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Biomedical subjects

H C Taylor

Publications and source records attributed to H C Taylor.

At least 19 recordsLinked to original sources

Biochemical and structural studies of tenascin/hexabrachion proteins.

Tenascin is a large, disulfide-bonded glycoprotein of the extracellular matrix. The predominant form of tenascin observed by electron microscopy is a six-armed oligomer, termed a hexabrachion. We have determined the molecular mass of the native human hexabrachion to be 1.9 x 10(6) Da by sedimentation equilibrium analysis and by electrophoresis on non-reducing agarose gels. On reducing polyacrylamide gel electrophoresis (SDS-PAGE), human tenascin showed a single prominent band at 320 kDa and minor bands of 220 and 230 kDa. The molecular weight of the native human hexabrachion is thus consistent with a disulfide-bonded hexamer of the 320 kDa subunits. Upon treatment with neuraminidase, the apparent molecular weights of all human and chicken tenascin subunits on reducing SDS-PAGE were decreased by about 10 kDa. Prolonged incubation with alpha-mannosidase, however, caused no apparent change in the apparent molecular weight of tenascin subunits. Sedimentation in a cesium chloride gradient gave a higher buoyant density for human tenascin than for fibronectin, suggesting that it has a higher degree of glycosylation. The far-UV circular dichroism spectrum indicates a predominance of beta-structure and a lack of collagen-like or alpha-helical structure. When human hexabrachions were reduced and acetylated, the resulting fragments were single arms which sedimented at 6 S in glycerol gradients and migrated at 320 kDa on non-reducing gels. Treatment of tenascin with trypsin and alpha-chymotrypsin also produced large fragments which were fractionated by gradient sedimentation and analyzed by non-reducing SDS-PAGE and electron microscopy. We present a structural model for the assembly of the observed fragments into the elaborate native hexabrachion.

Animals

Assessment of calcitriol and inorganic phosphate therapy before cure of oncogenous osteomalacia by resection of a mixed mesenchymal tumor.

A 57 year old white male with oncogenous osteomalacia due to a mixed mesenchymal tumor was evaluated by sequential histologic and metabolic studies over a period of 33 mos prior to identifying the location of the tumor. On the basis of these studies we conclude: (i) disorders of the enterohepatic circulation and/or acceleration of metabolism of calcitriol are not responsible for its diminished level in oncogenous osteomalacia, (ii) the Von Kossa stain is preferred to the modified Masson in evaluating osteomalacia, (iii) avascular necrosis of the femoral head may be part of the syndrome, (iv) heterogeneity may be the hallmark of the responsible mesenchymal tumor and account for the different histological interpretations in the literature, (v) in compliant patients with oncogenous osteomalacia, calcitriol and Pi therapy may be effective.

Bone Neoplasms

Hexabrachion proteins in embryonic chicken tissues and human tumors.

Cell cultures of chicken embryo and human fibroblasts produce a large extracellular matrix molecule with a six-armed structure that we called a hexabrachion (Erickson, H. P., and J. L. Iglesias, 1984, Nature (Lond.), 311:267-269. In the present work we have determined that the myotendinous (M1) antigen described by M. Chiquet and D. M. Fambrough in chicken tissues (1984, J. Cell Biol., 98:1926-1936), and the glioma mesenchymal extracellular matrix protein described by Bourdon et al. in human tumors (Bourdon, M. A., C. J. Wikstrand, H. Furthmayr, T. J. Matthews, and D. D. Bigner, 1983, Cancer Res. 43:2796-2805) have the structure of hexabrachions. We also demonstrate that the M1 antigen is present in embryonic brain, where it was previously reported absent, and have purified hexabrachions from brain homogenates. The recently described cytotactin (Grumet, M., S. Hoffman, K. L. Crossin, and G. M. Edelman, 1985, Proc. Natl. Acad. Sci. USA, 82:8075-8079) now appears to be identical to the chicken hexabrachion protein. In a search for functional roles, we looked for a possible cell attachment activity. A strong, fibronectin-like attachment activity was present in (NH4)2SO4 precipitates of cell supernatant and sedimented with hexabrachions in glycerol gradients. Hexabrachions purified by antibody adsorption, however, had lost this activity, suggesting that it was due to a separate factor associated with hexabrachions in the gradient fractions. The combined information in the several, previously unrelated studies suggests that hexabrachions may play a role in organizing localized regions of extracellular matrix. The protein is prominently expressed at specific times and locations during embryonic development, is retained in certain adult tissues, and is reexpressed in a variety of tumors.

