Abnormal pigmentation of schwannoma attributed to excess production of neuromelanin-like pigment.

Five cases of non-melanotic pigmented schwannoma with excess accumulation of neuromelanin are presented. The tumors were composed basically of spindle or fusiform tumor cells, compatible with those of classical schwannoma, together with varying numbers of tumor cells containing various amounts of light brown or grayish pigment. Fontana-Masson stain demonstrated argentaffin granules in some tumor cells of each tumor and bleaching with potassium permanganate abolished argentaffin reaction. Ultrastructural examination demonstrated the granules contained fine particles with heterogeneous density, occasionally together with coarse granular materials or amorphous high-density areas, indicating lysosome or autophagosome. Neither typical melanosomes nor neurosecretory granules were detected. In immunohistochemistry, neurogenic markers as well as CD68 were expressed in most tumor cells in each case and various numbers of tumor cells were positive for Leu7 and CD34. Lysozyme was also frequently positive in tumor cells, especially in granular cells. HMB45 was not expressed in any of the cases. These findings indicate that these cases are schwannomas with abnormal accumulation of neuromelanin-like pigment.

Characterization of a newly established human acinic cell adenocarcinoma cell line (HACC) originating from the salivary gland: morphological features and role of various growth factors on the growth of the HACC cell line.

Human acinic cell adenocarcinoma cell (HACC) line was established from the pleural effusion that contains metastatic tumor cells of acinic cell adenocarcinoma of papillary and microcystic type originating from the parotid gland. The HACC cells grew in an adherent monolayer with a doubling time of 66 h. Implanted tumor of SCID mice revealed similar histological findings to that of the primary tumor. The HACC cells produced mucin and expressed epithelial markers as well as alpha1-antitrypsin and lysozyme, whereas salivary peptide P-C was expressed in cultured HACC cells but not in the primary and implanted HACC cell tumors. S-100 protein was also expressed in both the primary tumor and HACC cell line. Neither amplification of common oncogenes nor expression of p53 was observed. The receptor for epidermal growth factor (EGF) was expressed, indicating EGF and transforming growth factor-alpha (TGF-alpha) enhanced the growth of the HACC line. Unexpectedly, tumor necrosis factor-a (TNF-alpha) also enhanced the growth of the HACC line significantly. However, there was no evidence of autocrine growth using these growth factors. In contrast, TGF-beta1 inhibited the growth of the HACC cell line through apoptosis. The HACC cell line has features similar to both acinar and intercalated ductal cells of the salivary gland. Epidermal growth factor, TGF-alpha and TNF-alpha are potential growth factors for the HACC cell line. The HACC cell line may be a good model for studying the biological behavior of salivary gland neoplasms.

Cloning of PCPTP1-Ce encoding protein tyrosine phosphatase from the rat cerebellum and its restricted expression in Purkinje cells.

Recently, cDNAs encoding brain-specific transmembrane-type protein tyrosine phosphatases (PTPs) with single catalytic domain have been cloned. These include PC12-PTP, PCPTP1, PTPBR7, and PTP-SL, whose cytoplasmic domains had high similarity to STEP, a brain-specific nontransmembrane-type PTP. Based on the high similarity and expression pattern, PCPTP1 seems to be identical with PC12-PTP1 and to be the rat homologue of murine PTPBR7. Here, we report the molecular cloning and expression profile of PCPTP1-Ce, a variant of PCPTP1. Both PCPTP1 mRNA and PCPTP1-Ce mRNA seem to be derived from a single common region gene. Nucleotide and deduced amino acid sequence comparison between PCPTP1-Ce and PCPTP1 revealed that the predicted protein product of PCPTP1-Ce is identical with that translated from the third initiation methionine of the longest ORF of PCPTP1, and that these two clones differ in the 5'-untranslated sequences. Northern blot analyses with specific probes for PCPTP1 and PCPTP1-Ce confirmed our previous observation that PCPTP1-Ce mRNA was almost exclusively expressed in the cerebellum, whereas PCPTP1 was widely expressed in various brain regions dissected including cerebellum. In situ hybridization study demonstrated that PCPTP1-Ce mRNA was exclusively expressed in Purkinje cells of the cerebellum. In contrast, PCPTP1 mRNA was predominantly expressed in granule cells and less in Purkinje cells. Moreover, immunohistochemical analysis using an affinity-purified polyclonal antibody raised against the cytoplasmic region of PCPTP1/PCPTP1-Ce demonstrated that Purkinje cells were strongly immunostained, whereas granule cells were stained only faintly in the cerebellum. These observations clearly demonstrated that PCPTP1-Ce mRNA and its protein products are expressed in Purkinje cells and suggest that PCPTP1-Ce may play an important role in Purkinje cell function in the rat cerebellum.

