Long-term Survival From Muscleinvasive Bladder Cancer With Initial Presentation of Symptomatic Cerebellar Lesion: The Role of Selective Surgical Extirpation of the Primary and Metastatic Lesion

A 59-year-old man was diagnosed with urothelial carcinoma involving an isolated cerebellar metastasis after presenting to the emergency department for headache complaints. After selective surgical excision of the symptomatic brain lesion and delayed cystectomy due to intractable hematuria, he survived 11 years without evidence of recurrence or subsequent systemic chemotherapy. He eventually expired after delayed recurrence in the lung, supraclavicular lymph node, and brain. To our knowledge, this is the only case of prolonged survival from urothelial carcinoma after selective surgical extirpation of the primary and metastatic lesion without subsequent systemic chemotherapy.Key words: Bladder cancer, Cystectomy, Metastasis, Urothelial carcinomaUsually, brain metastasis of bladder urothelial carcinoma is associated with widespread systemic disease and/or multiple brain lesions. It is exceedingly rare to have bladder cancer metastasize to the brain without evidence of additional systemic manifestations.¹ As with other forms of distant urothelial carcinoma metastasis, brain metastasis is associated with poor prognosis, with survival often less than 14 months in those with solitary brain lesions.² We report an isolated bladder urothelial carcinoma metastasis to the cerebellum with an 11-year survival fol-lowing extirpative therapy of both the primary lesion and brain metastasis.     

Factors Influencing the Enhancement of the Infectivity of Poliovirus Ribonucleic Acid by Diethylaminoethyl-Dextran

The enhancement by diethylaminoethyl-dextran (DEAE-D) of the infectivity of poliovirus ribonucleic acid (RNA) for cell cultures was demonstrated by infective-center as well as by plaque assays, both in nonprimate (L) and primate cell systems (MK, HeLa, LLC-MK(2)). The sensitivity of plaque assays was greatly improved by using a tris (hydroxymethyl)aminomethane-buffered synthetic medium (basal medium Eagle) and freshly confluent cell monolayers. Enhancement of nucleic acid infectivity was directly dependent on the molecular weight of the DEAE-D. Two observations bearing on the action of DEAE-D appeared important: ribonuclease activity was reduced by DEAE-D, and cells pretreated with DEAE-D remained susceptible to infection with RNA in isotonic medium. Appreciable susceptibility of the treated cells persisted for at least 2 hr; the susceptible state could be reversed at will by an application of heparin. Enhancement of nucleic acid infectivity was independent of an effect of DEAE-D on intact virus and agar inhibitors.     

Purification and characterization of a phosphonic acid-containing glycoprotein from the cell membranes of Tetrahymena

A protein which contains 2-aminoethylphosphonic acid (AEP) has been isolated from the ciliate protozoan Tetrahymena thermophila. The protein contains about 30% carbohydrate with both N- and O-glycosidic linkages to the polypeptide and 8% AEP which is attached only to the O-linked glycoside. The amino group of AEP is unreactive to dansyl chloride as is the amino terminus of the protein. The polypeptide portion of the molecule, M_r 22,500, contains 22% glycine, 5.5% hydroxyproline, and is quite acidic. The phosphoprotein is found in the cell membranes. Its synthesis is inhibited by tunicamycin to the same extent which the antibiotic inhibits cell division.     

Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1

The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs) function as a trimer, mediating virus entry by promoting the fusion of the viral and target cell membranes. HIV-1 Env trimers induce membrane fusion through a pH-independent pathway driven by the interaction between an Env trimer and its cellular receptors, CD4 and CCR5/CXCR4. We studied viruses with mixed heterotrimers of wild-type and dominant-negative Envs to determine the number (T) of Env trimers required for HIV-1 entry. To our surprise, we found that a single Env trimer is capable of supporting HIV-1 entry; i.e., T = 1. A similar approach was applied to investigate the entry stoichiometry of envelope glycoproteins from amphotropic murine leukemia virus (A-MLV), avian sarcoma/leukosis virus type A (ASLV-A), and influenza A virus. When pseudotyped on HIV-1 virions, the A-MLV and ASLV-A Envs also exhibit a T = 1 entry stoichiometry. In contrast, eight to nine influenza A virus hemagglutinin trimers function cooperatively to achieve membrane fusion and virus entry, using a pH-dependent pathway. The different entry requirements for cooperativity among Env trimers for retroviruses and influenza A virus may influence viral strategies for replication and evasion of the immune system.     

Intermediate states of ribonuclease III in complex with double-stranded RNA

Bacterial ribonuclease III (RNase III) can affect RNA structure and gene expression in either of two ways: as a processing enzyme that cleaves double-stranded (ds) RNA, or as a binding protein that binds but does not cleave dsRNA. We previously proposed a model of the catalytic complex of RNase III with dsRNA based on three crystal structures, including the endonuclease domain of RNase III with and without bound metal ions and a dsRNA binding protein complexed with dsRNA. We also reported a noncatalytic assembly observed in the crystal structure of an RNase III mutant, which binds but does not cleave dsRNA, complexed with dsRNA. We hypothesize that the RNase III*dsRNA complex can exist in two functional forms, a catalytic complex and a noncatalytic assembly, and that in between the two forms there may be intermediate states. Here, we present four crystal structures of RNase III complexed with dsRNA, representing possible intermediates.     

