Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 109 records · Page 6Linked to original sources

PubMed2001

Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis.

Previous biochemical data identified a host cell fraction, designated RAF-2, which stimulated influenza virus RNA synthesis. A 48-kDa polypeptide (RAF-2p48), a cellular splicing factor belonging to the DEAD-box family of RNA-dependent ATPases previously designated BAT1 (also UAP56), has now been identified as essential for RAF-2 stimulatory activity. Additionally, RAF-2p48 was independently identified as an influenza virus nucleoprotein (NP)-interacting protein, NPI-5, in a yeast two-hybrid screen of a mammalian cDNA library. In vitro, RAF-2p48 interacted with free NP but not with NP bound to RNA, and the RAF-2p48-NP complex was dissociated following addition of free RNA. Furthermore, RAF-2p48 facilitated formation of the NP-RNA complexes that likely serve as templates for the viral RNA polymerase. RAF-2p48 was shown, in both in vitro binding assays and the yeast two-hybrid system, to bind to the amino-terminal region of NP, a domain essential for RNA binding. Together, these observations suggest that RAF-2p48 facilitates NP-RNA interaction, thus leading to enhanced influenza virus RNA synthesis.

Adenosine Triphosphatases↗

PubMed2001

Targeted inactivation of Galpha(i) does not alter cardiac function or beta-adrenergic sensitivity.

Inhibitory Galpha(i) protein increases in the myocardium during hypertrophy and has been associated with beta-adrenergic receptor (beta-AR) desensitization, contractile dysfunction, and progression of cardiac disease. The role of Galpha(i) proteins in mediating basal cardiac function and beta-AR response in nonpathological myocardium, however, is uncertain. Transgenic mice with targeted inactivation of Galpha(i2) or Galpha(i3) were examined for in vivo cardiac function with the use of conscious echocardiography and for ex vivo cardiac response to inotropic stimulation with the use of Langendorff blood-perfused isolated hearts and adult ventricular cardiomyocytes. Echocardiography revealed that percent fractional shortening and heart rate were similar among wild-type, Galpha(i2)-null, and Galpha(i3)-null mice. Comparable baseline diastolic and contractile performance was also observed in isolated hearts and isolated ventricular myocytes from wild-type mice and mice lacking Galpha(i) proteins. Isoproterenol infusion enhanced diastolic and contractile performance to a similar degree in wild-type, Galpha(i2)-null, and Galpha(i3)-null mice. These data demonstrate no observable role for inhibitory G proteins in mediating basal cardiac function or sensitivity to beta-AR stimulation in nonpathological myocardium.

Adrenergic beta-Agonists↗

PubMed2001

Intracisternal increase of superoxide anion production in a canine subarachnoid hemorrhage model.

BACKGROUND AND PURPOSE: Reactive oxygen species (ROS) are thought to be primary in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, as direct evidence of ROS has not yet been demonstrated in cerebral vasospasm, we sought to substantiate superoxide anion (.O(2)(-)) generation in the subarachnoid space after SAH using a modification of Karnovsky's manganese/diaminobenzidine (Mn(2+)/DAB) technique. METHODS: SAH or sham operation was induced according to a 2-hemorrhage model in a total of 24 beagle dogs. On day 2 or 7 after SAH or sham operation, dogs were intrathecally infused with buffer containing Mn(2+) and DAB, and the brain stem was prepared for light and electron microscopy. Possible colocalization of ferrous (Fe(2+)) or ferric (Fe(3+)) iron ions with.O(2)(-) was also examined with the use of Turnbull blue or Berlin blue staining, respectively. RESULTS: Light microscopy revealed amorphous, amber deposits within the subarachnoid hematoma, the periarterial space, and the tunica adventitia of the basilar artery on days 2 and 7 after SAH.O(2)(-) deposits were eliminated by addition of superoxide dismutase or exclusion of either Mn(2+) or DAB from the perfusate, confirming the specificity of the reaction. These deposits were colocalized with blue reaction deposits indicating Fe(2+) and Fe(3+). Within the subarachnoid space,.O(2)(-) indicating electron-dense fine granules were preferentially located around degenerated erythrocytes and, secondarily, infiltrating macrophages and neutrophils. CONCLUSIONS: We show direct evidence for enhanced production of.O(2)(-) and Fe(2+)/Fe(3+) iron ions in the subarachnoid space after SAH, lending further support to the pathogenic role of ROS in cerebral vasospasm after SAH.

