ATPergic signaling disruption in human sepsis as a potential source of biomarkers for clinical use.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated inflammatory response to infection. To date, there is no specific treatment established for sepsis. In the extracellular compartment, purines such as adenosine triphosphate (ATP) and adenosine play essential roles in the immune/inflammatory responses during sepsis and septic shock. The balance of extracellular levels among ATP and adenosine is intimately involved in the signals related to immune stimulation/immunosuppression balance. Specialized enzymes, including CD39, CD73, and adenosine deaminase (ADA), are responsible to metabolize ATP to adenosine which will further sensitize the P2 and P1 purinoceptors, respectively. Disruption of the purinergic pathway had been described in the sepsis pathophysiology. Although purinergic signaling has been suggested as a potential target for sepsis treatment, the majority of data available were obtained using pre-clinical approaches. We hypothesized that, as a reflection of deregulation on purinergic signaling, septic patients exhibit differential measurements of serum, neutrophils and monocytes purinergic pathway markers when compared to two types of controls (healthy and ward). It was observed that ATP and ADP serum levels were increased in septic patients, as well as the A2a mRNA expression in neutrophils and monocytes. Both ATPase/ADPase activities were increased during sepsis. Serum ATP and ADP levels, and both ATPase and ADPase activities were associated with the diagnosis of sepsis, representing potential biomarkers candidates. In conclusion, our results advance the translation of purinergic signaling from pre-clinical models into the clinical setting opening opportunities for so much needed new strategies for sepsis and septic shock diagnostics and treatment.

The ß2-subtype of adrenoceptors mediates inhibition of pro-fibrotic events in human lung fibroblasts.

Fibrosis is part of airway remodelling observed in bronchial asthma and COPD. Pro-fibrotic activity of lung fibroblasts may be suppressed by ß-adrenoceptor activation. We aimed, first, to characterise the expression pattern of ß-adrenoceptor subtypes in human lung fibroblasts and, second, to probe ß-adrenoceptor signalling with an emphasis on anti-fibrotic actions. Using reverse transcription PCR, messenger RNA (mRNA) encoding ß(2)-adrenoceptors was detected in MRC-5, HEL-299 and primary human lung fibroblasts, whereas transcripts for ß(1)- and ß(3)-adrenoceptors were not found. Real-time measurement of dynamic mass redistribution in MRC-5 cells revealed ß-agonist-induced G(s)-signalling. Proliferation of MRC-5 cells (determined by [(3)H]-thymidine incorporation) was significantly inhibited by ß-agonists including the ß(2)-selective agonist formoterol (-logIC(50), 10.2) and olodaterol (-logIC(50), 10.6). Formoterol's effect was insensitive to ß(1)-antagonism (GCP 20712, 3 µM), but sensitive to ß(2)-antagonism (ICI 118,551; apparent, pA (2), 9.6). Collagen synthesis in MRC-5 cells (determined by [(3)H]-proline incorporation) was inhibited by ß-agonists including formoterol (-logIC(50), 10.0) and olodaterol (-logIC(50), 10.3) in a ß(2)-blocker-sensitive manner. α-Smooth muscle actin, a marker of myo-fibroblast differentiation, was down-regulated at the mRNA and the protein level by about 50% following 24 and 48 h exposure to 1 nM formoterol, a maximally active concentration. In conclusion, human lung fibroblasts exclusively express ß(2)-adrenoceptors and these mediate inhibition of various markers of pro-fibrotic cellular activity. Under clinical conditions, anti-fibrotic actions may accompany the therapeutic effect of long-term ß(2)-agonist treatment of bronchial asthma and COPD.

[Cinacalcet - an allosteric enhancer at the Ca2+-receptor]. / Cinacalcet - ein allosterischer Verstärker am Ca2+-Rezeptor.

Cinacalcet (trade name: Mimpara) enhances allosterically the action of Ca (2+)-ions at the parathyroid gland Ca (2+)-receptor which belongs to the superfamily of G protein-coupled receptors. As a consequence blood levels of Ca (2+) and parathyroid hormone decline. Cinacalcet is orally administered and approved for a) the treatment of secondary hyperparathyroidism in patients with end stage renal disease receiving hemodialysis and b) to lower hypercalcemia in patients with parathyroid carcinoma. Therapeutic monitoring includes measurement of blood levels of Ca (2+) and parathyroid hormone. The stable suppression of parathyroid hormone levels under chronic treatment was shown in clinical trials. Clinically relevant outcome parameters, such as bone mass and fracture risk, remain to be evaluated.

