Fine-needle aspiration cytology of sarcomatoid renal cell carcinoma: A morphologic and immunocytochemical study of 15 cases

Sarcomatoid renal cell carcinoma (SRCC), which accounts for 5% of all renal cell carcinomas (RCC), has a worse prognosis than conventional nonsarcomatoid RCC. making accurate diagnosis important. This study reports on the morphologic and immunocytochemical features of 15 cases of SRCC (9 primary tumors and 6 metastases) diagnosed by fine-needle aspiration (FNA) biopsy. All but three cases showed a dimorphic cell population consisting of varying proportions of a high-grade epithelial component, either clear or granular-cell type and a spindle cell (sarcomatoid) component, of either fibrosarcomatous, malignant fibrous histiocytoma (MFH), or unclassified types. The sarcomatoid component in the biphasic and monophasic tumors stained positively for cytokeratin in 12 of 14 (85%) cases, for vimentin in 10 of 11 (91 %) cases, and for muscle-specific action in 4 of 11 (36%) cases. Of note, the three cases that demonstrated a purely sarcomatoid morphology stained positively for cytokeratin. Unlike in studies performed on surgically resected specimens, neither the proportion of the sarcomatoid component nor the presence of necrosis had prognostic significance, the discrepancy most likely being related to the sampling. We conclude that SRCC, both primary and metastatic, can be accurately diagnosed by FNA when cytologic features are evaluated in conjunction with immunocytochemical findings.     

Clinical and cost-effectiveness of a new nurse-led continence service: a randomised controlled trial

BACKGROUND: Continence services in the UK have developed at different rates within differing care models, resulting in scattered and inconsistent services. Consequently, questions remain about the most cost-effective method of delivering these services. AIM: To evaluate the impact of a new service led by a continence nurse practitioner compared with existing primary/secondary care provision for people with urinary incontinence and storage symptoms. DESIGN OF STUDY: Randomised controlled trial with a 3- and 6-month follow-up in men and women (n = 3746) aged 40 years and over living in private households (intervention [n = 2958]; control [n = 788]). SETTING: Leicestershire and Rutland, UK. METHOD: The continence nurse practitioner intervention comprised a continence service provided by specially trained nurses delivering evidence-based interventions using predetermined care pathways. They delivered an 8-week primary intervention package that included advice on diet and fluids; bladder training; pelvic floor awareness and lifestyle advice. The standard care arm comprised access to existing primary care including GP and continence advisory services in the area. Outcome measures were recorded at 3 and 6 months post-randomisation. RESULTS: The percentage of individuals who improved (with at least one symptom alleviated) at 3 months was 59% in the intervention group compared with 48% in the standard care group (difference of 11%, 95% CI = 7 to 16; P<0.001) The percentage of people reporting no symptoms or 'cured' was 25% in the intervention group and 15% in the standard care group (difference of 10%, 95% CI = 6 to 13, P = 0.001). At 6 months the difference was maintained. There was a significant difference in impact scores between the two groups at 3 and 6 months. CONCLUSIONS: The continence nurse practitioner-led intervention reduced the symptoms of incontinence, frequency, urgency and nocturia at 3 and 6 months; impact was reduced; and satisfaction with the new service was high.     