Immunohistochemical localization of endothelin-1, endothelin-3 and endothelin receptors in human pheochromocytoma and paraganglioma.

Endothelin (ET) and its receptor system have been shown to exert various biological effects on different types of cells in addition to their well-known vasoconstrictor activity. Recently ET-1, ET-3 and the ETB receptor have been shown to play an important role in the development of neural crest-derived cells and, in this context, pheochromocytomas have been reported to harbor ET-1. Endothelin-3 or ET receptor subtypes, however, have not been examined in pheochromocytoma and paraganglioma so far. In the present study the immunohistochemical localization of ET-1/big ET-1, ET-3/big ET-3 and the ETA and ETB receptors were investigated to clarify the biological characteristics of these two tumors using 32 pheochromocytomas and 11 extra-adrenal paragangliomas. Endothelin-1/big ET-1 was detected in 19 pheochromocytomas (59%) and eight paragangliomas (72%), while ET-3/big ET-3 was detected in 10 pheochromocytomas (31%) and three paragangliomas (27%). The ETA receptor was found in 21 pheochromocytomas (66%) and in eight paragangliomas (73%), while the ETB receptor was found in 25 pheochromocytomas (78%) and in eight paragangliomas (73%). Normal adrenomedullary cells lacked each antigen examined. Endothelin-immunoreactive tumor cells were distributed focally or in a manner scattered, while receptor-immunostained tumor cells were distributed with a focal pattern for the ETA receptor and with a focal or diffuse pattern for the ETB receptor. Endothelin and its receptor coexisted in the same tumor in 21 of 28 ET-positive pheochromocytomas and in eight of 10 ET-positive paragangliomas. In addition, seven pheochromocytomas and two paragangliomas revealed positivity of the receptor(s) irrespective of the absence of ET-immunoreactivity. In conclusion, ET and its receptor are frequently and concomitantly expressed in the pheochromocytoma and paraganglioma. From the highly frequent expression of this system or the receptor(s), ET-receptor-mediated signal transduction of these tumors concerning growth and/or cell survival is expected, although definite biological significance of this ligand-receptor system in these tumors awaits further investigation.

Regular immunohistochemical localization of endothelin-1 and endothelin-B receptor in normal, hyperplastic and neoplastic human adrenocortical cells.

The localization of endothelin (ET)-1/big ET-1, ET-3/big ET-3, ET-A and ET-B receptor was immunohistochemically examined in human adrenal glands composed of 36 normal cases, nine hyperplasia, 70 adenomas and seven carcinomas of cortical cells. In normal adrenals, ET-1/big ET-1 and ET-B receptor were regularly detected in the cortical cells, especially in the zona fasciculata for ET-1 and zona glomerulosa for ET-B receptor but not in the medulla, while ET-A receptor localized occasionally in endothelial cells or rarely in cortical cells and ET-3/big ET-3 was very limited in the cortical cells. In hyperplasia, adenoma and carcinoma, ET-1/big ET-1 and ET-B receptor showed frequent localization, although focal distribution of the ET-B receptor was rather predominant in these groups. ET-A receptor and ET-3/big ET-3 were very infrequently expressed. Functioning versus non-functioning and hypertensive versus normotensive cases revealed no significant differences in the frequency of positive cells for ET-1/big ET-1, ET-3/big ET-3, ET-A receptor or ET-B receptor. Alternatively, the frequency of immunoreactivity to ET-1/big ET-1 or ET-B receptor significantly decreased in hyperplasia, adenoma and carcinoma, when compared with that of normal adrenal cortex. The present study, therefore, indicates that ET-1/big ET-1 and ET-B receptor are a prevalent ligand-receptor system in normal and hyperplastic/neoplastic adrenocortical cells, even with a malignant profile, and may contribute in maintaining adrenocortical cell function or cell viability but not cell growth or systemic hypertension.