Complications of transpedicular screw fixation in the cervical spine.

Today, posterior stabilization of the cervical spine is most frequently performed by lateral mass screws or spinous process wiring. These techniques do not always provide sufficient stability, and anterior fusion procedures are added secondarily. Recently, transpedicular screw fixation of the cervical spine has been introduced to provide a one-stage stable posterior fixation. The aim of the present prospective study is to examine if cervical pedicle screw fixation can be done by low risk and to identify potential risk factors associated with this technique. All patients stabilized by cervical transpedicular screw fixation between 1999 and 2002 were included. Cervical disorders included multisegmental degenerative instability with cervical myelopathy in 16 patients, segmental instability caused by rheumatoid arthritis in three, trauma in five and instability caused by infection in two patients. In most cases additional decompression of the spinal cord and bone graft placement were performed. Pre-operative and post-operative CT-scans (2-mm cuts) and plain X-rays served to determine changes in alignment and the position of the screws. Clinical outcome was assessed in all cases. Ninety-four cervical pedicle screws were implanted in 26 patients, most frequently at the C3 (26 screws) and C4 levels (19 screws). Radiologically 66 screws (70%) were placed correctly (maximal breach 1 mm) whereas 20 screws (21%) were misplaced with reduction of mechanical strength, slight narrowing of the vertebral artery canal (<25%) or the lateral recess without compression of neural structures. However, these misplacements were asymptomatic in all cases. Another eight screws (9%) had a critical breach. Four of them showed a narrowing of the vertebral artery canal of more then 25%, in all cases without vascular problems. Three screws passed through the intervertebral foramen, causing temporary paresis in one case and a new sensory loss in another. In the latter patient revision surgery was performed. The screw was loosened and had to be corrected. The only statistically significant risk factor was the level of surgery: all critical breaches were seen from C3 to C5. Percutaneous application of the screws reduced the risk for misplacement, although this finding was not statistically significant. There was also a remarkable learning curve. Instrumentation with cervical transpedicular screws results in very stable fixation. However, with the use of new techniques like percutaneous screw application or computerized image guidance there remains a risk for damaging nerve roots or the vertebral artery. This technique should be reserved for highly selected patients with clear indications and to highly experienced spine surgeons.

[Results of simple fragment excision in lumbar disc surgery]. / Ergebnisse der alleinigen Sequestrektomie bei lumbaler Bandscheibenoperation.

BACKGROUND: While performing microsurgical disc excision, usually the sequestrated disc fragments as well as loosened or degenerated parts of the nucleus pulposus are removed. It is controversial whether this strategy is always necessary. The aim of this study was to examine this question based on clinical results. MATERIAL AND METHODS: Prospectively all relevant data from 149 consecutive patients after sequestrectomy were collected including the clinical course of the patients with a mean follow-up of 2.3 years. A detailed analysis of the actual pain status, the functional capacity and possible additional spinal operations was performed. RESULTS: During early follow-up, there was one superficial wound infection, which was treated conservatively. The success rate, as measured by patient self-assessment, was 62% for excellent and good and 25% for fair results; 13% of the patients treated declared a poor result having no benefits from surgery. The average FFbH score during follow-up was 74% (100% means no functional restriction). Radicular pain and low back pain had the same intensity on the average, in contrast to some other investigations, where low back pain was lower than radicular pain [14]. Of the 149 patients, 4 underwent a second spine surgery at the same level, 2 of which were recurrent disc herniations (=1.3%). CONCLUSION: Simple fragment excision revealed similar results compared to standard microdiscectomy. There was an especially low number of recurrences in contrast to former reports [16]. This was probably caused by the conscientious selection of patients for sequestrectomy according to well-defined criteria. Whether simple sequestrectomy can effectively treat an additional low back pain component must be clarified by further prospective studies.

