Increased neonatal urinary ammonia: a marker for in utero caloric deprivation?

The decline in the urinary urea to ammonia ratio represents a simple measure of nutritional status in the adult. We examined the relationship of this ratio to nutrient-related fetal growth retardation. Levels of ammonia and urea nitrogen were measured in the first voided urine and cord blood from 15 term infants exhibiting a wide range of growth.

Localization of vasoactive intestinal peptide and peptide histidine isoleucine immunoreactivity and mRNA within the rat suprachiasmatic nucleus.

The distribution of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) mRNA within the suprachiasmatic nucleus (SCN) of rats was evaluated by immunocytochemistry and in situ hybridization. The pattern of VIP and PHI immunoreactivity corresponded closely to the distribution of VIP/PHI mRNA within the ventrolateral SCN. Clear hybridization signal was observed within the SCN of rats killed 5 h after light onset and in rats killed 2 h after the onset of the dark phase of the light-dark cycle.

DNA probes in diagnostic pathology.

Molecular pathology has become firmly established as a distinctive discipline in medicine. It has introduced radical changes in concepts of disease causation and in classification of disease states affecting humans and other organisms. In addition, molecular pathology represents a "new" diagnostic technology with many potentials that have been heretofore untapped.

Distribution and immunochemical characterization of a keratin-like antigen in epithelial tumors using mouse and human monoclonal antibodies.

Using conventional murine hybridoma technology, we have produced a monoclonal antibody (MAb), 89E5, which recognizes two keratin-like polypeptides (Mr 53,000 and 45,000), which are preferentially expressed by epithelial tumors. In addition to detection of tumor cells by immunohistochemistry, MAb 89E5 was able to localize to tumor xenografts in nude mice after iodination of its F(ab')2 fragments. To develop potentially less immunogenic antibodies to antigens defined by MAb 89E5, studies were performed to produce a human counterpart to the mouse MAb.

Acute stimulation of chromaffin cell proliferation in the adult rat adrenal medulla.

Susceptible strains of rats develop adrenal medullary hyperplasia and neoplasia after long-term administration of the antihypertensive drug reserpine, or of other pharmacologic agents which alter neuroendocrine function. These proliferative lesions are of potential medical importance as a model for familial multiple endocrine neoplasia syndromes, and are of fundamental interest because they might elucidate mechanisms regulating chromaffin cell proliferation during normal development. To study the initiation of the adrenal lesions, chromaffin cell mitoses were counted in adult male rats injected with reserpine or control solvent for 5 days, with the final injection containing colcemid to arrest cells in mitosis.

Determinants of morbidity in obese women delivered by cesarean.

Studies examining the increased surgical morbidity among obese gravidas have focused mainly on differences in outcome between obese and nonobese mothers. Little is known, however, about the cause for worsened operative outcome in obese mothers or the potential impact of perioperative interventions. To define more precisely the clinical determinants of postoperative morbidity, multivariate analysis was used to relate antepartum and intrapartum variables to three measures of morbidity in 107 consecutively delivered obese women undergoing cesarean.

Gastrin-releasing peptide gene expression in developing, hyperplastic, and neoplastic human thyroid C-cells.

Gastrin-releasing peptide (GRP), the mammalian homolog of bombesin, is often studied as a prototypic neuroregulatory hormone and growth factor, but its own regulation and physiological roles remain to be fully defined. We now demonstrate that the GRP gene is expressed in human thyroidal calcitonin (CT)-containing neuroendocrine cells (C-cells) in an ontogenic pattern similar to its expression in pulmonary neuroendocrine cells and is also expressed at high levels in C-cell hyperplasias and neoplasias (medullary carcinomas of the thyroid). Mean GRP-like immunoreactivity is 20 times higher in 3-week-old to 5-month-old infants than in normal adults, with six of seven infants having GRP levels 6- to 67-fold higher than those in normal adults, the highest levels occurring at 2-2.

The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience.