Polyl-histidine

Poly-l-histidine (PHSTD) of molecular weight 26,000 induced the generation of large amounts of Superoxide (O ₂ ^– ) and hydrogen peroxide (H₂O₂) in human neutrophils (PMNs). Despite its low solubility at neutral pH, PHSTD was bound very rapidly to the PMN surfaces. Maximal generation of O ₂ ^– took place with 4–5 ×10^–6 M of PHSTD, starting after a lag of about 25 sec and proceeding for 15–17 min at a rate of 150 nmol/10⁷ PMNs/min, suggesting that this polycation is one of the most potent stimulators of O ₂ ^– generation known, PHSTD was found to be non-toxic for PMNs even at millimolar concentrations. Generation of O ₂ ^– by PHSTD depended on extracellular calcium; it was inhibited by calcium channel blockers and by trifluoperazine, and it triggered a sharp rise in intracellular calcium as determined by the Quin 2 fluorescence technique. The generation of both O ₂ ^– and H₂O₂ by PHSTD was partially inhibited by cytochalasin B or (CYB, CYE). On the other hand, CYB markedly enhanced the generation of both O ₂ ^– and H₂O₂ following stimulation of PMNs either by PHSTD, polyarginine, histone, or by antibody-opsonized group A streptococci. Electron microscopic analysis and NBT reduction tests revealed that both PHSTD and PHSTD-opsonized streptococci were avidly phagocytosed by PMNs. Since CYB totally inhibited internalization of both PHSTD and the PHSTD-opsonized streptococci, it was suggested that these agents stimulated oxygen radical generation mainly on the leukocyte surfaces. Complexes (CX) formed between PHSTD and polyanethole sulfonate (a strong polyanion) or between histone and the polyanion mimicked immune CX in their ability to trigger the generation of large amounts of O ₂ ^– which were inhibited by CYB. Generation of O ₂ ^– and chemiluminescence either by PHSTD or by PHSTD-opsonized streptococci were markedly inhibited by poly-l-glutamate, suggesting that PHSTD acted as a cationic agent which interacted via electrostatic forces with some negatively charged sites in the leukocyte membrane. Generation of H₂O₂ by PHSTD was also markedly inhibited by deoxyglucose, KCN, DASA, as well as by the lipoxygenase inhibitors nordihydroguaiaretic acid, phenidone, and propylgallate. On the other hand, cyclooxygenase inhibitors such as aspirin, indomethacin, and piroxicam were inactive, suggesting that arachidonic acid metabolism via lipoxygenase pathway might have been involved in the activation by PHSTD of the NADPH oxidase in PMNs. PHSTD may mimic the effects of antibodies both as an opsonin and as a potent stimulator of the respiratory burst in PMNs and may thus serve as a model for further study of leukocyte-bacteria interactions in infectious and inflammatory sites and of the pathogenicity of immune complexes.Supported by a research grant from Dr. S. M. Robbins of Cleveland, Ohio.     

Redistribution of Na-K-ATPase in the dystrophic rat retinal pigment epithelium

Summary Our previous studies have shown that a breakdown in tight junctions in the dystrophic retinal pigment epithelium (RPE) of Royal College of Surgeons' rats is accompanied by changes in intramembrane structure which suggest a redistribution of intramembrane particles. We have now investigated, using thep-nitrophenyl phosphate technique, the possibility that a specific membrane protein, Na-K-ATPase, is redistributed as tight junctions break down in the dystrophic RPE. In the normal RPE, Na-K-ATPase activity is restricted to the apical membrane. Junctional membranes and membranes around phagosomes are free of enzyme activity, suggesting a segregation of the transport enzyme from the Junctional and phagocytic membrane. In the dystrophic RPE, prior to changes in tight junctions, enzyme activity is restricted to the apical membrane. During the initial stages of Junctional breakdown, Junctional membranes and membranes around cytoplasmic inclusions are also labelled. As the breakdown progresses, Na-K-ATPase activity is often present laterally and basolaterally and is sometimes absent apically. Enzyme activity is seen basally only where RPE cells have detached from Bruch's membrane and are superimposed over each other. These changes suggest that Na-K-ATPase redistributes during junctional breakdown, but that attachments between the RPE and Bruch's membrane may restrict the redistribution. The apparent reduction of enzyme activity apically suggests that active transport across the dystrophic RPE may be reduced as the tight junctions break down.     

Monoclonal Antibodies to Trypanosoma cruzi Inhibit Motility and Nucleic Acid Synthesis of Culture Forms

Monoclonal antibodies were raised against the surface of epimastigotes and metacylic trypomastigotes of Trypanosoma cruzi, as shown by electron microscopy, agglutination, and immunofluorescence. The antibodies were stage specific but not strain specific. A deleterious effect of the antibodies on T. cruzi culture forms was shown by the drastic reduction of parasite motility and incorporation of nucleic acid precursors. Some fraction of the parasite population, however, was viable and replicated and infected mouse macrophages in culture. The antibodies were found to also mediate complement-induced lysis of culture forms of T. cruzi.     

No germline TP53 mutations detected in familial and bilateral testicular cancer

Mutations in the TP53 gene are considered to be among the most common genetic alterations in human cancers. Both somatic and germline mutations have been found. Using potymerase chain reaction (PCR), constant denaturant gel electrophoresis (CDGE), and denaturing gradient gel electrophoresis (DGGE), we have examined 32 patients with bilateral and familial germ cell tumors (GCT) and two patients with sporadic GCT for germline mutations within the conserved regions of the gene. In addition, 15 tumors were screened for somatic mutations and analyzed for loss of heterozygocity (LOH) at the TP53 locus. Twelve tumors were analyzed for expression of TP53 via immunohistochemistry. Neither germline nor somatic TP53 mutations were deteeted. LOH was observed in one of five informative cases. No tumors showed increased expression of TP53 protein. These results indicate that alterations in the TP53 gene are not important for the predisposition to and development of GCT. © 1993 Wiley-Liss, Inc.     

Agouti-related peptide-expressing neurons are mandatory for feeding

Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.