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Biomedical subjects

C House

Publications and source records attributed to C House.

At least 19 recordsLinked to original sources
PubMed2006

The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study.

Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies.

Adult↗
PubMed2006

Diagnosing pancreatic cancer: the role of percutaneous biopsy and CT.

AIMS: To determine the sensitivity and complications of percutaneous biopsy of pancreatic masses, and whether typical computed tomography (CT) features of adenocarcinoma can reliably predict this diagnosis. MATERIALS AND METHODS: A 5 year retrospective analysis of percutaneous core biopsies of pancreatic masses and their CT features was undertaken. Data were retrieved from surgical/pathology databases; medical records and CT reports and images. RESULTS: Three hundred and three patients underwent 372 biopsies; 56 of 87 patients had repeat biopsies. Malignancy was diagnosed in 276 patients, with ductal adenocarcinoma in 259 (85%). Final sensitivity of percutaneous biopsy for diagnosing pancreatic neoplasms was 90%; for repeat biopsy it was 87%. Complications occurred in 17 (4.6%) patients, in three of whom the complications were major (1%): one abscess, one duodenal perforation, one large retroperitoneal bleed. CT features typical of ductal adenocarcinoma were: hypovascular pancreatic mass with bile and/or pancreatic duct dilatation. Atypical CT features were: isodense or hypervascular mass, calcification, non-dilated ducts, cystic change, and extensive lymphadenopathy. Defining typical CT features of adenocarcinoma as true-positives, CT had a sensitivity of 68%, specificity of 95%, positive predictive value (PPV) of 98%, and negative predictive value of 41% for diagnosing pancreatic adenocarcinoma. CONCLUSION: Final sensitivity of percutaneous biopsy for establishing the diagnosis was 90%. CT features typical of pancreatic adenocarcinoma had high specificity and PPV. On some occasions, especially in frail patients with co-morbidity, it might be reasonable to assume a diagnosis of pancreatic cancer if CT features are typical, and biopsy only if CT shows atypical features.

Adenocarcinoma↗
PubMed2001

Constitutive c-Myb amino-terminal phosphorylation and DNA binding activity uncoupled during entry and passage through the cell cycle.

The c-myb gene encodes a transcription factor that is central to hematopoietic cell growth. Phosphorylation of c-Myb by casein kinase 2 (CK2) at serines 11 and 12 has been variously implicated in the regulation of DNA binding. However, it is unclear when c-Myb phosphorylation at serines 11 and 12 occurs during the cell cycle and how this is regulated. We generated specific antisera that recognize phosphoserines 11 and 12 of c-Myb. C-Myb protein levels, extent of CK2 phosphorylation and DNA binding were then monitored following mitogenic stimulus and passage through the cell cycle in normal peripheral T-cells and the T leukemia cell line CCRF-CEM. We found that endogenous c-Myb is constitutively phosphorylated at serines 11 and 12. The amount of phosphorylated c-Myb correlates with DNA binding activity in cycling CEM cells but not upon entry of T-cells into the cell cycle. Exogenous expression of c-Myb with substitutions of serines 11 and 12 with glutamic acid or alanine had no effect on the transactivation of a c-Myb responsive reporter. These data strongly suggest that c-Myb is constitutively phosphorylated on serines 11 and 12 by CK2 or like activity and is not regulated during the cell cycle.

Casein Kinase II↗
PubMed2000

Self-pluralism: assessment and relations to adjustment, life changes, and age.

Individuals differ in the degree to which they see themselves as behaving and feeling similarly or differently in different situations and at different times. This dimension of the self-concept, which is conceived to extend from strong constancy of the self-concept at one extreme to marked variability at the opposite pole, is designated as self-pluralism. An inventory for the assessment of degree of self-pluralism--the Self-Pluralism Scale (SPS)--is presented, and the correlations of this scale with other relevant personality measures are reported. Several studies utilizing the SPS are presented. The results indicate that self-pluralism is negatively related to psychological adjustment, positively related to long-term real-life variability, and negatively related to age.

Age Factors↗
PubMed2000

Epizootic vesicular disease in captive California sea lions.

An epizootic of vesicular disease occurred in a group of semi-domesticated California sea lions (Zalophus californianus) during the months of April and May 1997. Ten castrated mature male sea lions, ages 12 to 19 yr, were housed in three adjacent open-ocean net enclosures in San Diego Bay (California, USA). Four animals (40%) developed oral and extremity vesicles, anorexia, and were reluctant to perform learned behaviors. One animal developed vesicles but maintained a normal appetite and behavior. The remaining animals showed no clinical signs of infection. Virus (designated FADDL 7005) was isolated from four of the five animals that developed vesicles. Serum antibody titers to FADDL 7005, a previously untyped calicivirus, were demonstrated in animals that showed any combination of clinical signs and in two animals that did not show any clinical signs. No virus was isolated from five fecal samples collected from four of the group animals. Clinical signs lasted 4 to 20 days in affected animals. All affected animals recovered from infection. An experimental swine was inoculated with FADDL 7005 and developed vesicular disease, which was transmitted to another experimental swine upon contact. It is proposed that FADDL 7005 is a new San Miguel sea lion virus.

