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W D Odell

Publications and source records attributed to W D Odell.

At least 19 recordsLinked to original sources
PubMed1997

Endocrine/metabolic syndromes of cancer.

In addition to producing symptoms directly by their mass or invasion of tissues, cancers may also make themselves evident by the secretion of cytokines, protein hormones, or hormone precursors, which in turn, results in recognizable clinical syndromes. This article reviews the endocrine syndromes of cancer, their pathophysiologic basis, and the means of diagnosis. Many of these protein hormones appear to be produced in small amounts by normal tissues where they act in paracrine fashion as cytokines. Furthermore, neoplastic transformation is associated with continued, or often dramatically amplified, production of paracrine substances, permitting them to circulate in the blood and to act as hormones. Thus, classical definitions of cytokines and hormones become blurred. In this context, so-called "ectopic" cancer production is not ectopic, but rather a modification of normal cell function. The majority of the endocrine syndromes of cancer are caused by cancer production of these cytokines or hormones. Except for cancers originating in the adrenals or gonads, cancers do not synthesize steroids and secrete them, although very rarely a cancer may metabolize a normal steroid precursor to produce a biologically active steroid.

Cytokines↗
PubMed1996

Contrasts in the gonadotropin-releasing hormone dose-response relationships for luteinizing hormone, follicle-stimulating hormone and alpha-subunit release in young versus older men: appraisal with high-specificity immunoradiometric assay and deconvolution analysis.

The secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is regulated by gonadotropin-releasing hormone (GnRH). As men age, mean serum concentrations of immunoreactive gonadotropic hormones tend to increase, while serum testosterone concentrations tend to decline. To evaluate age-related changes in gonadotroph cell function, we have assessed the dose-dependent secretory responses of immunoreactive LH, FSH and alpha-subunit to saline versus five doses of GnRH in older and young men. Ten older men, mean age 66 years (range 61-78), and nine young men, mean age 26 years (range 22-30), received iv bolus injections of GnRH (range 10-100 micrograms) in randomized order every 2 h, except that the 100-microgram dose was always given last. Blood samples for immunoradiometric assays of serum LH, FSH and alpha-subunit concentrations were obtained every 10 min for a total of 12 h, which included a 2-h preinjection baseline. Deconvolution analysis was performed to estimate gonadotropin and alpha-subunit secretory burst mass, amplitude and duration, as well as endogenous LH, FSH and alpha-subunit half-lives. The mean (+/- SEM) baseline 2-h serum FSH (IU/I) concentration was higher in older than younger men (5.9 +/- 0.8 vs 3.8 +/- 0.5, p < 0.05). The mean 2-h serum LH concentrations after GnRH were significantly higher than corresponding values in young men at GnRH doses of 25, 50 and 75 micrograms, and in the case of FSH at GnRH doses of 10 and 25 micrograms. Non-linear curve-fitting of these dose-response relationships revealed that the calculated maximal mean 2-h serum LH concentration response (IU/l) was higher in older than young men following GnRH stimulation: 15.4 (13.5-16.2) vs 10.8 (8.7-12.1) (95% confidence interval). The maximal mean 2-h serum FSH concentration response (IU/l) was also significantly higher in older men: 11.9 (10.2-13.1) versus 8.6 (7.2-9.6). Maximal alpha-subunit responses (microgram/l) were similarly increased in the older cohort: 1.16 (0.99-1.25) vs 0.83 (0.71-0.91). The incremental LH (p < 0.05) and FSH (p < 0.01) secretory burst mass from 10 to 25 micrograms GnRH was significantly greater in older than younger men. The LH and FSH half-lives and second component alpha-subunit half-lives were similar in older and young men. In addition, secretory burst durations were invariant of age. In contrast, by non-linear curve-fitting, the calculated mass of LH secreted was higher in older men at 13.5 (11.8-15) vs 10.6 (9.2-11.7) IU/l of distribution volume (p < 0.05) for the maximal absolute mass and 11.3 (9.5-12.7) vs 7.4 (6.0-8.4) IU/l (p < 0.05) for the maximal incremental mass of LH secreted after GnRH. The estimated maximal mass of FSH secreted after GnRH also was higher in older men: 4.6 (3.4-5.5) vs 3.2 (2.9-3.4) IU/l (p < 0.01). Finally, calculated maximal GnRH-stimulated alpha-subunit secretory burst mass was statistically greater in older individuals: 2.3 (1.8-2.5) vs 1.6 (1.4-1.8) micrograms/l. In contrast, half-maximally effective GnRH doses were not different in the two age groups. We conclude that older men show significantly increased maximal and incremental gonadotropin release due to amplified secretory burst mass in response to escalating doses of GnRH with no evident differences in LH, FSH, or alpha-subunit half-lives or secretory burst durations. Increased gonadotroph responsiveness may be due to diminished gonadal hormone negative feedback or primary alterations in the hypothalamo-pituitary unit with aging.

