Biomedical subjects

J Roth

Publications and source records attributed to J Roth.

At least 217 records · Page 12Linked to original sources

PubMed1995

Hodgkin and Reed-Sternberg cells do not carry T-cell receptor gamma gene rearrangements: evidence from single-cell polymerase chain reaction examination.

Hodgkin and Reed-Sternberg (H&RS) cells are generally accepted to be the neoplastic cells of Hodgkin's disease (HD), even though they represent only a minority of the cellular infiltrate in affected tissues. Recent immunologic studies and Southern blot analyses of DNA extracted from whole lymph node tissue favored, but did not convincingly prove a lymphoid origin of H&RS cells. To detect rearrangements of the T-cell receptor gamma chain (TCR gamma) genes at the single-cell level as an indication of early T-cell lymphoid differentiation, we isolated H&RS cells by micromanipulation from cytospin preparations of fresh biopsy material. TCR gamma chain rearrangement was detected by polymerase chain reaction using four "forward primers" that were constructed corresponding to all four V families and two "reverse primers" corresponding to consensus sequences of J segments. Rearrangements of all V families in combination with the different J segments were detected in human peripheral blood and tonsillar T cells. Although rearrangements of TCR gamma chain genes were shown in single cells of 10 of 10 T-cell leukemias, no rearrangement of these genes was found in single H&RS cells from 13 consecutive patients with HD. Our results indicate that H&RS cells from the vast majority of cases are not derived from T cells. This finding may have implications for the pathogenesis of HD and the development of more effective treatment regimens.

Base Sequence↗

PubMed1995

Changes in survival patterns of very low-birth-weight infants from 1980 to 1993.

OBJECTIVE: To determine changes in survival patterns among very low-birth-weight ( < 1500 g) infants between 1980 and 1993. METHODS: The records of 12,960 infants treated in nine perinatal intensive care centers in Florida were analyzed on the basis of survival (discharged alive from hospital) according to four independent variables: birth weight, race, sex, and transport status. Survival curves were generated using log linear regression techniques for each race by sex by transport status group. RESULTS: Race, sex, and transport status correlated significantly with survival: survival percentages were higher among black infants, female infants, and infants transported to the perinatal intensive care centers than among white infants, male infants, and those admitted initially to the tertiary care centers. After 1985, 95% of neonates with birth weights between 1200 and 1500 g survived. In addition, survival of 500- to 500-g transported black male infants increased from zero to near 80% during the 13-year period; that of 500- to 550-g inborn white female infants rose from 35% to 70%. CONCLUSIONS: These results illustrate the value of taking into account race, sex, and transport status in efforts to understand the contribution that neonatal intensive care of extremely low-birth-weight infants makes to the lowering of infant mortality, and of using multivariable statistical procedures to generate predicted survival probabilities for different subpopulations. These probabilities can be applied to (1) predicting survival for specific subgroups of extremely low-birth-weight infants, and (2) helping physicians develop clinical guidelines for extending care to infants at the threshold of viability.

Birth Weight↗

PubMed1995

Subcellular distribution of terminal alpha-D- and beta-D-galactosyl residues in Ehrlich tumour cells studied by lectin-gold techniques.

We have studied by high resolution in situ light and electron microscopic lectin-gold techniques the subcellular distribution of alpha-D-Gal residues using the Griffonia simplicifolia I-B4 isolectin and compared it with that of beta-D-Gal residues as detected with the Datura stramonium lectin in Ehrlich tumour cells grown as ascites or monolayer. The microvillar but not the smooth plasma membrane regions were labelled with the Griffonia simplicifolia I-B4 isolectin whereas both plasma membrane regions were equally well labelled with the Datura stramonium lectin. Elements of the endocytotic/lysosomal system such as coated membrane invaginations and vesicles, early and late endosomes and secondary lysosomes were positive for both alpha-D-Gal and beta-D-Gal residues. A particular feature of Ehrlich tumour cells is an elaborate tubular membrane system located in the pericentriolar region which is labelled throughout by both lectins and represents part of the endosomal system. In the Golgi apparatus labelling with both lectins was observed to commence in trans cisternae which is indirect evidence for a joint distribution of the sequentially acting beta 1,4 and alpha 1,3-galactosyl-transferases.

