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Biomedical subjects

R M Wolf

Publications and source records attributed to R M Wolf.

At least 19 recordsLinked to original sources

Effectiveness of a simulator in training anesthesiology residents. 1969.

The educational potential of a computer-controlled patient simulator was tested by the University of Southern California School of Medicine. The results of the experiment suggest unequivocally that there is a twofold advantage to the use of such a simulator in training anesthesiology residents in the skill of endotracheal intubation: (a) residents achieve proficiency levels in a smaller number of elapsed days of training, thus effecting a saving of time in the training of personnel, and (b) residents achieve a proficiency level in a smaller number of trials in the operating room, thus posing significantly less threat to patient safety. The small number of subjects in the study and the large within-group variability were responsible for a lack of statistical significance in 4 of 6 of the analyses performed; however, all differences were substantial and in the hypothesized direction. Thus, despite the narrowly circumscribed tasks to be learned by the experimental subjects, the findings suggest that the use of simulation devices should be considered in planning for future education and training not only in medicine but in other health care professions as well.

Anesthesiology↗

Tyrosine phosphorylation of p190 RhoGAP by Fyn regulates oligodendrocyte differentiation.

During development of the central nervous system, oligodendrocyte progenitor cells differentiate into mature myelinating cells. The molecular signals that promote this process, however, are not well defined. One molecule that has been implicated in oligodendrocyte differentiation is the Src family kinase Fyn. In order to probe the function of Fyn in this system, a yeast two hybrid screen was performed. Using Fyn as bait, p190 RhoGAP was isolated in the screen of an oligodendrocyte cDNA library. Coimmunoprecipitation and in vitro binding assays verified that p190 RhoGAP bound to the Fyn SH2 domain. Phosphorylation of p190 required active Fyn tyrosine kinase and was increased threefold upon differentiation of primary oligodendrocytes. Moreover, complex formation between p190 and p120 RasGAP occurred in differentiated oligodendrocytes. p190 RhoGAP activity is known to regulate the RhoGDP:RhoGTP ratio. Indeed, expression of dominant negative Rho in primary oligodendrocytes caused a hyperextension of processes. Conversely, constitutively activated Rho caused reduced process formation. These findings define a pathway in which Fyn activity regulates the phosphorylation of p190, leading to an increase in RhoGAP activity with a subsequent increase in RhoGDP, which in turn, regulates the morphological changes that accompany oligodendrocyte differentiation.

Acute-Phase Proteins↗

Difference between blocking and Néel temperatures in the exchange biased Fe3O4/CoO system.

The blocking temperature T(B) has been determined as a function of the antiferromagnetic layer thickness in the Fe3O4/CoO exchange biased system. For CoO layers thinner than 50 A, T(B) is reduced below the Néel temperature T(N) of bulk CoO (291 K), independent of crystallographic orientation or film substrate ( alpha-Al2O3, SrTiO3, and MgO). Neutron diffraction studies show that T(B) does not track the CoO ordering temperature and, hence, that this reduction in T(B) does not arise from finite-size scaling. Instead, the ordering temperature of the CoO layers is enhanced above the bulk T(N) for layer thicknesses approximately less than or equal to 100 A due to the proximity of magnetic Fe3O4 layers.

Journal Article↗

Morphological differentiation of oligodendrocytes requires activation of Fyn tyrosine kinase.

In the central nervous system, myelination of axons occurs when oligodendrocyte progenitors undergo terminal differentiation and initiate process formation and axonal ensheathment. Although it is hypothesized that neuron-oligodendrocyte contact initiates this process, the molecular signals are not known. Here we find that Fyn tyrosine kinase activity is upregulated very early during oligodendrocyte progenitor cell differentiation. Concomitant with this increase is the appearance of several tyrosine phosphorylated proteins present only in differentiated cells. The increased tyrosine kinase activity is specific to Fyn, as other Src family members are not active in oligodendrocytes. To investigate the function of Fyn activation on differentiation, we used Src family tyrosine kinase inhibitors, PP1 and PP2, in cultures of differentiating oligodendrocyte progenitors. Treatment of progenitors with these compounds prevented activation of Fyn and reduced process extension and myelin membrane formation. This inhibition was reversible and not observed with related inactive analogues. A similar effect was observed when a dominant negative Fyn was introduced in progenitor cells. These findings strongly suggest that activation of Fyn is an essential signaling component for the morphological differentiation of oligodendrocytes.

Animals↗

Molecular mechanics and dynamics studies on two structurally related amide-modified DNA backbones for antisense technology.