3,3'-Diaminobenzidine↗

PubMed2001

Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis.

Immune and inflammatory systems are controlled by multiple cytokines, including ILs and INFs. These cytokines exert their biological functions through Janus tyrosine kinases and STAT transcription factors. One such cytokine, IL-6, has been proposed to contribute to the development of rheumatoid arthritis (RA). We found that STAT3 was strongly tyrosine phosphorylated in synovial tissue of RA patients, but not those with osteoarthritis. Blockade of the IL-6-gp130-JAK-STAT3-signaling pathway might therefore be beneficial in the treatment of RA. We show here that the mRNA for the endogenous cytokine signaling repressor CIS3/SOCS3 is abundantly expressed in RA patients. To determine whether CIS3 is effective in treating experimental arthritis, a recombinant adenovirus carrying the CIS3 cDNA was injected periarticularly into the ankle joints of mice with antigen-induced arthritis or collagen-induced arthritis (CIA). Periarticular injection of CIS3 adenovirus drastically reduced the severity of arthritis and joint swelling compared with control groups. CIS3 was more effective than a dominant-negative form of STAT3 in the CIA model. Thus, induction of CIS3 could represent a new approach for effective treatment of RA.

Animals↗

PubMed2001

Intermittent isometric exposure prevents brain retraction injury under venous circulatory impairment.

It is recognized that surgical obliteration of the cerebral veins by additional brain compression using retractors is dangerous. However, there is a lack of satisfactory management of this problem. We investigated whether intermittent brain compression can reduce brain injury from cerebral venous circulation disturbances (CVCDs). In Wistar rats (n = 25), a solitary cortical vein was occluded photochemically. The brain surface was compressed by a spring balance and constant compression at 30 mmHg was carried out for 60 min. Intermittent procedure compression protocols included four 15 min compressions at 5 min intervals, intermittent isometric exposure (IM), and intermittent isotonic exposure (IT). Local cerebral blood flow (ICBF) in the compressed area was measured together by laser-Doppler (LD) with the degree of brain compression. After 24 h, the brains were examined histologically. The animals were divided into the following five groups (each n = 5): 1, a sham operated control; 2, cortical vein occlusion (VO); 3, VO + continuous brain compression (CC); 4, VO + IM; and 5, VO + IT. The ICBF decreased significantly during the compression; however, recovery after the series of compressions was observed only in the VO + IM group, not in the VO + CC and the VO + IT groups (p < 0.05). The depth of the brain surface increased stepwise in the VO + IT group compared with the VO + IM group (p < 0.01). The resulting tissue damage was significantly larger in the VO + CC and VO + IT groups than in the vein occlusion group (p < 0.05), but not in the VO + IM group. The results of the present study suggest that intermittent isometric exposure under CVCDs could decrease brain retraction injury during neurosurgical operations and be more beneficial than continuous compression, providing that the compression pressure declines as the process advances.

Animals↗

PubMed2001

A recombinant molt-inhibiting hormone of the kuruma prawn has a similar secondary structure to a native hormone: determination of disulfide bond arrangement and measurements of circular dichroism spectra.

In crustaceans, molt-inhibiting hormone (MIH) is presumed to regulate molting through suppressing synthesis and/or secretion of ecdysteroids by the Y-organ. Recently, a recombinant MIH of the kuruma prawn Penaeus japonicus was produced in E. coli. To approximate the secondary structure of native and recombinant MIH of P. japonicus containing six cysteine residues, the arrangements of disulfide bridges in both MIHs were determined by characterizing their enzymatic digests, and their circular dichroism spectra were measured. The arrangements of disulfide bonds in both MIHs were determined to be identical, and they were linked between Cys7 and Cys44, Cys24 and Cys40, and Cys27 and Cys53. The circular dichroism spectra of both MIHs were very close, and demonstrated that they were rich in a-helix. a-Helix contents in native and recombinant MIHs were calculated to be 49.3% and 46.0%, respectively. All these results strongly suggested that the recombinant MIH was folded in the same manner as the native MIH.

Animals↗

PubMed2001

Molecular cloning of horse Hsp90 cDNA and its comparative analysis with other vertebrate Hsp90 sequences.

