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Biomedical subjects

F Miller

Publications and source records attributed to F Miller.

At least 163 records · Page 9Linked to original sources

Renal pathology of prenatally diagnosed nephrosis.

Congenital Finnish nephrosis is a rare autosomal-recessive disorder, usually fatal at an early age. The disease is prenatally detected through elevation of alpha fetoprotein in the amniotic fluid of pregnancies at risk. This originates from fetal proteinuria. Maternal serum alpha fetoprotein reflects amniotic fluid levels. We describe a case of congenital nephrosis diagnosed through maternal serum screening in a low-risk population. The characteristic histology of congenital nephrosis is demonstrated, and evidence of proteinuria by electron microscopy, light microscopy, and immunofluorescence is presented.

Adult↗

Identification and localization of human pancreatic tumor-associated antigens by monoclonal antibodies to RWP-1 and RWP-2 cells.

Human pancreatic adenocarcinoma cell lines, RWP-1 and RWP-2 (Dexter, D. L., Matook, G. M., Meitner, P. A., Bogaars, H. A., Jolly, G. A., Turner, M. D., and Calabresi, P. Cancer Res., 42: 2705-2714, 1982), were used as immunogens for the production of monoclonal antibodies to tumor-associated membrane antigens. BALB/c mice were immunized by i.p. injection of viable cells and hybridomas resulting from the fusion of splenocytes to myeloma cell line P3 X 63/Ag8.653 were screened by enzyme-linked immunosorbent assay for antibodies which reacted with both RWP-1 and RWP-2 cells. Hybridomas AR2-20 and AR1-28, both IgG1 antibody-producing cell lines, demonstrated membrane staining by immunofluorescence cytochemistry on three of seven pancreatic tumor cell lines but not on six human tumor cell lines of nonpancreatic origin, or on normal human fibroblasts. The antibodies stained frozen sections of RWP xenografts, propagated s.c. in nude mice, and tumor cells in paraffin sections of seven of seven cases of pancreatic ductal adenocarcinoma, using indirect immunofluorescence and immunoperoxidase histochemistry, but not normal adult or fetal pancreas, or a number of other normal adult tissues. Immunoprecipitation of 125I-labeled RWP-2 cells resulted in a single band with a molecular weight of 190,000 under reducing conditions. Sequential immunoprecipitation demonstrated that both AR2-20 and AR1-28 bind to the same molecule.

Animals↗

Detection of human pancreatic adenocarcinomas by histochemical staining with monoclonal antibody AR1-28.

Hybridoma AR1-28 [Chin and Miller, Cancer Res 45:1723-1729, 1985] was produced using splenocytes from BALB/c mice which had been immunized with human pancreatic adenocarcinoma cell line RWP-1 [Dexter et al, Cancer Res 42:2705-2714, 1982]. This antibody cross reacted with the RWP-2 cell line. AR1-28, an IgG1 antibody, stained the membranes of five (RWP-1, RWP-2, BxPC-3, HPAF-2, and T3M4) out of ten human pancreatic tumor cell lines by immunofluorescence techniques. Electron microscopy on RWP-2 cells, stained by indirect immunoperoxidase, confirmed a membrane location for the AR1-28 antigen. Twenty-three of the 27 clinical specimens (83%) of formalin-fixed, paraffin-embedded pancreatic cancers tested were positive. Varying intensities of staining were observed and were related to the degree of differentiation achieved by the tumor: poorly differentiated tumors showing the least staining while well-differentiated tumors showed the greatest intensity of staining in a predominantly apical location. Immunoblotting showed that AR1-28 reacts with a 200,000-dalton antigen present in extracts of RWP-1 and RWP-2 cells. This monoclonal antibody may be useful in the classification of pancreatic tumor cells.

Adenocarcinoma↗

The role of calmodulin in the regulation of human lymphocyte activation.