E0771 and 4T1 murine breast cancer cells and interleukin 6 alter gene expression patterns but do not induce browning in cultured white adipocytes

Breast cancer remains a substantial clinical problem worldwide, and cancer-associated cachexia is a condition associated with poor prognosis in this and other malignancies. Adipose tissue is involved in the development and progression of cancer-associated cachexia, but its various roles and mechanisms of action are not completely defined, especially as it relates to breast cancer. Interleukin 6 has been implicated in several mechanisms contributing to increased breast cancer tumorigenesis, as well as a net-negative energy balance and cancer-associated cachexia via adipose tissue remodeling in other models of cancer; however, its potential role in breast cancer-associated white adipose browning has not been explored. In this study, we demonstrate localized white adipose tissue browning in a spontaneous model of murine mammary cancer. We then used an in vitro murine adipocyte culture system with the E0771 and 4T1 cell lines as models of breast cancer. We demonstrate that while the E0771 and 4T1 secretomes and cross-talk with white adipocytes alter white adipocyte mRNA expression, they do not directly induce white adipocyte browning. Additionally, we show that neither exogenous administration of interleukin 6 alone or with its soluble receptor directly induce white adipocyte browning. Together, these results demonstrate that neither the E0771 or 4T1 murine breast cancer cell lines, nor interleukin 6, directly cause browning of cultured white adipocytes. This suggests that their roles in adipose tissue remodeling are more complex and indirect in nature.     

A Ubiquitin-Binding Domain that Binds a Structural Fold Distinct from that of Ubiquitin

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Olfactory Cues Are Subordinate to Visual Stimuli in a Neotropical Generalist Weevil

The tropical root weevil Diaprepes abbreviatus is a major pest of multiple crops in the Caribbean Islands and has become a serious constraint to citrus production in the United States. Recent work has identified host and conspecific volatiles that mediate host- and mate-finding by D. abbreviatus. The interaction of light, color, and odors has not been studied in this species. The responses of male and female D. abbreviatus to narrow bandwidths of visible light emitted by LEDs offered alone and in combination with olfactory stimuli were studied in a specially-designed multiple choice arena combined with a locomotion compensator. Weevils were more attracted to wavelengths close to green and yellow compared with blue or ultraviolet, but preferred red and darkness over green. Additionally, dim green light was preferred over brighter green. Adult weevils were also attracted to the odor of its citrus host + conspecifics. However, the attractiveness of citrus + conspecific odors disappeared in the presence of a green light. Photic stimulation induced males but not females to increase their speed. In the presence of light emitted by LEDs, turning speed decreased and path straightness increased, indicating that weevils tended to walk less tortuously. Diaprepes abbreviatus showed a hierarchy between chemo- and photo-taxis in the series of experiments presented herein, where the presence of the green light abolished upwind anemotaxis elicited by the pheromone + host plant odor. Insight into the strong responses to visual stimuli of chemically stimulated insects may be provided when the amount of information supplied by vision and olfaction is compared, as the information transmission capacity of compound eyes is estimated to be several orders of magnitude higher compared with the olfactory system. Subordination of olfactory responses by photic stimuli should be considered in the design of strategies aimed at management of such insects.     

Reproduction of Mucohaemorrhagic Diarrhea and Colitis Indistinguishable from Swine Dysentery following Experimental Inoculation with “Brachyspira hampsonii” Strain 30446

Background

Mucohaemorrhagic diarrhea caused by Brachyspira hyodysenteriae, swine dysentery, is a severe production limiting disease of swine. Recently, pigs in western Canada with clinical signs indistinguishable from swine dysentery were observed. Despite the presence of spirochetes on fecal smears, recognized Brachyspira spp. including B. hyodysenteriae could not be identified. A phylogenetically distinct Brachyspira, called “B. hampsonii” strain 30446, however was isolated. The purpose of this study was to experimentally reproduce mucohaemorrhagic colitis and characterize strain 30446 shedding following inoculation.

Methods and Findings

Eighteen 13-week-old pigs were randomly assigned to inoculation (n = 12) or control (n = 6) groups in each of two trials. In trial 1, pigs were inoculated with a tissue homogenate collected from clinically affected field cases. In trial 2, pigs were inoculated with a pure broth culture of strain 30446. In both trials, mucohaemorrhagic diarrhea was significantly more common in inoculated pigs than controls, all of which remained healthy. In animals with mucohaemorrhagic diarrhea, significantly more spirochetes were observed on Gram stained fecal smears, and higher numbers of strain 30446 genome equivalents were detected by quantitative PCR (qPCR). Strain 30446 was cultured from colon and/or feces of all affected but no control animals at necropsy.

Conclusions

“Brachyspira hampsonii” strain 30446 causes mucohaemorrhagic diarrhea in pigs following a 4–9 day incubation period. Fecal shedding was detectable by day 4 post inoculation, and rarely preceded the onset of mucoid or haemorrhagic diarrhea by more than 2 days. Culture and 30446-specific qPCR are reliable methods of detection of this organism in feces and tissues of diarrheic pigs. The emergence of a novel Brachyspira spp., such as “B. hampsonii”, creates diagnostic challenges including higher risk of false negative diagnostic tests. We therefore recommend diagnostic laboratories routinely use Brachyspira culture, nox-based and species-specific PCR, and DNA sequencing to diagnose Brachyspira-associated colitis in pigs.