Susceptibility of Selected Ericaceous Ornamental Host Species to Phytophthora ramorum.

We assessed disease reactions of 51 species or varieties of ericaceous ornamental hosts to two isolates of Phytophthora ramorum, the causal agent of sudden oak death. Inoculation was performed with an A2 mating type U.S. isolate from rhododendron and the P. ramorum type culture of A1 mating type from Germany. For only one host were statistically significant differences in disease observed between the two isolates. Several different inoculation methods were compared. The 51 hosts tested varied widely in susceptibility, ranging from 0% to over 90% leaf area infected. Two cultivars of Vaccinium macrocarpon (cranberry) showed no disease, while three cultivars of Kalmia latifolia (mountain laurel) were all highly susceptible. The results indicate that many ornamental hosts grown in the United States are susceptible to P. ramorum under artificial inoculation conditions. Inoculum density studies with two susceptible host species showed that P. ramorum is capable of producing disease symptoms over sporangium concentrations ranging from 100 to 5,000 sporangia per ml. Mean numbers of chlamydospores forming in host tissue of 21 hosts ranged from 2 to over 900 chlamydospores per 6-mm-diameter leaf disk. Whether hosts showing susceptiblity under the experimental conditions used in this study would become infected with P. ramorum in the presence of inoculum under natural conditions is unknown.

Primary mediastinal germ cell tumors. Histologic patterns of treatment failures at autopsy.

Twenty-five patients presented with primary mediastinal germ cell tumors at Roswell Park Memorial Institute between 1959 and 1984. All patients were treated by surgery and chemotherapy with or without radiotherapy. Four patients are still alive, and 21 patients died of mediastinal germ cell tumor and its sequelae. Two patients were found to have testicular scars and were dropped from the study. Nongerm cell malignant transformation of a teratoma occurred in five of the remaining 17 patients (29%), resulting in three adenocarcinomas and two sarcomas. Another patient developed leukemia. Metastatic disease most commonly involved the lungs, mediastinal lymph nodes, liver, bone, retroperitoneum, and heart. Respiratory failure was the cause of death in 12 patients. Of the possible mechanisms of germ cell transformation into malignant nongerm cell tumors discussed, this study suggests that chemotherapy alone is unlikely to induce stem cell differentiation. The presence of mature, differentiated teratoma within the primary lesion may be indicative of a poorer prognosis.

Neural regulation of properties of the nicotinic acetylcholine receptor.

During nerve-muscle synapse formation, acetylcholine receptors become localized and modified to allow efficient transfer of information from nerve to muscle. In this paper we summarize our studies on two aspects of receptor modulation--their concentration at synaptic sites and their ability to desensitize in response to prolonged application of agonist. We demonstrate that receptor localization is a complex event which extensively reorganizes the structure of the junctional region. This allows the subsequent influences of contraction to be exerted differently in junctional and extrajunctional regions. We indicate that increases in muscle cell Ca2+ appear to mediate some of the effects of muscle contraction and suggest how regulation of Ca2+ levels may specify junctional and extrajunctional differences. Finally, we discuss the role of receptor phosphorylation in determining the rate of desensitization.

Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery.

Seventy patients with muscle-invading bladder carcinoma (clinical stages T2 to T4) who were not candidates for cystectomy were treated with combined cisplatin and full-dose external-beam radiation on a multi-institutional prospective protocol from 1980 through 1985. Thirty-six patients are alive, all but three without evidence of cancer. The complete response rate is 77% in the 62 patients completing planned irradiation and 70% for all patients. Among the complete responders, 73% are currently maintained, and this group has a significantly higher four-year survival than those not having a complete response and those with recurrence of disease--57% vs 11%. The observed high complete response rates in patients in all stages and the high survival rates suggest irradiation plus cisplatin therapy offers an important therapeutic gain over radiation therapy alone for invasive cancer of the bladder. These results encourage further evaluation of combining cisplatin-based, multidrug chemotherapy with irradiation in patients with locally very-advanced bladder tumors who are not suited for surgery.

