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R Lloyd

Publications and source records attributed to R Lloyd.

At least 19 recordsLinked to original sources
PubMed1992

Sites of synthesis of chromogranins A and B in the human brain.

The sites of synthesis of the chromogranins A and B, and their potential processed peptides, were examined by quantitating the levels of chromogranin A and B mRNA in various regions of the human brain by Northern blot analysis. Chromogranin A and B mRNA expression in the brain is region-specific and confined to grey matter. In situ hybridization histochemistry detected chromogranin A and B mRNA in pyramidal neurons of human cerebral cortex. Cell-specific expression in subpopulations of cerebrocortical neurons suggest that chromogranin A and B gene products may play a role in central neuronal function.

Brain↗
PubMed1992

Relationship between increased cyclic AMP-phosphodiesterase activity and abnormal adenylyl cyclase regulation in leukocytes from patients with atopic dermatitis.

Atopic dermatitis (AD) is characterized by a variety of abnormal physiologic and pharmacologic responses in the skin. Leukocyte abnormalities of the cyclic nucleotide system include increased cAMP phosphodiesterase (PDE) and adenylyl cyclase activities. We have evaluated the possibility that a defect of the inhibitory GTP-binding protein (Gi) might cause inadequate modulation of adenylyl cyclase activity in AD leukocytes. We carried out a series of studies assessing adenylyl cyclase and Gi subunits in monocyte membranes. Using both pertussis toxin ribosylation and direct monoclonal antibody labeling of Gi proteins, we have shown evidence for a decrease or possible absence of one of the Gi proteins in atopic monocyte membranes. A genetic defect or toxin-mediated abnormality in leukocyte membrane Gi could account for these findings. Increased cAMP degradation by PDE may be a compensatory mechanism for increased cAMP synthesis that is regulated by GTP-binding proteins. But this increased PDE activity also rendered AD leukocytes hypo-responsive to immunofunction regulatory signals mediated by cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

cis- and trans-cleavage activities of poliovirus 2A protease expressed in Escherichia coli.

The poliovirus protease, 2Apro, was produced in Escherichia coli from plasmids that encode a fusion protein consisting of the N-terminal portion of the bacterial TrpE protein linked to poliovirus 2Apro. This fusion protein underwent efficient autocatalytic cleavage at the N terminus of 2Apro, generating the mature protease. Extracts of bacteria expressing 2Apro induced the specific cleavage of the p220 subunit of the eukaryotic translation initiation factor 4F, similar to the 2Apro-mediated reaction that occurs in poliovirus-infected HeLa cells. A portion of the poliovirus polyprotein containing the 2Apro cleavage site at the P1/P2 junction was produced by translation of cDNA transcripts in rabbit reticulocyte lysates and then tested as a substrate for 2Apro-mediated cleavage. The protein was partially cleaved by 2Apro in trans. Finally, a 16-amino-acid synthetic peptide, representing the P1/P2 junction sequence, was analyzed as a substrate for 2Apro. The peptide was labeled with fluorescein at a lysine residue to facilitate its detection. Recombinant 2Apro cleaved the synthetic peptide into two half-peptide molecules which were resolved by high-pressure liquid chromatography. Direct sequence analysis of the isolated peptide products demonstrated that cleavage occurred at the expected tyrosine-glycine pair. A rapid cleavage assay for 2Apro activity on the synthetic peptide was developed, using separation of the fluorescein-labeled 8-amino-acid product from the 16-residue substrate by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels.

Base Sequence↗
PubMed1990

The use of somatostatin analog in gastroenteropancreatic tumors other than carcinoid.

We have used the gastrinoma syndrome to examine the effects of SMS. Acutely, SMS decreased acid secretion and restored the BAO/MAO to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized. Treatment for up to 2 years with SMS controlled symptoms, suppressed serum gastrin, and suppressed acid secretion. Treatment for 1 year or longer decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted for 48 hours after withdrawal of SMS. SMS treatment arrested progression of tumor growth only in patients in whom there was a reduction in gastrin and gastric acid secretion. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 24 months did not inhibit tumor growth or decrease gastrin levels. In those patients in whom a reduction in the blood flow to liver tumors was shown angiographically, there was a progressive improvement in hormone secretion and in tumor size in the ensuing year of treatment, suggesting that a major target of SMS is that vascular supply of the tumors. Tumors shown to produce peptides other than gastrin, for example ACTH, were found to be markedly resistant to the action of SMS and continued to grow in an unbridled manner.

