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Biomedical subjects

A P McLaughlin

Publications and source records attributed to A P McLaughlin.

At least 19 recordsLinked to original sources
PubMed2001

Role of PLCgamma and Ca(2+) in VEGF- and FGF-induced choroidal endothelial cell proliferation.

Although both vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) receptors have been shown to be important in the regulation of vascular endothelial cell growth, the roles of phospholipase C (PLC)gamma and Ca(2+) in their downstream signaling cascades are still not clear. We have examined the effects of VEGF and FGF on PLCgamma phosphorylation and on changes in intracellular Ca(2+) levels in primary endothelial cells. VEGF stimulation leads to PLCgamma activation and increases in intracellular Ca(2+), which are correlated with mitogen-activated protein (MAP) kinase (MAPK) activation and cell growth. Inhibition of Ca(2+) increases by the Ca(2+) chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM resulted in marked inhibition of MAPK activation, which was shown to be linked to regulation of cell growth in these cells. In contrast, FGF stimulation did not lead to PLCgamma activation or to changes in intracellular Ca(2+) levels, although MAPK phosphorylation and stimulation of cell proliferation were observed. Neither BAPTA-AM nor the PLC inhibitor U-73122 had an effect on these FGF-stimulated responses. These data demonstrate a direct role for PLCgamma and Ca(2+) in VEGF-regulated endothelial cell growth, whereas this signaling pathway is not linked to FGF-mediated effects in primary endothelial cells. Thus endothelial cell-specific factors regulate the ability of VEGF receptors and FGF receptors to couple to this signaling pathway.

Antibodies, Monoclonal↗
PubMed1982

Risk factors for the development of distant metastases in patients undergoing pelvic lymphadenectomy for prostatic cancer.

Sixty-two patients with clinically localised prostatic cancer underwent pelvic lymphadenectomy between 1972 and 1975. Thirty-one patients had concomitant total prostatectomy. The objectives of this study included determination of the relation of findings at lymphadenectomy, with and without total prostatectomy, to subsequent clinical course, identification of histologic parameters related to the subsequent appearance of distant metastatic disease, and determination of the vital status of patients initially having a staging pelvic lymphadenectomy. Follow-up of at least 5 years was obtained for 52 patients, including 28 who had concomitant total prostatectomy. Ten patients were lost to follow-up. Fifty-four percent are alive with metastatic disease 10 percent have died with metastatic disease, 10 percent have died with metastatic cancer, and 12 percent have died without prostate cancer. Metastases have developed in 11 (37 percent) of 30 patients with negative pelvic lymph nodes, reflecting either seminal vesicle or transcapsular invasion. Minimal lymph node involvement (one or two pelvic nodes) alone may not be as poor a prognostic sign as originally thought. Metastases have developed in 22 percent of nine patients with tumor considered stage B2. No recurrences or metastases were noted in the seven patients with stage B1 disease. Patients with high grade lesions were at no increased risk for distant metastases, although they constituted a relatively small segment of our series. Thus the extent of local disease correlates with the subsequent development of distant metastasis. Adjuvant systemic treatment (endocrine manipulation, chemotherapy, or both) has a rational basis in patients with one or more of these identifiable risk factors.

Adenocarcinoma↗
PubMed1977

Clinicopathologic features of unsuspected regional lymph node metastases in prostatic adenocarcinoma.

Histologic features of the primary tumor and their effects on the incidence of unsuspected pelvic lymph node metastases have been studied in a prospective series of 62 patients with clinical stage B1, B2, or C prostatic adenocarcinoma who underwent pelvic lymph node removal. Twenty-one patients (34%) proved to have unsuspected nodal metastases. Differentiation of the primary tumor and extent of involvement of the prostate by carcinoma were the only two features that correlated significantly with the incidence of pelvic nodal metastases, 56% of those with undifferentiated tumors had metastases. Thirty-one of these patients underwent total prostatectomy; an average of only 46% of the sections of prostate contained tumor in the patients without metastases but an average of 65% of the sections were involved by carcinoma in those patients who did have nodal metastases.

Adenocarcinoma↗
PubMed1977

The effect of pregnancy on the growth of primary methylcholanthrene sarcoma isografts.

Primary isografts of a highly immunogenic methylcholanthrene tumor were injected into pregnant C57/BL mice. Tumor growth was studied and compared to isografts injected into virgin C57/BL mice preimmunized with fetal antigens. Significant in vivo enhancement of MCA tumor growth was noted in both intra-and interstrain pregnant mice compared with virgin controls. In addition, active preimmunization of virgin mice with hybrid fetal liver did not result in rejection of primary tumor isografts, suggesting that fetal antigens did not contribute to the immunogenicity of this MCA tumor.

Animals↗
PubMed1977

Effects of immunosuppression on the rejection of methylcholanthrene tumor isografts.

The effect of immunosuppression with azathioprine, methylprednisolone, or both, on primary and secondary immune responses to a transplanted tumor was studied. The ability to reject a methylcholanthrene-induced squamous cell carcinoma of the prostate in Lewis rats was determined by rechallenge with tumor cells after amputation of the primary transplant. Oral azathioprine (20 mg/kg/day) increased the incidence of tumors in a primary challenge, but did not affect the ability of immunized rats to reject subsequent tumor isografts. Similar results were obtained with 2 mg/kg day intraperitoneal (IP) azathioprine, 2 mg/kg IP methylprednisolone, and the combination of 2 mg/kg/day IP methylprednisolone and 10 mg/kg/day IP azathioprine. It appears that immunosuppression by azathioprine affects the proliferation of sensitized cells during the immunological response to antigens of this specific tumor. Immunosuppression does not appear to alter substantially the processing of tumor-specific antigens or the cytotoxic effectiveness of the immune system. This data is reassuring to the concern of whether transplantation in patients previously cured of cancer is safe.