Adult↗
PubMed1995

Complete sequence of the gene encoding a chorionic gonadotropin-like protein from Xanthomonas maltophilia.

Our laboratory has previously reported that: (i) Xanthomonas maltophilia (Xm) produces a protein which has immunological resemblance to the beta-subunit of human chorionic gonadotropin (hCG) and (ii) possesses a high-affinity receptor which binds holo hCG, and the endogenous ligand, Xm chorionic gonadotropin (xCG), but does not bind human luteinizing hormone (hLH). We have also previously published a 492-bp partial nucleotide sequence of the gene (xcg) coding for xCG. We report herein the entire xcg sequence of 1362 bp, which codes for a 48-kDa protein. This sequence confirmed the 492-bp sequence, as well as two partial amino acid (aa) sequences which we have previously reported. The sequence has a region which is homologous to aa 56-139 of the beta-subunit of hCG, and a second region homologous to the C-terminal tail of hCG. This is the first report of a prokaryotic gene homologous to the hCG beta-subunit-encoding gene.

Amino Acid Sequence↗
PubMed1994

Characterization and purification of the chorionic gonadotropin-like protein binding site in Candida albicans.

Recent studies from our laboratory have shown that human chorionic gonadotropin (hCG), human luteinizing hormone (hLH), and CG-like proteins from Xanthomonas maltophilia (xCG) and Candida albicans (CaCGLP) induce Candida albicans transition from blastospores to hyphal forms. Xanthomonas maltophilia CG-like protein (xCG), hCG, and hLH also bind to Candida albicans blastospores with a high-affinity nM Kd, indicating that these substances can control Candida albicans pathogenicity. The work reported herein describes the purification of the binding site for these CG-like proteins from Candida albicans. The purification developed involved alcohol extraction followed by affinity chromatography. The product obtained was a protein of 64-69 kDa, as analyzed by sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE), Western blot and Sephadex G-100 column chromatography. This binding site reacted in a Western blot with both 125I-hCG and 125I-CaCGLP. Purified CaCGLP was able to displace specifically 125I-hCG bound to Candida albicans blastospores. Scatchard plot analysis showed that the Kd of this reaction was of high affinity in the nM range, and also indicated the presence of one single binding site. These results lead us to conclude: 1) Candida albicans possesses a binding site which is able to bind hCG, hLH and CG-like proteins from Xanthomonas maltophilia and Candida albicans; 2) This binding site is a hydrophobic protein of approximately 64 kDa and; 3) We postulate that CaCGLP is the natural ligand for this binding site and this system is used to control Candida albicans transition and, therefore, pathogenicity.

Binding Sites↗
PubMed1994

The presence of a human chorionic gonadotropin-like protein and its binding site in Saccharomyces cerevisiae.

In this study, we characterize from Saccharomyces cerevisiae: 1) a protein that has immunological similarities to human chorionic gonadotropin (hCG), and 2) a binding site for this hCG-like protein which also binds hCG and human luteinizing hormone (hLH). Saccharomyces cerevisiae chorionic gonadotropin-like protein (ScCGLP) was purified in several steps. This protein when analyzed by SDS-PAGE, under nondenaturing conditions, produced two bands, one at 110-kDa, and another at 57.5-kDa. Under denaturing conditions, only the 57.5-kDa band appeared. This 57.5-kDa band also reacted in a Western blot, using a polyclonal antibody directed against hCG. Purified ScCGLP reacted in the following hCG immunoassays: 1) polyclonal rabbit anti-hCG equilibrium assay, 2) carboxyl-tail hCG equilibrium assay, 3) two equilibrium assays using monoclonal antibodies, and 4) free alpha-chain subunit equilibrium assay using a monoclonal antibody. Characterization of hCG/hLH binding sites in Saccharomyces cerevisiae was performed, and the ability of the ScCGLP to displace I125-hCG was also shown. Human CG and hLH were able to compete for I125-hCG binding to Saccharomyces cerevisiae blastospores (Kds of approximately 10(-8) M), while ScCGLP competed with higher affinity (Kd = 9.41 x 10(-10) M). The hCG-like immunoactivity was also present in Saccharomyces growth media, as well as in all brands of commercial beer studied.