Thymolipoma associated with myasthenia gravis.

In a 29-year-old woman with myasthenia gravis and no visible mediastinal mass, the resected thymus was found to contain a small thymolipoma. Relief of the neuromuscular symptoms followed thymectomy. A very small thymolipoma may be associated with myasthenia gravis even if the content of though thymic tissue is low.

Experience of expandable metallic stents for central airway obstruction.

The aim of this study was to investigate retrospectively the efficacy of expandable metallic stents (EMSs) for severe respiratory distress in patients with central airway obstruction. Twenty patients with central airway obstructions were treated with an EMS. An intraluminal stricture was present in 15 and an extraluminal stricture in 5 patients. Of the 15 patients with intraluminal stenosis, 11 exhibited symptomatic improvement. All 11 patients had tumor infiltration occupying less than 50% of the endoluminal diameter. The other four patients with intraluminal stenosis had tumor infiltration occupying > 50% of the endoluminal diameter and demonstrated no improvement. All five patients with extraluminal stenosis were improved. EMS is useful for an extraluminal stricture in the central airway and the effect of EMS for intraluminal stenosis is related to the degree of infiltration and of tumor progression itself.

Uterine leiomyosarcoma with osteoclast-like giant cells: histopathological and cytological observations.

A 56 year old woman presented with abnormal uterine bleeding. Except for a myomatous uterus, no other abnormalities were noted on physical examination and in radiographic and serologic studies. The hysterectomy specimen revealed an 8 cm uterine fundic tumor composed of two histologically different patterns that merged with one another; one was a well differentiated leiomyosarcoma and the other a mixture of osteoclast-like giant cells (OGC) and plump spindle cells whose cell borders blended, resembling the histology of giant cell tumor of bone. Immunohistochemical studies showed positive staining for muscle actin, alpha-smooth muscle actin, and KP-1 (CD68) in both the spindle cells and OGC. The latter also stained for alpha-1-antitrypsin and alpha-1-antichymotrypsin. These findings suggested that OGC may be formed by the fusion of spindle cells of leiomyosarcoma and also express histiocytic markers.

Functional nerve growth factor receptor in von Recklinghausen neurofibromatosis: an immunocytochemical and short-term culture study.

Immunocytochemistry reveals 75 kDa low affinity type nerve growth factor receptor (NGFR) on the cell membrane of human neurofibroma cells of von Recklinghausen disease in vivo and in vitro. NGF-immunoreactivity is detected in the primary and cultured tumor cells. Growth augmentation of cultured neurofibroma cells by exogenous NGF is also confirmed. Phosphotyrosine-immunoreactivity is demonstrated by immunocytochemistry in the in vivo and in vitro neurofibroma cells suggesting possible phosphorylation of tyrosine residue in the NGFR or a cellular protein downstream of signal transduction through the ligand receptor system. These results indicate human neurofibroma cells possess functional NGFR and the growth is potentiated through the NGF-NGFR system in the paracrine and/or autocrine fashion.

Neoplastic endocrine cells in prostatic carcinoma: a case report with immunocytochemical and electron microscopic findings.

A case of a 68-year-old male with prostatic carcinoma which was partially well differentiated but largely poorly differentiated is presented in this report. The poorly differentiated area of the adenocarcinoma seemed to arise from the well-differentiated portion. The former was populated with Grimelius argyrophilic cells, and occasionally contained round, eosinophilic intracytoplasmic inclusions which appeared to be composed of a secretory substance. Immunocytochemistry revealed that endocrine cells were present in the normal portion of the gland as well as in the well-differentiated adenocarcinoma, but were more numerous in the poorly differentiated portion. The latter portion was positive for chromogranin A, endocrine granule constituents, neuroendocrine markers, serotonin, Leu 7, ACTH and neuron specific enolase. In addition, cells of poorly differentiated portion were reactive with CEA, prostatic acid phosphatase and human prostate specific antigen. Ultrastructural features observed in the poorly differentiated adenocarcinoma included five kinds of round neurosecretory granules. This was a rare case of prostatic adenocarcinoma in which the evolution from well differentiated to poorly differentiated tissue containing neuroendocrine constituents could be clearly observed.