Animals↗
PubMed2000

A morbillivirus antibody survey of Atlantic walrus, narwhal and beluga in Canada.

A longitudinal serologic survey was conducted for morbillivirus antibodies in Atlantic walruses (Odobenus rosmarus rosmarus), narwhal (Monodon monoceros), and beluga (Delphinapterus leucas) from the Northwest Territories, Nunavut and the St. Lawrence estuary (Canada). Sixty-five of 131 (50%) walruses sampled between 1984 and 1993 had detectable morbillivirus neutralizing antibodies. Positive walrus were identified from four of five Arctic sampling sites, to as far back as 1984. Prevalence of morbillivirus neutralizing antibodies in walruses from Foxe Basin ranged from a high of 76% (n = 21) in 1993 to a low of 22% (n = 28) in 1984. Limitations in sample acquisition may have produced underestimates for the 1984 data. There are no reports of clinical morbillivirus infection in walruses. Our results are consistent with the hypothesis that a morbillivirus similar or identical to phocine distemper virus (PDV) has circulated among walrus populations of the eastern Canadian Arctic, at least since the early 1980s. No narwhal (n = 79) or beluga (n = 445) from Arctic waters were identified as having antibodies to dolphin morbilivirus (DMV) above the threshold serum dilution of log2 4. Also, none of the beach-cast cetacean carcasses (n = 28) from the Gulf of St. Lawrence and the St. Lawrence estuary were positive for antibodies to DMV. This indicates that Gulf of St. Lawrence, St. Lawrence estuary, and Arctic cetaceans either have not been exposed to DMV or an antigenically related morbillivirus, or are not susceptible to infection.

Animals↗
PubMed1999

Brucella-induced abortions and infection in bottlenose dolphins (Tursiops truncatus).

Two bottlenose dolphins (Tursiops truncatus) aborted fetuses that died as a result of Brucella infection. Brucella placentitis occurred in both cases. Infected placenta and vaginal/uterine fluids may transmit Brucella species to other cetaceans. In a third case, an identical organism was cultured from lung necropsy tissue of an adult female T. truncatus. Microbiology, specific polymerase chain reaction, and pulsed-field gel electrophoresis results supported the designation of an additional genomic group(s), Brucella delphini, for isolates adapted to T. truncatus. Current serologic diagnostic tests reliable for known Brucella species are unreliable in detecting dolphin brucellosis. Our findings, together with previous reports, suggest that dolphin brucellosis is a naturally occurring disease that can adversely impact reproduction in cetaceans. The zoonotic significance of cetacean brucellosis is unknown, although the disease has not been reported in people who have frequent contact with dolphins. Further studies on the zoonotic aspects, distribution, prevalence, virulence, and impact of this disease in cetaceans and other marine mammal species are needed.

Abortion, Veterinary↗
PubMed1998

Viral serologic survey of bowhead whales in Alaska.

Serum samples from 21 of 36 Eskimo harvested bowhead whales (Balaena mysticetus) were positive by virus neutralization (50% endpoint titer > or = 1:28 and/or 100% endpoint titer > or = 1:20) for antibodies to at least one virus serotype from the calicivirus family, vesicular exanthema of swine virus (VESV) and San Miguel sea lion virus (SMSV). Many animals were positive to more than one serotype when using the Spearman-Karber (S-K) method for calculating antibody titers. The most common serotype detected was VESV F55 with 6 of 36 (17%) by the Monto and Bryan (MB) titer calculation method, and 17 of 36 (47%) by the S-K titer calculation method. Vesicular exanthema of swine virus 1934B antibody was detected in 3 of 36 (8%) and 5 of 36 (14%) whales using the MB and S-K methods, respectively. Vesicular exanthema of swine virus J56 antibody was detected in 3 of 36 (8%) by the S-K method only. All whales < 8.5 m (estimated yearlings, n = 6) were seronegative for VESV J56 and 1934B while 10% and 17% of the whales > 8.5 m were positive, respectively. Whales assumed to be sexually mature (> 13 m) had a higher prevalence of antibody to VESV 1934B and SMSV 8 than those < 13 m. Gender had an effect on seroprevalence of antibody to VESV 1934B as titers > or = 1:28 (S-K method) occurred in 18% of the females and 7% of the males. Antibody to other serotypes (SMSV 8 and 12) occurred less frequently (< 6%) at an antibody titer > or = 1:28 by the S-K method. All 36 whale sera were negative for antibody to VESV-A48, B51, C52, D53, E54, G55, H54, I55, and K54; Tillamook calicivirus, and dolphin morbillivirus; and SMSV-1, 2, 4, 5, 6, 7, 9, 10, 11, and 13 by the S-K method.