An important question facing physicians who care for families with multiple endocrine neoplasia type 2a is whether prospective screening to detect early abnormalities of the thyroid, parathyroid, or adrenal glands favorably influences the ultimate course of the disease. An 18-year study of a large family has allowed us to examine the effect of early treatment on the clinical course of the disease. Of 22 patients who underwent thyroidectomy for early C-cell abnormalities, 19 remained free of detectable medullary thyroid carcinoma according to all criteria, at a mean of 11 years after thyroidectomy.

S-100 protein positivity in breast carcinomas: a potential pitfall in diagnostic immunohistochemistry.

S-100 protein, originally isolated from neural tissues, has also been identified in various normal and neoplastic cells, including malignant melanomas. A systematic immunohistochemical investigation of this antigen was performed on formalin-fixed paraffin-embedded samples of benign and malignant breast tissues with use of the avidin-biotin-peroxidase complex immunoperoxidase technique and a polyclonal antiserum that recognizes both the alpha and beta subunits of S-100 protein. In benign breast tissue, S-100 protein was present in both epithelial and myoepithelial cells of terminal ducts and lobules; the staining was cytoplasmic and sometimes nuclear.

Contributions of immunohistochemical and molecular biological techniques to endocrine pathology.

Histochemistry has played a major role in the development and implementation of new methods for analysis of gene expression at the cellular level. With the techniques of immunocytochemistry and in situ hybridization, the products of RNA translation as well as specific messenger RNAs and genomic DNAs can be demonstrated and can provide highly dynamic analyses of gene transcription and translation in individual cells. In endocrine pathology, these approaches have been particularly effective for correlation of functional abnormalities with the varying manifestations of disease at the cellular level.

Thyroid hormone regulates TRH biosynthesis in the paraventricular nucleus of the rat hypothalamus.

Thyroid hormone is important in the regulation of synthesis and secretion of thyroid-stimulating hormone (TSH) in the anterior pituitary, but its role in the control of hypothalamic thyrotropin-releasing hormone (TRH) is controversial. To determine whether thyroid hormone regulates the function of TRH in the hypothalamic tuberoinfundibular system, a study was made of the effect of hypothyroidism on thyrotropin-releasing hormone messenger RNA (proTRH mRNA) and TRH prohormone in the rat paraventricular nucleus. Extracts of rat hypothalamic paraventricular nucleus were examined by quantitative Northern blot analysis, and coronal sections of rat brain were examined by in situ hybridization histochemistry and immunocytochemistry.

Transient elevation of messenger RNA encoding gastrin-releasing peptide, a putative pulmonary growth factor in human fetal lung.

Gastrin-releasing peptide (GRP), the mammalian homologue of the amphibian peptide bombesin, is present in pulmonary neuroendocrine cells and appears to be a growth factor for both normal and neoplastic pulmonary cells. Previously we have reported the cloning of the messenger RNAs (mRNAs) and gene that encode human GRP. We now report that GRP mRNAs are markedly elevated in human fetal lung during the canalicular phase of pulmonary development (from approximately 16 to 30 wk gestation).

Peptide YY. Structure of the precursor and expression in exocrine pancreas.

Peptide YY is a 36-residue gastrointestinal hormone which inhibits both pancreatic and gastric secretion. We have isolated a cDNA encoding the peptide YY precursor by screening a rat intestinal lambda gt11 cDNA library with an antiserum directed against the porcine hormone. The nucleotide sequence of the cDNA encodes a 98-residue protein (molecular weight, 11, 121) which has an amino acid sequence identical to that of porcine peptide YY.

Fetal hemorrhage from umbilical cord hemangioma.

Hemangiomas of the umbilical cord are rare. In this case, an acute, massive fetal hemorrhage from a ruptured umbilical hemangioma occurred after spontaneous rupture of membranes. Ectopic small intestinal mucosa covered the proximal surface of the umbilical cord.

Recurrent small for gestational age birth: perinatal risks and outcomes.

