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K Hobbs

Publications and source records attributed to K Hobbs.

At least 19 recordsLinked to original sources

Persistent organic pollutants and mercury in marine biota of the Canadian Arctic: an overview of spatial and temporal trends.

This review summarizes and synthesizes the significant amount of data which was generated on mercury (Hg) and persistent organic pollutants (POPs) in Canadian Arctic marine biota since the first Canadian Arctic Contaminants Assessment Report (CACAR) was published in 1997. This recent body of work has led to a better understanding of the current levels and spatial and temporal trends of contaminants in biota, including the marine food species that northern peoples traditionally consume. Compared to other circumpolar countries, concentrations of many organochlorines (OCs) in Canadian Arctic marine biota are generally lower than in the European Arctic and eastern Greenland but are higher than in Alaska, whereas Hg concentrations are substantially higher in Canada than elsewhere. Spatial coverage of OCs in ringed seals, beluga and seabirds remains a strength of the Arctic contaminant data set for Canada. Concentrations of OCs in marine mammals and seabirds remain fairly consistent across the Canadian Arctic although subtle differences from west to east and south to north are found in the proportions of various chemicals. The most significant development since 1997 is improvement in the temporal trend data sets, thanks to the use of archived tissue samples from the 1970s and 1980s, long-term studies using archeological material, as well as the continuation of sampling. These data cover a range of species and chemicals and also include retrospective studies on new chemicals such as polybrominated diphenyl ethers. There is solid evidence in a few species (beluga, polar bear, blue mussels) that Hg at some locations has significantly increased from pre-industrial times to the present; however, the temporal trends of Hg over the past 20-30 years are inconsistent. Some animal populations exhibited significant increases in Hg whereas others did not. Therefore, it is currently not possible to determine if anthropogenic Hg is generally increasing in Canadian Arctic biota. It is also not yet possible to evaluate whether the recent Hg increases observed in some biota may be due solely to increased anthropogenic inputs or are in part the product of environmental change, e.g., climate warming. Concentrations of most "legacy" OCs (PCBs, DDT, etc.) significantly declined in Canadian Arctic biota from the 1970s to the late 1990s, and today are generally less than half the levels of the 1970s, particularly in seabirds and ringed seals. Chlorobenzenes and endosulfan were among the few OCs to show increases during this period while summation operatorHCH remained relatively constant in most species. A suite of new-use chemicals previously unreported in Arctic biota (e.g., polybrominated diphenyl ethers (PBDEs), short chain chlorinated paraffins (SCCPs), polychlorinated naphthalenes (PCNs), perfluoro-octane sulfonic acid (PFOS) and perfluorocarboxylic acids (PFCAs)) has recently been found, but there is insufficient information to assess species differences, spatial patterns or food web dynamics for these compounds. Concentrations of these new chemicals are generally lower than legacy OCs, but there is concern because some are rapidly increasing in concentration (e.g., PBDEs), while others such as PFOS have unique toxicological properties, and some were not expected to be found in the Arctic because of their supposedly low potential for long-range transport. Continuing temporal monitoring of POPs and Hg in a variety of marine biota must be a priority.

Animals↗

In-vitro uptake of radioactive lipiodol I-131 and I-125 by hepatoblastoma: implications for targeted radiotherapy.

Lipiodol, a stable iodine addition product of fatty ethyl esters derived from poppyseed oil, has been used as a vehicle for targeted cytotoxic or radiotherapeutic treatment in adults with unresectable hepatocellular carcinoma and in a few children with advanced hepatoblastoma (HB). Prolonged retention of lipiodol by the cancer cells might enable more effective targeted therapy to advanced, multifocal, or metastatic HB. To investigate the uptake and cytotoxic efficacy of beta and Auger electron-emitting radioconjugates on HB cells, monolayers of HB (C3a, Hep Tow1) and normal human hepatocyte cell lines were exposed to lipiodol131 (L131), lipiodol125 (L125), or a cocktail of both isotopes. Uptake of radioactivity was assessed autoradiographically using phosphoimages and the cytotoxicity assessed by trypan blue exclusion and clonogenic assay. The uptake of the different radioconjugates was identical in both HB cell lines. The "cocktail" of both radioactive lipiodols caused the greatest cytotoxicity to HB C3a, and HepTow1. L125 alone had a similar level of uptake and cytotoxicity as L131. Radioactive iodine alone did not show any cytotoxicity on any of the liver cell lines in culture for up to 72 h. These experimental results provide support for a clinical strategy of combinations ("cocktails") of radioconjugates in targeted radiotherapy in patients with HB.

