Biomedical subjects
Publications and source records attributed to C Busch.
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The correlation of blood group to grade, stage and tumor markers at diagnosis and to the subsequent clinical course was investigated in a consecutive retrospective series of 230 patients with primary transitional cell carcinoma of the urinary bladder. The follow-up period was 5-9 years. There were no significant differences in grade, stage or DNA ploidy between patients of blood groups A and O. However, the deletion of ABH blood group isoantigen was found more frequently in tumors from patients of blood group O. Concerning progression of superficial bladder tumors, this was found earlier among patients of blood group O, and in a multivariate analysis this emerged as an independent prognostic factor. The crude and corrected mortality was not significantly higher among patients of group O than among those of other blood groups.
Retinoids (vitamin A derivatives) are important for normal embryogenesis and retinoic acid, an acidic derivative of vitamin A, was recently proposed to be an endogenous morphogen. Several retinoids are also potent teratogens. Using an autoradiographic technique, we have identified tissues and cells in early mouse embryos that are able to specifically accumulate a radiolabelled synthetic derivative of retinoic acid. Strong accumulation of radioactivity was seen in several neural crest derivatives and in specific areas of the CNS. Gel filtration analyses of cytosols from embryos that received the radiolabelled retinoid in utero suggested that cellular retinoic acid-binding protein (CRABP) was involved in the accumulation mechanism. Immunohistochemical localization confirmed that cells accumulating retinoids also expressed CRABP. Strong CRABP immunoreactivity was found in neural crest-derived mesenchyme of the craniofacial area, in visceral arches, in dorsal root ganglia and in cells along the gut and the major vessels of the trunk region. In CNS, CRABP expression and retinoid binding was largely restricted to the hindbrain, to a single layer of cells in the roof of the midbrain and to cells in the mantle layer of the neural tube. Our data suggest that cells in the embryo expressing CRABP are target cells for exogenous retinoids as well as endogenous retinoic acid. Retinoic acid may thus play an essential role in normal development of the CNS and of tissues derived from the neural crest. We propose that the teratogenic effects of exogenous retinoids are due to an interference with mechanisms by which endogenous retinoic acid regulates differentiation and pattern formation in these tissues.
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1. Resting metabolic rate and body temperature in function of ambient temperature were determined for two species of Ctenomys. 2. Oxygen consumption was lowest between 25 and 30 degrees C and was 0.946 +/- 0.030 and 0.968 +/- 0.022 in Ctenomys talarum (from Mar de Cobo and Necochea, respectively). Resting metabolic rate was 0.343 +/- 0.053 at 30 C in C. australis. 3. Mean rectal temperature at thermoneutrality was 36.1 +/- 0.13 and 37.3 +/- 0.17 in C. talarum and C. australis, respectively. 4. Limited thermoregulation occurred in C. talarum down to 20 degrees C but C. australis maintained body temperature down to 10 degrees C. 5. Both species of tuco-tucos became hyperthermic at ambient temperatures above thermoneutrality.
The prognostic value of DNA ploidy and blood group (ABH) antigen reactivity was studied in a consecutive retrospective study of 230 patients with primary transitional cell carcinoma of the urinary bladder. In 195 cases the DNA ploidy and ABH reactivity could be assessed in paraffin-embedded tissue. Early progression (in the first 3 years) occurred in 2% of the patients with diploid ABH positive tumours and in 31% of those with aneuploid ABH negative tumours. The 5-year survival rates corrected for intercurrent mortality were 95 and 56% respectively. In a Cox multivariate analysis, T category, age at diagnosis and histological grade emerged as significant independent prognostic indicators of bladder cancer death, whereas ABH reactivity and DNA ploidy had no significant independent value. However, if the combination of ABH reactivity and DNA ploidy was included in the Cox model, this and T category were independent predictors. When this Cox model was applied to assess the risk of progression, the only independent prognostic factor was the combination of ABH reactivity and DNA ploidy.