The risk of recurrent small for gestational age birth, as well as maternal and fetal-neonatal characteristics associated with recurrence, was examined in 174 mothers of consecutively delivered small for gestational age infants followed through an additional 240 livebirths. There was a twofold and fourfold increase in the risk for small for gestational age birth after one and two small for gestational age births, respectively. Although an intervening average for gestational age birth decreased the risk of recurrence, these women remained at increased risk over the general population.

Hypertrophy of pheochromocytoma cells treated with nerve growth factor and activators of adenylate cyclase.

PC12 pheochromocytoma cells treated with nerve growth factor (NGF) in combination with high concentrations of the activators of adenylate cyclase, forskolin or cholera toxin, become more neuron-like in size than cells treated with NGF or with activators of adenylate cyclase alone. Cells treated simultaneously with NGF plus forskolin or cholera toxin paradoxically show less process outgrowth than cells treated with NGF alone. Addition of forskolin or cholera toxin to cells pretreated with NGF, however, produces enlarged cells with intact processes that are indistinguishable from cultured neurons.

New techniques in gene product analysis.

Many of the new technologies that have developed as a result of advances in cellular and molecular biology, genetics, and immunology have had a major impact in clinical medicine and will continue to provide important diagnostic and investigative tools in the future. The ability to localize a wide variety of gene products in tissues has been accomplished largely through the use of immunohistochemistry. Characterization of gene expression at the levels of specific messenger RNAs and genomic DNAs is now possible through the use of both blot and in situ hybridization techniques.

Localization of thyrotropin-releasing hormone prohormone messenger ribonucleic acid in rat brain in situ hybridization.

We studied the distribution of pro- TRH mRNA in rat brain by in situ hybridization histochemistry using radiolabeled single stranded cRNA probes to confirm the hypothesis that the TRH precursor is distributed beyond regions that contain immunoreactive TRH. All regions of the central nervous system previously recognized to contain TRH showed hybridization. Hypophysiotropic neurons in the medial parvocellular division of the paraventricular nucleus showed more intense hybridization than anterior parvocellular division cells, suggesting regional differences in expression.

Fluorescence properties of calmodulin-binding peptides reflect alpha-helical periodicity.

A basic amphiphilic alpha-helix is a structural feature common to many calmodulin-binding peptides and proteins. A set of fluorescent analogues of a very tight binding inhibitor (dissociation constant of 200 picomolar) of calmodulin has been synthesized. The fluorescent amino acid tryptophan has been systematically moved throughout the sequence of this peptide.

Tissue distribution, immunochemical characterization, and biosynthesis of 47D10, a tumor-associated surface glycoprotein.

This report describes a new monoclonal antibody (MAb) designated 47D10 which was produced by immunizing mice against a human lung adenocarcinoma line, A549. The MAb 47D10 reacts with a surface antigen found in 95% of adenocarcinomas of the pancreas as well as on high percentages of adenocarcinomas from colon, breast, lung, and bile duct. The antigen was not detected in normal pancreas, in pancreatitis, or in a variety of normal tissues with the exception of colon and mature granulocytes.

Predicted calmodulin-binding sequence in the gamma subunit of phosphorylase b kinase.

A basic, amphiphilic alpha helix is a structural feature common to a variety of inhibitors of calmodulin and to the calmodulin-binding domains of myosin light chain kinases. To aid in recognizing this structural feature in sequences of peptides and proteins we have developed a computer algorithm which searches for sequences of appropriate length, hydrophobicity, helical hydrophobic moment, and charge to be considered as potential calmodulin-binding sequences. Such sequences occurred infrequently in proteins of known crystal structure.

Medullary thyroid carcinoma in the Syrian golden hamster: an immunohistochemical study.

Spontaneously occurring thyroid neoplasms exhibiting solid and/or anaplastic growth patterns in the Syrian golden hamster have been thought to be derived from follicular cells. Eight neoplasms of this type have been analyzed immunohistochemically and have been classified as medullary thyroid carcinomas (MTC) on the basis of their content of calcitonin (CT). Well differentiated MTCs in this species were composed of polyhedral cells showing uniform CT immunoreactivity while the poorly differentiated MTCs most often had spindle patterns of growth with marked variation in CT immunoreactivity.