Animals

Clonidine suppression test for pheochromocytoma: examples of misleading results.

Baseline plasma norepinephrine (NE) and epinephrine (E) levels over 2000 pg/ml or failure to suppress to less than 500 pg/ml after oral clonidine have been considered diagnostic of the presence of a pheochromocytoma. We found a false negative clonidine suppression test in a patient with an asymptomatic ACTH-secreting pheochromocytoma who had minimally increased resting plasma NE and E values of 669 and 419 pg/ml, respectively. Clonidine suppression caused decreases at 2 and 3 h to 372 and 408 pg/ml, respectively. A positive test was found in a patient with repeatedly elevated baseline plasma NE and E concentrations; the two highest results were 2501 and 3022 pg/ml. Clonidine administration on five occasions failed to decrease plasma NE and E levels to less than 500 pg/ml. However, no pheochromocytoma was found by selective venous catheterization, two laparotomies, and, ultimately, postmortem examination. Diffuse infiltration of lymphoplasmacytic cells throughout sympathetic ganglia and adrenal medulla raise the possibility of a diffuse autoimmune disorder, resulting in excessive catecholamine production. These examples suggest that the clonidine suppression test does not always indicate the presence or absence of a pheochromocytoma.

Adrenal Gland Neoplasms

Effect of nifedipine on TRH stimulation of TSH and PRL release by the pituitary gland.

Studies in vitro and in vivo have shown that thyrotropin-releasing hormone (TRH)-induced calcium ion changes in the adenohypophysial cells play an important role in release of hormones by the anterior pituitary. To determine the effect of the calcium blocker nifedipine on TRH-induced thyroid-stimulating hormone (TSH) and prolactin (PRL) release, TRH stimulation tests were performed before and after 74 hours of nifedipine therapy in ten patients. Although the magnitude of the TSH and PRL mean peak increase above baseline was slightly lower during calcium blocker administration (TSH 14.1 +/- 4.8 SEM v 16.4 +/- 4.5 SEM; PRL 37.7 +/- 4.5 SEM v 41.7 +/- 5.4 SEM), this was not statistically significant. Use of nifedipine in clinically effective doses does not appear to significantly interfere with TRH-stimulated release of TSH or PRL, in vivo.

Adult

Crystallographic structure of an active, sequence-engineered ribonuclease.

X-ray diffraction methods were used to test a synthetic-modeling approach to the sequence engineering of bovine pancreatic ribonuclease. A model of RNase S-peptide (residues 1-20), having a simplified amino acid sequence but retaining elements deduced to be essential for conformation and function, was previously synthesized and found to form a catalytically active and stable complex with native S-protein (residues 21-24). We have now obtained a 3-A-resolution electron density map of this semisynthetic complex which reveals that the conformation of model peptide closely mimics that of native S-peptide, as intended by sequence design. Some small differences from the native structure are observed: Glu-2 and Arg-10 of the model complex are not close enough to form a salt bridge, the position of the His-12 imidazole ring is slightly shifted in the active site, and the peptide's amino terminus is reoriented. Nonetheless, the major structural features predicted to be essential by computer-aided peptide-design analysis are preserved in the model peptide portion of the complex. These include (i) the alpha-helical framework involving residues 3-13, (ii) the catalytically competent orientation of His-12, and (iii) complex-stabilizing non-bonding interactions involving Phe-8 and Met-13 of S-peptide and hydrophobic residues in the cleft region of S-protein. Further, sequence simplification has not introduced any non-native, potentially stabilizing contacts between the model peptide and S-protein. The results emphasize the usefulness, in redesigning native proteins, of categorizing sequence into residues providing conformational framework and those determining intra-and intermolecular surface recognition.

Amino Acid Sequence

The social responsibility of the obstetrician.

Recognition is at once given to the responsibility to support the highest standard of maternity care. Beyond the strictly medical issues, however, is a wide range of social problems associated with human reproduction toward the solution of which the obstetrician has unique opportunities. These include measures directed toward the optimum timing and number of births, efforts for the adoption of appropriate codes of sexual behavior, and the prevention or early diagnosis of a number of special diseases and functional disorders. Undertakings in these fields are the responsibility of the individual obstetrician, and collectively of his societies, including the International Federation of Gynaecology and Obstetrics.

Abortion, Legal

Oncogenic osteomalacia and inappropriate antidiuretic hormone secretion due to oat-cell carcinoma.

