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Type VI secretion systems (T6SSs) have been identified recently in several Gram-negative organisms and have been shown to be associated with virulence in some bacterial pathogens. A T6SS of Yersinia pestis CO92 (locus YPO0499-YPO0516) was deleted followed by investigation of the phenotype of this mutation. We observed that this T6SS locus of Y. pestis was preferentially expressed at 26 degrees C in comparison to 37 degrees C suggesting a possible role in the flea cycle. However, we found that the deletion of T6SS locus YPO0499-YPO0516 in Y. pestis CO92 had no effect on the ability of this strain to infect the oriental rat flea, Xenopsylla cheopis. Nevertheless, this mutant displayed increased intracellular numbers in macrophage-like J774.A1 cells after 20 h post-infection for bacterial cells pre-grown at 26 degrees C indicating that expression of this T6SS locus limited intracellular replication in macrophages. In addition, deletion of the YPO0499-YPO0516 locus reduced the uptake by macrophages of the Y. pestis mutant pre-grown at 37 degrees C, suggesting that this T6SS locus has phagocytosis-promoting activity. Further study of the virulence of the T6SS mutant in murine bubonic and inhalation plague models revealed no attenuation in comparison with the parental CO92 strain.

Objectives: The aims of this study were to characterize hypersensitivity reactions to chemotherapy in patients with gynecologic malignancies and to determine the utility of oral and intravenous desensitization., Methods: We retrospectively reviewed patients with hypersensitivity reactions identified by direct physician query and by review of charts with ICD9 code E933.1 (Adverse Effect Anti-Neoplastic)., Results: Thirty-two patients were identified: 27 with ovarian cancer, 4 with primary peritoneal cancer, and 1 with cervical cancer. Nine patients experienced hypersensitivity reactions during the primary regimen and 23 during chemotherapy for recurrent disease. Hypersensitivity occurred following an average of nine courses. Hypersensitivity occurred secondary to paclitaxel (10) carboplatin (16), cisplatin (4), bleomycin (1), and paclitaxel/carboplatin combination therapy (1). Patients had previously received the agent in 93.8% of carboplatin reactions, in 54.5% of paclitaxel reactions, and in all other agent reactions. Hypersensitivity reactions most commonly included flushing, dyspnea/bronchospasm, back pain, chest discomfort, pruritus, erythema, and nausea and occasionally included alterations in blood pressure or pulse rate. Reactions were successfully treated in 96.9% of patients by interrupting the infusion and administering steroids, antihistamines, benzodiazepines, nebulized beta-agonists, and/or pressors. Seventeen patients underwent desensitization, one to two agents, with 94% success. Nine of ten patients had successful iv desensitization, and 8/10 patients had successful oral desensitization. One failure on the oral regimen had previous successful iv desensitization., Conclusions: Hypersensitivity reactions to chemotherapeutic agents do not necessarily require exclusion of a compound from the treatment regimen. Intravenous and oral desensitization protocols are useful for successful and safe administration of paclitaxel and platinum compounds in patients with prior hypersensitivity reactions., (Copyright 2001 Academic Press.)

Objective: The aim of this study is to determine whether cavitational ultrasonic surgical aspiration (CUSA) is effective and safe for treating vaginal intraepithelial neoplasia (VAIN)., Methods: We conducted a retrospective chart review of 46 patients who were treated with CUSA for VAIN in a single gynecologic oncology practice between 1981 and 1999., Results: At initial presentation, 39% of treated patients had grade I VAIN, 20% had grade II, and 41% had grade III. The mean duration of follow-up from initial CUSA treatment was 21 months. Twenty-nine patients (63%) were initially treated with CUSA, 7 patients (15%) with laser vaporization, 7 patients (15%) with surveillance by Papanicolaou smear, 1 patient (2%) with partial vaginectomy, 1 patient (2%) with 5-fluorouracil, and 1 patient (2%) with loop excision. Patients initially treated with CUSA had a higher percentage of grade III VAIN at diagnosis (48%) than did patients initially treated with other methods (29%). A significantly greater proportion of patients initially treated with CUSA had no recurrence of VAIN (66%) compared with patients initially treated with other methods (0%) (P < 0.0001). A significantly greater proportion of patients who were treated for recurrent disease with CUSA had no further recurrence (52%) compared with patients treated for recurrent disease with other methods (9%) (P < 0.001). No patient treated with CUSA reported adverse effects; 7 patients treated with other methods reported dysuria, burning, and pain., Conclusion: These initial data suggest that CUSA is a safe and effective method for treating VAIN and may be an appropriate treatment for many patients., (Copyright 2000 Academic Press.)

