Primary carcinosarcoma of the vagina

Primary carcinosarcoma of the vagina is a very rare tumor, with only eight cases diagnosed as carcinosarcoma in the literature that we are aware of. We recently encountered a case of primary carcinosarcoma of the vagina in a 75-year-old woman. The patient had a history of hysterectomy and bilateral ovariectomy for uterine corpus cancer at 55 years of age. Recurrence of the cancer was suspected 17 years after the operation and irradiation therapy was performed, but the patient died 3 years after the recurrence. Autopsy revealed a mass lesion in the pelvic cavity that originated in the vagina. Histological examination showed that the tumor contained anaplastic carcinoma, rhabdomyosarcoma, leiomyosarcoma and chondrosarcoma components, and it was diagnosed as carcinosarcoma. The histological diagnosis of the uterine corpus cancer was well-differentiated adenocarcinoma, and there was no sarcomatous component. The carcinosarcoma occurred 17 years after the hysterectomy, and it was concluded to be a primary carcinosarcoma of the vagina. This is the first case of primary vaginal carcinosarcoma in which the epithelial and sarcomatous components were clearly identified histologically and immunohistochemically.     

Structural change in dopamine D2 receptor gene in a patient with neuroleptic malignant syndrome

Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D₂ receptor (DRD₂) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG→TCG) of exon 7 of the DRD₂ gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. © 1995 Wiley-Liss, Inc.     

Neurokinin-1 receptor antagonist inhibits short-term sulfuric-acid-induced airway hyperresponsiveness in sensitized guinea pigs

BACKGROUND: Tachykinins are involved in the development of bronchial inflammation and airway hyperresponsiveness (AHR); however, the role of the neurokinin-1 (NK(1)) receptor in acid-aerosol-induced bronchial impairment in asthmatic patients remains controversial. METHODS: To investigate the effects on the NK(1) receptor antagonist FK888 the neurokinin-2 (NK(2)) receptor antagonist SR48968 on sulfuric-acid (H(2)SO(4))-induced AHR in guinea pigs, specific airways resistance (sRaw) and airways responsiveness to methacholine (MCh) were measured before and after 6 h of exposure to H(2)SO(4) aerosol (pH 1.7, 82 mg/m(3)) in ovalbumin-sensitized guinea pigs. RESULTS: Airway responsiveness to MCh significantly increased (p<0. 05) after the exposure, however sRaw did not. Treatment with FK888 significantly inhibited (p<0.05) H(2)SO(4)-induced AHR in a dose-dependent manner, as did SR48968. CONCLUSIONS: These results suggest that not only NK(2) but also NK(1) receptors might have important roles in the development of acid-aerosol-induced AHR.     

Genomic alterations in primary cutaneous melanomas detected by metaphase comparative genomic hybridization with laser capture or manual microdissection: 6p gains may predict poor outcome

To clarify the correlation of genomic alterations with clinical and histological features, we performed metaphase comparative genomic hybridization analysis on 20 primary cutaneous melanomas, which were obtained by laser capture or manual microdissection, and 16 melanoma cell lines. There were no differences in the average number of aberrations between acral melanomas (AM) and non-AM, although gains of 5q and 11q13 were more frequent (P=0.05) and 10q loss was less frequent (P=0.01) in AM than in non-AM. Although tumor thickness is considered a measurable estimate of clinical expression, there were no differences in the average number of aberrations among 4 groups, classified by thickness of the tumor. While the majority of aberrations were equally distributed among the 4 groups, 6p gains were found only in the thickest tumors. Patients with 6p or 1q gains had a lower overall survival rate than those without them (P=0.0002 or P=0.013). While gains of 1q, 2q, 3p, 3q, 7q, 20p, and 20q were more frequent in the cell lines than in the primary tumors (P<0.01), losses of 6q, 9p, 10p, and 10q were equally found in both cell lines and primary tumors. The present study showed that chromosomal aberrations had already occurred in the thinner tumors, and that 6p and 1q gains may be a prognostic factor.     