Carcinoma, Hepatocellular↗

Skewing of the brain midline in schizophrenia.

Our laboratory has observed marked craniofacial dysmorphology along the frontonasal-maxillary juncture in schizophrenic probands and their relatives. Embryologic fate-mapping studies relate this craniofacial juncture to the diencephalic-mesencephalic border, and on the basis of this correspondence we have predicted brain midline maldevelopment arising at this border in schizophrenia. Analysis of magnetic resonance images has borne out this prediction, with midline deviation scores in schizophrenia exceeding control values. High deviation scores were also observed among the siblings of these schizophrenic patients. Further, brain and face dysmorphology scores cohered within subjects, supporting this embryologically derived model.

Adult↗

Fuel metabolism in men and women during and after long-duration exercise.

This study aimed to determine gender-based differences in fuel metabolism in response to long-duration exercise. Fuel oxidation and the metabolic response to exercise were compared in men (n = 14) and women (n = 13) during 2 h (40% of maximal O2 uptake) of cycling and 2 h of postexercise recovery. In addition, subjects completed a separate control day on which no exercise was performed. Fuel oxidation was measured using indirect calorimetry, and blood samples were drawn for the determination of circulating substrate and hormone levels. During exercise, women derived proportionally more of the total energy expended from fat oxidation (50.9 +/- 1.8 and 43. 7 +/- 2.1% for women and men, respectively, P < 0.02), whereas men derived proportionally more energy from carbohydrate oxidation (53.1 +/- 2.1 and 45.7 +/- 1.8% for men and women, respectively, P < 0.01). These gender-based differences were not observed before exercise, after exercise, or on the control day. Epinephrine (P < 0.007) and norepinephrine (P < 0.0009) levels were significantly greater during exercise in men than in women (peak epinephrine concentrations: 208 +/- 36 and 121 +/- 15 pg/ml in men and women, respectively; peak norepinephrine concentrations: 924 +/- 125 and 659 +/- 68 pg/ml in men and women, respectively). As circulating glycerol levels were not different between the two groups, this suggests that women may be more sensitive to the lipolytic action of the catecholamines. In conclusion, these data support the view that different priorities are placed on lipid and carbohydrate oxidation during exercise in men and women and that these gender-based differences extend to the catecholamine response to exercise.

Adult↗

Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma.

Interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) are inhibitory for B and T cells, IgE production, and mast cell proliferation, and they induce apoptosis in eosinophils. These cytokines are therefore candidate genes which could contribute to the development of asthma or allergies. We investigated the hypothesis that polymorphic nucleotides within the IL-10 and TGF-beta gene promoters would link to the expression of allergies and asthma. DNA taken from families with an asthmatic proband was examined for base exchanges by single-stranded conformational polymorphism (SSCP). We demonstrated the presence of a polymorphism in the promoter region of the IL-10 gene and four in the TGF-beta gene promoters (3 in TGF-beta1 and 1 in TGF-beta2). The IL-10 gene polymorphism was a C-to-A exchange 571 base pairs upstream from the translation start site and was present between consensus binding sequences for Sp1 and elevated total serum. This polymorphism was associated with elevated total serum IgE in subjects heterozygotic or homozygotic for this base exchange (p < 0.009). The base exchange at -509 (from the transcription initiation site) in the TGF-beta promoter also linked to elevated total IgE (p < 0.01). This polymorphism represented a C-to-T base exchange which induced a YY1 consensus sequence and is present in a region of the promoter associated with negative transcription regulation.

Adenine↗

Homochirality as the signature of life: the SETH Cigar.

A characteristic hallmark of life is its homochirality: all biomolecules are usually of one hand, e.g. on Earth life uses only L-amino acids for protein synthesis and not their D mirror images. It is therefore suggested that a search for extra-terrestrial life can be approached as a Search for Extra-Terrestrial Homochirality (SETH). A novel miniaturized space polarimeter, called the SETH Cigar, is described which could he used to detect optical rotation as the homochiral signature of life on other planets. Moving parts are avoided by replacing the normal rotating polarizer by multiple fixed polarizers at different angles as in the eye of the bee. It is believed that homochirality will be found in the subsurface layers on Mars as a relic of extinct life.