Heat shock protein 90 (Hsp90), a molecular chaperone, is ubiquitous and involved in numerous cellular processes. To contribute to the relatively small collection of vertebrate Hsp90 sequences in the gene data bank, we cloned and sequenced horse (Equus caballus) Hsp90 alpha and beta cDNAs. This enabled identification of horse-specific primers for development of a convenient PCR-based method that could monitor horse stress tolerance. We analyzed the sequence data comparatively and phylogenetically with other Hsp90 cDNA sequences, and identified vertebrate-specific and isoform-specific conserved regions to facilitate future molecular investigations of Hsp90 functions. We found 4 highly conserved regions to vertebrate Hsp90 exclusively and 27 amino acids conserved among but differing between Hsp90 alpha and Hsp90 beta sequences. Protein-based phylogenetic trees revealed high conservation between mammal species within Hsp90 alpha and beta clusters. Comparison of nucleotide and amino acid substitution levels suggests that horse Hsp90 beta has undergone strong purifying selection, while rat Hsp90 beta and hamster Hsp90 alpha have been positively selected. Surprisingly, fish Hsp90 alpha genes clearly clustered with Hsp90 beta genes, and no distinct placement of fish Hsp90 alpha protein was found. The Hsp90 alpha isoform is apparently the result of beta gene duplication. Our results highlight the importance of organism- and isoform-specific Hsp90 functional analyses in describing the role of Hsp90 in cells.

Amino Acid Sequence↗

PubMed2001

Differential effects of oxidised and non-oxidised polyethylene particles on human monocyte/macrophages in vitro.

Sterilisation by gamma irradiation in the presence of air causes free radicals generated in polyethylene (PE) to react with oxygen, which could lead to loss of physical properties and reduction in fatigue strength. Tissue retrieved from failed total hip replacements often has large quantities of particulate PE and most particles associated with peri-implant osteolysis are oxidised. Consequently, an understanding of the cellular responses of oxidised PE particles may lead to clarification of the pathogenesis of osteolysis and aseptic loosening. We have used the agarose system to demonstrate the differential effects of oxidised and non-oxidised PE particles on the release of proinflammatory products such as interleukin-1beta (IL-1beta), IL-6, and tumour necrosis factor-alpha (TNF-alpha) from monocytes/macrophages (M/M). Oxidised PE particles were shown to stimulate human M/M to phagocytose and to release cytokines. Oxidation may alter the surface chemistry of the particles and enhance the response to specific membrane receptors on macrophages, such as scavenger-type receptors.

Cells, Cultured↗

PubMed2001

Effectiveness of an antiplatelet agent for coronary artery ectasia associated with silent myocardial ischemia.

A 74-year-old Japanese male was referred to our hospital because of an abnormal electrocardiogram. The electrocardiogram revealed tall P waves in leads II, III, and aV(F). Echocardiography disclosed hypokinesis extending from the anteroseptal region to the apex. Iodine-123 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123-BMIPP) scintigraphy revealed reduced uptake from the anteroseptal region to the apex. Coronary arteriography demonstrated diffuse dilatation of the right and left coronary arteries without organic stenosis, and left ventriculography showed hypokinesis at the same area. Furthermore, the coronary flow reserve in the left anterior descending artery was decreased. He was treated with an antiplatelet agent. Ten months later, the left ventriculography, 123I-BMIPP scintigraphy findings and coronary flow reserve were normalized. These findings demonstrate that antiplatelet therapy may be useful in the preservation of left ventricular function in patients with coronary artery ectasia.

Aged↗

PubMed2001

Polymorphism of the WAF1 gene is related to susceptibility to cervical cancer in Japanese women.