The syndrome of tumor-induced osteomalacia has been previously thought to occur only in association with mesenchymal tumors, although one report has linked prostatic carcinoma with the syndrome. We report the case of a patient who presented first with the clinical and biochemical features of the syndrome of inappropriate antidiuretic hormone secretion, and then oncogenic osteomalacia. The first syndrome was characterized by headaches, nausea, and vomiting; serum sodium determinations ranged between 107 and 118 meq/L with simultaneous urine spot sodium concentrations of 100 to 116 meq/L. The circulating antidiuretic hormone level was markedly elevated to 261.5 microU/mL. The osteomalacia was discovered incidentally when depressed serum phosphorus levels of 1.2 to 1.7 mg/dL were noted in association with 24-hour urine phosphorus excretion exceeding 1000 mg/24 h. Undecalcified tetracycline-labeled bone biopsy samples confirmed oncogenic osteomalacia. Only afterward was a small-cell carcinoma of the lung identified as the likely source of both of these syndromes.

Carcinoma, Small Cell

Adrenal insufficiency secondary to carcinoma metastatic to the adrenal gland.

Four patients are reported in whom adrenocortical insufficiency developed consequent to carcinoma metastatic to the adrenal glands. Recognition and treatment of this entity may lead to palliation of symptoms and prolongation of useful life. The computerized axial tomographic scanner is a valuable diagnostic aid in diagnosing adrenal enlargement.

Adrenal Cortex

Effect of arm ergometry training on physical work capacity of individuals with spinal cord injuries.

The purpose of this study was to evaluate arm cycle ergometry as an aerobic training method in the rehabilitation of individuals with spinal cord injuries. Four male subjects with spinal cord injuries trained for five weeks with arm cycle ergometry. Training sessions were 30 minutes long three times a week at an intensity of 60 to 80 percent of maximal heart rate. Pretraining and posttraining maximal exercise testing consisting of noncontinuous, multistage graded arm ergometry was completed by each subject. Heart rates, oxygen consumption, and work loads were measured. Mean increases of 64.32 percent and 60.54 percent were found for posttraining maximal work loads and maximal oxygen consumption values, respectively. A paired t test (p less than .05) revealed that only the change in posttraining mean maximal oxygen consumption value to be statistically significant. That only this value was significant may be attributable to the small sample size and the large intersubject variability. Implications of these results for clinicians and the limitations of the study are discussed.

Adult

Symptomatic osteomalacia after jejunoileal bypass surgery in a patient with primary hyperparathyroidism. A study of the change in bone morphology and vitamin D metabolites before and during treatment.

A 48-year-old woman underwent jejunoileal bypass surgery for obesity while hypercalcemic. Three years later, she developed symptomatic osteomalacia impairing her daily activities. Bone biopsy confirmed the clinical diagnosis of osteomalacia, and treatment with 8000 U daily of vitamin D and milk resulted in striking improvement of clinical symptoms and resolution of her osteomalacia both chemically and histologically. The patient, however, again became hypercalcemic and a parathyroid adenoma was subsequently removed with restoration of serum calcium values to normal. Neither the occurrence and successful treatment of gross symptomatic osteomalacia consequent to jejunoileal bypass surgery, nor the obscuration of primary hyperparathyroidism by osteomalacia has been hitherto well documented in the United States.

25-Hydroxyvitamin D 2

Recurrence and heterogeneity in painless thyrotoxic lymphocytic thyroiditis. Report of five cases.

Five patients had recurrent episodes of spontaneously resolving thyrotoxicosis (SRT). Three displayed only the classic low-intake variety of this disorder, while two had alternating episodes of high-uptake and low-uptake thyrotoxicosis. Two of the three with low uptake only who had thyrotropin displacement activity (TDA) assays had negative results on this test, while one of the patients with alternating high- and low-uptake thyrotoxicosis had a positive TDA assay result, suggesting that the pathogenesis in the two types of SRT may differ.

Adult

An international system for the education of students of medicine and other health professionals in human reproduction. The FIGO teaching manual: a status report.

An analysis of the effectiveness of FIGO's Teaching Manual on Human Reproduction is reported on the basis of answers to a questionnaire received from 100 heads of teaching departments, chiefly of obstetrics and gynecology. These represented 32 countries widely distributed throughout the developing countries of the world. The most significant finding was the evidence of the very large number of medical and other students that could be reached through the principle of placing superlatively good teaching material in the hands of key educators in their native country. Additional answers to the questionnaire provided information on the way courses were organized about the material and suggestions as the useful changes, possible expansion of subject matter, and the felt need for an updated edition.

Education, Medical, Undergraduate