[Huge right atrial myxoma].

Myxomas are account for approximately half of primary cardiac tumors, and 75% cases originate in left atrium. We report our experience of a right atrial myxoma. A 68-year-old woman was referred to us due to anorexia, general fatigue and facial edema. Echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), and catheter angiocardiogram revealed a huge tumor in right atrium. The tumor was resected completely with the attached right atrial free wall under cardiopulmonary bypass. Pathological examination showed myxomatous tissue. Postoperative course was uneventful. She discharged the hospital on the 37th day after the operation, and is now doing well without any symptoms.

Proliferating cell nuclear antigen expression and argyrophilic nucleolar organizer regions as factors influencing prognosis of surgically treated lung cancer patients.

Cell proliferation in 211 primary non-small cell lung carcinomas was assessed by using an immunostaining of proliferating cell nuclear antigen (PCNA) and a silver staining of argyrophilic nucleolar organizer region (Ag-NOR). More than 5% PCNA positive cells was designated PCNA(+), and less than 5% was PCNA(-). A mean number or more of the Ag-NOR was a high Ag-NOR count, and less than the mean number was a low Ag-NOR count. The proportion of the tumors with PCNA(+) and high Ag-NOR counts showed an increase in patients in an advanced stage of the disease (P < 0.05). In 125 patients with stage I disease, the 5-year survival rate was 20% in patients with PCNA(+) and high Ag-NOR counts, compared with 47% in those with either PCNA(+) or high Ag-NOR counts and 76% in those with PCNA(-) and low Ag-NOR counts (P < 0.05). Our data suggest that the tumors with PCNA(+) and high Ag-NOR counts have a high proliferative activity. The combination analysis of PCNA and Ag-NOR may be useful in assessing prognosis in lung cancer, even in stage I disease.

Immunohistochemical evidence of autocrine growth factors in adenocarcinoma of the human lung.

We immunohistochemically examined 131 primary human lung adenocarcinomas for the possible presence of autocrine factors. Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) were considered growth factors with epidermal growth factor receptor (EGFR) as the receptor. Of these tumors, 87 (66%) showed a high expression of TGF alpha, 66 (50%) showed a high expression of EGF, and 55 (42%) were positive for EGFR reactivity. In the EGFR-positive cases, the 5-year survival rates of patients with high TGF alpha and low TGF alpha were 36% and 85%, respectively (P less than 0.05). The 5-year survival rates of patients with high EGF and low EGF were 25% and 77%, respectively (P less than 0.05). In contrast, in the EGFR-negative cases, there was no statistical difference between the 5-year survival rates of patients with either high TGF alpha or EGF and low TGF alpha or EGF. Because autocrine growth mechanisms are present in adenocarcinoma of the human lung, these events may contribute to clarification of tumor development, and perhaps even to a better prognosis.

[Valve-in-valve replacement of primary tissue valve failure of bovine pericardial valve minor].

A 73-year-old woman who underwent mitral valve replacement with a 31 mm Carpentier Edwards Pericardial Xenograft 19 years ago. She revealed sudden onset of a grade IV/VI a seagull like diastolic murmur at the apex, and severe hematuria. Echocardiography demonstrated severe mitral regurgitation. These findings were consistent with acute primary tissue valve failure. Therefore we performed emergency reoperation. At operation, valve leaflet was torn at the commissural stitch, and bioprosthesis strut was buried in the left posterior ventricular wall. The mitral prosthetic valve replaced with a 25 mm CarboMedics OptiForm using a technique of valve-in-valve replacement. This procedure would be one option for replacement of bioprosthetic mitral valve.

Lateral Asymmetry and Spatial Difference of Iron Deposition in the Substantia Nigra of Patients with Parkinson Disease Measured with Quantitative Susceptibility Mapping.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping is useful for assessing iron deposition in the substantia nigra of patients with Parkinson disease. We aimed to determine whether quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference in iron deposits in the substantia nigra of patients with Parkinson disease. MATERIALS AND METHODS: Our study population comprised 24 patients with Parkinson disease and 24 age- and sex-matched healthy controls. They underwent 3T MR imaging by using a 3D multiecho gradient-echo sequence. On reconstructed quantitative susceptibility mapping, we measured the susceptibility values in the anterior, middle, and posterior parts of the substantia nigra, the whole substantia nigra, and other deep gray matter structures in both hemibrains. To identify the more and less affected hemibrains in patients with Parkinson disease, we assessed the severity of movement symptoms for each hemibrain by using the Unified Parkinson's Disease Rating Scale. RESULTS: In the posterior substantia nigra of patients with Parkinson disease, the mean susceptibility value was significantly higher in the more than the less affected hemibrain substantia nigra (P < .05). This value was significantly higher in both the more and less affected hemibrains of patients with Parkinson disease than in controls (P < .05). Asymmetry of the mean susceptibility values was significantly greater for patients than controls (P < .05). Receiver operating characteristic analysis showed that quantitative susceptibility mapping of the posterior substantia nigra in the more affected hemibrain provided the highest power for discriminating patients with Parkinson disease from the controls. CONCLUSIONS: Quantitative susceptibility mapping is useful for assessing the lateral asymmetry and spatial difference of iron deposition in the substantia nigra of patients with Parkinson disease.