[Management of obstetrical brachial plexus palsy--own experience with the primary operative technique]. / Management bei geburtstraumatischen Läsionen des Plexus brachialis - Eigene Erfahrungen mit der primären operativen Behandlung -

Obstetrical brachial plexus palsy occurs at a frequency of 0.6 to 2.5 per 1000 births. 80 to 95% of these lesions recover spontaneously. If spontaneous recovery does not occur within the first six months of life, investigations like electrophysiology, and CT-myelography and surgical exploration of the brachial plexus are recommended. During the last ten years 73 children with obstetrical brachial plexus lesions were examined in our department. 29 newborns underwent surgery on the brachial plexus. In 20 out of 29 children nerve root avulsions were diagnosed preoperatively. We performed in 16 cases nerve grafting after neuroma excision, in four cases nerve grafting combined with neurotization, in seven cases external or internal neurolysis, and in the remaining two cases neurotization and plexo-plexal transfer, respectively. The children were followed up between 18 and 50 months (range 27 months) in 18 cases. Elbow function according to Gilbert scale achieved one half of the patients four to five points and the other half two to three points. We found shoulder function with abduction between 45 degrees to 128 degrees and external rotation in 61% (Grade II to V, according to Gilbert scale). In 31% hand function showed Grade III and IV (Gilbert and Raimondi scale). We recommend decision for surgery at the age of six months. Operation should be planned between six to nine months of life. In addition, physical therapy and options including muscle transfers and orthopaedic procedures must be available to ensure the optimal outcome for these children.

Probing the selectivity of allosteric modulators of muscarinic receptors at other G-protein-coupled receptors.

1. The aim of the present investigation was to analyse whether three prototype allosteric modulators of ligand binding to muscarinic receptors, i.e. alcuronium, gallamine, and the alkane-bis-ammonium compound W84 (hexane-1,6-bis[dimethyl-3'-phthalimidopropylammonium bromide]), may have allosteric effects on radioligand-binding characteristics at other G-protein-coupled receptors, such as cerebral A1 adenosine receptors (Gi-coupled), cardiac left ventricular alpha1-adrenoceptors (Gq), and beta-adrenoceptors (Gs). 2. The modulators were applied at concentrations known to be high with regard to the allosteric delay of the dissociation of the antagonist [3H]-N-methylscopolamine (NMS) from muscarinic M2-receptors: 30 micromol l(-1) W84, 30 micromol l(-1) alcuronium, 1000 micromol l(-1) gallamine. As radioligands, we used the adenosine A1-receptor ligand [3H]-cyclopentyl-dipropylxanthine (CPX), the alpha1-adrenoceptor ligand [3H]-prazosin (PRAZ), and the beta-adrenoceptor ligand (-)-[125I]-iodocyanopindolol (ICYP). Allosteric actions on ligand dissociation and the equilibrium binding were measured in the membrane fractions of rat whole forebrain (CPX) and of rat cardiac left ventricle (PRAZ, ICYP, NMS), respectively. 3. CPX and PRAZ showed a monophasic dissociation with half-lives of 5.88+/-0.15 and 12.27+/-0.46 min, respectively. In the case of CPX, neither the binding at equilibrium nor the dissociation characteristics were influenced by the allosteric agents. With PRAZ, the binding at equilibrium remained almost unaltered in the presence of W84, whereas it was reduced to 36+/-2% of the control value with alcuronium and to 42+/-2% with gallamine. The dissociation of PRAZ was not affected by W84, whereas it was moderately accelerated by alcuronium and gallamine. In the case of ICYP, the binding at equilibrium was not affected by the allosteric modulators. The dissociation of ICYP was slow, and after 3 h, more than 50% of the radioligand was still bound, so that a reliable half-life could not be calculated. ICYP dissociation was not affected by W84. In the presence of alcuronium and gallamine, the dissociation curve of ICYP revealed an initial drop from the starting level, followed by the major phase of dissociation being parallel to the control curve. 4. In summary, the allosteric action of the applied agents is not a common feature of G-protein-coupled receptors and appears to be specific for muscarinic receptors.

Electromyographic analysis of the deltoid and rotator cuff muscles in persons with subacromial impingement.