Alaska↗
PubMed1998

Morbillivirus infection in stranded common dolphins from the Pacific Ocean.

From August 1995 to August 1997, six of 18 common dolphins (Delphinus delphis) that stranded along beaches of southern California (USA) tested antibody positive for dolphin morbillivirus (DMV). Titers ascertained by virus neutralization ranged from 1:50 to 1:910 while those determined by ELISA ranged from 1:80 to 1:195. The first individual to strand survived and was released back into the Pacific Ocean 14 mo later. Histopathologic examination of tissues from the other five dolphins did not reveal lesions characteristic of morbilliviral disease; however, morbilliviral RNA was detected in three of the five by reverse transcriptase-polymerase chain reaction testing. This is the first report of morbilliviral infection in any marine mammal species in the northern hemisphere of the Pacific Ocean. These data indicate that DMV, or a closely related morbillivirus, is present in the Pacific Ocean and infection of common dolphins may not be associated with morbillivirus disease.

Animals↗
PubMed1998

Health evaluation of free-ranging guanaco (Lama guanicoe).

Twenty free-ranging guanaco (Lama guanicoe) in Chubut Province, Argentina, were immobilized for health evaluations. All but two animals appeared to be in good condition. Hematology, serum chemistry, and vitamin and mineral levels were measured, and feces were evaluated for parasites. Serology tests included bluetongue, brucellosis, bovine respiratory syncitial virus, bovine viral diarrhea/mucosal disease, equine herpesvirus 1, infectious bovine rhinotracheitis, Johne's disease (Mycobacterium paratuberculosis), foot and mouth disease, leptospirosis (17 serovars), parainfluenza-3, and vesicular stomatitis. Blood samples from 20 domestic sheep (Ovis aries) maintained in the same reserve with the guanaco were also collected at the same time for serology tests. No guanaco had positive serologic tests. Sheep were found to have antibody titers to bovine respiratory syncytial virus, Johne's disease, leptospirosis, and parainfluenza-3. There was no apparent difference in external appearance or condition, or statistical difference in blood test values, between the animals that were positive or negative for parasite ova.

Analgesics, Opioid↗
PubMed1997

Epizootiology of morbillivirus infection in harp, hooded, and ringed seals from the Canadian Arctic and western Atlantic.

Using a virus neutralization technique, we found phocine distemper virus (PDV) antibody in 130 (83% of 157) harp seals (Phoca groenlandica) from the western North Atlantic sampled between 1988 and 1993 inclusive. In contrast, only 44 (24% of 185) hooded seals (Cystophora cristata) had antibodies against PDV even though they were sympatric with harp seals and were sampled over a similar period, from 1989 to 1994 inclusive. Antibodies occurred in 106 (41%) of 259 ringed seals (Phoca hispida); this prevalence was higher than expected given the solitary behavior and territoriality characteristic of this species. Seropositive ringed seals were found at each of seven locations across Arctic Canada from Baffin Bay to Amundsen Gulf at which samples were collected between 1992 and 1994. However, the prevalence of infection was highest where ringed seals are sympatric with harp seals in the eastern Canadian Arctic.

Animals↗
PubMed1995

Morbillivirus infection in cetaceans of the western Atlantic.

We report serologic evidence of morbillivirus infection in eleven of fifteen species of odontocete cetaceans from the western Atlantic since 1986. Blood samples were obtained both from free-ranging and stranded animals. Virus neutralizing titers were higher against porpoise and dolphin morbilliviruses than against peste des petits ruminants virus, phocine distemper virus or canine distemper virus (CDV). Serum from five species, tested in a heterologous immunoprecipitation assay using radiolabelled CDV, precipitated the nucleocapsid (N) protein. Clinical morbillivirus infection may potentially impact already threatened species such as the harbour porpoise and precipitate mass strandings of socially cohesive odontocetes.

Animals↗
PubMed1995

Serologic comparison of four isolates of rabbit hemorrhagic disease virus.

An acute, fatal disease of rabbits, termed Rabbit Hemorrhagic Disease (RHD), has occurred in Asia, Europe, and North America since 1984. The clinical signs, pathologic lesions, and epidemiologic features seen in the various outbreaks were very similar. Although RHD virus (RHDV) was initially characterized as a picornavirus or a parvovirus, it is now proven to be a calicivirus. This study compared the immune responses generated following the vaccination and challenge inoculation of rabbits with isolates of RHDV obtained from Italy, Korea, Mexico, and Spain. The cross-reactivity of antisera was demonstrated using the hemagglutination inhibition (HI) test. There were minimal differences between the homologous and heterologous responses. Statistical analysis of the HI results showed no difference between the isolates within the Italian, Korean, and Spanish vaccinate groups. The difference obtained between the Mexican and Korean antigens within the Mexican vaccinate group is likely due to individual animal variation. The similarity of the isolates was also demonstrated using a monoclonal antibody directed against RHDV.

Animals↗