Astronomy↗

Dermatoglyphics, fetal growth, and insulin dependent diabetes in children under 5 years.

Examination of dermatoglyphic patterns in 112 diabetic children under 5 years and matched controls found no difference between the groups. Either those developing diabetes under 5 do not experience the same genetic and environmental conditions that influence its development in later life or the dermatoglyphic abnormalities described in later onset insulin dependent diabetes mellitus reflect the vast number of pattern formations available for study, which has inevitably led to some statistically significant associations.

Age Factors↗

Value of exfoliative cytology for investigating bile duct strictures.

The cause of a biliary tract stricture may be difficult to determine radiologically. Exfoliative biliary cytology was evaluated in 62 patients (median age 65 years, range 30-94) with biliary tract strictures presenting to the Hepatobiliary Unit between January 1984 and December 1989. Bile samples were taken during endoscopic retrograde cholangiopancreatography (ERCP) in 42 patients, percutaneous cholangiography in 14, and both in six. The site of stricturing was upper third of the bile duct in 43% (n = 27), middle third in 10% (n = six), and lower third in 47% (n = 29). Of the 47 patients with radiological appearances of a malignant stricture, 22 (47%) had histological confirmation by biopsy either under computed tomography guidance, at endoscopy, at operation, or at necropsy. Fourteen of the 47 patients had positive cytology (30%). In seven patients cytology alone established the presence of malignancy (15%) and in the other seven positive cytology was confirmed by histology. The addition of cytology to tissue biopsy therefore allowed malignancy to be confirmed in 29 of the 47 patients (62%). None of the 15 patients subsequently shown to have benign disease had positive cytology. Sensitivity of the technique was 30% and specificity 100%. Samples for exfoliative cytology are simple to obtain, the results are highly specific and should be a routine part of the investigation of biliary strictures.

Adult↗

A prospective controlled study comparing brush and bile exfoliative cytology for diagnosing bile duct strictures.

Imaging of biliary strictures may suggest malignancy but cytology can provide a tissue diagnosis. The aim of this study is to compare the diagnostic value of brush cytology and bile cytology. Thirty two patients (20 males, 12 females, median age 66 years, range 31-84) with biliary strictures at endoscopic retrograde cholangio pancreatography (24) or percutaneous transhepatic cholangiography (8) had bile cytology and brush cytology. Brushings were taken using a modified Geenan cytology brush (6 Fr gauge, Wilson Cook) passed alongside a guide wire placed through the stricture. Bile was aspirated after insertion of an internal/external catheter or an endoprosthesis. Bile and brushings were examined by one experienced cytologist (AD) and was reported as positive or negative for malignant cells. Twenty nine patients had malignant strictures. Sixteen were confirmed by histology and 13 had malignancy suggested by clinical follow up. Three patients had resection of histologically benign strictures. The overall sensitivity of brush cytology (17 of 29 positive, 59%) was significantly greater than bile cytology (seven of 29 positive, 24%) (p < 0.01) as was the diagnostic accuracy (63 v 31%, p < 0.01). None of the patients had positive bile cytology with negative brush cytology. There were no procedure related complications and the average sampling time once the guide wire had been inserted was less than five minutes. It is concluded that brush cytology is more sensitive than bile cytology and with the technique described is safe and rapid.

Adult↗

Duodeno-jejunal varicosities following extrahepatic portal vein thrombosis.

A 31 year old man, under investigation for melena, was found at endoscopy to have varicosities at the site of a duodeno-jejunostomy which had been performed for duodenal atresia when he was three days old. Angiography revealed an occluded portal vein with an extensive collateral circulation. At laparotomy some of the collateral vessels were found to pass through the anastomotic site and directly into the left lobe of the liver. The portal pressure was found to be minimally elevated. Resection of the anastomotic segment was performed with reconstruction using a Roux en Y jejunal loop. Bleeding from collateral vessels passing through an anastomosis site in a patient with extrahepatic portal vein thrombosis has not previously been reported.

Adult↗

Ablation of recurrent primary liver cancer using 131I-lipiodol.