Ossifying fibromyxoid tumor of soft parts. Cytogenetic findings

Ossifying fibromyxoid tumor (OFMT) of soft parts is a recently described, rare but morphologically distinctive soft tissue tumor. The histogenesis of this lesion remains uncertain, although several immunohistochemical and ultrastructural features suggest that it is an unusual neural tumor, possibly of Schwann cell origin. We report here a case of a malignant variant of OFMT that occurred in the foot of a 52-year-old man. The karyotype of a pulmonary metastasis exhibited the following complex numeric and structural aberrations:72 approximately 74,XXY,-5,+6,+del(8)(p21),del(9)(p22),+10,der(11)t(3;11)(p21;p15),del(12) (q13),der(13)t(5;13)(q13;q34),+18,+19,+20,-22 [cp10]. A kidney metastasis exhibited the following karyotypic abnormalities: 46,XY,add(3)(p11),+der(3)t(3;?;11)(3qter-->3p11::?::11q13-->11qter), -5,del(8)(p21),add(9)(q22),del(9)(p22),der(11)t(3;11)(p21;p15),del(12)(q13),+der(13)t(5;13) (q13;q34),-22. To our knowledge, this is the first reported case of OFMT in which clonal chromosomal aberrations have been shown.     

Isolation and phenogenetics of a novel circadian rhythm mutant in zebrafish

Widespread use of zebrafish (Danio rerio) in genetic analysis of embryonic development has led to rapid advances in the technology required to generate, map and clone mutated genes. To identify genes involved in the generation and regulation of vertebrate circadian rhythmicity, we screened for dominant mutations that affect the circadian periodicity of larval zebrafish locomotor behavior. In a screen of 6,500 genomes, we recovered 8 homozygous viable, semi-dominant mutants, and describe one of them here. The circadian period of the lager and lime (lag(dg2)) mutant is shortened by 0.7 h in heterozygotes,and 1.3 h in homozygotes. This mutation also shortens the period of the melatonin production rhythm measured from cultured pineal glands, indicating that the mutant gene product affects circadian rhythmicity at the tissue level, as well as at the behavioral level. This mutation also alters the sensitivity of pineal circadian period to temperature, but does not affect phase shifting responses to light. Linkage mapping with microsatellite markers indicates that the lag mutation is on chromosome 7. A zebrafish homolog of period1(per1) is the only known clock gene homolog that maps near the lag locus. However, all sequence variants found in per1 cDNA from lag(dg2) mutants are also present in wild type lines, and we were unable to detect any defect in per1 mRNA splicing, so this mutation may identify a novel clock gene.     

Renal primitive neuroectodermal tumor: An immunohistochemical and cytogenetic analysis

The cytogenetic and morphologic characteristics of a case with a primitive neuroectodermal tumor (PNET) arising from the left kidney in a 22 year old man are presented. The patient was detected as having a left renal mass with a tumor embolus In the inferior vena cava and multiple pulmonary metastases. A radical nephrectomy with tumor embolectomy of the Inferior vena cava, along with a resection of the pulmonary nodules were performed. Histologic examination revealed a dense proliferation of small round cells with many Homer-Wright type rosettes and perlvascular pseudo-rosettes. Immunohlstochemically, the tumor cells stained strongly positive for HBA71(p30/32^{M IC2}), a surface glycopro-teln specific to PNET and Ewlng's sarcoma. In addition, the tumor cells expressed several neural markers (neuron specific enolase, neurofilament, synaptophysin, and Leu-7) and vimentin, while the epithelial, muscular, and lymphocytlc markers were negative in the tumor cells. Cytogenetic analysis of cultured tumor cells showed a reciprocal translocation t(11; 22)(q24; q12) that is considered to be specific to PNET and Ewing's sarcoma. In conclusion, this case suggested that a karyotyping analysis is a useful diagnostic tool for renal PNET, and it may therefore be utilized to help distinguish between difficult cases of small round cell tumors and Wilms' tumor of the kidney.     

Further Survey of Aflatoxin M1 in Milk Powders by ELISA

A survey of AFM₁ residues in 58 commercial milk powder samples was carried out using an enzyme‐linked immunosorbent assay (ELISA) based on a monoclonal antibody against aflatoxin M₁ (AFM₁). The samples were collected from the USA (10), China (28), Italy (14), New Zealand (3) and Poland (3). The ELISA was performed without the need for clean‐up procedures. The data revealed that 4 (US), 21 (Chinese) and 1 (Polish) samples were positive for AFM₁, with an average of 95.5, 102.8 and 85.0 pg g^‐1 of the AFM₁respectively.