Adult↗
PubMed1989

The accuracy of urinary luteinizing hormone testing in predicting ovulation.

Transvaginal ultrasonography and daily urinary luteinizing hormone testing were used to evaluate the accuracy of urinary luteinizing hormone testing in predicting ovulation in 33 spontaneously ovulating women beginning on cycle day 10. Ovulation was confirmed in all patients with luteal phase progesterone levels and endometrial biopsy specimens. The results demonstrated that transvaginal ultrasonography and urinary luteinizing hormone testing detected ovulation in all cycles. However, the onset of urinary luteinizing hormone occurred after follicle rupture was documented by ultrasonography in 9% of the women studied. Thus the question of accuracy of urinary luteinizing hormone testing in prediction contrasted to detection of ovulation is raised. This observation is of importance in patients in whom prediction of ovulation is critical to treatment management. Therefore, an ultrasonographic examination to confirm the presence of an unruptured follicle on the day of onset of urinary luteinizing hormone surge is recommended, particularly in patients failing to conceive after three to six cycles of artificial insemination when the inseminations are timed with the onset of urinary luteinizing hormone surge.

Adult↗
PubMed1989

Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization.

Pituitary adenomas, removed surgically from three women with normal or slightly elevated serum growth hormone levels and no evidence of acromegaly, were studied. The tumor cells were shown by electron microscopy to correspond to sparsely granulated somatotrophs but immunocytochemistry showed that they contained no, moderate, or little growth hormone. Two tumors examined in vitro secreted small amounts of growth hormone in the tissue culture medium initially with a spontaneous rise after several days, and responded to growth hormone-releasing hormone stimulation with increased growth hormone release. In situ hybridization demonstrated growth hormone mRNA expression in adenoma cells. Clinically silent somatotroph adenomas represent a hitherto undescribed entity; electron microscopy shows that they consist of somatotrophs, and express growth hormone mRNA but do not secrete growth hormone in amounts needed to raise substantially serum growth hormone levels and cause acromegaly. Further work is required to clarify the mechanisms accounting for the lack of clinical and biochemical evidence of hormone excess associated with these tumors.

Adenoma↗
PubMed1989

Work site blood pressure control: the evolution of a program.

In 1976, in an employee population of approximately 8700, there was little information about the prevalence of hypertension or the level of control in the known hypertensive workers. The problem was approached initially by screening and then by aggressive follow-up. Ultimately, 21.4% of the employees were identified as hypertensive or in a borderline range. In the population treated at the work site and those treated by outside sources, the level of control was brought to a point consistently over 80% by 1987. It is apparent that continued efforts to identify hypertension, combined with aggressive follow-up, can achieve a significant level of control in a work site population.

Absenteeism↗
PubMed1988

Localization and imaging of radiolabeled monoclonal antibodies against colorectal carcinoma in tumor-bearing nude mice.

Four monoclonal antibodies (MoAbs) (35, 115, 17-1A, and B72.3) directed towards human carcinoma surface antigens have been studied in athymic nude mice with LS174T, CO112, or SW948 colon carcinoma xenografts or negative control melanoma (MEL-1), lymphoma (Namalwa), and breast (MCF-7) carcinoma xenografts to evaluate the effects of antigenic heterogeneity and time after administration on localization and imaging. 125I-labeled 115 showed the highest uptake of any antibody in LS174T tumors. MoAbs 35 and B72.3 showed similar but lower levels of uptake in LS174T and CO112 tumors, but B72.3 concentrated less in SW948 tumors. 17-1A showed the highest degree of accumulation in SW948 tumor xenografts. No specific uptake of the four anti-carcinoma MoAbs was observed in MEL-1, Namalwa, or MCF-7 xenografts. The specificity of the in vivo tumor localization of the four anti-carcinoma MoAbs was confirmed by the low degree of accumulation of a control MoAb against influenza virus in LS174T tumors. Imaging studies with 131I-labeled colorectal cancer MoAbs showed specific uptake and retention in LS174T tumors, with progressive clearance from the whole body. The colorectal cancer MoAbs were compared for immunohistochemical binding against biopsies from patients with colorectal cancer and adjacent normal colonic tissue. Most colorectal cancer specimens showed moderate to strong staining with the four MoAbs. The percentage of positive cells varied within and between tumors demonstrating antigenic heterogeneity. Absent to slight focal staining was seen with normal colon tissue. B72.3 showed the highest degree of staining specificity. This study indicates a difference in the immunohistochemical binding of a panel of MoAbs against biopsies of colon adenocarcinoma and a dependence of in vivo localization on the human colon cancer cell line used as target. This has important implications for future clinical diagnostic and therapeutic studies.

