Molecular definition of a small amplification domain within 3q26 in tumors of cervix, ovary, and lung

A common amplification target encompassing chromosome region 3q25 to q27 has been identified by comparative genomic hybridization analyses in tumors of the cervix, ovary, endometrium, lung, and head and neck. Because this segment spans at least 30 megabases, we undertook a molecular analysis of copy number to more precisely define the amplification domain. Our Southern blot and fluorescence in situ hybridization results with the use of 17 markers confirmed the presence of low-level 3q amplification events in cervical, ovarian, and variant SCLC tumors. Most of the tumor types studied appeared to have similar, broad amplification domains centered within 3q26.2, suggesting that the same target is being affected in all. The ovarian carcinoma cell line NIH:OVCAR3 had a highly restricted amplification domain spanned by four overlapping YAC clones, suggesting a small target. The region of highest amplification included the gene for the RNA component of telomerase (hTR), supporting it as a potential target. Although the importance of low-level amplification is unknown, the consistent and reproducible nature of this event in a variety of carcinomas suggests that 3q26.2 harbors an oncogene whose low-level amplification has a significant influence on tumor biology.     

Analysis of mesenteric thickening on computed tomography

Computed Tomography (CT) provides a noninvasive information in the evaluation of abnormalities of the gastrointestinal tract by direct imaging of the bowel wall and adjacent mesentery. Several prior studies have discussed the variable CT appearances of mesenteric abnormalities, such as lymphoma, metastasis, inflammatory disease and edema. Although mesenteric thickening was mentioned in these studies, no study has provided a detailed analysis of the CT appearance of the thickened mesentery. Two characteristic types of mesenteric thickening were identified in 47 patients. Type I is "Intra-mesenteric thickening", which was noted in 25 patients with vascular obstruction, inflammatory disease and edema. Type II is "Mesenteric surface thickening", which was noted in 22 patients with peritonitis carcinomatosa, peritoneal mesothelioma, tuberculous peritonitis and pseudomyxoma peritoneal. An understanding of these two types of mesenteric disease is important in the identification of mesenteric pathology.     

Effect of protease inhibitors on degradation of recombinant human epidermal growth factor in skin tissue

Recombinant human epidermal growth factor (rhEGF), a polypeptide of 53 amino acid residues, is subject to degradation by numerous enzymes, especially proteases, when it is applied on the skin for the treatment of open wound. Amastatin, aprotinin, bestatin, EDTA, EGTA, gabexate, gentamicin, leupeptin, and TPCK were investigated for the possible protease inhibitors, which may use to protect rhEGF from degradation by the enzymes in the skin. Skin homogenates containing protease inhibitors and rhEGF were incubated at 37°C for 30 minutes. After the reaction was stopped with trifluoroacetic acid, the amount of rhEGF remaining in the sample was determined with an HPLC method. The percentages of rhEGF degraded, at the skin/PBS ratio of 0.25, in the mouse, rat, and human skin homogenate were 85%, 70%, and 46%, respectively. The degree of degradation of rhEGF in the cytosolic fraction was higher than that in the membrane fraction and these enzyme reactions were completed in 30 minutes. Bestatin, EGTA, and TPCK showed significant inhibitory effects on the degradation of rhEGF in the two fractions (p<0.05), while the other protease inhibitors had no significant inhibitory effects or, even resulted in deleterious effects. Therefore, the formulation containing one or several inhibitors among these effective inhibitors would be a promising topical preparation of rhEGF for the treatment of open wound.     

DNA gyrase gyr A gene mutations in ofloxacin-resistant Staphylococcus aureus

A total of 106 clinical isolates of Staphylococcus aureus were classified into nine pattern types correlated with gyrA mutations. In 62 strains, mutations were found at a single codon (84, 85, 86 and 88), while 22 strains showed double mutations either at codons 84 and 85 or at codons 84 and 88. The double mutations led to the highest levels of ofloxacin resistance (MIC, >/= 128 mug/ml). All isolates with a single Ser-84--> Leu change had an ofloxacin MIC of 8-128 mug/ml, whereas others showed an MIC range of 8-16 mug/ml. Twenty-two wild type strains and one strain with a single mutation at codon 86 (silent mutation) were ofloxacin-susceptible. Thus, gyrA mutations seem to play a definite role in the high-level of resistance to ofloxacin.     