The purpose of this study was to compare subjects with subacromial impingement and subjects with normal shoulders with respect to muscle activity. Fifteen subjects in each group were studied by means of fine-wire electromyography. The middle deltoid and rotator cuff muscles were evaluated during isotonic scaption from 30 to 120 degrees. Overall, the impingement group demonstrated decreased mean muscle activity in comparison with the group of normal subjects. The magnitude of diminished activity was statistically significantly different (P < .05) during the 30- to 60-degrees arc for the infraspinatus, subscapularis, and middle deltoid muscles; in addition, the infraspinatus muscle demonstrated significantly depressed activity during the 60- to 90-degrees arc. In the impingement group, the supraspinatus and teres minor revealed a diminution of muscle function in comparison with shoulders in the normal group; the difference was not significant. This study demonstrates that muscle activity in subjects with impingement is most notably decreased in the first arc of motion. Also of clinical relevance is the fact that the inferior force vector (from the infraspinatus and subscapularis) is less functional in subjects with impingement than is the superior compressive vector (from the supraspinatus). Thus, humeral head depression during the critical first portion of elevation may be insufficient in people with subacromial impingement.

Elbow injuries in the throwing athlete. Difficult diagnoses and surgical complications.

Elbow injuries in throwing athletes can be challenging from the diagnostic and management perspectives. The stress of repetitive throwing does predispose athletes to certain conditions with which treating clinicians need to be familiar. An understanding of the anatomy of the elbow and the biomechanics of throwing is essential to making the correct diagnosis and instituting proper care. Failure of nonoperative measures often requires surgical intervention. A thorough understanding of the anatomy and the spectrum of conditions that can occur is needed before decisions regarding surgical management can be made. The operative approach to elbow pathology, whether performed open or arthroscopically, should be completed by orthopedists who have experience with the clinical conditions and the appropriate technical facility to provide comprehensive care. This article has reviewed the anatomy, biomechanics, and spectrum of conditions that affect throwing athletes' elbows as well as the potential complications that can be associated with surgical management.

Shoulder reaction time and muscle-firing patterns in response to an anterior translation force.

The primary restraint preventing humeral head translation is the capsuloligamentous system. Muscle forces can also decrease translation; however, the timing and magnitude of muscle response has not been previously reported. Fine wire electromyographic analysis of the biceps long head, anterior deltoid, pectoralis major, latissimus dorsi, and rotator cuff muscles was performed after an anterior translation force was applied to 15 normal shoulders. The reflex response time (time to 5% maximal muscle test), the protection response time (time to 20% maximal muscle test), the duration of the protection response, and the magnitude of the protection response were calculated. The shoulder reaction data showed 2 consistent patterns. Activation of the anteriorly located muscles preceded the posteriorly located muscles, and the rotator cuff muscles fired with greater magnitude than the more peripherally located muscles.

Detection of immunoreactive parathyroid hormone-related protein in human cerebrospinal fluid.

Immunoreactive parathyroid hormone-related protein (PTH-rP) was measured in simultaneously obtained cerebrospinal fluid (CSF) and plasma from 51 patients suspected of suffering from a prolapsed intervertebral disc. Endocrine or psychiatric diseases were excluded. In addition, immunoreactive parathyroid hormone (PTH) in the CSF samples was measured. Both, PTH-rP and PTH were assayed by immunoradiometric assay. The results indicate the presence of both, PTH-rP and PTH in CSF. The following concentrations (mean values +/- SD) were found: PTH-rP (pmol/l) in CSF without pleocytosis (n = 17) 0.432 +/- 0.157, with pleocytosis (n = 34) 0.654 +/- 0.675; in plasma (pmol/l) 54.1 +/- 14.632; PTH (nmol/l) in CSF without pleocytosis (n = 17) 0.454 +/- 0.099, with pleocytosis (n = 34) 0.437 +/- 0.140, and in plasma 4.272 +/- 0.794. The concentrations of both, PTH-rP and PTH, in CSF with and without pleocytosis were not significantly different. No correlation was found between PTH-rP and PTH values. The present study demonstrated PTH-rP as a normal constituent in human CSF.

Lack of inotropic effect of cyclosporin A in isolated guinea pig left atria.