The WAF1 gene, located on chromosome 6p21.2, has been cloned and identified as a p53 mediator and an inhibitor of G1 cyclin-dependent kinases (CDKs). The present study was performed to investigate the possible role of the WAF1 gene in the pathogenesis of human cervical carcinoma. Matched venous blood and cancer tissues from 66 patients with cervical cancer were screened for WAF1 mutation by reverse transcription-polymerase chain reaction (RT-PCR) and DNA sequencing. A polymorphism in the WAF1 gene involving a cytosine (C) to an adenine (A) transversion at the third base of codon 31 was observed in 52 of 66 (78.8%) patients with cervical carcinoma and 68 of 108 (63%) normal individuals (P=0.02). A total of 7 patients (10.6%) were found to have a change of the WAF1 gene at codon 31 on comparison of blood and tumor specimens. An A-->C transversion in 5 tumors and a C-->A transversion in 2 tumors, that were not found in matching normal specimens, were observed. In addition, the presence of loss of heterozygosity (LOH) on chromosome 6p21.2 in tumor and normal tissue DNA were analyzed by PCR at three polymorphic microsatellite loci (D6S276, D6S1624, D6S1583). In two cases, there was a change of Arg/Ser in blood to Ser/Ser in the tumor, which did not involve LOH on 6p21.2. Therefore, somatic mutation of the WAF1 gene was detected in 3% (2 of 66) of patients with cervical cancer in this series. In conclusion, the increased frequency of WAF1 polymorphism in the patients studied implied that codon 31 Arg allele of the WAF1 gene may be associated with a tendency to develop cervical carcinoma. To our knowledge, this is the first report of WAF1 somatic mutations in primary human cervical cancer.

Cyclin-Dependent Kinase Inhibitor p21↗

PubMed2001

Mutation of the PTEN gene in advanced cervical cancer correlated with tumor progression and poor outcome after radiotherapy.

Improvement in management of advanced cervical cancer after radiotherapy requires a better understanding of its biological behavior. PTEN/MMAC/TEP(PTEN), a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be frequently mutated in several different types of human tumors. In contrast, rare mutations of the PTEN gene have been reported in cervical cancer. The aim of this study was to determine whether mutation of PTEN leads to increased genomic alteration in advanced cervical carcinoma, and to identify the correlation between mutation of PTEN and patient outcome after radiotherapy. We examined 50 primary advanced cervical carcinomas (37 patients of Stage IIIB, 13 patients of Stage IVA) treated with definitive radiotherapy using a PCR-based assay followed by SSCP and direct sequencing. The PTEN gene was mutated in 8 of the 50 (16%) patients (2 of Stage III, and 6 of Stage IV). There was a significant difference in Stage III versus IV between the wild-type PTEN patients and mutant PTEN patients (P=0.002). The tumor size was 6+/-2.1 cm in the wild-type PTEN tumors versus 8.5+/-2 cm in the mutant PTEN tumors (P=0.009). In addition, there was a significant difference in survival between the wild-type PTEN patients and mutant PTEN patients (P=0.009). The results of this study suggest that the PTEN gene mutation rate increases with tumor progression, and that the PTEN gene may play a role in both progression of cervical carcinoma and treatment outcome.

Adult↗

PubMed2001

Enzymatic characterization and interspecies difference of phenol sulfotransferases, ST1A forms.

Cytosolic sulfotransferases, which mediate activation and detoxification of both endogenous and exogenous compounds, consist of at least five different gene families (ST1 to ST5) in mammals. Several cDNAs corresponding to ST1A forms have been reported, but their functional properties are not well characterized. In addition, only a single form of ST1A sulfotransferase has been reported in each experimental animal species despite the expressions of plural forms in humans. Therefore, enzymatic properties of human ST1A3, ST1A5, rat ST1A1, mouse St1a4, and newly isolated rabbit ST1A8 have been characterized and compared by use of their recombinant proteins to clarify the functional difference between human and experimental animal ST1A forms. From the results using more than 25 phenolic chemicals, all the experimental animal ST1A forms showed substrate specificities similar to human ST1A3 rather than ST1A5. They showed high affinities toward p-nitrophenol and 6-hydroxymelatonin as found in human ST1A3. These forms also showed high activities toward umbelliferone and naringenin, but very low activities toward catecholamines, representative substrates of human ST1A5. Hepatic contents of experimental animal ST1A forms varied (66-250 pmol/mg of cytosolic protein) but showed the same order as observed with human ST1A3 (120 pmol/mg). Hepatic content of human ST1A5 was about 19-fold less than that of ST1A3. Therefore, ST1A forms identified in experimental animal species correspond to human ST1A3 functionally. For chemicals such as troglitazone and 2-amino-4'-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine, clear species differences were detected among the ST1A forms examined.