The effect of the replacement of the natural phosphodiester linkage -C3'-O-PO2-O-CH2-C4'- in the DNA strand of RNA.DNA hybrid duplexes by either of the two amide linkages -C3'-CH2-CO-NH-CH2-C4'- or -C3'-CH2-NH-CO-CH2-C4' has been investigated by molecular mechanics (MM) and molecular dynamics (MD) simulations. Conformational analysis has been used to assess various low-energy conformers of the amide-modified backbones. MD simulations have been carried out to study the dynamic behavior of the modified duplexes. The modified RNA.DNA hybrid double helices kept a conservative base pairing scheme during the MD simulations. Although the general behavior has been found to be similar to that of the corresponding wild-type hybrid duplexes, some notable differences, especially regarding the sugar puckering in the amide-modified DNA strands, have been observed. The behavior of the RNA strands in the hybrid duplexes has not been affected by the modified DNA strands and is similar to that in wild-type RNA.DNA duplexes.

Amides↗

Molecular dynamics simulations of a r(GA12G).d(CT12C) hybrid duplex.

RNA.DNA hybrid duplexes are relevant in various biological mechanisms like transcription and replication. Enzymes like RNase H cleave specifically the RNA strand in RNA.DNA duplexes. In antisense technology the complexation of mRNA with "modified" oligo(deoxy)-nucleotides leads to new hybrid duplexes. The knowledge about structure and dynamical behavior on an atomic level is fundamental for the understanding of any process involving hybrid duplexes. Therefore, molecular dynamics studies (200 picoseconds of trajectory) on a hybrid duplex structure r(GA12G).d(CT12C) were performed. During the stimulations, the deoxyribose residues assumed a puckering state between C2'-endo and C3'-endo, with an average mode around O4'-endo-C1'-exo, whereas the riboses of the RNA strand remained in the C3'-endo puckering domain. The results are compared to those obtained for the DNA.DNA duplex d(GA12G).d(CT12C) under identical simulation conditions. The DNA strand in the hybrid duplex behaves similar to that in a standard B-type DNA duplex. The helical parameters of the hybrid duplex however are closer to A- than to B-type. These observations suggest that RNA.DNA hybrid double helices are neither clearly A-form nor B-form. The furanoses in both strands can assume different puckering modes without the appearance of major geometrical constraints. The simulation results are in excellent agreement with recent experimental data.

Base Sequence↗

The use of transrectal ultrasound in the detection and evaluation of local pelvic recurrences after a radical urological pelvic operation.

Transrectal ultrasound was performed in 20 patients with suspected local pelvic recurrence after a radical pelvic operation: 9 had undergone radical prostatectomy and 11 had undergone radical cystoprostatectomy. Transrectal sonography verified the presence of recurrence in 19 of 20 patients (95%) and this was confirmed by biopsy of the visualized lesions. Analysis of the sonographic echo patterns encountered revealed that in 14 of 19 recurrent neoplasms (71.5%) the echogenic pattern was hypoechoic. In the remaining 6 patients (31.5%) the echo pattern was isoechoic. No hyperechoic lesions were noted. Based upon our findings and because of the low costs compared to other diagnostic modalities transrectal ultrasound represents an ideal technique to compliment the digital rectal examination in evaluation of patients suspected of harboring a local pelvic recurrence after a radical pelvic operation.

Carcinoma, Transitional Cell↗

A phase I clinical trial of recombinant human tumor necrosis factor given daily for five days.

A phase I trial of human recombinant tumor necrosis factor (rH-TNF) has been carried out in patients with advanced solid tumors. Sixty-six courses of the drug were given by 1 h IV infusion, daily for 5 days to 33 patients at doses of 5, 10, 20, 30, 45, 60, and 80 x 10(4) U/m2/day. All patients received isotonic saline (up to 21/day) and either indomethacin or ketoprofen. Acute toxicity resembled that seen with the phase I study of a single dose (5). Dose limiting toxicity was acute, rapidly reversible, hepatic dysfunction and hypotension. Hypertension during drug infusion and dyspnea were marked in some patients. There was one complete and one minor response, both in patients with renal cell carcinoma. The dose of 80 x 10(4) U/m2/day x 5 was poorly tolerated and the recommended starting dose for phase II studies is 60 x 10(4) U/m2/day x 5. Caution is recommended in treating patients with pre-existing hepatic function abnormalities, hypertension, hypotension or significant obstructive airway disease.

Adult↗

Development of a patient satisfaction scale.