Calmodulin (Cam) was isolated from normal and from transformed human lymphocytes by affinity chromatography on CAPP-Sepharose 4B, followed by chromatofocusing. In the presence of Ca2+, lymphocyte Cam migrated as a single protein on 2-DE, and was located on the same position as Cam extracted from dog brain and rat testis; its MW was 17,500, with a pI of 3.9. In the presence of Ca2+, lymphocyte Cam stimulated activator-depleted dog brain phosphodiesterase; this effect was inhibited by trifluoperazine (TFP) or by EGTA. By the RIA technique, the EGTA-soluble Cam content of resting lymphocytes constituted 0.58% of the total protein; the total Cam was comparable to the content of other major proteins in lymphocytes, such as actin, tubulin, and intermediate filament protein. The amount of Cam per cell and the rate of incorporation of L-[35S]methionine into Cam increased after mitogen-induced transformation. Immunofluorescence labeling of normal, mitogen-transformed, and EBV-genome-positive lymphocytes with affinity-purified anti-Cam antibodies showed bright fluorescence in the region of the Golgi apparatus, as well as diffuse cytoplasmic but scant nuclear staining. Similar patterns were observed in T suppressor, T helper, and B cells. Normal lymphocytes cultured in the presence of 2 X 10(-5) M TFP remained viable, but failed to undergo blastogenic transformation after stimulation with allogeneic cells, concanavalin A (Con A), or pokeweed mitogen (PWM). The same concentration of TFP inhibited the replication of EBV-genome-positive and of leukemia cells. Exposure of natural killer cells or allospecific killer cells to this concentration of TFP inhibited the effector phase of killing in a dose-dependent manner. In the presence of lower concentrations of TFP (0.25-1.0 X 10(-5) M) strong MLC responses were inhibited, while weak reactions were markedly amplified. A similar effect was not observed in lymphocytes stimulated into blastogenesis by lectins, suggesting that different Cam-dependent secondary messenger(s) may be involved in the blastogenic responses evoked by alloantigenic determinants. The amplification of weak MLC responses by 0.25-1.0 X 10(-5) M TFP constitutes the first biological illustration of the capacity of a Cam-binding agent to enhance as well as to inhibit cellular activation. The paradoxical effect may have been a consequence of a shift in the relative concentrations of the four known molecular Cam X Ca2+ conformers. The results are also consistent with the suggested capacity of Cam X Ca2+ conformers to activate different enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens↗

The use of bone allograft: a survey of current practice.

A questionnaire was sent to all chairmen of American orthopedic training programs, requesting information on their use of bone allograft and banking methods. Of the 93% who responded, 55% reported using bone allograft most commonly for benign tumor defects or spine fusions. Methods of procurement, preservation, and storage varied widely.

Bone Transplantation↗

Continuous infusion epidural analgesia in parturients receiving bupivacaine, chloroprocaine, or lidocaine--maternal, fetal, and neonatal effects.

The effects of epidural analgesia for labor and delivery using a continuous infusion technique on fetal heart rate, uterine activity, maternal blood pressure, Apgar scores, neonatal acid-base status, and the Neurologic and Adaptive Capacity Scoring System were studied in 61 parturients. Group I (n = 23) received initial test and therapeutic doses of 2 and 6 ml of 0.5% bupivacaine followed by an infusion of 0.125% at a rate of 14 ml/hr. Group II (n = 19) received 2 and 6 ml of 2% chloroprocaine followed by an infusion of 0.75% at a rate of 27 ml/hr. Group III (n = 19) received 2 and 6 ml of 1.5% lidocaine followed by an infusion of 0.75% at a rate of 14 ml/hr. None of the three local anesthetics used had any significant effect on baseline fetal heart rate or uterine activity. In cases in which monitoring of fetal heart rate was both technically satisfactory and continuous, late and variable decelerations in fetal heart rate were seen in 10 of 17, 3 of 18, and 2 of 19 of the fetuses in groups I, II, and III, respectively. The incidence was significantly higher in group I than in groups II or III (P less than 0.05). Apgar scores and neonatal acid-base status were equally good in all three groups. Neurologic and adaptive capacity scores did not differ among the three groups of neonates, nor did any of the neonates in the three groups score lower than a control group of 19 neonates whose mothers did not receive any analgesia or medications for labor and delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Carcinoma of the breast metastatic to the skeleton.