A technique for reconstruction of the medial patellofemoral ligament

Additional medial patellofemoral ligament reconstruction was performed successfully on six consecutive patients with recurrent dislocation of the patella because of residual patellar instability after medial transfer of the tibial tubercle. A technique for medial patellofemoral ligament reconstruction is described, and complications and postoperative management are discussed. The reconstruction was performed using a double strand hamstring tendon graft in five patients and iliotibial allograft in one. Good stabilization of the patella was achieved in all six patients, resulting in improved confidence in higher levels of activity. The satisfactory outcome of additional medial patellofemoral ligament reconstruction suggests the possibility that the procedure may be part of the optional procedure in proximal realignment for recurrent dislocation of the patella.     

Etoposide (VP-16) as first-line, single agentchemotherapeutic drug in low-risk gestational trophoblastic disease

Matsui H, Iitsuka Y, Seki K, Sekiya S. Etoposide (VP-16) as first-line,single agent chemotherapeutic drug in low-risk gestational trophoblasticdisease. Int J Gynecol Cancer 1997; 7: 400–404.
We reviewed the records of 73 patients with low-risk gestationaltrophoblastic disease (GTD) treated with etoposide from 1986 to 1995 at ChibaUniversity. All patients received courses of etoposide every 10 to 14 days until their human chorionicgonadotropin (hCG) concentrations had reached <1 mIU/ml or drug resistanceand/or unacceptable toxicityoccurred. Fifty-one patients (69.9%) were treated with chemotherapyalone and 22 patients (30.1%) also underwent planned hysterectomy.
Sixty-seven patients (92%) achieved a primary remission, while sixpatients (8%) required a change in drugs due to drug resistance (4patients, 5%) or toxicity (2patients, 3%). All 73 patients achieved complete remission. However, onepatient (1.4%) relapsed later.
We have demonstrated that etoposide is one of the most effective drugsagainst GTD and that the short-term toxicity is, except for alopecia,relatively mild and acceptable.Patients should, however, be informed of the possibilities of secondarymalignancies and followed-up cautiously.     

Primary Transitional Cell Carcinoma of the Fallopian Tube: A Case Report and Review of the Literature

Primary carcinoma of the fallopian tube is extremely rare and the preoperative diagnosis is often misdiagnosed as an ovarian carcinoma. We report a patient with primary carcinoma of the fallopian tube, strongly suspected preoperatively on the basis of characteristic clinical symptoms, elevated CA125 levels, and transvaginal sonography, computed tomography, and magnetic resonance imaging findings. The histology of fallopian tube carcinoma was demonstrated as transitional cell carcinoma. Extensive review of the literature showed that our case seemed to be the 14th case of primary transitional cell carcinoma of the fallopian tube.     

Nonsense Mutation at Codon 63 of the BRCA1 Gene in Japanese Breast Cancer Patients

The involvement of abnormalities of the BRCA1 gene in breast cancers in Japanese patients without any family history of this cancer was investigated by polymerase chain reaction-based single-strand conformation polymorphism analysis of the DNA sequences corresponding to the zinc finger domain (exons 2, 3 and 5) and the binding domain with Rad51 (exon 11) of the BRCA1 protein. An identical nonsense mutation at codon 63 (TTA to TAA) was found in 2 of 56 (3.5%) breast cancers from independent patients. The nucleotide change was also detected in the DNAs from non-cancerous tissues of both patients and therefore was a germline mutation. One of the patients was a member of a pedigree involving 3 ovarian cancer and 1 gastric cancer patients, while the other patient had no family history of malignancy. The same germline mutation at codon 63 was reported in four other independent Japanese pedigrees with frequent breast cancer, but not in such families in other countries. These observations suggest that the mutation commonly originated from a single Japanese ancestor. No other mutation of the BRCA1 gene was observed in the samples analyzed in this study. A low incidence of germline mutation and the absence of somatic mutation suggest that the aberration of the BRCA1 gene is involved only in a subset of Japanese breast cancers.