Animals↗

PubMed1995

The ability to re-express polysialylated NCAM in soleus muscle after denervation is reduced in aged rats compared to young adult rats.

The neural cell-adhesion molecule, NCAM, contains an unusual homopolymer of sialic acid units, polysialic acid. This carbohydrate seems to be involved in neurite outgrowth, bundling and branching, processes which are important during reinnervation. In aged rats, reinnervation of denervated muscle fibres is incomplete. In this study, age-related changes in the degree of polysialylation of NCAM re-expressed after denervation were examined using a monoclonal antibody recognizing polysialic acid and a polyclonal antibody recognizing NCAM. The results show that, after denervation, the degree of polysialylation on NCAM was clearly reduced in rat soleus muscle of aged, compared to young, adult rats. This age-related change in expression of polysialic acid probably influences the reinnervation process in aged muscle.

Animals↗

PubMed1995

[A comparative study of the imaging quality and picture dosage of a new conventional film-screen system for skeletal x-ray diagnosis].

PURPOSE: This paper compares a new film-screen system (FSS) called INSIGHT Skeletal Imaging System with the previously used Lanex/T-MAT G FSS. MATERIAL AND METHODS: Using a Bronder phantom, measurements were made of dose, resolution and contrast. 135 skeletal phantom images were assessed in order of quality by six observers. RESULTS: Comparable high resolution film-screen combinations (FSC) showed similar geometric resolution. Comparing high intensifying screens, the new INSIGHT Skeletal Regular FSS showed better resolution than the Lanex medium FSC. Dose reduction for the INSIGHT Skeletal Imaging FSS was 29-56%. The new FSS showed image quality similar to high resolution screens but was significantly better when using high intensifying screens. CONCLUSION: The new INSIGHT Skeletal Imaging System can replace the Lanex/T-MAT G FFS by retaining quality but reducing radiation dose by 29-56%. Using the new high intensifying FSC, images showed in addition improved film quality.

Bone and Bones↗

PubMed1995

[Fatal soccer injury as an unfortunate sequela of collision].

The tragic death of a 26-year old hobby soccer player is described, who had a collision with the opposing goalie and suffered from a fracture of the left lateral process of the atlas, an extensive subarachnoid haemorrhage, tamponade of the third and fourth cerebral ventricles, bleeding into both lateral cerebral ventricles, infratentorial and supratentorial cerebral oedema. Furthermore, a survey of the literature concerning acute death in soccer is presented.

Adult↗

PubMed1995

Uterine vascularity during stimulation and its correlation with implantation in in-vitro fertilization.

The changes in uterine artery blood flow in women undergoing in-vitro fertilization cycles were studied throughout stimulation after gonadotrophin-releasing hormone (GnRH) desensitization. The data obtained showed that the uterine vascularity was related to hormonal changes. The GnRH agonist effect was seen only after the third week of administration, and the uterine perfusion was significantly (P = 0.002) improved by the oestradiol secretion. Human chorionic gonadotrophins increased the resistance index (RI) significantly (P = 0.0001) for a period of 48 h. Then the progesterone secretion modified the curve with a significant improvement in the uterine blood flow (P = 0.03). Comparison of the RI value 2 days before human menopausal gonadotrophin (HMG) commencement, in patients with and without pregnancy, showed a higher RI in patients who did not conceive but no difference was observed on the day of embryo transfer. The pregnancy rates were similar whatever the range of the RI observed. The data available so far suggest that haemodynamic parameters alone, detected by Doppler sonography, do not provide full information on endometrial receptivity on the day of embryo transfer. A resistance index > 0.79 before HMG commencement seems to indicate poor uterine vascularity and may necessitate an increase in the HMG doses to prevent endometrial immaturity.