[The simultaneous evaluation of preoperative cardiopulmonary functions of esophageal cancer patients in the analysis of expired gas with exercise testing].

By analyzing expired gas with exercise testing, we examined the relationship between test results and postoperative cardiopulmonary complications. The analysis was evaluated for its accuracy and reliability in comparison with general pulmonary function tests including spirometry, flow volume curves, diffusing capacity and arterial blood gas analysis. Enrolled were 52 of patients admitted between a period from 1991 to 1993 for thoracic esophageal cancer, who underwent a radical operation of right thoracolaparotomy. Patients were divided into two groups according to postoperative cardiopulmonary complications; one with complications (group C, n = 11) and the other without complication (group NC = 41). The two groups were compared in maximum oxygen consumption (VO2 max)/m2, anaerobic threshold (AT)/m2, VC/m2, %VC, FEV1.0/m2, V25/m, V50/V25, %DLCO and PaO2. In the results, there were significant differences between the two groups only in VO2 max/m2 (p < 0.001), AT/m2 (p < 0.001), and V50/V25 (p < 0.05), while there were no significant differences between the two groups in VC/m2, %VC, FEV1.0/m2, FEV1.0%, V25/m, %DLCO or PaO2. The above results suggest that analysis of expired gas with exercise testing is able to measure easily both cardiac and pulmonary reserve forces, which conventional pulmonary function tests are unable to do, and is evaluating surgical indications for esophageal cancer patients and predicting postoperative cardiopulmonary complications.

[Pre-operative screening tests for lung cancer using the analysis of expired gas with exercise testing--principally VO2 max/m2].

The analysis of expired gas with exercise testing was conducted preoperatively with lung cancer patients in order to examine the relationship between maximum oxygen consumption (VO2 max) and postoperative complications, determining the cut-off of VO2 max/m2. The usefulness of the test as a preoperative screening test for both pulmonary ventilation and circulation was evaluated in comparison to pulmonary ventilation tests with spirometry and pulmonary circulation tests with Swan-Ganz catheter. Preoperative VO2 max/m2 was calculated from VO2 max in 111 patients with lung cancer who underwent lobectomy of more than one lobe. Also preoperatively conducted were pulmonary ventilation tests by spirometry and pulmonary circulation tests using the Swan-Ganz catheter to measure VC, %VC, FEV1.0, FEV1.0%, mean pulmonary arterial pressure (PPA) and cardiac output coefficient (C.I.). Form theses measurements, VC/m2, FEV1.0/m2 and total pulmonary vascular resistance (TPVR) were calculated. After the cut-off values of VO2 max/m2 were set tentatively at three stages, 600, 650 and 700 ml/min/m2 based on the incidence of postoperative complications, the 111 patients were divided into two groups in each cut-off value; one with VO2 max/m2 greater than the cut-off value and the other less than the cut-off value. Comparison of measurements obtained by spirometry between the two groups disclosed significant differences (p < 0.001) in VC/m2, %VC and FEV1.0/m2 in all cut-off values. Similarly, comparison of measurements obtained using the Swan-Ganz catheter between the two groups yielded significant differences (p < 0.05 to p < 0.01) in PPA and TPVR in all cut-off values.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the exercise capacity recovery process after lung cancer surgery by exercise test and expire gas analysis].