Acetylcholine receptor clustering and nuclear movement in muscle fibers in culture.

We have studied the formation of acetylcholine receptor (AChR) clusters and the behavior of myonuclei in rat and chick skeletal muscle cells grown in cell culture. These cells were treated with a factor derived from Torpedo electric extracellular matrix, which causes a large increase in their number of AChR clusters. We found that these clusters were located preferentially in membrane regions above myonuclei. This cluster-nucleus colocalization is explained by our finding that most of the nuclei near clusters remain relatively stationary, while most of those away from clusters are able to translocate throughout the myotube. In some cases, clusters clearly formed first, then nuclei migrated underneath and became immobilized. If clustered AChRs later dispersed, their associated nuclei resumed moving. These results suggest that AChR clustering initiates an extensive cytoskeletal rearrangement that causes the subcluster localization of organelles, potentially providing a stable source of newly synthesized AChRs for insertion into the cluster.

Bleomycin-induced nodular pulmonary fibrosis masquerading as metastatic testicular cancer.

Bleomycin has become an important component of combination chemotherapy, particularly in the treatment of metastatic testis carcinoma. Pulmonary toxicity is a major risk and irreversible pulmonary fibrosis or even death may result from its use. Rarely diffuse fibrosis may lead to discrete nodularity mimicking pulmonary metastasis. We report such a case, and discuss the various clinical, radiographic and histopathological forms of bleomycin-induced pulmonary toxicity.

Comparative evaluation of National Prostatic Cancer Treatment Group and Gleason systems for pathologic grading of primary prostatic cancer.

Multivariable analysis was used to investigate the relationship between risk of disease progression or death in patients who were treated with adjuvant therapy after definitive treatment for prostatic adenocarcinoma and the components of the National Prostatic Cancer Treatment Group (NPCTG) and Gleason systems for pathologic grading of prostatic cancer. Data were available for 203 patients who were treated on NPCTG Protocols 900 and 1,000, which involve surgical and radiation therapy as definitive treatment. Since less than 10 per cent of these patients have died, analysis of survival was not attempted. The study focus was progression-free survival, which is the minimum of time to progression or death. The analysis demonstrates that a new measure, the NPCTG score (the sum of the glandular and nuclear grades) is superior to the previously reported NPCTG grade (the maximum of the two grades). In addition, the Gleason score is somewhat superior to the new NPCTG score. All of this, however, applies only to the primary tumor and not the nature of any present or future metastatic lesions.

Immunohistochemical demonstration of prostate-specific antigen in metastases with the use of monoclonal antibody F5.

With the use of a murine monoclonal antibody (F5), a panel of metastatic tumors was evaluated for the expression of prostate-specific antigen (PA) under immunoperoxidase staining procedures. Specimens studied included 25 of prostatic origin and 73 originating from nonprostatic primary sites. Regardless of the site of dissemination or the malignancy grade, all metastases from the prostate were antibody-reactive. In contrast, nonprostatic metastases were negative in each case, including those originating from other genitourinary neoplasms. Thus, PA expression as detected with monoclonal antibody F5 is a stable characteristic of disseminated prostatic tumors.

Prognostic factors in localized prostatic carcinoma.

Serial histological sections were performed in 54 radical prostatectomy specimens in an attempt to identify prognostic factors responsible for dissemination of prostatic cancer. Factors considered in the study included clinical versus pathological staging, histological grading of the biopsy specimen compared to the final pathological result, intraprostatic tumor distribution and deoxyribonucleic acid analysis of the tumor by flow cytometry in the last 33 cases. In patients with clinical stages A2 and B1 disease pathological findings were in accord in 78 per cent (11 of 14). However, only 3 of 40 patients with clinical stage B2 tumor had pathological stage B2 disease. Histologically, 72 per cent of the tumors were bilateral. Microscopic involvement of the capsule per se did not appear to influence lymph node invasion, since only 1 of 27 patients with microscopic capsular involvement had pelvic lymph node metastasis. However, 9 of 13 patients with seminal vesicle involvement had pelvic lymph node metastasis. The addition of flow cytometry to the Gleason score improves the predictive value of histological grade in higher stage lesions.