Adult↗

PubMed1995

Five promoters integrate control of the cob/pdu regulon in Salmonella typhimurium.

Propanediol is degraded by a B12-dependent pathway in Salmonella typhimurium. The enzymes for this pathway are encoded in a small region (minute 41) that includes the pdu operon (controlling B12-dependent degradation of propanediol) and the divergent cob operon (controlling synthesis of cobalamin, B12). Expression of both operons is induced by propanediol and globally controlled by the ArcA and Crp systems. The region between the two operons encodes two proteins, PduF, a transporter of propanediol, and PocR, which mediates the induction of the regulon by propanediol. Insertion mutations between the pdu and cob operons have been characterized, and their exact positions have been correlated with mutant phenotypes. The region includes five promoters, four of which are controlled by the PocR protein and induced by propanediol. The cob and pdu operons each have one regulated promoter; the pduF gene is expressed from two regulated promoters (P1 and P2). The P1 and P2 transcripts extend beyond pduF to include the pocR gene; thus the PocR protein autoregulates its expression from these promoters. The fifth promoter, PPoc, is adjacent to the pocR gene and associated with a Crp binding site. We suggest that all global control of the regulon is exerted by regulating the level of PocR protein at the P1, P2, and PPoc promoters. A putative binding site for the PocR protein has been identified by computer analysis. Eight close matches to this proposed site were found in regions near the four promoters known to be regulated by PocR protein: PPdu, P1, P2, and PCob. A three-state model is proposed in which the regulon uses all five of its promoters to control expression.

Bacterial Outer Membrane Proteins↗

PubMed1995

Isolation of NAD cycle mutants defective in nicotinamide mononucleotide deamidase in Salmonella typhimurium.

The NAD or pyridine nucleotide cycle is the sequence of reactions involved in the breakdown of NAD to nicotinamide mononucleotide (NMN) and regeneration of NAD. This cycle is fivefold more active during aerobic growth of Salmonella typhimurium and under this condition breaks down half of the NAD pool every 90 min. DNA ligase is known to convert NAD to NMN but is only a minor contributor to the NAD cycle during aerobic growth. The dominant aerobic route of NMN formation is otherwise uncharacterized. Accumulated NMN generated by either of these routes is potentially dangerous in that it can inhibit the essential enzyme DNA ligase. The reactions which recycle NMN to NAD may serve to minimize the inhibition of ligase and other enzymes by accumulated NMN. The predominant recycling reaction in S. typhimurium appears to be NMN deamidase, which converts NMN directly to the biosynthetic intermediate nicotinic acid mononucleotide. Mutants defective in this recycling step were isolated and characterized. By starting with a ligase-deficient (lig mutant) parent strain that requires deamidase to assimilate exogenous NMN, two classes of mutants that are unable to grow on minimal NMN media were isolated. One class (pncC) maps at 83.7 min and shows only 2% of the wild-type levels of NMN deamidase. Under aerobic conditions, a lig+ allele allows a pncC mutant to grow on NMN and restores some deamidase activity. This growth ability and enzyme activity are not found in lig+ strains grown without oxygen. This suggests that the existence of a second NMN deamidase (pncL) dependent on ligase and stimulated during aerobic growth. The second class of mutants (pncD) gains a requirement for isoleucine plus valine with growth in the presence of exogenous NMN. We propose that pncD mutations reduce the activity of an ilv biosynthetic enzyme that is naturally sensitive to inhibition by NMN.

Amidohydrolases↗

PubMed1995

The end of the cob operon: evidence that the last gene (cobT) catalyzes synthesis of the lower ligand of vitamin B12, dimethylbenzimidazole.