OBJECTIVE: Cyclosporin A is being widely used to prevent graft rejection in organ transplantation and to treat autoimmune diseases. Since various toxic side effects have been observed, the aim of this study was to look for even a subtle deleterious effect of cyclosporin A on cardiac inotropy in electrically stimulated guinea pig left atria. METHODS: The left atrial muscles of guinea pigs, in Tyrode's solution containing 2.7 or 5.4 mM potassium, were electrically stimulated by one of two methods: (1) continuously at 3 Hz, during which cyclosporin A was applied cumulatively (from 10(-9) to 10(-5) M); or (2) stimulated intermittently at 2.5 Hz in 5 mM cyclosporin A, with rest periods of 4 s duration interposed every 4 min. The effects of cyclosporin A on contractile force were observed for 150 min in the first stimulation method, and the effects on the steady state contractile force and amplitude of post-rest contraction were observed for 240 min in the second method. RESULTS: The steady state contractile force of the atria declined within the 4 h period at 2.7 mM potassium in Tyrode's solution both in the cyclosporin A group (n = 10) and in the control group (n = 5) to 68(SD 11)% and to 63(4)%, respectively. After 4 h the amplitudes of the post-rest contraction were 101(16)% and 101(4)% in cyclosporin A and control groups, respectively. At 5.4 mM potassium, the following values were obtained (cyclosporin A v control): steady state force 70(8)% (n = 11) v 69(8)% (n = 5); post-rest force 105(9)% v 102(7)%. CONCLUSIONS: Cyclosporin A does not influence the steady state contractile force or the amplitude of the post-rest contraction, suggesting the absence of inotropic effects on isolated guinea pig left atria.

A related epitope is consistently present on glycoprotein C of herpes simplex virus type 1 and 2.

A monoclonal antibody (VE8) directed to glycoprotein C of herpes simplex virus type 1 (HSV-1) cross-reacted with all HSV type 2 (HSV-2) strains tested. Positive reaction was also observed with all investigated HSV-1 strains, indicating that the related epitope is consistently present in HSV-1 and HSV-2.

Different mechanisms of protection by monoclonal and polyclonal antibodies during the course of herpes simplex virus infection.

Young adult C57BL mice intravaginally inoculated with herpes simplex virus type 1 and passively immunized with a monoclonal antibody directed against herpes simplex virus type 1 glycoprotein gB were shown to be more effectively protected against infection as compared with mice treated with polyclonal immune serum. In contrast to polyclonal antiserum, the monoclonal antibody markedly restricted viral multiplication in the infected mucous membranes. Consequently, skin lesions were completely prevented, and the extent of ganglionic infection was significantly reduced. The mechanism by which a monoclonal antibody, specific to glycoprotein gC, effected protection also differed from that of the hyperimmune serum, since premature latency was not induced. The data provide strong evidence that the mechanisms of protection mediated by antibodies depend on their epitope specificity. The inhibition of active antibody response after passive immunization was inducible by polyclonal antibody only, not by monoclonal antibodies.

Inducible expression of herpes simplex virus type 1 glycoprotein C in NIH 3T3 cells.

Antibodies directed against the glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) are known to be mainly HSV-1-specific, whereas antibodies against other major HSV-1 glycoproteins cross-react with HSV-2 antigens. To investigate the immunological features of gC-1, the gene encoding gC-1 was isolated and cloned from DNA of cells infected with HSV-1. The 3.6 kbp SalI fragment R of HSV-1 DNA was modified in order to place the gene under transcriptional control of the glucocorticoid dependent promoter of the MMTV-LTR. NIH 3T3 cells were transfected with the resulting plasmid. Cell lines established by selection for the vector-encoded marker gene were tested for the ability to synthesize gC-1 after addition of dexamethasone to the growth medium. Glycoprotein-enriched cell extracts of several clones were shown to contain gC-1 by immunoblotting using a gC-1-specific monoclonal antibody. One cell line was used to show the presence of gC-1 also in the culture supernatant. gC-1 synthesis decreased after several passages of the cells but could be restimulated by the addition of 5-azacytidine to the cultures.

Interaction of the hexamethonium derivative W84, an allosteric effector at muscarinic cholinoreceptors, with rat brain nicotinic binding sites.