Visualization of the Medial and Lateral Geniculate Nucleus on Phase Difference Enhanced Imaging.

BACKGROUND AND PURPOSE: The precise identification and measurement of the medial geniculate nucleus and lateral geniculate nucleus on MR imaging remain technically challenging because the thalamic nuclei are small structures. We compared the visualization of the medial geniculate nucleus and lateral geniculate nucleus on phase difference enhanced imaging with 3D high-resolution phase imaging, 2D-T2WI, STIR, proton attenuation-weighted imaging, and DTI acquired at 3T. We also measured the volume and height of the medial geniculate nucleus and lateral geniculate nucleus on phase difference enhanced imaging. MATERIALS AND METHODS: Phase difference enhanced, 2D-T2-weighted, STIR, proton attenuation-weighted, and DTI were acquired on a 3T MR imaging unit in 10 healthy volunteers. Two neuroradiologists recorded the qualitative visualization scores of the medial geniculate nucleus and lateral geniculate nucleus, specifically the identification of their boundaries, for all images. Measurement differences were assessed with the Wilcoxon signed rank test. The volume and height of the medial geniculate nucleus and lateral geniculate nucleus were measured on phase difference enhanced imaging and compared with previously reported values. RESULTS: The qualitative visualization scores of the lateral geniculate nucleus and medial geniculate nucleus were significantly higher on phase difference enhanced images than on T2-weighted, proton attenuation-weighted, STIR, or DTI (P < .05). On phase difference enhanced imaging, the medial geniculate nucleus and lateral geniculate nucleus were bordered by low-intensity structures: the cerebral peduncle, the origin of the optic radiation, and the superior and inferior quadrigeminal brachia. The volume of the medial geniculate nucleus and lateral geniculate nucleus varied from 74.0 to 183.75 mm(3) (mean, 129.0 ± 34.7 mm(3)) and from 96.5 to 173.75 mm(3) (mean, 135.2 ± 28.0 mm(3)), respectively. CONCLUSIONS: For the depiction of the medial geniculate nucleus and lateral geniculate nucleus on 3T MR imaging, phase difference enhanced imaging is superior to conventional MR imaging. The medial geniculate nucleus and lateral geniculate nucleus volumes vary among individuals.

Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma.

203 primary human lung tumours, of which 119 were adenocarcinoma and 84 were squamous cell carcinoma, were investigated immunohistochemically for the expression of c-erbB-2 protein. Positive staining was evident in 33 (28%) of adenocarcinomas and 2 (2%) of squamous cell carcinomas. In cases of adenocarcinoma, c-erbB-2 was present in 18% of those with stage I disease. In stage IIIA, stage IIIB and stage IV cases, c-erbB-2 was present in 39%, 50% and 60%, respectively (I vs. IIIA and I vs. IIIB: P less than 0.05, I vs. IV: P less than 0.01). The 5-year survival rates of c-erbB-2 positive patients and those who were negative were 30% and 52%, respectively, with a statistically significant difference (P less than 0.01). These observations suggest that when the expression of c-erbB-2 correlates with invasiveness of the tumour, this correlation may serve as a prognostic indicator, particularly in cases of adenocarcinoma of the lung.

Sensitivity to functors in Japanese aphasics.

Forty-two aphasic patients (11 amnesic, 11 Wernicke's, and 20 Broca's) and 10 controls were tested for sensitivity to functors in affirmative declarative sentences with sentence- verification tasks. The stimuli were constructed according to the following factors: Reversibility of Subject and Object, Voice, Word Order and Truth. The task required the subject to decide if a sentence presented auditorily was true or false with respect to a picture. The results indicated that functors differed among themselves in their understandability depending on sentence types in which they were embedded, and that there were no qualitative differences in sensitivity to functors among different clinical types of aphasia.

Specific induction by glucocorticoids of steroid esterase in rat hepatic microsomes and its release into serum.

