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Biomedical subjects

J P Harvey

Publications and source records attributed to J P Harvey.

At least 19 recordsLinked to original sources

Epidermal growth factor receptor ectodomain in the urine of patients with squamous cell carcinoma.

In this study we determined the levels of the epidermal growth factor receptor (EGFR) in the urine of patients with squamous cell carcinoma compared to levels in the urine of normal volunteers and patients with nonsquamous cell carcinoma. A 24-h urine specimen was collected from 50 normal volunteers, 50 patients with nonsquamous cell carcinoma, and 42 patients with squamous cell carcinoma. An ELISA using mAbs to the external domain of the EGFR was used to measure levels of the receptor in the urine samples. Measurement of the EGFR ectodomain in the 24-h urine specimens showed detectable levels in 15 (36%) of 42 squamous cell carcinoma patients compared to 3 (6%) of 50 controls and 8 (16%) of 50 nonsquamous patients. It was also observed that 10 (53%) of 19 patients with metastatic squamous cell carcinoma had detectable EGFR ectodomain levels compared to 5 (22%) of 23 squamous cell patients with localized disease. Thus, we concluded that the EGFR ectodomain was detectable in the urine in a significantly higher number of patients with squamous cell carcinoma than normal volunteers or patients with nonsquamous cell carcinoma.

3T3 Cells↗

Retinoblastoma gene product-associated proteins in human colon cancer cell lines.

The expression of cellular proteins that associate with the human retinoblastoma (RB1) gene protein was examined in three colorectal carcinoma cell lines (SW480, SW403, DiFi) by immunoprecipitation analysis, using the mouse monoclonal antibody (RB-MAb-1) directed against the RB1 gene product (RB). The potential of RB-MAb-1 to detect RB-associated proteins by immunoprecipitation analysis was confirmed using three control cell lines (WI-38, J82, T24) known to express RB and/or RB-associated proteins. In all colon cancer cell lines tested, multiple RB-associated protein (RAP) bands were found with molecular weights of 30-50 kDa. Because involvement of the RB1 gene in colorectal tumorigenesis appears to differ from its role in other cancer types (wherein RB1 is lost or inactivated), it will be important to characterize the role of RAPs in RB growth regulatory mechanisms of colonic epithelial cells.

Adenocarcinoma↗

RB1 protein in normal and malignant human colorectal tissue and colon cancer cell lines.

The pattern of human retinoblastoma (RB1) gene protein expression was directly examined in normal and malignant human colorectal tissues and in seven colorectal carcinoma cell lines by immunohistochemistry using the mouse monoclonal antibody (RB-MAb-1) directed against the retinoblastoma protein (RB). This is the first demonstration of RB immunostaining in adult human colonic epithelium and colorectal carcinomas. Specificity using RB-MAb-1 was confirmed by western blot analysis, which showed bands of 110-116 kDa corresponding to the sizes of unphosphorylated and phosphorylated RB. RB staining of normal adult colonic epithelium was confined to the nucleus and was most intense in the transitional zone of the crypt, whereas lumenal cells (fully differentiated) were RB negative. Primary colorectal carcinomas and all the colon cancer cell lines stained positively for nuclear RB, but the expression was heterogeneous with varying fractions of RB negative cells present. Because we and others have previously shown that loss or inactivation of the RB1 gene is infrequent in colorectal carcinomas, reduced RB expression in such cells is probably due to a cellular regulatory mechanism. For example, RB negative cells may be those in early-G1 phase (known to have reduced RB levels) or growth-arrested cells that have differentiated. The ability to directly detect RB in primary colorectal carcinomas will permit assessment of whether heterogeneous expression of the RB1 gene product has prognostic significance for survival of patients with this cancer.

Antibodies, Monoclonal↗

Similarities of low-dimensional chaotic auditory attractor sequences to quasirandom noise.

The production of sequences of sounds of various pitch levels from the algebra of chaotic attractors' trajectories is relatively straightforward. Meyer-Kress (cited in Kaneko, 1986) suggested that such sequences would be distinguishable from random independent identically distributed sequences. In psychophysical terms, this is a pattern-discrimination or pattern-similarity perception task, but these two tasks are not exactly the same thing. Nine attractors from the algebras of Henon, Zaslavskii (1978), Kaplan and Yorke (1979), Lorenz, and Gregson, and the logistic and Baker transformations, were paired with 10 realizations of a random series. The identification of the random member in each pair, the confidence of identification, and the perceived pairwise similarity were recorded by 65 subjects without initial feedback and by 76 subjects with initial feedback on five trials only, for each of 20 such pairs. The results indicate varying degrees of discriminability; they can be expressed in an analog of the receiver-operating characteristics of the attractors. There is no evidence of any homogeneous basis for the discrimination, and subjects who perform better are apparently not using the same bases as those who perform poorly. The fractal dimensionality of attractors may furnish a basis for their recognition, or the consequent autoregressive spectra induced in finite (short) samples, but recent work suggests the latter spectra can be insensitive to low-dimensional attractor dynamics.