Amino Acid Sequence↗

PubMed2001

Fipronil modulation of gamma-aminobutyric acid(A) receptors in rat dorsal root ganglion neurons.

The gamma-aminobutyric acid (GABA) receptor is an important site of action of a variety of chemicals, including barbiturates, benzodiazepines, picrotoxin, bicuculline, general anesthetics, alcohols, and certain insecticides. Fipronil is the first phenylpyrazole insecticide introduced for pest control. It is effective against some insects that have become resistant to the existing insecticides. To elucidate the mechanism of fipronil interaction with the mammalian GABA system, whole-cell patch-clamp experiments were performed using rat dorsal root ganglion neurons in primary culture. Fipronil suppressed the GABA-induced whole-cell currents reversibly in both closed and activated states. The IC(50) values and Hill coefficients for fipronil block of the GABA(A) receptor were estimated to be 1.66 +/- 0.18 microM and 1.23 +/- 0.14 for the closed receptor, respectively, and 1.61 +/- 0.14 microM and 0.96 +/- 0.06 for the activated receptor, respectively. The association rate and dissociation rate constants of fipronil effect were estimated to be 673 +/- 220 M(-1) s(-1) and 0.018 +/- 0.0035 s(-1) for the closed GABA(A) receptor, respectively, and 6600 +/- 380 M(-1) s(-1) and 0.11 +/- 0.0054 s(-1) for the activated GABA(A) receptor, respectively. Thus, both the association and dissociation rate constants of fipronil for the activated GABA(A) receptor are approximately 10 times as large as those for the closed receptor. Experiments with coapplication of fipronil and picrotoxinin indicated that they did not compete for the same binding site to block the receptor. It is concluded that although fipronil binds to the GABA(A) receptor without activation, channel opening facilitates fipronil binding to and unbinding from the receptor.

Animals↗

PubMed2001

[Public music concerts in a psychiatric hospital: effects on public opinion and as therapy for patients].

We investigate the effects of music therapy concerts, which were held 60 times over a four year period, 1992 to 1996, in Geiyo Psychiatric Hospital, Kochi Prefecture and found that; 1) Musicians who performed at the concerts were not only from Kochi prefecture but also from other prefectures (10 times) and from four foreign countries (7 times). 2) Live concerts in a small hall had a positive influence on patients and drew the patient's attention and interest away from their hallucinations and delusions to the real world. Moreover, the concerts provided the patients with chances to acquire social graces such as being well-groomed. 3) Explanations by the musicians, interviews with the musicians and the seasonal choruses accompanied by the musicians were helpful to give the patients motives for recovering communication skills and to interact with society. 4) Inquiries to the patients about the concerts indicated discrepancies between the poor observed estimations during the concerts (83.3%) and the good subjective impressions expressed by the patients (82.0%), suggesting that the patients were not good at expressing their internal emotions through facial expressions or attitudes. 5) Many citizens including children came to the concerts and/or gave aid to the hospital because the concerts were open to the public and we suggest that this contributed to improving the general publics' image of psychiatric hospitals. Questionnaires revealed that 90% of people in a control group had a bad image of psychiatric hospitals in Japan, but only 32% of the members of the general public who attended our concerts had a bad image of psychiatric hospitals. In addition, the revolving ratio of the hospital beds rose from 0.4 to 1.2 over the four years, which also suggests a beneficial effect on the patients.

Hospitals, Psychiatric↗

PubMed2001

[Current availability of genetic information of drug metabolizing enzymes, particularly on cytochrome P450(CYP)].

Genetic polymorphisms of drug metabolizing enzymes often associated with clinical alteration among individuals. Current understanding of the molecular basis of the polymorphism of drug metabolizing enzymes is reviewed, particularly on cytochrome P450(CYP). Pharmacogenetic/pharmacogenomic studies are started for the estimation of pharmacokinetics of drugs, but now expanding for a tool of individual optimization of drug therapy for both drug efficacy and safety, and also for the development of new drugs. Genotyping is a powerful tool for these purposes, but not always simple because of the existence of more than 20 alleles for a single enzyme in some cases. Accumulated evidence, however, shows that occurrences of ethnic difference are rather common for allele distribution of drug metabolizing enzymes. These data indicate the necessity of the genetic analyses of Japanese population prior to the application of the genetic information for drug therapy.