The hexamethonium derivative W84 (hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)-ammonium bromide]) combined with atropine has an overadditive protective action against organophosphorus intoxications. It affects allosterically the binding of (-) [3H]N-methylscopolamine [(3H]NMS) to muscarinic cholinoceptors. Because nicotinic receptors are involved in organophosphorus intoxications, the interaction of W84 with nicotinic cholinoceptors was investigated. (-) [3H]nicotine (2.5 nM) was used to label nicotinic binding sites in rat brain membranes in 50 nM Tris, pH 7.3 at 23 degrees. Under control conditions, (-) [3H]nicotine-binding revealed a KD of 4 X 10(-9) M and a Bmax of 53 fmol/mg membrane protein. W84 inhibited (- ) [3H]nicotine-binding with an IC50 of 3 X 10(-5) M by reducing the binding affinity. The IC50 of hexamethonium was 20 X 10(-5) M. At 10(-4) M, W84 did not affect the dissociation rate of (-)[3H]nicotine, suggesting a lack of allosteric activity. For sake of comparison, the action of W84 was checked on [3H]NMS-binding (control: KD approximately 1 X 10(-9) M, Bmax approximately 500 fmol/mg prot). W84 inhibited the binding of [3H]NMS (0.5 nM) with an IC50 of 1.5 X 10(-9) M. At 10(-4) M, W84 prevented [3H]NMS-dissociation almost completely, thus displaying the allosteric action at muscarinic cholinoceptors. In conclusion, the results of the (-)[3H]nicotine-binding experiments point to a pure competitive action of W84 at nicotine cholinoceptors, lacking any allosteric effect. This competitive action may contribute to the protective effect of W84 in organophosphorus poisoning.

Comparison of the dominant lethal effects of acrylonitrile and acrylamide in male Fischer 344 rats.

Acrylonitrile (ACN) and acrylamide (AA), structurally similar vinyl monomers, are both animal carcinogens. ACN is weakly mutagenic in bacteria and induces sister-chromatid exchange, unscheduled DNA synthesis and cell transformation in cells in culture. AA induces chromosomal aberrations in bone marrow, blood and germ cells in vivo, and dominant lethal mutations in the germ cells of male mice and rats. In the current study, the ability of AA and ACN to induce dominant lethal mutations in the germ cells of male Fischer 344 rats was compared. Three groups of 50 males were gavaged daily for 5 days with ACN (60 mg/kg in normal saline), AA (30 mg/kg in normal saline) or vehicle only; an additional group of 20 males received a single i.p. injection of 0.2 mg/kg triethylenemelamine (TEM) on the afternoon of day 5. Starting 1 day after exposure, each male was bred to one female per week for 4 weeks (TEM-exposed group) or 10 weeks (ACN, AA and control groups). Mating rates were reduced only during week 1 in the TEM-treated group; pregnancy rates were reduced only during week 2 in the AA-exposed group and week 4 in the TEM-treated group. Females were necropsied 13 days after the end of the appropriate mating week and the amount of pre- and post-implantation loss calculated. ACN treatment of male rats induced no increases in either pre- or post-implantation loss in females in any of the 10 weeks post-exposure examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Light and electron microscopical morphometry of pituitary adenomas in hyperprolactinemia.

Two highly differentiated acidophil prolactin-cell adenomas with hyperprolactinemia (group I), 8 large cell chromophobe adenomas with hyperprolactinemia (group II), and 2 small cell chromophobe adenomas (group III), one of which was combined with hyperprolactinemia, were studied immunohistologically. Morphometry was performed on the light- and electron microscopical level. The 11 active adenomas were immunohistologically positive for prolactin, the 12th adenoma with normal prolactin plasma level was negative for prolactin. Light microscopical morphometry displayed significantly more cells of smaller size in the "small cell chromophobe" adenomas, whereas the large cell chromophobe adenomas and the highly differentiated prolactin cell adenomas were not different. Ultrastructural morphometry demonstrated significant differences between highly differentiated prolactin cell adenomas (group I), and large cell chromophobe adenomas (group II). The latter contain smaller "relative volumes" of nucleoli and of secretory granules, whereas the rough endoplasmic reticulum, the Golgi fields and the nuclei were not different. Comparison of large cell chromophobe adenomas (group II), and small cell chromophobe adenomas (group III) revealed significantly larger relative volumes of nuclei and of mitochondria but smaller volumes of rough endoplasmic reticulum and of Golgi fields in the small cell chromophobe adenomas. Significant differences between the active and the inactive adenoma of small cell chromophobe type in the group III were not found. In spite of the low quantity of small cell chromophobe adenomas and of acidophil prolactin cell adenomas, our data demonstrate that there exist distinct and significant light microscopical and ultrastructural differences between the three adenoma types.(ABSTRACT TRUNCATED AT 250 WORDS)