Adult↗

Mouse monoclonal antibody to a latent epitope of leucocyte receptors for leukotriene B4.

Human blood polymorphonuclear (PMN) leucocytes and human leucocytes of the HL-60 line, which were induced to differentiate by 1,25-dihydroxyvitamin D3, express stereospecific receptors for the potent chemotactic mediator, leukotriene B4 (LTB4), that is derived by 5-lipoxygenation from arachidonic acid. Monoclonal antibodies to LTB4 receptors (LTB4-R) were generated by immunizing BALB/c mice with partially purified PMN leucocyte membrane proteins, and fusing their splenocytes with P3X63Ag8 mouse myeloma cells. Hybridoma supernatants were screened initially by binding to PMN leucocyte LTB4-R protein, which had been affinity cross-linked with aminopropylamide (APA)-LTB4 and immobilized in plastic wells through attachment of the linked APA-LTB4 to adherent Fab of monoclonal anti-LTB4. Of the three clones producing antibodies which bound to LTB4-R, 0.5 mg/ml of one IgG3k antibody, termed E2, precipitated over 90% of the [3H]LTB4-binding activity of solubilized PMN leucocyte membrane proteins. E2 also bound to a radiolabelled protein of 70,000-80,000 MW from 125I-labelled PMN leucocyte membranes [35S]-labelled HL-60 cell membranes, and PMN leucocyte membranes affinity-labelled with [3H]APA-LTB4, that was identical in size to the LTB4-R precipitated by the rabbit IgG anti-idiotypic antibodies. E2 did not bind to intact PMN leucocytes or modify the binding of [3H]LTB4 by PMN leucocytes. The binding of E2 to LTB4-R in purified membranes of PMN leucocytes was less than one-fourth of that observed for the anti-idiotypic antibodies, but increased substantially after solubilization of the LTB4-R. The E2 monoclonal antibody thus recognizes a partially latent substituent of LTB4-R, which does not contribute to combining site function.

Animals↗

Transient penetration of the hip joint during in situ cannulated-screw fixation of slipped capital femoral epiphysis.

Before the routine intraoperative use of fluoroscopy at our institution during procedures to stabilize a slipped capital femoral epiphysis, twenty-five patients (thirty hips) had in situ cannulated-screw stabilization of a slipped capital femoral epiphysis with use of biplane radiography. Thus, a permanent record of the procedure was available for review. Fourteen hips in fourteen patients had an intraoperative episode during which the joint was penetrated by the guide-pin assembly or cannulated screw, or both. This penetration was corrected at the time of the operation. Eleven patients were followed for a minimum of two years (mean, thirty-nine months; range, twenty-four to sixty-three months). All physes went on to closure. None of the patients had clinical or radiographic evidence of chondrolysis. Transient penetration of the hip joint did not lead to chondrolysis in this series. This suggests that a single episode of penetration by a pin or screw, with immediate removal from the joint, is not associated with the development of chondrolysis.

Adolescent↗

Processing of the human IM-9 lymphoblast substance P receptor. Biosynthetic and degradation studies using a monoclonal anti-receptor antibody.

Cellular membrane receptors for the immunostimulatory neuropeptide substance P have been previously identified on the cultured lymphoblast cell line, IM-9. The regulation of this receptor by ligand and the contribution to its molecular weight by N-linked sugars was studied by incubating IM-9 cells for 14 hr in the presence of [35S]met with or without substance P and tunicamycin, respectively. Cells were lysed and the receptor proteins were immunoprecipitated with an anti-receptor monoclonal antibody. SDS-PAGE analysis of untreated cellular lysates revealed specifically precipitated proteins of 38 kD and 33 kD, which were down-regulated by substance P. In tunicamycin-treated cells, whose substance P binding was not affected, the major immunoprecipitated protein had an apparent Mr of 29 kD. The time course of receptor processing was studied by pulse chase analysis. Three proteins of molecular weights 38 kD (mature receptor), 36 kD and 33 kD (receptor precursors) were identified for time periods of 30 min to 4 hr. The half life of the mature receptor and its precursors was approximately 1 hr and 0.5 hr, respectively. Results from the present studies suggest that the lymphocyte substance P receptor is translated as a precursor protein that is glycosylated.

Antibodies, Monoclonal↗

Ipsilateral diaphyseal femur fractures and knee ligament injuries.

Three hundred and nine consecutive patients with 320 diaphyseal femur fractures were retrospectively reviewed to determine the incidence of ligament injury in the ipsilateral knee. Ligamentous injuries were diagnosed if serious (Grades II and III) instability was apparent on admission, found at surgery for femoral stabilization, or disclosed on roentgenograms during closed management. Seventeen patients with unilateral shaft fractures of the femur had ipsilateral knee ligament injuries, or 5.3%. There was no relationship between specific ligament damage and the cause of the injury or level of fracture. Twelve patients were followed for an average of 34 months. Five patients lacked full extension and ten lacked full flexion. Two of seven patients with ligament repair and three of five patients without ligament repair had at least one unstable ligament. Better range of knee motion was obtained when both the femur and ligament injuries were surgically managed, but most (seven of 12) patients were disabled.