This study was conducted to evaluate the numerical changes and the recovery process in exercise capacity over time, and to establish new criteria that will objectively evaluate the recovery in exercise capacity after lung surgery using an expired gas analysis incorporating an exercise test. The subjects consisted of 47 patients that underwent curative resection (only lobectomy) for lung cancer in the four years from 1989 to 1992 that were able to undergo expired gas analysis incorporating an exercise test before and after surgery. The expired gas analysis were performed within one week prior to surgery and over a period from 14 to 449 days after surgery, maximum oxygen consumption (VO2max) and anaerobic threshold (AT) measured, and the VO2max/m2 and AT/m2 were calculated as an index by dividing by the body surface area (m2). In addition, in order to examine the changes in exercise capacity after surgery, the presurgical values were used as 100, and the rate of change after surgery found. These rate were divided into the following measuring times, and the postsurgical changes over time analyzed. The postsurgical measuring times were divided into five groups from 14-30 days (n = 11), from 31-90 days (n = 25), from 91-180 days (n = 8), from 181-270 days (n = 19), and greater than 271 days (n = 8) after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Preferential localization of c-kit product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human: immunohistochemical study on formalin-fixed, paraffin-embedded tissues.

Eighteen hundred and eighty-four cases of human solid tumours and 833 samples of normal human tissues, formalin-fixed and paraffin-embedded, were examined immunohistochemically for expression of c-kit oncogene product using polyclonal antibody against synthesized c-kit peptide. Seminoma/dysgerminoma and small cell lung carcinoma (SCLC) show preferential c-kit expression at 92% and 36% frequency, respectively, whereas only sporadic cases of cervical carcinoma and non-SCLC lung carcinoma show c-kit positivity. A normal tissue counterpart positive for c-kit product is detected in the testis (spermatocyte) and ovary (oocyte) but not in the lung or the cervix. In contrast, normal epithelial cells of the breast, skin basal cells and tissue mast cells harbour c-kit product, but transformed cells of the former two are largely deficient in the c-kit protein. One hundred and thirty-nine neuroendocrine tumours and 39 non-pulmonary small cell carcinomas were all negative, except for two cases of neuroblastoma. This indicates a distinct character for SCLC in c-kit expression. The c-kit product may be a useful marker in diagnostic pathology of seminoma/dysgerminoma and SCLC among human solid tumours, and in distinction of SCLC from non-pulmonary small cell carcinoma.

Frequent expression of 75 kDa nerve growth factor receptor and phosphotyrosine in human peripheral nerve tumours: an immunohistochemical study on paraffin-embedded tissues.

One hundred and three benign, and 10 malignant peripheral nerve tumours were examined immunohistochemically for expression of 75 kDa nerve growth factor receptor (NGFR). In benign tumours NGFR was demonstrated at 61% in neurinoma, 71% in neurofibroma, 93% in neurofibromatosis and 90% in traumatic neuroma. Malignant neurogenic tumours were 100% positive for NGFR. Phosphotyrosine-immunoreactivity was detected in 76% of NGFR-positive tumours but the frequency of immunostained tumour cells was low. These results suggest that both benign and malignant peripheral nerve tumours express 75 kDa NGFR. The receptor seems to serve as growth signal transduction of the tumour cells in terms of phosphorylation of the tyrosine residue of the receptor or the target protein of the NGFR protein tyrosine kinase.

Stage I adenocarcinomas of the lung: survival of females and males.

Seventy-two cases of Stage I lung adenocarcinomas in females were analyzed and compared with 84 cases in males, all of which were surgically resected at the National Kyushu Cancer Center Hospital in Japan. The females with Stage I adenocarcinomas had a tendency, that was not significant, towards a longer survival than the male patients. When subdivided by age into less than 50, between 50 and 70, and more than 70 years-old, the female patients had a tendency, that was not significant, towards a longer survival in each group. In each age group, the ratio of smokers to non-smokers was higher in the males. The female group of ages 50 to 70 had the best 5-year survival rate. By multiregression analysis, age was found to be the most important factor for improved survival. The results indicate that a hormonal factor in Stage I lung adenocarcinoma does not influence survival.

Direct-writing color vectorcardiograph.

By employing a specially designed instrument, a "color vectorcardiogram," a single, colored horizontal plane vectorcardiogram (VCG) was written directly on the recording paper. At first, the voltage in the X, Y and Z axes was memorized into the digital memory cells. After that, the voltage in the X and Z axes was slowly read out so that a horizontal plane vectorcardiogram was written directly on the paper of the X-Y recorder. The color of the recording pen varied according to the voltage in the Y axis, which was read out simultaneously with the voltage in the X and Z axes.