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Biomedical subjects

C M Johnson

Publications and source records attributed to C M Johnson.

At least 199 records · Page 11Linked to original sources

Polymorphonuclear leukocyte chemotaxis in generalized pustular psoriasis.

We studied polymorphonuclear leukocyte (PMNL) chemotaxis in 3 patients with generalized pustular psoriasis using 3 chemoattractants: Zymosan-activated serum from both the patients and normal individuals, and n-formyl-methionyl-leucyl-phenylalanine (FMLP). These attractants were assayed against both patient-derived and normal PMNLs. All patients had quiescent skin disease at the time of assay. We found that all patients had decreased PMNL chemotaxis to autologous Zymosan-activated serum, but not to FMLP. PMNLs from normal individuals responded normally to serum from the patients. We conclude that patients with generalized pustular psoriasis, when free of symptoms, may have an isolated PMNL chemotactic defect that is restricted to serum-derived attractants.

Adult↗

Complete primary structure of prostatropin, a prostate epithelial cell growth factor.

Bovine brain prostatropin is a potent and essential mitogen for prostate epithelial cell growth. The major form of prostatropin contains 154 amino acid residues in a single amino terminally blocked chain corresponding to a molecular weight of 17,400. The amino acid sequence of the 150 carboxy-terminal residues of prostatropin was derived by Edman degradation of overlapping peptides primarily generated by cleavage at lysyl and glutamyl residues. Analysis of the amino-terminal tetradecapeptide by fast atom bombardment mass spectrometry identified the blocking group as an acetyl moiety, and tandem mass spectrometry provided the sequence of the first 12 residues. Prostatropin residues 15-154 contain the sequence of bovine brain polypeptides recently described as acidic fibroblast growth factor and class I heparin-binding growth factor. The sequence of the first 25 residues of prostatropin is acetyl-Ala-(Gly, Glu)-Glu-Thr-Thr-Thr-Phe-Thr-Ala-Leu-Thr-Glu-Lys-Phe-Asn-Leu-Pro-Leu-Gly -Asn-Tyr-Lys-Lys-Pro. Reduced and carboxymethylated prostatropin exhibits mitogenic activity, suggesting that disulfide bonds among cysteine residues 30, 61, and 97 are not functionally essential. These results demonstrate by rigorous structural analysis that the brain-derived polypeptide previously described only as a mesenchymal and neuroectodermal cell mitogen is also an epithelial cell growth factor that may be involved in support of prostate hyperplasia and adenocarcinoma.

Amino Acid Sequence↗

The susceptibility towards proteolysis of intermediates during the renaturation of yeast phosphoglycerate mutase.

The renaturation of the tetrameric enzyme phosphoglycerate mutase from baker's yeast after denaturation in guanidinium chloride was studied. Three proteinases (trypsin, chymotrypsin and thermolysin) cause extensive loss of activity of samples taken during the early stages of refolding. As judged by SDS/polyacrylamide-gel electrophoresis, the proteinases cause substantial degradation of the polypeptide chain with no evidence for large quantities of fragments of Mr greater than 6500. These data suggest that the early intermediates in the refolding, especially the folded monomer, possess a number of sites that are susceptible to proteolysis.

Binding Sites↗

Characterization of multiple forms of prostatropin (prostate epithelial cell growth factor) from bovine brain.

Two molecular forms of prostatropin distributed among five chromatographic peaks have been isolated from bovine brain by heparin-Sepharose affinity and reverse phase high performance liquid chromatography. One form has an apparent molecular weight of 16000 and an amino terminal sequence of asn-tyr-lys-lys-pro-lys-leu-leu-tyr-x-ser-asn-gly. The other form has an apparent molecular weight of 18000 and a blocked amino terminus. Both forms are similar in amino acid composition. The sequence of a proteolytic fragment from the blocked form overlaps the NH2-terminal sequence of the unblocked form, therefore, the smaller form may be derived from the larger form through proteolytic processing. Both forms contain regions identical in sequence to brain-derived, heparin-binding growth factors that have been isolated on the basis of mitogenic activity for fibroblasts and endothelial cells. Both forms of prostatropin exhibit potent mitogenic activity for normal and tumor prostate epithelial cells.