Animals↗
PubMed1987

Somatostatinomas, PPomas, neurotensinomas.

We have reviewed data pertinent to three tumor syndromes that derive from overproduction of three GEP peptide hormones. The clinical syndrome of somatostatin excess remains well defined with diabetes, diarrhea, steatorrhea being predominant features. With the availability of assays and increasing awareness, more cases are being diagnosed in the intestine and these differ somewhat in their presentation with cholecystitis, GI bleeding, or a mass as the cardinal features. An unusual association with MEN II pheochromacytoma and neurofibromatosis is emerging. PPomas remain enigmatic. Although diarrhea is a feature, these tumors are usually silent and present with hypatomegally, abdominal pain, and jaundice because of the large size and malignant nature. Neurotensinomas remain rare and truly difficult to separate from the symptom complex produced by VIP excess. Edema, hypotension, cyanosis and flushing should alert one to the possibility of a neurotensin-secreting tumor.

Adenoma, Islet Cell↗
PubMed1987

Iodine-131 MIBG scintigraphy of neuroendocrine tumors other than pheochromocytoma and neuroblastoma.

Metaiodobenzylguanidine (MIBG) locates most pheochromocytomas and neuroblastomas. The tracer is concentrated in intracellular storage vesicles by an active process. Many other neuroendocrine tumors of the amine precursor uptake and decarboxylation (APUD) series have hormonal storage vesicles and, thus, the potential to take up [131I]MIBG. A variety of neuroendocrine tumors in 57 patients were studied 1, 2, and 3 days after 0.5 mCi [131I]MIBG. Views from skull to pelvis were obtained. Results of MIBG scans were compared with all available imaging modalities (including plain radiography, liver scan, ultrasound, computed tomography, and angiography) and surgical exploration. The neuroendocrine nature of the tumor was determined by histology, immunohistochemistry, electron microscopy, and the assay of appropriate biogenic amines and peptide hormones. Results were (positive/total cases): carcinoids (four of ten), nonsecreting paragangliomas (three of three), sporadic medullary carcinomas of the thyroid (MCT) (one of five), familial MCT (one of 26), chemodectomas (two of five), oat cell carcinomas (zero of four), choriocarcinoma (one of one), atypical schwannoma (with storage granules) (one of one), Merkel cell skin cancer (one of one), islet cell carcinoma (zero of one). We conclude that a wide range of neuroendocrine tumors show [131I]MIBG uptake; tumors other than pheochromocytomas and neuroblastomas are less often seen scintigraphically, but in certain cases (e.g., carcinoid and nonsecreting paragangliomas) scintigraphy may be useful in depicting the extent and location of disease and may indicate therapeutic potential. Iodine-131 MIBG shows promise in the diagnosis and staging of tumors of varied types.

3-Iodobenzylguanidine↗
PubMed1986

Immunohistochemical localization of a specific ileal peptide in the pig.

The tissue distribution of a polypeptide purified from pig ileal mucosa tentatively called porcine ileal polypeptide (PIP) and known to have potent acid secretagogue activity has been studied with immunohistochemical methods together with extraction of different tissues followed by radioimmunoassay for PIP content. Histochemically the peptide is found in superficial epithelial cells in the mucosa of the distal 20% of the small intestine and to some extent in the mucosa of the urinary tract. There is no staining of goblet cells or crypt cells. The staining in the urinary tract mucosa is due to antigenic peptides with Mr identical to PIP. While the presence of PIP in the ileum is compatible with a function as an enterooxyntin, it is not possible at present to explain the physiologic role of PIP entirely as a hormone regulating acid secretion in light of the immunohistochemical distribution.

Animals↗
PubMed1985

Familial extra-adrenal pheochromocytoma. A new syndrome.

Pheochromocytomas in the same anatomic site, the right renal hilum, occurred in a family over three successive generations. For two patients in the latter two generations, scintigraphy with iodine 131-tagged metaiodobenzylguanidine (MIBG) showed tumors only in the region of the right renal hilum, thus indicating that they were primary lesions. At surgery, except for lymph node metastases noted microscopically in one patient, tumors were found only near the right renal hilum. The adrenal glands seemed normal on inspection, palpation, and computed tomography. In another family, a mother and son had primary pheochromocytomas arising from the urinary bladder. We suggest that primary extra-adrenal pheochromocytoma is a syndrome in which specific genetic abnormalities determine sites of tumor development.

Adolescent↗