The cob operon of Salmonella typhimurium includes 20 genes devoted to the synthesis of adenosyl-cobalamin (coenzyme B12). Mutants with lesions in the promoter-distal end of the operon synthesize vitamin B12 only if provided with 5,6-dimethylbenzimidazole (DMB), the lower ligand of vitamin B12. In the hope of identifying a gene(s) involved in synthesis of DMB, the DNA base sequence of the end of the operon has been determined; this completes the sequence of the cob operon. The cobT gene is the last gene in the operon. Four CobII (DMB-) mutations mapping to different deletion intervals of the CobII region were sequenced; all affect the cobT open reading frame. Both the CobT protein of S. typhimurium and its Pseudomonas homolog have been shown in vitro to catalyze the transfer of ribose phosphate from nicotinate mononucleotide to DMB. This reaction does not contribute to DMB synthesis but rather is the first step in joining DMB to the corrin ring compound cobinamide. Thus, the phenotype of Salmonella cobT mutants conflicts with the reported activity of the affected enzyme, while Pseudomonas mutants have the expected phenotype. J. R. Trzebiatowski, G. A. O'Toole, and J. C. Escalante Semerena have suggested (J. Bacteriol. 176:3568-3575, 1994) that S. typhimurium possesses a second phosphoribosyltransferase activity (CobB) that requires a high concentration of DMB for its activity. We support that suggestion and, in addition, provide evidence that the CobT protein catalyzes both the synthesis of DMB and transfer of ribose phosphate. Some cobT mutants appear defective only in DMB synthesis, since they grow on low levels of DMB and retain their CobII phenotype in the presence of a cobB mutation. Other mutants including those with deletions, appear defective in transferase, since they require a high level of DMB (to activate CobB) and, in combination with a cobB mutation, they eliminate the ability to join DMB and cobinamide. Immediately downstream of the cob operon is a gene (called ORF in this study) of unknown function whose mutants have no detected phenotype. Just counterclockwise of ORF is an asparagine tRNA gene (probably asnU). Farther counterclockwise, a serine tRNA gene (serU or supD) is weakly cotransducible with the cobT gene.

Amino Acid Sequence↗

PubMed1995

Endotoxin tolerance alters thermal response of guinea pigs to systemic infusions of tumor necrosis factor-alpha.

In guinea pigs, intra-arterial infusions of 5 micrograms/kg tumor necrosis factor-alpha (TNF; specific activity 20,000 U/micrograms; duration of infusion 45-50 min) evoked a biphasic elevation of abdominal temperature lasting approximately 6 h. One week after systemic infusion of TNF, the animals started to receive either five intramuscular injections of bacterial lipopolysaccharide (LPS from Escherichia coli; 20 micrograms/kg) or equivalent volumes of solvent (0.9% NaCl) in intervals of 3 days. Fever in response to repeated injections of LPS was progressively attenuated; the animals developed endotoxin tolerance. Repeated injections with solvent did not cause any measurable changes in abdominal temperature. Three days after the fifth injection of LPS or solvent, all animals again received an intra-arterial infusion of 5 micrograms/kg TNF. In guinea pigs injected five times with solvent, the biphasic elevation of abdominal temperature could again be observed in response to systemic infusions of TNF. In endotoxin-tolerant animals, however, only the first peak of the biphasic thermal response lasting approximately 60 min could be monitored after infusions with TNF. The second phase of the thermal response to administration of TNF, which normally lasts > 5 h, was abrogated almost completely. The significant suppression of the febrile response to TNF infusions did not seem to be caused by a more rapid elimination of TNF from the circulation of endotoxin-tolerant guinea pigs. Circulating levels of TNF, measured 60 and 180 min after the start of TNF infusions, were not different before and after development of endotoxin tolerance. In conclusion, the development of endotoxin tolerance in guinea pigs is accompanied by a reduced responsiveness to TNF administered exogenously.

Animals↗

PubMed1995

Production of systemic and hypothalamic cytokines during the early phase of endotoxin fever.