Amino Acid Sequence↗

Directed intravascular precipitation of bisantrene for pelvic malignant lesions: preclinical studies.

Bisantrene, a clinically active anticancer drug with limited solubility at physiologic pH, was delivered by selective injection into the internal iliac artery of male calves. The percutaneous transfemoral angiographic techniques used in the calves were identical to those used in adult human patients. Directed intravascular precipitation of bisantrene at the maximal tolerable clinical dose for intravenous administration (260 mg/m2) caused severe tissue damage in 5 of 10 animals that received these intra-arterial injections. (One calf in this study group died of unknown causes 10 days after the drug infusion). A reduced intra-arterial dose (50 mg/m2) was used in seven calves, and no local tissue damage was evident on gross or microscopic examination. Nevertheless, resultant concentrations of bisantrene deposited in the ipsilateral bladder wall were 10- to 100-fold those concentrations found after intravenous administration of a dose 5 times higher. These animal toxicology and pharmacology data support initiation of a phase I clinical trial of directed intravascular precipitation of bisantrene in humans. This clinical trial will be developed for patients with advanced refractory cancers of the anatomic true pelvis, such as those originating in the urinary bladder, prostate, rectum, and uterine cervix.

Angiography↗

Transplantation of normal bone marrow into a pig with severe von Willebrand's disease.

Bone marrow from a normal male pig was transplanted into a related female pig with severe homozygous von Willebrand's disease (vWd). After engraftment the circulating leukocytes were of the male karyotype, and the platelets were strongly positive for von Willebrand factor (vWF) by indirect immunofluorescence. The average level of vWF was 1.96 U/dl and of ristocetin cofactor was 2.8 U/dl. The ear immersion bleeding time before transplantation was consistently more than 15 min and afterwards varied between 5 min and more than 15 min. Transfused vWF corrected the bleeding time at a level of 10 U/dl, which is lower than that required for a von Willebrand pig. We concluded that: the plasmatic compartment is only minimally replenished by the vWF from platelets and megakaryocytes; and the platelet vWF alone only partially corrects the abnormal tests of the hemostatic mechanism in severe vWd.

Animals↗

Disposable plastic diapers: a foreign body hazard.

Foreign body ingestion and aspiration in children has been a serious problem, occasionally resulting in airway obstruction and death. Airway obstruction by balloons and subsequent asphyxiation is well documented. Respiratory blockage by plastic dry-cleaning sacks has resulted in warning labels on most such materials. Two recent cases of nasal aspiration of plastic coating from a commonly used disposable diaper are compared to reports of similar occurrences documented by the U.S. Consumer Product Safety Commission. On the basis of these reports we recommend that disposable diapers be continuously covered by other clothing to prevent the child's access to the plastic. Otolaryngologists and pediatricians should be aware of the potential hazard when examining diapered children with chronic rhinorrhea or sudden respiratory distress.

Accident Prevention↗

Endothelial cell cytotoxicity of cotton bracts tannin and aqueous cotton bracts extract: tannin is the predominant cytotoxin present in aqueous cotton bracts extract.

Using an in vitro cytotoxicity assay based on the release of 51Cr from cultured porcine thoracic aortic and pulmonary arterial endothelial cells, we have demonstrated that cotton bracts tannin is a potent endothelial cell cytotoxin. It produces dose-dependent lethal injury to both types of endothelial cells with the aortic cells being somewhat more sensitive to tannin-mediated injury than the pulmonary arterial cells. Cytotoxic injury to the cells was biphasic. During the first 3 hr of exposure to tannin, no lethal injury was detected. However, during this period, profound changes in morphology were observed suggesting sublethal injury to the cells preceded the ultimate toxic damage. Comparison of the cytotoxicity dose curves for aqueous bracts extracts with those for tannin demonstrated that tannin was the major cytotoxin present in bracts.