A review of 319 patients with breast carcinoma metastatic to the skeleton revealed a large variation in age at diagnosis, interval between diagnosis of primary disease and metastasis, and survival time with metastasis. The presence of bony metastasis only is a good prognostic sign, and the presence of neurologic defects without successful correction is a poor prognostic sign. Bone lesions are radiosensitive, and fractures usually heal with radiation. It is difficult to define impending fractures, but large lytic lesions, increased body weight, increased activity, and areas of high stress are factors that can be used to determine the risk of fracture. Femoral neck fractures should be treated by endoprostheses or total hip arthroplasty and femoral shaft fractures by appropriate internal fixation. In the present series humeral fractures were successfully managed conservatively, but it is possible that with a wider data base the advantages of immediate rigid fixation by internal fixation with methylmethacrylate cement would be more obvious. Use of methylmethacrylate should be restricted to patients with short-term survival expectancies and large defects. Most spinal metastases can be treated by radiation and orthoses, but an aggressive approach is indicated for patients with neurologic deficits. Laminectomy is indicated for lesions that produce posterior compression, anterior decompression for lesions producing anterior compression, and stabilization for alignment deformities or instability.

Adult↗

Method for computation of cardiac output in mitral stenosis independent of left ventricular dimensions and kinetic state: correlation with cardiac catheterization via the Fick method.

An hydraulic orifice formula offering the possibility of quantifying cardiac output in conditions of mitral stenosis is tested using potentially noninvasive portions of catheterization data from patients evaluated for obstructive mitral valve disease. The equation studied is V = (1/21) R A T2, where V is the cardiac output (ml/min), R is the heart frequency, A is the mitral valve area (cm2), and T is the diastolic filling interval (sec/min). The mitral valve area was determined by the Gorlin formula, and R and T were measured from the pressure tracings recorded at cardiac catheterization. The degree of correspondence between the equation tested and the measured cardiac output as determined by the Fick principle technique is characterized by r = 0.87, SE = 450 ml/min, N = 10. The results suggest that the new formulation may offer a noninvasive method for estimating the cardiac output status of patients with mitral valve disease once mitral valve area is measured either at catheterization or by two-dimensional echocardiography.

Cardiac Catheterization↗

Sleep apnea and nocturnal hypoventilation after western equine encephalitis.

That viral encephalitis can produce daytime hypoventilation is well appreciated, but an association of this infection with the development of a prolonged disturbance of breathing during sleep once the ventilatory disorder during wakefulness has resolved, has not been reported. We describe a young male who required assisted mechanical ventilation in association with western equine encephalitis. Normal waking ventilation returned over 3 to 4 wk, but frequent apneas and severe hypoventilation persisted during sleep with a near absence of waking ventilatory response to chemical stimuli. Over 3 months there was considerable improvement in breathing during sleep associated with an increase in both hypoxic and hypercapnic ventilatory responsiveness.

Adolescent↗

Mitochondrial inclusions in selenium-treated mouse mammary epithelial cell lines.

The effects of selenium on three mammary epithelial cell lines (YN-4, WAZ-2t, and CL-S1) grown in vitro were examined by immunocytochemical and transmission electron microscopy technique. The primary effect of selenium at the ultrastructural level was the appearance of electron-dense inclusions within the mitochondrial matrix. The mitochondrial inclusions were seen in all three cell lines, although most readily induced in YN-4 cells, the cell line which is most sensitive to selenium-mediated growth inhibition. Selenium at 5 x 10(-8) and 5 x 10(-6) M did not alter cytoplasmic microtubules or intermediate filament networks, as determined by immunocytochemical staining. Immunocytochemical staining for cytoplasmic filaments and microtubules, and transmission electron microscopy observations, supported the contention that cells from all three cell lines were epithelial in origin, since they contained abundant desmosomes and were uniformly positive for keratin intermediate filaments. Whereas line YN-4 was negative for vimentin intermediate filaments, a minority (5 to 24%) of the cells in lines CL-S1 and WAZ-2t stained positively. In addition, the tumorigenicity of these three cell lines was assessed by in vitro growth assays and in vivo transplantation assays. Cell lines YN-4 and WAZ-2t, but not line CL-S1, were tumorigenic in syngeneic mice. All tumors were mammary adenocarcinomas. Cytochalasin B-induced multinucleation assay and growth as multicellular spheroides correlated positively with in vivo tumorigenicity, whereas saturation density and growth in low Ca2+ medium were not correlated with tumorigenicity. It is speculated that one of the early effects of selenium-mediated growth inhibition may be a modulation of mitochondrial function.