Changes in concentrations of cytokines in plasma and in hypothalamic push-pull perfusates of guinea pigs were measured within the 1st hour after intramuscular injections of bacterial lipopolysaccharide (LPS; Escherichia coli, 20 micrograms/kg) or solvent (0.9% saline). In control animals injected with solvent, interleukin (IL)-1 and tumor necrosis factor alpha (TNF-alpha) were not detectable in plasma. Only IL-6 was present in picogram quantities. Within 45 min after injection of LPS, the concentrations of IL-1, TNF-alpha, and IL-6 increased in the plasma: by several orders of magnitude for TNF-alpha and about tenfold for IL-G. Picogram amounts of biologically active IL-1 were detected in plasma after injection of LPS. No steady state levels of systemic cytokines were reached during the experimental period. In hypothalamic perfusates of animals injected with the solvent, no IL-1 was detectable. TNF-alpha could be detected at higher concentrations than IL-6. IL-6 was detectable at tenfold lower concentrations than in the plasma. In animals injected with LPS, the hypothalamic concentration of IL-6 started to increase during the period 15-30 min and the concentrations of TNF-alpha during the period 30-45 min after LPS injection. The concentrations of IL-6 increased by 300-400% and did not exceed picogram values. No progressive increase of hypothalamic levels of these cytokines was observed during the time course of the experiment. The method used did not detect any changes in the amount of biologically active IL-1 in hypothalamic perfusates of LPS-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Glucagon-like peptide-1 affects gene transcription and messenger ribonucleic acid stability of components of the insulin secretory system in RIN 1046-38 cells.

It has been previously demonstrated that the enteric hormone glucagon-like peptide-1 (7-36 amide) (GLP-1) has acute effects on glucose-induced insulin secretion by RIN 1046-38 cells. In this study, we investigated the effects of extended exposure of RIN 1046-38 cells to GLP-1 and examine the mechanism by which GLP-1 synergizes with glucose in stimulating insulin secretion. Compared with cells cultured with glucose alone, incubation of cells with glucose plus 1 or 10 nM GLP-1 for 12 or 24 h significantly increased insulin release by about 3-fold, intracellular insulin content by 1.5-fold, and insulin messenger RNA (mRNA) by almost 2.5-fold. The insulinotropic effects of GLP-1 on RIN 1046-38 cells were accompanied by an up-regulation of both glucose transporter-1 (GLUT-1) and hexokinase I mRNA by about 2-fold. mRNA levels of GLUT-2 and glucokinase, which were low in controls, were unchanged by GLP-1 treatment. Treatment of cells with a transcription inhibitor, actinomycin D, demonstrated that elevated insulin mRNA levels after a GLP-1 exposure are mainly due to stabilization of the mRNA. In contrast, the elevated mRNA levels of GLUT-1 and hexokinase I are the result of increased transcription stimulated by GLP-1 exposure. Actinomycin D blunted the GLP-1 effect on insulin release but did not affect GLP-1 mediated elevation of insulin mRNA. This suggests that actinomycin D inhibits the transcription of the proteins necessary for insulin biosynthesis and insulin release, such as GLUT-1 and hexokinase I. Our study suggests that the mechanisms by which extended exposure of RIN 1046-38 cells to GLP-1 increases glucose-stimulated insulin secretion include significant up-regulation of glucose-sensing elements.

Animals↗

PubMed1995

Patterns of evoked otoacoustic emissions associated with acoustic neuromas.