Binding Sites↗
PubMed1993

A bacterial protein has homology with human chorionic gonadotropin (hCG).

Studies from our laboratory have demonstrated the presence of a 48.5 kD cell wall protein in the bacterium, Xanthomonas maltophilia, which immunologically resembles the beta subunit of human chorionic gonadotropin. Primers were designed from the amino acid sequences of enzymatically cleaved peptide fragments of this protein. These primers were used to obtain PCR amplified products, which were subsequently cloned in a PCR11TA cloning vector, and a 492 base pair nucleotide sequence was obtained with a 164 amino acid open reading frame. When this nucleotide sequence was aligned with exon 2 of genes 5 and 6 of the beta hCG gene, a 53% homology was observed. The translated protein sequence had a 35% homology with hCG and a 25% homology with human luteinizing hormone.

Amino Acid Sequence↗
PubMed1993

Partial nucleotide sequence of the Xanthomonas maltophilia chorionic gonadotropin-like receptor.

Xanthomonas maltophilia possesses a unique high-affinity binding site which binds human chorionic gonadotropin (hCG), but not human luteinizing hormone (hLH) or other glycoprotein hormones. We designed primers from the known nucleotide sequence of the human LH/CG receptor, spanning an area extending from transmembrane region 2 to transmembrane region 6. Genomic DNA extracted from Xanthomonas maltophilia was used to obtain a PCR amplified product using the above primers. The primary amplification product was cloned in a pCR11 TA cloning vector, and the partial nucleotide sequence of the gene determined. This determined sequence showed 73% identity with the human, as well as the rat LH/CG receptor. Comparison of the translated protein sequence with the human, rat and porcine receptor protein sequences showed a 52% similarity.

Amino Acid Sequence↗
PubMed1993

Characterization of a human chorionic gonadotropin-like protein from Candida albicans.

Studies from our laboratory have demonstrated that human CG (hCG), human LH, (hLH), and an hCG-like protein extracted from Xanthomonas maltophilia were able to induce Candida albicans transition from the blastospore to the germ tube stage. In the present study, we describe the characterization of an hCG-like material extracted from Candida albicans blastospores (CaCGLP), which is potent in inducing transition and presumably represents the endogenous transition-inducing substance. This material was extracted from Candida albicans blastospores with glacial acetic acid and purified by affinity chromatography using a polyclonal rabbit anti-hCG antibody. The product obtained is a 68-kilodalton single band protein, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. Under reduced conditions a protein smear is seen. Amino acid analysis showed a predominance of glycine (22%), followed by serine (12%), and glutamate (12%). This protein reacted in the following hCG immunoassays: 1) a polyclonal rabbit anti-hCG equilibrium assay, 2) a carboxyl-tail hCG equilibrium assay, 3) two hCG equilibrium assays using monoclonal antibodies (CG no. 4 and CG no. 9), 4) a free alpha-subunit equilibrium assay using a monoclonal antibody, and 5) an ultrasensitive immunoradiometric assay for hCG which does not cross-react with hLH, nor the free beta-subunit of hCG. The CaCGLP showed no reaction in a specific hLH immunoradiometric assay. When CaCGLP was tested in the transition assay, in the presence of 4% rat serum, it was found that this protein was 100 times more potent than hCG in producing Candida albicans transition. We conclude that Candida albicans produces a protein that has certain tertiary structure similarities to hCG and that this material is able to induce germ tube formation. We postulate that CaCGLP has an autocrine/paracrine effect in Candida albicans as a transition factor to control its own pathogenicity.

Amino Acids↗
PubMed1993

Evidence for an autocrine/paracrine function of chorionic gonadotropin in Xanthomonas maltophilia.

In the human and all other mammalian systems studied, LH and hCG bind to a common high affinity receptor with equal affinity. We have recently reported that a unique high affinity binding site in Xanthomonas maltophilia preferentially binds hCG and a native CG-like ligand over LH or other glycoprotein hormones. In the current studies, we have analyzed the effect of hCG or the native ligand on culturing Xanthomonas maltophilia. Both the human and native ligand caused a dose-dependent alteration in the pattern of the growth cycle and a change in the morphology of the bacteria during the stationary phase of the growth cycle. The protein concentration reached during the stationary phase was significantly (P < 0.005) higher in cultures supplemented with hCG or the native ligand. When an aliquot of the culture was diluted and plated on Earl's Martin Balanced agar plates, the number of subsequent colonies was increased (P < 0.02) in the fractions supplemented with the ligands. The increased growth was significant (P < 0.05) to the lowest concentration of 50 ng/ml ligand. When grown under partially anaerobic conditions, the effects of hCG were observed earlier in the growth cycle. The active hormones, hCG and native ligand, also changed bacterial morphology. These data indicate that hCG may have an autocrine and/or paracrine function in bacteria.