The effect of nitrofurantoin on bladder tumor cell lines: in vitro growth and implantation in the cauterized mouse bladder.

Nitrofurans compounds and derivatives demonstrate antineoplastic activity in vitro as well as in vivo. Nitrofurantoin caused in vitro growth inhibition of a FANFT-induced murine bladder tumor (MBT2) and a human transitional cell carcinoma cell line (GIBB) in concentrations of 125 microM, 250 microM and 500 microM. The implantation and growth of MBT2 in the cauterized mouse bladder was inhibited by 250 microM nitrofurantoin. The bladder mucosa of two groups of C3Hf/HeHa female mice was electrically cauterized. In group I, 1 X 10(6) MBT2 cells were injected into the bladders of 42 mice, while in group II 1 X 10(6) MBT2 cells in 250 microM nitrofurantoin solution were injected into the bladders of 51 mice. Positive tumor implantation was seen in 25 bladders (59.5 per cent) of group I as compared to 15 bladders (29.5 per cent) of group II. All tumors in group I were large, occupying more than 50 per cent of bladder cross sectional area with 24 per cent showing extravesical extention. Sixty-six per cent of tumors in groups II were less than 25 per cent of bladder cross sectional area and 13.4 per cent had extravesical extention.

Estrogen and progestin receptors in human prostatic carcinoma.

Cytosol receptors for estrogens (ER) and progestins (PR) were assayed in human prostatic carcinoma (CaP) and benign prostatic hyperplasia (BPH). Specimens were obtained from either the peripheral or the periurethral zone of the prostate. Stringent criteria were used to identify and measure 7-8S specific receptor using sucrose gradient analysis in a vertical tube rotor. Progesterone receptor was found in 14 BPH samples assayed and in 12 of 13 prostate cancers. In contrast, the 7-8S estrogen receptor was found in none of the nine benign samples assayed and in all prostate cancers. BPH samples were taken from either peripheral or periurethral zones and gave similar results. The histology of individual specimens did not correlate with either the ER or PR present, and, in the cancers, there was no correlation between the pathologic stage or the Gleason score and receptor content.

Secondary tumors of the prostate.

The significance and clinical implications of secondary neoplasms of the prostate are discussed. These neoplasms are rare except for those that involve the gland by direct extension from adjacent structures. We report on 185 such cases found on a review of almost 6,000 male autopsies during the last 25 years.

Relationship between DNA ploidy, glandular differentiation, and tumor spread in human prostate cancer.

DNA ploidy was evaluated by flow cytometry for 45 human prostate carcinomas (34 prostatectomy specimens and 11 biopsies). Twenty tumors (44.4%) contained a distinct aneuploid stem line. All 11 tumors confined to the prostate gland (pathological Stage B) were diploid. The frequency of aneuploidy increased with advancing stage, and most tumors with distant metastases were aneuploid. The degree of glandular differentiation was characterized by the Gleason score. One-third of tumors with a Gleason score of 5 to 6 were aneuploid, whereas over 70% of poorly differentiated tumors with a Gleason score of 9 to 10 were aneuploid. Among diploid tumors, 45.5% were localized carcinomas (Stage B), 36.4% were characterized by invasion outside the prostate (Stage C), and 18.2% formed pelvic nodal or distant metastases (Stages D1 and D2). In nearly two-thirds of patients with aneuploid tumors, pelvic nodal or distant metastases were found. When tumors were classified according to both DNA ploidy and degree of glandular differentiation, then subgroups of tumors with the highest and lowest degree of malignant potential became apparent. Only 7.1% of diploid tumors with a Gleason score of 5 to 6 formed metastases, but 80% of aneuploid tumors with a higher Gleason score (7 to 10) formed metastases. Diploid tumors with higher Gleason scores and aneuploid tumors with lower Gleason scores had intermediate frequencies of metastases. The presence of an aneuploid stem line in prostate carcinomas indicated that the tumor had spread outside the prostate gland or had metastasized. DNA ploidy may be an important prognostic factor for human prostate cancer. DNA ploidy and the degree of glandular differentiation considered together may improve prognostic evaluation of prostate carcinomas.