Three studies to develop and test an instrument to measure hospitalized patients' satisfaction with nursing care are reported. Content validation procedures involved both clinicians and patients (N = 75). An inverse relationship of satisfaction scores to negative mood states demonstrated evidence of construct validity. Factor analytic procedures (N = 664) failed to confirm the existence of the subscales initially conceptualized for this instrument and others in common use. Three new factors were identified: dissatisfaction, interpersonal support, and good impression. The dissatisfaction subscale explained 73.6% of the variance and had a high internal consistency (alpha = .91); the reliability coefficients of the other subscales also were high (alpha = .92 and .89). Reliability coefficients for the total instrument in successive testings were .92 (N = 100) and .95 (N = 533).

Adolescent↗

Early complications of combined pelvic lymphadenectomy and radical prostatectomy versus lymphadenectomy alone.

A comparison of the early morbidity of pelvic lymphadenectomy plus radical prostatectomy versus lymphadenectomy alone is reported. Fifty-one patients underwent the combined procedure; 26 had lymphadenectomy alone. Incidence of early complications was 35% in patients undergoing prostatectomy and node dissection and 27% in patients undergoing lymph node dissection only, a difference which is not statistically significant. Thrombophlebitis and pulmonary embolus occurred after the combined procedure. There was one postoperative death in the combined surgery group. The results of this study suggest that lymph node dissection may be performed at the time of radical prostatectomy rather than as a staging procedure, and emphasize the importance of pelvic lymph node dissection in the evaluation and treatment of clinically localized prostate cancer.

Adenocarcinoma↗

Pelvic rhabdomyosarcoma: a review of the RPMI experience.

Between 1959 and 1983, 16 patients with pelvic rhabdomyosarcoma were treated at Roswell Park Memorial Institute (RPMI). A multidisciplinary approach was utilized consisting of surgery, radiotherapy (XRT), and combined chemotherapy which resulted in prolonged survivals of thirteen to one hundred forty-four months in 10 patients. This improved survival was observed despite the fact that 63 per cent of the patients (10/16) presented with advanced stages of the disease. Herein we present a retrospective study of these 16 patients.

Adult↗

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.

Aged↗

Vaginal recurrence after cystectomy for bladder cancer.

The records of 14 patients with vaginal recurrence following cystectomy were reviewed in an attempt to find factors responsible for the local failure. Comparison was made with female patients who underwent cystectomy for bladder cancer during the same period but who did not have vaginal recurrence. Patients with previous surgery and radiation to the pelvic organs appear to be at risk for local recurrence, probably because of the difficulties associated with surgical removal of the bladder. Patients with tumors other than transitional cell carcinoma, especially those located at the bladder neck and urethra, also appear to be at high risk. Proper surgical technique with en bloc cystourethrectomy, including excision of the anterior vaginal wall, is of paramount importance to avoid local recurrence.

Aged↗

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.

Carcinoma↗

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.

Aged↗

Presumptive downstaging from preoperative irradiation for bladder cancer as determined by flow cytometry: preliminary report.

Presumptive tumor downstaging was evaluated in 28 patients with grade II or III, solid, muscle-infiltrating bladder cancer (clinical category T3) treated by integrated irradiation (2000 rad to the whole pelvis in 5 days) and cystectomy (1-14 days later) by comparing the results of flow cytometry (FCM) on barbotage specimens obtained before and after irradiation (at the time of cystectomy) and the results of pretreatment clinical stage (T category) and post cystectomy pathological stage (P category). The patients were divided into three groups: (1) P greater than T, (2) P = T, and (3) P less than T. All of the patients in this study had positive FCM specimens with an aneuploid stemline in the pre-irradiation specimen. A complete radiation response (CRR) was defined by FCM as disappearance of the aneuploid stem cell line. Of the 5 patients in the P less than T group, 4 showed a CRR; of 20 patients in the P = T group, 8 showed a CRR; of the 3 patients in the P greater than T group, none showed a CRR. The proportion of patients in the various T/P groups is consistent with that previously observed in patients receiving integrated irradiation (2000 rad in 5 days) and cystectomy (1-14 days later). The overall downstaging response of 43%, as determined by FCM, correlates well with the pathological downstaging rates of 40%-68% reported by others following high dose (4000-5000 rad) integrated irradiation cystectomy regimens; however, it is more than the 27% rate reported with the low dose short course (2000 rad in 5 days) regimen. The correlation of the FCM findings with clinico-pathological downstaging is consistent with the possibility that FCM may be useful in identifying a favorable radiation response.

Carcinoma, Squamous Cell↗