Aerobiosis↗
PubMed1993

Xanthoma disseminatum, a rare cause of diabetes insipidus.

A 33-yr-old male developed typical symptoms and findings of diabetes insipidus. A computed tomographic scan of the hypothalamus/pituitary was normal, and he was diagnosed as having idiopathic diabetes insipidus. At age 38 yr, he developed two 1- to 2-mm reddish papules on his skin. Biopsy revealed infiltrative histiocytes laden with lipid. Bone scans and bone x-rays showed widespread osteolytic and osteoblastic disease. The disease was diagnosed as a rare disseminated histiocytic disorder, xanthoma disseminatum. A classification of histiocytic disease is presented.

Adult↗
PubMed1993

Estradiol stimulates cortisol production by adrenal cells in estrogen-dependent primary adrenocortical nodular dysplasia.

Adrenal glands from a patient with ACTH-independent Cushing's syndrome, whose symptoms worsened during pregnancy and oral contraceptive use, were cultured in different concentrations of estradiol. Estradiol stimulated cortisol secretion in a dose-response manner in the absence of ACTH. Since immunoglobulins G from this patient did not stimulate corticosterone production in a mouse adrenal bioassay, an adrenal-stimulating immunoglobulin is unlikely to be the cause of adrenal hyperfunction in this case. This is the first description of estradiol stimulation of cortisol production by cultured adrenal cells in ACTH-independent Cushing's syndrome.

Adrenal Cortex↗
PubMed1993

Characterization of the 48.5 kDa chorionic gonadotropin-like protein from Xanthomonas maltophilia.

Our laboratory has previously reported the isolation of a 48.5 kDa membrane protein from Xanthomonas maltophilia (ATCC 13637) which immunologically cross-reacts with the beta-subunit of human chorionic gonadotropin (hCG) in both polyclonal and monoclonal radioimmunoassays (RIA) (1). The protein showed no reaction in RIAs for human LH, TSH, or the free alpha subunit of hCG. We have now improved the protein purification procedure and have obtained adequate bacterial protein to characterize the pure protein (designated xCG) in RIAs and also to obtain amino acid composition and partial sequence. We present these data and compare homology to hCG. An RIA for the bacterial protein has also been developed.

Amino Acid Sequence↗
PubMed1993

Osteoporosis: pathophysiology, prevention, diagnosis, and treatment.

Bone is a living tissue; throughout life, new bone formation coexists with bone resorption. Although a large number of hormones and cytokines modulate osteoblast and osteoclast function, osteoporosis results from any disorder in which bone formation becomes uncoupled from bone resorption. Many disorders are associated with the uncoupling of bone formation and resorption. The most common is loss of gonadal steroid action on bone, as occurs in menopause or in male and female hypogonadism not associated with menopause. Other relatively common causes include primary hyperparathyroidism and endogenous or exogenous hypercortisolism and thyrotoxicosis. A large number of other, less frequent disorders also cause osteoporosis. Treatment of osteoporosis consists first of removing the cause if possible, for example, abolishing hypercortisolism, thyrotoxicosis, or hyperparathyroidism. In menopausal women or hypogonadal men or women, replacement of estrogens or androgens represents effective therapy. Estrogens and androgens given to hypogonadal subjects strikingly reduce bone resorption. For patients with established osteoporosis who either cannot take gonadal steroids or who are not hypogonadal, calcitonin decreases bone resorption and may stabilize bone mass. Estrogen replacement and calcitonin are approved by the Food and Drug Administration for treatment of osteoporosis. Experimental therapies presently include 1,25-dihydroxyvitamin D (calcitriol), bisphosphonates in intermittent treatment regimes, and fluoride in lower dosages than were used in previous studies. The use of fluoride is controversial, and to some extent it has fallen into disrepute. Effective use of any treatment is predicated on understanding the pathophysiology in any particular disease setting.

Bone Density↗
PubMed1993

Development of third-generation immunochemiluminometric assays of follitropin and lutropin and clinical application in determining pediatric reference ranges.