Steroid esterase hydrolysing methylprednisolone 21-hemisuccinate was induced specifically and markedly in hepatic microsomes and serum of rats by various glucocorticoids. Among the glucocorticoids examined, dexamethasone and betamethasone showed the highest potency to induce the hepatic steroid esterase, the induction ratio being 32 and 33 times higher than the basal level (about 160 mU/g liver), respectively. Steroid esterase in the serum was induced greatly by fluocinolone acetonide and betamethasone to 92 and 79 times of the basal level of about 16 mU/mL, respectively, followed by dexamethasone and methylprednisolone. When dexamethasone was given to rats, the enzyme in other tissues except for duodenum and small intestine (of which activity was lowered to 50% of the basal level) was also elevated, but the induction ratio was much lower than that in the liver and serum. The induction of the steroid esterase is probably due to stimulation of de novo synthesis of the enzyme by glucocorticoids, because the elevation of esterase activity was inhibited by treatment with cycloheximide (a translation inhibitor) and actinomycin D (a transcription inhibitor), and about 4- and 10-hr lag time was observed before the elevation of esterase activity in liver and serum, respectively. Coupled with these observations the following results indicate that the steroid esterase in serum is probably synthesized in the liver and subsequently released into the blood via the Golgi apparatus: (1) when the liver of rats treated with dexamethasone was subjected to perfusion with a recycling system, significant amounts of steroid esterase were released into the perfusate; (2) anti-hepatic esterase antibody inhibited the steroid esterase activity not only in the liver but also in serum; and (3) monensin, which prevents the secretion of various kinds of secretory proteins by disrupting the function of the Golgi apparatus, inhibited the elevation of the steroid esterase activity in serum by dexamethasone but did not affect the induction in liver.

A novel pathway for formation of thiol metabolites and cysteine conjugates from cysteine conjugate sulphoxides.

p-Bromothiophenol and S-(p-bromophenyl)-L-cysteine were formed enzymatically from S-(p-bromophenyl)-L-cysteine sulphoxide in the in vitro systems with isolated rat hepatocytes or purified cysteine conjugate beta-lyases. Isotope dilution study with non-radiolabelled carrier of each product suggested the initial liberation of the thiol and subsequent formation of the cysteine conjugate. C-S bond cleavage pathway to liberate sulphenic acid and thiol are postulated to play an important role in in vivo generation of toxic intermediates and products from cysteine conjugates.

Involvement of leukocytes in the oxygenation and chlorination reaction of phenylbutazone.

A center carbon atom of 1,3-diketone moiety of phenylbutazone was oxidized to give three metabolites--4-hydroxyphenylbutazone (metabolite I), 4-hydroperoxyphenylbutazone (metabolite II) and 4-chlorophenylbutazone (metabolite III)--by the action of enzymes present in leukocyte extract obtained from peritoneal exudate of rats. Both metabolites II and III were produced by peroxidases, while metabolite I was produced by enzymes other than the peroxidases.

Purification and characterization of 3-mercaptolactic acid S-conjugate oxidases.

Two enzymes catalysing the oxidative formation of 3-mercaptopyruvic acid S-conjugates from L-3-mercaptolactic acid S-conjugates were purified to apparent homogeneity from rat liver cytosol. The two enzymes, tentatively designated MLO-I and MLO-II, showed a molecular mass of 160 and 250 kDa and were composed of four and six subunits of 41 and 39 kDa, respectively. Both enzymes possessed flavin mononucleotide as prosthetic group and oxidized several aromatic and aliphatic S-substituted L-3-mercaptolactic acids as well as alpha-hydroxy acids such as L-3-phenyllactic acid and L-2-hydroxyisocaproic acid. Glycolic acid and 3-(4-hydroxyphenyl)-lactic acid were the specific substrates for MLO-I and MLO-II, respectively. Neither of the enzymes oxidized beta- and gamma-hydroxy acids such as 3- and 4-hydroxybutyric acid. 2-Hydroxyisobutyric acid, ethyl-2-hydroxybutyrate, malic acid, 1-butanol, benzyl alcohol and L-leucine did not act as substrates for the enzymes. MLO-I and MLO-II exerted their maximum activities around pH 5.5 with Km of 0.5 and 0.25 mM and Vmax of 0.9 and 0.2 mumol/min/mg, respectively, when S-(4-bromophenyl)-3-thiolactic acid was used as substrate. MLO-I was inhibited by sulphydryl-modifying agents, while MLO-II was not. Both enzymes were strongly inhibited by divalent metal ions. These results indicate that MLO-I and MLO-II are different from L-amino acid oxidase (EC 1.4.3.2), malate oxidase (EC 1.1.3.3), L-alpha-hydroxy acid oxidase (EC 1.1.3.15) and glycolate oxidase (EC 1.1.3.1). The present enzymes are likely to be involved in the formation of cysteine conjugates from L-3-mercaptolactic acid S-conjugates in conjunction with cysteine conjugate aminotransferases.