Evoked otoacoustic emissions (OAEs) are assumed to reflect healthy outer hair cell function. Over the past few years, evoked OAEs have been shown to be useful as indicators of cochlear hearing loss. Because basic studies have shown that OAEs are extremely sensitive to cochlear anoxia and hypoxia, as well as to the adverse effects of many inner ear diseases, it is possible that these objective tests can provide some insight into the fundamental basis of the hearing loss exhibited by patients with acoustic neuromas. The primary aim of the present study was to examine the effects of acoustic neuromas on the amplitudes of evoked OAEs and to compare these findings with tumor-induced hearing levels. To this end, tests of behavioral audiometry, distortion-product otoacoustic emissions and transiently evoked otoacoustic emissions were performed on 44 patients with verified acoustic neuromas. The results demonstrated that the majority of ears with acoustic neuromas displayed one of two distinct patterns of evoked OAEs: a cochlear pattern or a noncochlear pattern. Although behavioral hearing thresholds were higher with larger tumors, OAE levels exhibited no clear relationship to tumor size. The present findings support the notion that acoustic neuromas may cause hearing impairment according to two types of influence that act at different levels of the peripheral auditory system. The tumor's cochlear effect on evoked OAE activity is most likely caused by an indirectly mediated compromise of the organ of Corti's vascular supply. It is probable that the direct pressure of the tumor on the eighth cranial nerve is responsible for the observed noncochlear effects.

Audiometry↗

PubMed1995

Absence of RET proto-oncogene point mutations in sporadic hyperplastic and neoplastic lesions of the parathyroid gland.

We investigated the possible role of RET proto-oncogene mutations in the development of sporadic hyperplastic, benign, and malignant parathyroid lesions. DNA extracted from paraffin-embedded specimens of forty parathyroid lesions was screened for RET proto-oncogene point mutations in exons 10, 11, and 16 by nonisotopic polymerase chain reaction-based single-strand conformation polymorphism and heteroduplex gel electrophoresis. The nucleotide sequence of samples with aberrant band patterns was identified by nonisotopic direct sequencing of polymerase chain reaction-amplified DNA. Parathyroids of seven patients with multiple endocrine neoplasia type 2A (MEN 2A) and MEN 2B served as positive controls. None of the eight hyperplastic lesions, three cases of parathyromatosis, ten parathyroid adenomas, eleven carcinomas or one normal parathyroid gland contained mutations in each of the three RET exons tested. Six MEN-2A-associated hyperplastic glands exhibited identical band shifts in the polymerase chain reaction single-strand conformation polymorphism analysis of exon 11, which corresponded to a Cys 634-->Arg substitution in the nucleotide sequence analysis (TGC-->CGC), whereas in the MEN 2B parathyroid specimen a point mutation was found at codon 918 of exon 16 (ATG-->ACG), causing a Met 918-->Thr substitution. Our data indicate that RET mutations of the MEN 2 loci in exons 10, 11, and 16 are not involved in the development of sporadically occurring benign or malignant parathyroid lesions. Furthermore, our results are in accordance with the observation that MEN 2A patients with Cys 634-->Arg (germline) mutations have a higher risk of developing parathyroid disease than those with other mutations at codon 634.

Adenoma↗

PubMed1995

Topographic abnormalities of proinsulin to insulin conversion in functioning human insulinomas. Comparison of immunoelectron microscopic and clinical data.

It has been proposed that the major defect in human insulinomas is a decreased hormone storage capacity resulting in uncontrolled release of proinsulin and insulin. By immunoelectron microscopy with monoclonal antibodies we studied the subcellular distribution of proinsulin and insulin in benign and malignant functioning insulinomas of different histology and compared the findings with various clinical and pathohistological parameters. We found that, in contrast to normal B cells, the proinsulin to insulin conversion in insulinomas occurs already in the trans Golgi apparatus but remains incomplete, resulting in the formation of secretory granules containing both proinsulin and insulin. Thus, in functioning insulinomas, sorting into secretory granules is not a prerequisite for hormone conversion. Furthermore, proinsulin and insulin storage and most probably subsequent secretion occurs through the secretory granules via the regulated pathway. A substantial variability for both proinsulin and insulin immunolabeling in secretory granules was found not only in individual tumor cells but also among the insulinomas studied. This observed variability may account for the lack of correlation between pathohistological, immunohistochemical, and clinical parameters in functioning insulinomas.