Alleles↗

PubMed2001

Chemical structure and biological activity of a lipid A component from Helicobacter pylori strain 206.

The chemical structure of a lipid A, which was obtained as a minor component from lipopolysaccharide of Helicobacter pylori strain 206-1, was determined to be a glucosamine beta-(1 -6) disaccharide 1-(2-aminoethyl)phosphate acylated by (R)-3-hydroxyoctadecanoic acid, (R)-3- hydroxyhexadecanoic acid, and (R)-3-(octadecanoyloxy)octadecanoic acid at the 2-, 3- and 2'-positions, respectively. Compared with the other major lipid A from the same strain, which was previously reported [Suda Y, Ogawa T, Kashihara W et al. Chemical structure of lipid A from Helicobacter pylori strain 206-1 lipopolysaccharide. J Biochem 1997; 121: 1129--1133], the structure was very similar with one exception. An (R)-3-hydroxyhexadecanoic acid was present at the 3-position of the novel lipid A component. The structure is apparently identical to one of the proposals by Moran et al. [Moran AP, Lindner B, Walsh EJ. Structural characterization of the lipid A component of Helicobacter pylori rough- and smooth-form lipopolysaccharides. J Bacteriol 1997; 179: 6453--6463], who concluded the same structure as the so-called major lipid A from the H. pylori strain NCTC 11637 but without isolating a homogeneous component. The endotoxic properties and pro-inflammatory cytokine-inducing activities of this novel tetra-acyl type lipid A were lower than those of previously reported major tri-acyl type lipid A.

Animals↗

PubMed2001

[Functional outcome of primary pontine hemorrhage: conservative treatment or stereotaxic surgery].

In this study we compared the outcome of patients with primary pontine hemorrhage (PPH) in those who underwent stereotaxic aspiration and those treated non-surgically. Out of 75 PPHs, 37 patients were selected. Their consciousness on admission was somnolent to semicoma (alert and deeply comatose cases were excluded). Patients admitted between 1988 and 1990, and between 1995 and 1996 underwent CT guided stereotaxic aspiration (18 cases: Surgical Group), and those admitted between 1991 and 1994 were treated conservatively (19 cases: Conservative Group). The outcome was analyzed three months after the onset from the viewpoint of level of consciousness and severity of paresis, according to the location of the hemorrhage. With regard to consciousness, 13 of 18 cases in the Surgical Group showed remarkable improvement, while only 8 of 19 cases in the Conservative Group did. The severity of paresis was evaluated only among the patients who could obey commands three months after the onset. Paresis improved in 7 of 13 patients in the Surgical Group, vs. in 3 of 8 patients in the Conservative Group (p < 0.05). According to the location of hemorrhage (CT classification), in the Unilateral tegmental type and the Massive type, the Surgical Group and the Conservative Group showed no difference. On the other hand, in the Bilateral tegmental type and the Basal tegmental type, surgery seemed to be more effective than conservative treatment. In conclusion, CT guided stereotaxic aspiration may improve not only the consciousness level but also the functional outcome.

Adult↗

PubMed2001

[Aggressively metastatic neuroendocrine carcinoma in the middle mediastinum].

A 50-year-old male patient with no symptoms was admitted to our hospital for further evaluation of a right superior mediastinal mass shadow found in chest radiographs during a health examination. Computed tomographic (CT) scans demonstrated a middle mediastinal mass of 4 cm in diameter surrounded by the SVC, the ascending aorta and the trachea at the subaortic level. Routine examination disclosed no metastatic or primary lesion elsewhere. A surgical biopsy resulted in a diagnosis of neuroendocrine carcinoma of unknown primary organ. The patient was given 1 course of chemotherapy with CAV-PE, but little effect was seen. However, when a PE regimen combined with thoracic radiation was used, the tumor shrank to half of its size. After the patient subsequently received high-dose treatment with Etoposide, CT imaging and cytologic analysis revealed multiple metastases to the subcutaneous tissue, both adrenal glands and the liver. Lung lesions also spread aggressively, and the patient died of metastasis. Although neuroendocrine carcinomas can arise from the systemic neuroendocrine cells including those in the mediastinum, their appearance in the middle mediastinum is rarely reported.

Adrenal Cortex Neoplasms↗