We developed dioxatane-based immunochemiluminometric assays (ICMAs) for lutropin (LH) and follitropin (FSH), using monoclonal antibodies. These ICMAs have a minimal detectable dose (analytical sensitivity) of 0.01 IU/L, extending the lower limit of sensitivity 10-fold (from 0.10 IU/L) when compared with immunoradiometric assays (IRMA) (second generation), and thus provide a true third-generation assay. Daytime FSH and LH concentrations were measured in 236 boys and 195 girls. Unlike the previous assays, all the samples had detectable concentrations of LH and FSH. In agreement with results from earlier methods, the present results indicate that for both sexes mean FSH and LH concentrations are relatively high during the early months of life, fall to baseline prepubertal concentrations by 12-18 months, and remain low until the onset of puberty. During puberty, the mean concentrations of FSH and LH increase significantly in both girls and boys with each stage of puberty, but there is considerable overlap between stages. These third-generation FSH and LH ICMAs reliably separate daytime plasma FSH and LH concentrations of prepubertal children from those of sexually mature children, and therefore can more reliably distinguish between the major causes of precocious puberty (e.g., gonadotropin dependent and independent). Our LH assay is also useful in monitoring the gonadotropin-releasing hormone therapy of patients with gonadotropin-dependent precocious puberty.

Adolescent↗
PubMed1992

Partial characterization of the 30 kD Ig-binding protein from Pseudomonas maltophilia.

We have previously demonstrated that Pseudomonas maltophilia (ATCC 13637) possess a 30 kDa cell wall protein which binds various subclasses of IgG's and IgA by their Fc region. The protein was solubilized by papain and purified by affinity chromatography on cyanogen bromide activated sepharose beads conjugated with human IgG. The eluent was electrophoresed on a 12% polyacrylamide gel under denaturing conditions, and the immunoactive bands identified by Western blot analysis, a second gel was stained with Coomassie blue. The affinity purified eluent was electrophoresed on a one-dimensional 15% polyacrylamide gel and stained with Coomassie blue. The protein band of interest was cut. The protein band was then digested in situ with Staphylococcus aureus V-8 protease. The peptide bands were separated by electrophoresis on a second one dimensional 15% polyacrylamide gel and then electroblotted into a polyvinylidine difluoride membrane. The bands were visualized by staining with Coomassie blue, cut out, and sequenced using an automated gas phase sequencer. Minimal amino acid composition was determined in a similar fashion. We have thus obtained partial N-terminal amino acid sequence data from the above method.

Amino Acid Sequence↗
PubMed1992

Stimulation of Candida albicans transition by human chorionic gonadotrophin and a bacterial protein.

Candida albicans, a dimorphic fungus, is involved commonly in human infections with the mycelium form more associated with pathogenicity. The influence of various hormones and a bacterial protein on the transition from blastospore to mycelium was assessed. Human luteinizing hormone (hLH), chorionic gonadotrophin (hCG), and an hCG-like material purified from a bacteria, Xanthomonas maltophilia (PCG), were able to increase the rate of transition when compared with the controls. The effect of the two hormones and the bacterial peptide were specific, as human follicle stimulating hormone (hFSH), thyroid stimulating hormone (hTSH), growth hormone (hGH), prolactin (hPrl) and rat and bovine LH (rLH, bLH), and bovine albumin and gamma globulin did not affect the transition. The binding of 125I-hCG or 125I-LH to spheroplasts of Candida albicans were competitively displaced by hCG, hLH, and PCG. Scatchard analysis of binding of all three ligands revealed two binding sites with a high-affinity nM Kd. Thus, hCG, hLH, and PCG induce transition of Candida albicans from a blastospore state to a mycelium form, suggesting that these hormones may modify the pathogenicity of Candida albicans.

Bacterial Proteins↗
PubMed1992

ACTH immunoactivity in normal rat tissues: modulation by hypophysectomy and adrenalectomy.

This study investigates the effect of pertubation of the normal pituitary-adrenal axis on concentrations of adrenocorticotropin (ACTH)-like immunoactivity in peripheral tissues. We used a polyclonal antibody (West antibody) to measure ACTH-like immunoactivity in glacial acetic acid extracts of five tissues in adult male rats at increasing times (1, 7, 14, and 28 days) after hypophysectomy or adrenalectomy, and in normal control rats. Concentrations of ACTH-like immunoactivity were similar to those previously reported in liver, colon, heart, and small intestine and were not significantly affected by either hypophysectomy or adrenalectomy. While hypophysectomy also had no effect in the kidney, adrenalectomy resulted in a four-fold increase in extractable immunoactivity, first noticeable at seven days (p less than 0.005), but increasing progressively to 28 days (p less than 0.0005). Gel filtration showed that most of the increase in activity in kidneys of adrenalectomized rats corresponded to the 4.5 kD form comprising most of the serum ACTH immunoactivity and suggesting that the activity increase in kidney was largely due to ACTH derived from blood.

Adrenalectomy↗