Purification and characterization of glucocorticoid-inducible steroid esterase in rat hepatic microsomes.

A steroid esterase hydrolysing methylprednisolone 21-hemisuccinate was purified from the hepatic microsomes of rats treated with dexamethasone, a potent inducer of the esterase. The enzyme was solubilized by Lubrol WX and purified up to 30-fold over the microsomal fraction by ammonium sulfate fractionation and successive chromatographies with gel permeation, DEAE-cellulose and hydroxylapatite. The steroid esterase thus purified showed a single band and a molecular mass of 58 kDa on SDS-polyacrylamide gel electrophoregram. The enzyme appears likely to exist as two interconvertible forms, which can be distinguished by pI values, pI 4.9 and 5.1. The enzyme was completely inhibited by organic phosphates, indicating that it can be classed as a carboxylesterase (EC 3.1.1.1). Both negatively charged and uncharged esters of several steroids (methylprednisolone, hydrocortisone, deoxycorticosterone and dehydrotestosterone) as well as various non-steroidal esters including 4-nitrophenyl esters were hydrolysed by the enzyme, but none of the amides were substrates. The enzyme showed higher activity with increasing lipophilicity of the substrates. It is noticeable that the optimum pH for charged esters was 5.5, whereas the highest activity was observed around pH 7-8 for uncharged esters. When methylprednisolone 21-hemisuccinate (one of the charged esters) was used as substrate, the Km value was 2.8 mM and Vmax was 59.3 mumol/mg protein for 1 min at the optimum pH of 5.5. Regarding the methyl ester of methylprednisolone 21-hemisuccinate, Km and Vmax values were 1.8 mM and 193 mumol/mg protein/min, respectively, at the optimum pH of 7.0. On the basis of these results, the enzyme is most likely a carboxylesterase.

Purification and characterization of 3-mercaptopyruvic acid S-conjugate reductases.

Three kinds of 3-mercaptopyruvic acid S-conjugate reductase (MPR-I, MPR-II and MPR-III) were purified from rat liver cytosol. These enzymes reduced 3-mercaptopyruvic acid S-conjugates derived from cysteine conjugates and some endogenous alpha-keto acids to the corresponding alpha-hydroxy acids in the presence of either NADH (for MPR-I and MPR-II) or NADPH (MPR-III), while simple aldehydes or ketones did not significantly induce substrate activity. The molecular weight of the present enzymes was about 80 kDa composed of two subunits of the same molecular weight. Km values of MPR-I, MPR-II and MPR-III were 0.38, 0.06 and 0.29 mM for S-(4-bromophenyl)-3-thiopyruvic acid, respectively, and 0.15 mM for NADH (MPR-I, MPR-II) and NADPH (MPR-III). Vmax values of MPR-I, MPR-II and MPR-III for this substrate were 5.3, 20 and 13 nmol/min/mg, respectively. The sulphydryl-modifying agents inhibited the enzyme activities of all the three reductases. Based on the properties including substrate selectivity for alpha-keto acids derived from aromatic amino acids, we assumed that MPR-II and aromatic alpha-keto acid reductase are the same enzyme, while enzymes similar to MPR-I and MPR-III have not been reported. From the viewpoints of metabolism of xenobiotics, these enzymes are likely to be important in biotransformation of cysteine conjugates to 3-mercaptolactic acid S-conjugates.

Neoadjuvant chemotherapy in patients with small-cell lung-cancer - radiographic and clinicopathological analysis.

A comparative study on the effect of neoadjuvant chemotherapy was performed for small cell lung cancer, by radiographic and histopathological examinations. Four patients with small cell lung cancer were preoperatively treated with the combination of cyclophosphamide, doxorubicin, vincristine, nimustine, cisplatin and vindesine, for 2 to 3 cycles. The clinical responses to the neoadjuvant chemotherapy included 2 complete, one partial response and one no change. All four patients underwent a planned operation. Based on microscopical evidence, the two complete responders had a residual tumor in the resected specimens. One was tumor-free after 28 months, while the other succumbed to operation-related death at 2 months. The remaining two inadequate responders relapsed and died shortly following operation. We believe a clinically complete responder should be differentiated from a 'true' complete responder by histopathological examination.

Carcinosarcoma and spindle cell carcinoma of the lung. Clinicopathologic and immunohistochemical studies.