Animals↗

Antigen size and charge in immune complex glomerulonephritis. II. Passive induction of immune deposits with dextran-anti-dextran immune complexes.

Utilizing dextrans of restricted sizes (10,000, 70,000, 500,000 daltons), modified with regard to charge (neutral, polycationic, polyanionic) and an anti-dextran murine IgA myeloma, W3129, the authors have examined a model that may be used in the study of the combined effect of size and charge on renal deposition of immune complexes. Polycationic DEAE dextran complexes, using the 10,000 dalton antigen, showed a mesangiocapillary pattern of deposition. The other antigens showed focal to diffuse mesangial localization of varying degree. This indicates the potential usefulness of this system in examining the factors important in glomerular immune injury. The relevance to other observations, importance of polysaccharide antigens, and role in circulating versus in situ or "planted" immune complex models are considered.

Animals↗

Early progressive kyphosis following compression fractures. Two case reports from a series of "stable" thoracolumbar compression fractures.

In an 18-year-old man and an 18-year-old woman, significant kyphotic deformity progressively developed in the course of the healing of apparently stable thoracic compression fractures. The common features were: (1) multiple adjacent fractures; (2) location in the thoracic spine; (3) associated thoracic injury; and (4) youth. The possibility of early progressive kyphotic deformity should be carefully monitored so that appropriate treatment can be instituted before the deformity becomes significant. Although both isolated fractures and multiple-level fractures of the thoracolumbar spine occur predominantly between T12 and L2, there is a secondary area that is predisposed to compression fractures in sequence from T5 to T7.

Accidents↗

Fetal and maternal cardiovascular effects of atropine and glycopyrrolate.

This study compared the effects of intravenous atropine and glycopyrrolate on maternal and fetal heart rates and variability, maternal blood pressure, and uterine activity in 20 normal full-term parturients in labor. Group 1 (N = 10) received 0.005 mg/kg of glycopyrrolate, and group 2 (N = 10) received 0.01 mg/kg of atropine. There were no statistically significant changes in fetal heart rates or variability in either group. Uterine activity increased in a normal manner as labor progressed. Maternal heart rate increased significantly and essentially equally in all patients in both groups ranging from 15 to 78 beats/min and a mean (+/- SD) of 36 +/- 16 in group 1 and from 15 to 65 beats/min with a mean of 35 +/- 17 in group 2. There were no statistically significant changes in maternal blood pressure in either group.

Adult↗

The incidence of thromboembolic disease.

The incidence of thromboembolism was determined by a survey of 7986 orthopedic patients who had 5966 operations at a university hospital during a three-year period. Patients were analyzed to determine thromboembolic risks with respect to the orthopedic diagnosis to assist in providing the patient with informed consent and to identify patients who need prophylactic anticoagulation therapy. The patient population was divided into three risk classes: Class 1, low-risk patients, including children, all upper-extremity patients, and adult non-surgical ambulatory rehabilitation patients; Class 2, medium-risk patients, including all adult lower-extremity patients and patients with spine problems and no history of thromboembolic disease; Class 3, high-risk patients, including all patients with a previous history of thromboembolic disease or venous stasis disease. Class 1 patients require no prophylactic anticoagulation, Class 2 patients should be treated with dextran or aspirin, and Class 3 patients should be treated with warfarin. The calculated mortality for Class 2 patients, excluding hip problems, is 0.26%; mortality for acute spinal cord injuries is 2.9% and for hip surgery 2.2%.

Adolescent↗