A case of recurrent hepatocellular carcinoma following resection is reported. The patient received 2 treatments of 131I-lipiodol administered via the hepatic artery at angiography. Good localization in tumour tissue was observed on subsequent computed tomographic scans and no adverse effects were seen after either treatment. After the first treatment 2 nodules of recurrent tumour were resected and proved to be totally necrotic. The patient remains well 9 months later with a persistently elevated serum alphafetoprotein but no evidence of residual tumour. It is suggested that 131I-lipiodol may be the treatment of choice for small tumours in elderly high-risk patients.

Aged↗

Biological differences among MCF-7 human breast cancer cell lines from different laboratories.

MCF-7 human breast cancer cells are used widely for studies of tumor biology and hormone mechanism of action. Conflicting results have often been obtained in studies reported from different laboratories. In this report several biological properties were studied in four MCF-7 cell lines obtained from different laboratories. MCF-7 (ATCC), MCF-7, MCF-7 (KO), and MCF-7 (S) demonstrated similar morphology in monolayer culture. Chromosome analysis revealed that three of the lines shared several structural chromosome alterations and marker chromosomes; however, MCF-7 (ATCC) was distinctly different with virtually no chromosomal alterations shared in common with the other lines. All four lines contained variable amounts of estrogen receptor (ER) and progesterone receptor (PgR). The growth rate of MCF-7 (ATCC) was 50% slower than that of the other lines, and, unlike the other three lines, cell proliferation was unaffected by estrogen or antiestrogen treatment despite the presence of receptors. Cloning efficiency of the four lines varied over a 10-fold range. Tumorigenicity in athymic nude mice also varied considerably among these lines. MCF-7 (ATCC) grew well in ovariectomized nude mice, while the other lines required estrogen supplementation. MCF-7 (S) and MCF-7 grew rapidly with estrogen supplementation; MCF-7 (KO) grew very slowly. Antiestrogen therapy inhibited growth of MCF-7, MCF-7 (S), and MCF-7 (KO) tumors, but it had no effect on MCF-7 (ATCC). These data demonstrate that MCF-7 lines from different laboratories may have unique biological properties, despite having a similar karyotype (MCF-7, MCF-7 (S), MCF-7 (KO]. The fundamental differences in karyotype and biological properties of the MCF-7 (ATCC), and the previously reported differences in DNA restriction fragment polymorphism analyses, demonstrate that this line is derived from an entirely different patient. Investigators should carefully document the source and identity of MCF-7 cells used in published experiments.

Agar↗

Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic nude mice.

Endocrine therapy with estrogen deprivation or with antiestrogens results in tumor regression in a subset of patients with advanced breast cancer. To better understand the mechanisms by which estrogens and antiestrogens modulate breast cancer growth in vivo, we have studied the effects of endocrine manipulation on the development and growth of tumors derived from cultured human breast cancer cells in the athymic nude mouse. MCF-7 breast cancer cells were inoculated into 6-week-old female BALB/c athymic nude mice. Tumor growth did not occur in ovariectomized mice. Cells remained viable, however, since estrogen supplementation more than 30 days later resulted in tumor formation. Minimal tumor growth was observed in intact female nude mice which have low circulating estrogen levels. Tumor development and growth in ovariectomized or intact mice supplemented with 17 beta-estradiol in the form of a s.c. pellet were dose dependent; growth rates increased with estrogen doses ranging from 0.01 to 0.5 mg. Antiestrogen treatment with either tamoxifen or LY156758 caused transient stimulation of tumor growth, followed by a prolonged stationary phase. Growth resumed with estrogen supplementation. Treatment of mice bearing established MCF-7 tumors with estrogen withdrawal (removal of estrogen pellet) resulted in cessation of tumor growth, but not in tumor regression. Growth inhibition was also observed with antiestrogens and was dose dependent. However, tumor regression did not occur, even in mice treated with high doses of tamoxifen (serum concentration of 1.0 microM) for as long as 60 days. Tumor growth was restored in these mice with estrogen replenishment. Tumor cells also remained viable histologically despite prolonged (1 month) estrogen deprivation or antiestrogen therapy, although the mitotic index was markedly reduced. Similar observations were made with mice inoculated with the hormone-responsive ZR75-1 human breast cancer cells, but not with hormone-independent MDA-231 cells which were not influenced by estrogen or antiestrogen treatment. In summary, development and growth of MCF-7 and ZR75-1 tumors in nude mice are estrogen dependent. Endocrine therapy by estrogen deprivation or antiestrogen treatment inhibits tumor cell proliferation in nude mice, but does not cause tumor regression or loss of cell viability.

Animals↗