We examined pulmonary carcinomas with prominent sarcoma-like lesions both clinicopathologically and immunohistochemically. Grossly, two tumors had predominantly endobronchial growths, four bulky parenchymal growths, and two endobronchial, parenchymally mixed growths. In these eight patients, six tumors were completely resected, one patient was given irradiation only, and one patient died in the early postoperative period. On the basis of specific differentiation of the sarcoma-like lesions, the tumors were separated into three groups: two with "true" sarcoma differentiated into soft tissues such as striated muscle or osteoid tissue; three with a fibromatous sarcoma resembling atypical pseudosarcomatous stroma; and three with spindle cell carcinoma with evidence of epithelial differentiation. The prognosis was poor, and tumors with specific differentiation into rhabdomyosarcoma, chondrosarcoma, or spindle cell carcinoma progressed more rapidly than did those with a fibromatous sarcoma. Because the fibromatous sarcoma-like lesions were found to relate to a longer survival time for the patients, we wish to emphasize that a distinction of sarcomatous components should be made with regard to assessing the prognosis of pulmonary carcinoma with sarcoma-like lesions.

Large cell carcinoma of the lung. Prognostic implications of histopathologic and immunohistochemical subtyping.

Fifty-four patients with large cell carcinoma of the lung were treated surgically, and the prognostic factors were examined histologically and immunohistochemically. Based on evidence of intercellular cohesion, as seen in the histologic results, the patients were placed into two subtypes, compact growth type and louse structure type. The survival rates were 46% and 28% at five years, respectively (P less than 0.05). Immunohistochemically, keratin, epithelial membrane antigen (EMA), secretory component, lactoferrin, and carcinoembryonic antigen (CEA), as histologic markers of epithelial differentiation, were detectable in large cell carcinoma of both types and more frequently in the compact growth type than in the loose structure type. The difference was significant in case of detection of keratin, EMA, and CEA (P less than 0.05). These observations suggest that a large cell carcinoma may differentiate into an adenocarcinoma or squamous cell carcinoma. The presence of intercellular cohesion and use of these markers reflect prognosis of the disease.

Longer survival after resection of non-small cell lung cancer in Japanese women.

From 1974 to 1988, 492 patients (361 male and 131 female) with non-small cell lung cancer underwent pulmonary resection at our department. A retrospective study was done with special reference to the sex of the patients. There was no sex-related association with age distribution, operation, pathological T or N status, or staging. On the other hand, 77.9% of women had an adenocarcinoma and only 44.6% of men had this type of lesion. This was considered at least partly a result of sex difference in smoking habits. Women survived for a significantly longer time (p = 0.0036), and this difference could not be explained by differences in histological type. Presumably, hormonal factor(s) may contribute to the prognosis.

Strategy for lymphadenectomy in lung cancer three centimeters or less in diameter.

We have surgically treated 221 patients with a primary lung cancer 3.0 cm or less in diameter. There were 8 patients with a tumor 1.0 cm or less in diameter (group A), 84 with a tumor 1.1 to 2.0 cm in diameter (group B), and 129 with a tumor 2.1 to 3.0 cm in diameter (group C). The incidence of N0, N1, and N2 disease was 100%, 0%, and 0%, respectively, for patients in group A; 83%, 5%, and 12% in group B; and 62%, 12%, and 25% in group C (N0 versus N2, p less than 0.01). For the 63 patients with regional lymph node involvement, "skipping" metastasis was present in 28.6%. The 5-year survival rate was 80% for group A, 74% for group B, and 51% for group C (group B versus group C, p less than 0.01). Of the 121 patients who underwent complete resection and were followed up for 5 years, 41% had recurrence, 8% with local recurrence and 33% with distant metastasis. Therefore, it is important to do as complete a resection as possible together with mediastinal lymphadenectomy. Efforts to detect systemic spread should be made at the time of preoperative evaluation, even when the lung tumor is small.

Inflammatory pseudotumor of the lung in adults: radiographic and clinicopathological analysis.

Inflammatory pseudotumors of the lung are rare in adults. We treated 7 patients with such tumors and describe the histological evidence, radiographic findings, and surgical treatment. In 5 patients, lung cancer was suspected preoperatively on the basis of the radiographic findings. Intraoperatively, the gross appearance of the pleura resembled lung cancer in 6 patients; the parietal pleura was involved in 3, and pleural indentation was present in the other 3. Two patients underwent partial resection, as the frozen section revealed a benign tumor, and 5 patients underwent lobectomy for what appeared to be lung cancer or a large mass. All of the patients are doing well without other therapy. We believe the lesion should be differentiated from lung cancer at operation by frozen sections, even though this proved pertinent in only 2 of the 7 patients. Limited resection is recommended if the lesion is an inflammatory pseudotumor.