Histological patterns of treatment failures in testicular neoplasms.

We reviewed 77 consecutive autopsies performed between 1965 and 1982 on patients who had been treated for germ cell tumors of the testis at our institute. Identifiable germ cell tumor was present at autopsy in 64 cases. On review, a single pattern was seen at autopsy in the majority of the cases (69.7 per cent) compared to the primary tumors, in which single patterns were seen in only 45 per cent. The occurrence of yolk sac tumor as the sole element in 6 of 29 autopsy specimens of nonseminomatous tumors after the introduction of the current standard 3-drug therapy and only once in 32 autopsies before 1976 appears significant. A possible explanation for this finding is that the yolk sac element was obscured by more aggressive and rapidly growing varieties of tumor in the earlier years but proved less responsive to chemotherapy.

Experimental photodynamic treatment of canine bladder.

In urology, important limiting factors in the application of hematoporphyrin derivative and photodynamic therapy appear to be the problems of standardization of dosimetry and the technique of transurethral photoradiation. Experimental photodynamic therapy on canine bladder with normal and altered epithelium was performed using an argon laser as an energy source. A 630 nanometer wavelength of light was delivered through a quartz-optical fiber with either a regular flat end for focal illumination or a bulb-type end which produced an isotropic light pattern. It was demonstrated that normal canine bladder was resistant to photodynamic therapy and that the bulb tip produced whole bladder illumination. With a moderate light dose of 18 to 30 Joules/cm.2 the effect following whole bladder illumination on the bladder was generalized and superficial. This approach appears to be ideal for treating superficial transitional cell carcinoma of the bladder. Additional work is needed in selecting appropriate energy doses.

Evaluation of bladder washings and urine cytology in the diagnosis of bladder cancer and its correlation with selected biopsies of the bladder mucosa.

We report a prospective study of 136 patients with biopsy proved bladder tumor who underwent 311 evaluations with cystoscopy, urinary cytology, bladder washing and, when indicated, bladder biopsies. Cytology results from bladder washings were superior to routine urinary cytology studies in detecting abnormal cells. Also, there was a significant increase in the number of positive cytology studies in bladder washings from patients with no evidence of tumor by cystoscopy but who had biopsy proved dysplasia. Multiple selective bladder biopsies showed a higher incidence of mucosal abnormalities if the primary tumor was of a higher grade.

Multilocular cyst of the kidney: a case report.

A 69-year-old female was referred to Roswell Park Memorial Institute for management of a right kidney tumor. Her evaluation included excretory urography, ultrasound, computerized axial tomography (CT scan), and selective renal angiography. Fine needle aspiration cytology was felt to be consistent with primary renal cell carcinoma. In spite of the radiological appearance of a benign lesion, a right radical nephrectomy was performed because of the positive cytology on fine needle aspiration. The pathological diagnosis was a solitary multilocular cyst of the kidney.

Aspiration biopsy of testis: another method for histologic examination.

The most important method for evaluating the pathogenesis of male infertility is open testicular biopsy. Herein we describe a method of aspiration biopsy of testis for histologic examination. Sexually mature dogs and rats treated with chemotherapeutic agents and ionizing radiation were followed with periodic testicular aspiration biopsy during and after treatment. The histologic findings from the aspiration biopsy compare with the results of routine histologic examinations in assessing spermatogenetic activity and delineating pathologic changes. The puncture in the experimental animals was performed under general anesthesia. In human patients testicular biopsy could be done under local anesthesia in an outpatient clinic. The procedure would be less painful, minimally invasive, and more cost-effective.

Biphasic malignant mesothelioma (malignant adenomatoid tumor) of paratesticular tissue.

This article describes a metastasizing tumor of the paratesticular tissue which has features similar to that of malignant mesothelioma commonly seen in other mesothelial surfaces. The tumor is composed of two types of cells, epithelial-like and spindle-shaped malignant cells.