Adult↗

PubMed1995

[Dose-volume histograms for optimization of radiotherapy planning based on the example of esophageal carcinoma].

PURPOSE: The tissue tolerance of a small radiation dose to a large tissue volume applied in small fractions is expected to be different from the tolerance of a high dose to a small volume given in large fractions. Corresponding criteria for judgment have to be worked out. METHODS: Using the example of oesophagus carcinoma, dose-volume histograms for diverse treatment techniques are calculated and judged by means of multiplanar isodose representations. RESULTS: The selected treatment plans are ranked with the aid of the dose-volume histograms. We distinguish the tissue inside and outside of the target volume. CONCLUSIONS: The description of the spatial dose distribution in dependence of the different volumes and the respective fractions of the tumor dose therein with the help of dose-volume histograms brings about a correlation between the physical parameters and the biological effects. In addition one has to bear in mind the consequences of measures that influence the reaction and the side-effects of radiotherapy (e.g. chemotherapy), i.e. the recuperation of the tissues that were irradiated intentionally or inevitably. Taking all that into account it is evident that the dose-volume histograms are a powerful tool for assessing the quality of treatment plans.

Esophageal Neoplasms↗

PubMed1995

Overlapping expression of immunohistochemical markers and synaptophysin mRNA in pheochromocytomas and adrenocortical carcinomas. Implications for the differential diagnosis of adrenal gland tumors.

BACKGROUND: The differential diagnosis of cortical versus medullary tumors of the adrenal gland may be a problem in diagnostic pathology. Conflicting results have been reported about the distribution of various immunohistochemical markers in the normal as well as neoplastic adrenal cortex and medulla. EXPERIMENTAL DESIGN: Archival, formaldehyde-fixed, and paraffin-embedded material comprising 27 adrenocortical carcinomas (ACC, meeting Weiss' histologic criteria), 28 pheochromocytomas (PCC), and adjacent nontumorous tissue (13 glands) were analyzed by immunogold-silver staining for the expression of polysialic acid (poly Sia), cytokeratins (CK), synaptophysin (SYN), chromogranin A (CrgA), somatostatin (SOM), calcitonin (CT), and the "adrenocortical marker" D11. Further, SYN mRNA expression was studied by nonradioactive in situ hybridization using digoxigenin-labeled oligonucleotide probes. RESULTS: In the normal adrenal gland, poly Sia was exclusively detected in the medulla and in cortical nerves. In ACCs, SYN immunoreactivity was present in 23 of 27 tumors (85%), D11 was present in 22 of 27 (81%), poly Sia was present focally in 8 of 27 (29%), and CK was present in 7 of 27 (25%). Synthesis of SYN in ACCS was demonstrated by mRNA in situ hybridization. Immunoreactivity for CrgA, SOM, or CT was not detectable. No difference of the marker profiles was seen in the nine clinically hormone-producing (three androgen, five corticosteroid, one mineralocorticoid) ACCs compared with the clinically silent tumors. In PCCs, all 28 tumors were immunoreactive for poly Sia and SYN; CrgA was detectable in 26 of 28 (93%), CT was detectable in 6 of 28 (21%), and SOM was detectable in 2 of 28 (7%) tumors. Staining for D11 or CK was undetectable. By immunohistochemistry, no distinction was possible between the 4 clinically malignant, the 6 multiple endocrine neoplasia type 2A-associated, and the 18 sporadic benign PCCs. CONCLUSIONS: Poly Sia of the neural cell adhesion molecule is consistently detected in normal adrenal medullary cells as well as in PCCs, and is occasionally focally expressed in ACCs. CrgA, CK, and D11 are reliable markers to immunohistochemically distinguish ACC from PCC. Immunoreactivity for SYN and detection of its mRNA in the majority of ACCs indicates the existence of tumor cells sharing both cortical and medullary features. Such focal neuroendocrine differentiation in ACCs can lead to confusion with PCCs.

Adrenal Cortex Neoplasms↗