Animals↗

Toxicity to endothelial cells mediated by cotton bract tannin. Potential contribution to the pathogenesis of byssinosis.

Byssinosis is an occupational disease of textile workers caused by exposure to the bract portion of the cotton plant in the form of mill dust. The authors established an in vitro cytotoxicity assay using 51Cr release to assess time- and dose-dependent toxicity of condensed tannin, a component of bracts, on porcine aortic and pulmonary arterial endothelial cells. Tannin produced dose-dependent toxicity to both types of endothelial cells; aortic endothelial cells were more sensitive than were endothelial cells from the pulmonary artery. Skin fibroblasts were relatively insensitive to tannin. Cytotoxicity was not immediate. Release of 51Cr was preceded by a several-hour period during which the endothelial cells underwent profound morphologic changes (as assessed by light and electron microscopy). Even brief exposure of endothelial cells to tannin produced later toxicity and morphologic changes. Condensed tannin causes time- and dose-dependent injury to endothelial cells in vitro at doses potentially achievable in vivo.

Animals↗

Aziridinylbenzoquinone in recurrent, progressive glioma of the central nervous system. A Phase II study by the Illinois Cancer Council.

Aziridinylbenzoquinone (AZQ) was studied in a Phase II protocol for persons with glioma of the central nervous system (CNS) recurrent or progressive after surgery and radiotherapy. Patients received AZQ, 30 mg/m2 intravenously every 3 weeks if previously untreated or 27.5 mg/m2 if previously exposed to cytotoxic drugs. Partial response was defined as a reduction of at least 50% reduction in the product of the two longest perpendicular diameters of the indicator lesion persisting for a minimum of 28 days. Twenty-eight patients are evaluable for response at this time. Objective response (OR) occurred in four (14.3%): two complete and two partial. Stabilization of disease (SD) was seen in 7 (25.0%). Median survival, in weeks, was greater than 46.0 for responders, 41.7 for SD, and 19.3 for those with progressive disease. The survival experiences are significantly different (P = 0.030 [Breslow]). The OR rate was 21.1% in 19 without prior chemotherapy and 0% in 9 previously treated patients. There were two AZQ-related deaths in patients with prior exposure to nitrosoureas (1 CNS hemorrhage; 1 aspiration pneumonia). One patient had an anaphylactic reaction. Three patients whose tumor initially increased in size subsequently had marked tumor shrinkage. AZQ is an active agent that must be used with added caution in patients who have received nitrosoureas. Initial tumor enlargement may precede response. Although response appears to prolong survival, the correlation between stabilization of disease and survival is not well-defined.

Adolescent↗

Complete mandibular agenesis. Report of a case.

A child had complete mandibular agenesis, with associated anomalies of microstomia, left choanal stenosis, and a cleft soft palate. This child had evidence of disruption in development at about the four-week stage by the persistence of several developmental remnants, specifically, the buccopharyngeal membrane, tongue remnants, and the laryngotracheal groove. The etiology of this condition is unclear at this time.

Abnormalities, Multiple↗

The forehead lift. A review.

Our forehead lift technique is a modification of several techniques that have evolved since Lexer first elucidated a surgical approach to diminish the signs of aging in the upper part of the face. It essentially consists of the development of a forehead advancement-rotation flap through a coronal incision to deal with ptosis, and muscle incision and excision to deal with forehead and glabellar creases. The surgical goals are achieved readily in the vast majority of cases. Morbidity is minimal, but real, and can be decreased by astute observance of the details of the surgical techniques outlined. A review of 51 cases assessed success in achieving the surgical goals and the morbidity associated with the procedure.

Aging↗