Objective: Several spots exist of human immunodeficiency virus (HIV)-positive patients developing epithelial ovarian cancer. The optimal chemotherapeutic regimen has been unclear due to potential immunotoxicity from chemotherapy in these already immunocompromised patients. This is the first report of paclitaxel-based combination chemotherapy in an HIV-positive patient with ovarian cancer., Method: A 39-year-old woman with HIV was diagnosed with poorly differentiated serous carcinoma. She underwent optimal cytoreductive surgery and received six courses of paclitaxel and cisplatin., Results: The patient experienced a complete clinical response to therapy with no adverse effect on surrogate markers for human immunodeficiency virus (CD4 count, beta2 microglobulin, neopterin, p24 antigen, and viral load)., Conclusion: Paclitaxel- and platinum-based chemotherapy, the standard of care for adjuvant chemotherapy in advanced ovarian carcinoma, is appropriate therapy for ovarian cancer patients with HIV. There is no evidence that the paclitaxel/cisplatin regimen is associated with progression of HIV or increased chemotherapy-associated morbidity., (Copyright 2000 Academic Press.)

Objective: The aim of this study was to report a case of extraovarian granulosa cell tumor and to describe its relevance to the histologic origin of granulosa cell tumors and to clinical practice., Methods: The clinical course and histopathology of the case were reviewed, and a literature search for other reported cases was performed., Results: A 67-year-old woman presented with postmenopausal bleeding and a pelvic mass. Laparotomy revealed a 16-cm mass arising from the right pelvic sidewall, filling the pelvis, and involving the bladder and rectosigmoid colon. Both ovaries appeared normal and were separate from the mass. Pathologic examination revealed granulosa cell tumor. A literature search revealed no recently reported cases of extraovarian granulosa cell tumor., Conclusions: Granulosa cell tumors can arise in locations other than the ovary and may be derived from the mesenchyme of the genital ridge. Women who have undergone oophorectomy may have the potential to develop granulosa cell tumors., (Copyright 1999 Academic Press.)

Brain metastases from cervical cancer are uncommon and are usually considered incurable. Characterization of presentation and a consensus on standard effective treatment have not been published. We present a case in which long-term disease-free survival has been achieved by surgical resection of a solitary brain metastasis with postoperative whole brain radiation. The world literature is examined and discussed in relation to this experience.

Binding of enzymes of the Krebs TCA cycle to biological membranes was characterized with respect to intracellular location, susceptibility to various chemical and physical treatments, and extractability as a macromolecular component of the mitochondrial inner membrane. It was shown that citrate synthase and malate dehydrogenase bind to the inner membrane in an ionic strength-sensitive, saturable, and specific manner to a relatively thermostabile component manifested on the inner (matrix) surface of the inner membrane of the mitochondrion. From these data several arguments in support of the physiological applicability of these processes were deduced, and the question of whether these two enzymes bind to the same or different membrane components was considered. Also, experiments preliminary to purification of the citrate synthase binding component were presented.

In the present investigation an attempt was made to ascertain whether nonviral liver impairment in rats affects the THelper/TSuppressor ratio. Two hepatotoxic agents were used: (i) galactosamine (GA), which causes a drug-induced hepatitis-like damage, and (ii) orotic acid (OA), which induces fatty changes. Since these two substances act as antidotes to one another they were administered to rats either separately or simultaneously. GA caused severe liver damage documented by a 104-, 48-, and 1.6- fold rise in the plasma concentrations of ALT, AST, and ALP and by multiple foci of hepatocyte necrosis. This was followed by a drop in TH/TS ratio from 2.25 observed in the controls to 0.89 in the GA-treated rats. All of these phenomena were prevented by concurrent administration of GA and OA. OA alone did not show an effect on the liver with respect to changes in plasma enzyme concentrations and by light microscopic analysis. However, OA caused a drop in the TH/TS ratio from 2.25 to 1.55. Neither GA nor OA produced a change in TH/TS ratios in in vitro experiments.