A consecutive series of 230 patients with transitional cell carcinoma of the urinary bladder was analyzed with respect to the DNA content of the primary tumor, as determined by flow cytometry on material obtained from paraffin blocks. A new method for this analysis was elaborated, based on proteolytic digestion with protease (type VII, Sigma) and density separation of the nuclei by Percoll centrifugation. The method provided DNA flow histograms with less baseline debris and a smaller coefficient of variation in the peaks than published techniques. In eight of 70 cases tested (11%) the method revealed aneuploid peaks that were not distinguished with the original technique and in 197/230 case (86%) interpretable DNA histograms were obtained. The distribution of diploid and aneuploid tumors in different grades and T categories was assessed. None of the grade 1 tumors was aneuploid; 11% of grade 2A, 63% of grade 2B and 83% of grade 3-4, respectively, were aneuploid. The corresponding figures for categories Ta, T1, T2, T3 and T4 were 16, 55, 72, 65 and 100%, respectively.
Immunohistochemical determination of ABO blood group antigens was performed on parathyroid tissue to see if the presence or absence of such antigens could be used as an aid to distinguish adenoma from hyperplasia in primary hyperparathyroidism. Material from nine cases of solitary adenoma and seven cases of hyperplasia fixed in formalin and embedded in paraffin was studied using monoclonal antibodies and avidin-biotin-peroxidase complex technique. The two categories of tissue did not show any consistent differences in the extent or intensity of immunoreactivity, and the method tested did not permit distinction between adenomatous and hyperplastic disease of the parathyroid glands.
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The structure-function relationship of the nicotinic acetylcholine receptor (AChR) has been effectively studied by the combination of complementary DNA manipulation and single-channel current analysis. Previous work with chimaeras between the Torpedo californica and bovine AChR delta-subunits has shown that the region comprising the hydrophobic segment M2 and its vicinity contains an important determinant of the rate of ion transport through the AChR channel. It has also been suggested that this region is responsible for the reduction in channel conductance caused by divalent cations and that segment M2 contributes to the binding site of noncompetitive antagonists. To identify those amino acid residues that interact with permeating ions, we have introduced various point mutations into the Torpedo AChR subunit cDNAs to alter the net charge of the charged or glutamine residues around the proposed transmembrane segments. The single-channel conductance properties of these AChR mutants expressed in Xenopus laevis oocytes indicate that three clusters of negatively charged and glutamine residues neighbouring segment M2 of the alpha-, beta-, gamma- and delta-subunits, probably forming three anionic rings, are major determinants of the rate of ion transport.
A bovine adrenal cDNA library was constructed and a clone corresponding to cellular retinoic-acid-binding protein (CRABP) mRNA was isolated and sequenced. The insert of the clone corresponds to 75 bp of the 5' untranslated portion, the whole translated and the complete 3' untranslated portion of the bovine CRABP mRNA. A genomic Southern blot, probed with CRABP cDNA, indicated that only one copy of the gene is present in the human genome. Hybridizing bands in restricted chicken and fish DNA were also observed. Using the CRABP cDNA as probe we have located the human CRABP gene to chromosome 3 in hybridizations to mouse-human, hamster-human and rat-human cell hybrids. In situ hybridizations on rat testis cells probed with CRABP and cellular retinol-binding protein antisense mRNA indicate that both proteins are expressed in tubuli cells.
The immunohistochemical expression of blood-group substances and carcinoma-associated antigens were compared in rectal carcinoids and adenocarcinomas. Rectal carcinoid tumors, in contrast to rectal carcinomas, were consistently negative for CEA, gastrointestinal cancer antigen GICA (or CA 19-9), and carcinoma-associated antigen CA-50 (except in one case where less than 10 percent of the cells expressed CA-50). The carcinoids and rectal carcinomas extensively expressed blood-group substance A, B, and H, Lewis B antigen, and difucosylated carbohydrate antigens (DFCA). Thus, rectal carcinoids and adenocarcinomas possess both similar and different tumor antigen profiles. The occurrence of discrepant antigen determinants may be used in the differential diagnosis of these two types of tumors. The coexpression of blood-group substance A, B, and H, Lewis B antigen, and DFCA is consistent with the opinion that both rectal carcinomas and carcinoids have a common entoderm origin, but carcinoids are considered to rise from the endocrine-differentiated and the adenocarcinomas from the nonendocrine-differentiated enterocytes.
1. Captive vampires consume blood to an average of 59.5% of their body weight in a period no longer than 30 min. 2. Fluid consumption by the vampire is mainly dependent on the presence of plasma in fluid. 3. Ingestion of blood is accompanied and followed by diuresis, urine flow attained a peak 20-25 min after feeding. 4. Urine osmolality increased with time after feeding. Vampires concentrate urea in urine to 2630 mmol/l but cannot concentrate electrolytes beyond 453 mmol/l. 5. Inorganic salts other than sodium chloride never contribute more than 9% to the total osmotic activity. 6. Na to Cl ratio and concentration of non-nitrogenous organic acids increase with urine osmolality. 7. Vampires drink free water if available.