Adult↗

Recognition of human polymorphonuclear leukocyte receptors for leukotriene B4 by rabbit anti-idiotypic antibodies to a mouse monoclonal antileukotriene B4.

Rabbit anti-idiotypic IgG antibodies to the combining site of a mouse monoclonal IgG2b antibody to leukotriene B4 (LTB4) cross-reacted with human polymorphonuclear (PMN) leukocyte receptors for LTB4. Anti-idiotypic IgG and Fab both inhibited the binding of [3H]LTB4, but not [3H]N-formylmethionyl-leucylphenylalanine (fMLP), to PMN leukocytes with similar concentration-effect relationships, whereas neither nonimmune rabbit IgG nor Fab had any inhibitory activity. At a concentration of anti-idiotypic IgG that inhibited by 50% the binding of [3H] LTB4 to PMN leukocytes, the antibodies preferentially recognized high affinity receptors. Anti-idiotypic IgG and Fab inhibited PMN leukocyte chemotactic responses to LTB4, but not fMLP, with concentration-effect relationships resembling those characteristic of the inhibition of binding of [3H] LTB4, without altering the LTB4-induced release of beta-glucuronidase. Chemotaxis and increases in the cytoplasmic concentration of calcium equal in magnitude to those elicited by optimal concentrations of LTB4 were attained at respective concentrations of anti-idiotypic IgG equal to and 1/25 the level required for inhibition of binding of [3H]LTB4 by approximately 50%. Thus, the anti-idiotypic antibodies bound to PMN leukocyte receptors for LTB4 with a specificity, preference for high affinity sites, and capacity to alter PMN leukocyte functions that were similar to LTB4.

Animals↗

Tibial plateau fractures: definition, demographics, treatment rationale, and long-term results of closed traction management or operative reduction.

Results of a decade of experience with 988 tibial plateau fractures are presented. Maximum plateau depression was measured on initial and follow-up x-ray studies, and knee instability was clinically evaluated to identify minor and major fractures as a guide to management. Demographic, treatment, and complication data were gathered prospectively in 753 fractures. Four hundred thirty-seven "major" tibial plateau fractures (44% of cases) were treated operatively; the remainder were treated by traction. Three hundred twenty patients who sustained only a plateau fracture were followed from 1 to 10 years, with an average of 3.7 years. Nonsurgical treatment included Buck's traction (89% of closed treatment cases) or a "knee exerciser" device utilizing skeletal traction in a Hodgson-Pearson apparatus. Early intermittent passive and active knee motion was encouraged. The complication rate of traction was 8%. The complication rate in operated patients was 19%, much of which was due to infection. Methods for objective and subjective scoring of both traction and operative results were developed and utilized. Results show that anatomic reduction of plateau fractures, in addition to early motion, is a major factor contributing to successful management of this potentially disabling injury.

Adolescent↗

Results of compression-plating of closed Galeazzi fractures.

Diaphyseal fractures of the distal third of the radius that are associated with disruption of the distal radio-ulnar joint accounted for eighty-four (6.8 per cent) of 1236 fractures in the forearm that were treated during a five-year period at the Los Angeles County-University of Southern California Medical Center. Thirty-six closed Galeazzi fractures, twenty-eight in male and eight in female patients, were followed for 1.5 to seven years after treatment using standard AO-compression plates with four to seven holes. Complications included seven injuries to the sensory or dorsal interosseous branch of the radial nerve, two infections, two non-unions, two re-fractures after plate removal, and shortening of the radius of five millimeters in one patient. The complication rate was 39 per cent. The average grip strength at follow-up was 71 per cent of the calculated normal value. The loss of strength was not related to use of a volar or dorsal surgical approach, the patient's age, or a delay of surgery for more than ten days after injury. The average loss of grip strength in the seven upper extremities with restricted motion of the wrist and forearm was 48 per cent, compared with an average loss of 29 per cent in the whole group. Of the twelve patients who were operated on more than ten days after injury, six had loss of motion at follow-up, compared with three who had such a loss among the twenty-four patients who were operated on within ten days after injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Plastic bowing of the femur in a neonate.

Acute plastic bowing injuries in children characteristically heal with little periosteal callus and exhibit a limited potential to remodel. A case of plastic bowing of the femur in a neonate is reported in which follow-up radiographs demonstrated periosteal new bone formation and rapid remodeling of the deformity. This report suggests that plastic bowing injuries in the neonate show a greater remodeling potential than similar lesions in older children.

Birth Injuries↗