Animals↗
PubMed1977

Replacement of the damaged or neoplastic ureter by ileum.

Ileum was used as a ureteral replacement in 12 patients, 7 of whom had solitary kidneys. The conditions that necessitated an operation included renal pelvic and ureteral complications of calculi, a variety of traumatic ureteral injuries, retroperitoneal fibrosis and ureteral neoplasms. Renal function has been well preserved and electrolyte imbalance has been minimal.

Adult↗
PubMed1977

Morbidity of pelvic lymphadenectomy and radical prostatectomy for prostatic cancer.

Radical retroperitoneal pelvic lymphadenectomy is associated with rather minimal morbidity but, when combined with radical prostatectomy, the morbidity is increased. The only complication that seemed to be solely owing to the lymphadenectomy was lymphocele formation, which occurred in 10 per cent of the patients. This rate is below that reported in the gynecologic-oncology literature.

Adult↗
PubMed1976

Prostatic carcinoma: incidence and location of unsuspected lymphatic metastases.

Prospective pathologic staging by pelvic lymphadenectomy in 60 patients with clinically localized carcinoma of the prostate disclosed a high incidence (35 per cent) of clinically silent and unsuspected lymph node metastases. When present, metastatic disease was frequently bilateral (57 per cent) and most commonly involved the obturator-hypogastric lymph nodes (87 per cent). Micrometastases alone were found in 5 patients and the potential significance of this finding on survival is discussed. Although the presence or absence of metastases could not be accurately predicted by histologic analysis of biopsy or prostatectomy specimens, the finding of undifferentiated tumor, marked anaplasia and penetration through the capsule correlated positively with nodal metastases. Pelvic lymphadenectomy is a safe and important diagnostic tool in the accurate staging of these patients. Its widespread use is advocated in patients with clinical stage B1, B2 and C tumors prior to definitive therapy. Based on the prospective data generated in this study lymphatic metastasis appears to be an early event in the spread of prostatic cancer.

Adult↗
PubMed1976

Amyloidosis of the lower genitourinary tract.

Three patients with amyloidosis of the lower genitourinary tract are described. In the cases of primary localized amyloidosis of the urethra and primary systemic amyloidosis involving the prostate the clinical presentation mimicked cancer of the respective sites. In the case of secondary localized amyloidosis of the seminal vesicles chronic perineal pain suggested seminal vesiculitis.

Adenocarcinoma↗
PubMed1975

Live donor nephrectomy.

Donor nephrectomy was performed on 39 living related renal donors. The preoperative evaluation, surgical technique, and postoperative follow-up are presented. Major or minor complications developed in 23 per cent of the patients and included acute myocardial infarction, brachial plexus injury, acute glomerulonephritis, ileus, pneumonia, and urinary tract infection. All complications had resolved by six months postoperatively.

Adolescent↗
PubMed1975

"Positive" bone scan--a contraindication to surgery?

Eleven patients with urologic cancer had an abnormal 99mTc (technetium-99m) bone scan as the sole evidence of metastatic disease. Potentially curative therapy should not be withheld on the basis of a "positive" bone scan if such an area is accessible to selected bone biopsy and proves to be negative for tumor histologically.

Adenocarcinoma↗
PubMed1975

The gravity suit: a useful device in complicated urologic hemorrhage.

External counterpressure with a gravity suit was used to control intractable postoperative bleeding in 4 urologic patients. Two patients had coagulation defects, and 2 had been unsuccessfully reexplored prior to application of the G-suit. The bleeding was controlled with preservation and restoration of vital signs in each case. In 3 cases external counterpressure may have been lifesaving.

Aged↗
PubMed1975

Spontaneous rupture of renal cysts into the pyelocaliceal system.

Patients with spontaneous rupture of renal cortical cysts into the pyelocalciceal system present with gross hematuria, usually associated with flank or abdominal pain. Diagnosis is established by retrograde filling of the cyst cavity with contrast material through a wide pyelocaliceal communication visualized during IVP with nephrotomography. Percutaneous renal puncture with histochemical analysis of the aspirate is indicated in certain patients for diagnostic confirmation. Renal angiography and/or an operation should be performed when the differential diagnosis remains unclear. Antibiotics in the patients with urinary tract infections along with conservative medical management is sufficient treatment, since rapid closure of the cyst-pyelocaliceal communication with cessation of hemorrhage occurs rapidly in most patients.

Adult↗
PubMed1975

Renal artery dissection: a complication of catheter arteriography.

Renal artery dissection is a rare complication of catheter arteriography. Predisposing factors include atherosclerosis and fibromuscular dysplasia. Optimum management requires aortographic documentation of the extent of vascular obstruction. Dissections causing incomplete obstruction of blood flow can be treated with systemic anticoagulation to prevent downstream thrombosis and should be followed with serial isotope blood flow studies and LDH measurements. Dissection causing complete vascular obstruction usually requires immediate surgery, although spontaneous reestablishment of flow may occur. The 3 patients discussed illustrate a spectrum of findings, including the acute development of renovascular hypertension.

Adult↗