The reaction patterns of eight antibodies directed against blood group substances A, B, and H and against Lewis B antigen, difucosylated carbohydrate antigens (DFCA), gastrointestinal cancer antigen (GICA) CA 19-9, carcinoma-associated antigen CA-50, and carcinoembryonic antigen (CEA) were studied in mucosa and adenomas of the rectum. Antigenic heterogeneity was a common feature of rectal mucosa and was observed to a considerable degree in adenomas. In general, the rectal mucosa expressed only a few antigens and to a limited extent. The adenomas were more extensively stained than the rectal mucosa. The proportion of positive cells increased with the grade of dysplasia but was relatively unrelated to the histologic type. The proportion of individual antigens expressed and the number of antigens extensively expressed increased between rectal mucosa, benign adenomas, and adenomas with early invasive carcinoma. These findings support the concept of an adenoma (dysplasia)-carcinoma sequence.
CellCAM 105 is an integral membrane glycoprotein, with apparent Mr 105,000, which has been purified from rat liver plasma membranes. It consists of two structurally similar, highly glycosylated polypeptide chains and is involved in cell-cell adhesion of adult rat hepatocytes in vitro. In this communication we report on the distribution and cell surface location of cellCAM 105 in rat tissues, obtained by using highly sensitive immunodetection systems based on complex formation between biotinylated antibodies, biotinylated peroxidase and avidin, or on antibodies coupled to alkaline phosphatase. CellCAM was found in many organs and organ systems, including liver, kidney, blood, blood vessels, glands, respiratory system, and gastrointestinal tract. It was mainly localized to epithelial structures but showed a varying cell surface distribution. In some cell types it was predominantly localized to cell-cell contact areas. In other cell types the highest concentrations were seen in brush-border areas containing densely packed microvilli. In addition to epithelial structures, cellCAM 105 was found in rat platelets, where it became strongly expressed on the cell surfaces after activation with ADP or collagen, suggesting that it might be involved in platelet adhesion and/or aggregation mechanisms. Granulocytes also contained cellCAM 105. By SDS-PAGE/immunoblotting, significant differences were found in the apparent Mr values of cellCAM 105 in different tissues. The collected data suggest that cellCAM 105 participates in several different cell surface membrane interactions, of which the common denominator might be membrane-membrane binding.
Auditory Evoked Magnetic Fields (EFs) to tonal stimuli were recorded at homotopic maxima over the left and right auditory areas in nine subjects. Recordings were made during two conditions, both involving simultaneous presentation of the probe tone stimuli and a set of tape-recorded verbal material. During the control condition subjects were instructed to attend to the tones and ignore the verbal material. In the phonological processing condition they were instructed to ignore the tones and attempt to identify a phonological target item which was embedded in the verbal material. EFs obtained during both conditions were characterized by an early N1m and a later P2m component corresponding to the N1 and P2 components of auditory evoked potentials (EPs). During the phonological condition, the amplitude of the N1m was significantly reduced in both hemispheres symmetrically whereas the amplitude of the P2m was attenuated to a significantly greater degree in the left hemisphere. These data are in agreement with previous EP evidence of greater interference of linguistic processing with processing of irrelevant probe stimuli in the left hemisphere, indicative of greater left hemisphere involvement in language tasks.
The expression of ABH blood group isoantigen was determined with the avidin-biotin-peroxidase complex method in a retrospective consecutive material of 230 patients with transitional cell bladder carcinoma. The follow-up period was 5 to 9 years. The five-year corrected survival for 65 patients whose primary tumours showed predominant expression of ABH antigens ('positive') was 80% and for 146 patients with predominant deletion ('negative') 60% (p less than 0.01). Of 107 patients with superficial tumours there were 60 negative and 47 positive. In an analysis of early progression, the negative tumours were found to progress more frequently than positive ones (p less than 0.03). Twenty-three per cent of the negative tumours finally progressed during the whole follow-up, compared with 15% of the positive ones; this difference was not significant. Almost all progressing tumours became negative when they reached an advanced stage.