.6 +/- 1.4% vs 20.1 +/- 0.9%; P < 0.05). 4. The reduction in cardiac hypertrophy and pulmonary remodelling with the AT1 antagonist was greater than that achieved by a dose of sodium nitroprusside (SNP) that produced a comparable attenuation of the rise in pulmonary arterial pressure during hypoxia. 5. The data suggest that AII, via the AT1 receptor, has a role in the early pathogenesis of hypoxia-induced pulmonary hypertension in the rat.     

Ultrastructural immunocytochemical studies of the localization and distribution of somatostatin, calcitonin, calcitonin gene-related peptide, and substance P in the bat thyroid follicle

Electron microscope immunocytochemistry was used to determine the intracellular localization and distribution among follicular elements of four peptides: calcitonin, somatostatin, calcitonin gene-related peptide (CGRP), and substance P in the thyroid glands of bats captured in the prehibernation phase of their annual life cycle. Previous studies have shown that this period of the hibernation-activity cycle is characterized by the accumulation and storage of secretory granules in parafollicular cells. Sites of binding of primary antisera to each of the four peptides were identified by means of affinity-purified secondary antisera directly coupled to colloidal gold particles. Calcitonin and somatostatin immunoreactivities were found in all parafollicular cells examined and in every secretory granule within these cells. CGRP was also found in all parafollicular cells examined (n = 75) but only in about half of their secretory granules. In contrast to these peptides, substance P immunoreactivity was not found in any parafollicular cells, but was localized exclusively in nerve endings within the basement membrane of the follicle.     

Fine-needle aspiration biopsy of the pancreas: a study of 61 cases

Eighty-six fine-needle aspirates (FNAs) of pancreas from 74 patients were reviewed. Histological confirmation or clinical follow-up of the final diagnosis was available in 61 aspirates from 49 patients. Of 42 proven malignant cases, FNAs were diagnosed as positive in 21 (50%), suspicious in 4 (9.5%), negative in 12 (28.6%), and unsatisfactory in 5 (11.9%). Of 19 proven benign cases, FNAs were diagnosed as negative in 15 (78.9%) and unsatisfactory in 4 (21%). This resulted in a 50% sensitivity, a 100% specificity, a diagnostic efficiency of 59%, a predictive value of a positive test of 100%, and a predictive value of a negative test of 55.6%. Thirty-six primary pancreatic adenocarcinomas and six metastatic tumors to the pancreas were encountered. Benign cases were attributed to anatomical pancreatic variants, acute pancreatitis, abscess, chronic pancreatitis, and pseudocysts. Pancreatic FNA was safe, accurate, and relatively inexpensive, but it was relatively insensitive in the diagnosis of malignancy.     

Localization of a highly specific neuronal protein,serotonin binding protein,in thyroid parafollicular cells

A highly specific serotonin binding protein (SBP) has been found in serotonergic neurons in both brain and gut. This protein has an extremely high affinity for serotonin and may be a storage protein. Serotonin is found in many endocrine cells, including parafollicular cells of the sheep thyroid, as well as in neurons. SBP is also present in sheep thyroid. The present study was done to localize the protein in the gland. Thyroid glands were divided into five segments. Concentrations of serotonin and SBP, as well as parafollicular cell volume were measured in each. Serotonin was assayed by enzymatic conversion to melatonin using tritiated S-adenosylmethionine. SBP was assayed by molecular sieve chromatography on sephadex G-50. The relative volume of parafollicular cells was obtained by stereological analysis of electron micrographs. Experiments were also done to demonstrate these cells by histofluorescence and radioautography following incubation with tritiated 5-hydroxytryptophan. Good correlations were found between serotonin and SBP concentrations, and parafollicular cell volume. These peaked in the rostro-central portion of the gland and were minimal at the poles. We conclude that thyroid SBP is probably localized in parafollicular cells.     

Differential neuronal survival in the avian ciliary ganglion after chronic acetylcholine receptor blockade

We have described in the preceding 2 papers the development of the pharmacological and contractile properties of all targets of the ciliary ganglion: the iris and ciliary body (Pilar et al., 1987), and the choroidal coat (Meriney and Pilar, 1987). In this paper, we examine the chronic effects of ACh receptor (AChR) blockade on ciliary ganglion neuron survival. Nicotinic or muscarinic AChR blockers were administered daily to developing chicken embryos during the normal neuronal death period in the ciliary ganglion. The effects of the blockers on ganglionic and neuromuscular transmission were assessed, and neuronal survival was assayed by counting both the total number of ganglion neurons and the selectively HRP-labeled ciliary neurons after the normal neuronal death period. Blockade of ganglionic transmission decreases survival in both populations of neurons. Blockade of neuromuscular muscular transmission increases survival in the ciliary population, which innervates the striated iris and ciliary body muscle. In contrast, blockade of synaptic activity has various influences on the survival of the choroid population, which innervates the smooth muscle of the choroid coat. Smooth muscle muscarinic receptor blockade with atropine does not influence survival. At higher doses (which block ganglionic transmission), atropine decreases choroid survival. Survival of the choroid population is increased by nicotinic blockade with 75 micrograms alpha bungarotoxin (alpha BTX), but decreased by 12.5 micrograms alpha BTX. Two main conclusions arise from these studies. Activation of postsynaptic AChRs in both the ganglion and the periphery are important in the regulation of neuronal survival. These effects usually occur in opposite directions: Blockade of ganglionic transmission decreases neuronal survival, while paralysis of neuromuscular transmission increases neuronal survival. This embodies the "balance" hypothesis (Cunningham, 1982) for neuronal survival, which states that motoneurons must balance afferent and target interactions during a critical period after synapses are formed in both regions. The present observations support this hypothesis. However, although both ciliary and choroid neurons have been shown to depend on the presence of the periphery for survival, target muscle paralysis via AChR blockade rescues the ciliary neurons but does not influence survival in the choroid population. Target-dependent regulation of choroid neuron survival during the normal neuronal death period is clearly different from the regulation of ciliary neuron survival.     

Radiographic evaluation of the cocaine smuggler

A retrospective analysis of the plain abdominal films of 53 "body packer" drug smugglers was performed to ascertain the importance of radiographic studies in the diagnosis and management of these patients. Eighty-nine percent had studies diagnostic for foreign body ingestion. Multiple, well-defined, homogeneous oval or oblong densities, especially if surrounded by a crescent of air (double-condom sign), are key findings. If these densities were found in the proximal ascending colon or upper gastrointestinal tract, the diagnosis was almost assured. Six percent of patients exhibited complications suggested on serial radiographs, proving the necessity for follow-up studies until complete expulsion or removal of the foreign body. Radiologic evaluation is essential in the diagnosis and management of the cocaine smuggler.