Biomedical subjects
Publications and source records attributed to R E Reid.
Cytosol androgen receptor content of transitional cell bladder cancer tissue was found to be substantially higher than its content in normal bladder mucosa and lower than in control benign prostatic hypertrophy tissue. Tumors arising in female patients had a lower androgen receptor content than those arising in male patients. High-grade tumors had a lower androgen receptor content than low-grade tumors.
Intraoperative profilometry measurements were done on 28 patients during various types of urethropexy to determine whether useful information could be provided to the operating surgeon. Successful Burch, Marshall-Marchetti and Stamey-Pereyra procedures resulted in a 50 per cent increase in urethral length. Closure pressure increases were noted only with the Stamey-Pereyra procedure (plus 49 per cent). Intraoperative profilometry measurements were considered to be informative and useful, particularly during the Stamey-Pereyra urethropexy in which case suture ties could be regulated to provide desired urethral elongation and closure pressure changes.
Unilateral partial ureteral obstruction was induced in 32 dogs followed by total ileal replacement of the obstructed ureter. The morphologic and functional effects on the kidney using a freely refluxing versus a nonrefluxing ileovesical anastomosis were compared, as well as the effect of total tapering of the reimplanted ileal segment. The tapered ileovesical anastomosis proved more reliable for prevention of reflux than the nontapered technique. Reflux prevention does not appear necessary for maintaining renal morphology and function when bladder function is normal and the observation period short. Total tapering of the ileal segment did not prove to be advantageous in protecting against hyperchloremic acidosis in this short-term canine study.
The pressure characteristics and cinefluoroscopic appearances of a refluxing, nonrefluxing, and totally tapered ileal " neoureter " were compared in 22 dogs with normal bladder function. The totally tapered ileal segment with a reflux preventing ileovesicostomy simulates normal ureteral peristalsis most closely on cinefluoroscopic evaluation. Pressure gradients across the ileovesical junction though were similar in refluxing and nonrefluxing ileovesicostomies , as well as in totally tapered ureters.
To evaluate the role of the anterior urethra in the male in micturition dynamics, 9 patients with urethral strictures who were undergoing a two-stage Turner-Warwick urethroplasty were evaluated with flow and pressure flow measurements, pre- and post-second-stage urethroplasty. Any decrease in flow or increase in resistance after closure would suggest an anterior "urethral effect." None was found, indicating that the anterior urethra in the male functions as an inert conduit.
The records of 196 patients with transitional cell carcinoma of the bladder diagnosed up to 1975 were analyzed for age, sex, tumor histology, and survival parameters. Analysis of the series as a whole showed it to be comparable to literature controls in the male to female ratio, average age at presentation, and in survival data. Sex stratification combined with parametric analysis showed that females had longer recurrence-free survivals and died less frequently of bladder cancer than their male counterparts. In addition, the incidence of high-grade tumors was lower in females. These facts and the comments that follow point to a probable less aggressive natural history of transitional cell carcinoma of the bladder in females.
Demonstration of major tranquillizer binding to bovine brain calmodulin and a fragment of the natural protein as well as a synthetic analog of a single calcium binding site in calmodulin has led to the hypothesis that the drug binding site is located in one or both of two possible linear amino acid sequences in the natural protein. The sequences are approximately ten residues in length and both consist of a calcium sensitive alpha-helical segment of the protein which is characterized by a hydrophobic region and an acidic hydrophilic region separated by one half turn of the alpha-helix. The protein hydrophobic region contains two aromatic phenylalanine residues which are oriented by the alpha-helix in such a way as to overlap the II orbitals of the aromatic groups in the major tranquillizers thus explaining the preference of the binding site for phenothiazine like structures. The hydrophilic region of the protein's drug binding site consists of two and possibly three acid residues which are postulated to interact with the basic center in the side chain of the major tranquillizers.
The effects of nine drugs on the CD spectra of a synthetic calcium binding analog of site III of rabbit skeletal troponin C, can generally be divided into 3 groups: (1) that consisting of haloperidol, benperidol, molindone and promethazine, had no effect on the CD spectrum or calcium sensitivity of the apopeptide; (2) that composed of structurally rigid thioxanthenes, induced CD-detectable structural change in the apopeptide but prevented Ca2+-induced structural change; (3) that consisting of chlorpromazine, trifluoperazine and fluphenazine, induced structural change in the peptide but had no effect on the Ca2+-induced structural change.
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Three peptide analogs of the helix-loop-helix Ca2+ binding unit, 21-, 26-, and 34-residues in length, similar in sequence to rabbit skeletal troponin C site III have been prepared by the solid-phase method. The CD spectra of the 21-residue fragment indicated very little secondary structure in aqueous medium in the absence of Ca2+. Addition of Ca2+ increased the secondary structure of the peptide but the KCa was very weak, 3.1 x 10(2) M-1. The same peptide in hydrophobic medium in the absence of Ca2+ had considerable secondary structure and the KCa value increased considerably, 3.5 x 10(5) M-1. The 26-residue peptide, containing 5 more residues on the NH2 terminus of the 21-residue peptide, showed slightly more secondary structure in aqueous medium in the absence of Ca2+. Addition of Ca2+ to this peptide raised the amount of secondary structure in the metal ion-peptide complex and resulted in a higher KCa value, 3.8 x 10(4) M-1. By assuming that the COOH-terminal region of the 26-residue peptide-metal ion complex assumes a structure similar to that of the 21-residue peptide-metal ion complex, one is able to assign the increase in structure to the NH2-terminal side of the Ca2+-binding loop. Hydrophobic medium further increased the secondary structure of this peptide and also increased the KCa value to 4.5 x 10(5) M-1, a value similar to that obtained for the 21-residue peptide. The 34-residue peptide contained a further 8 amino acid residues on the NH2 terminus of the 26-residue peptide. This peptide had considerable secondary structure in aqueous medium which increased in the presence of Ca2+. The peptide has a reasonable affinity for Ca2+ in aqueous medium, KCa = 2.6 x 10(5) M-1. Again, a hydrophobic medium increased both the amount of secondary structure and the Ca2+ affinity constant, KCa = 9.2 x 10(5) M-1. A model of Ca2+-induced folding of the three peptides under different conditions is described and results obtained from this model are used to describe Ca2+ binding to the four Ca2+ binding units in rabbit skeletal troponin C.
A 43-residue peptide analog of tropomyosin Ac-AB4C-OH (A = Lys-Cys-Ala-Glu-Leu-Glu-Gly, B = Lys-Leu-Glu-Ala-Leu-Glu-Gly, C = Lys-Leu-Glu-Ala-Leu-Glu-Gly-Lys) was synthesized. The 86-residue disulfide-linked dimer was prepared by air oxidation of the single cysteine residue in the NH2-terminal Fragment A of the 43-residue peptide to provide a two-stranded alpha-helical coiled-coil of defined molecular weight with the chains in-register and parallel. The physical properties of the 86-residue dimer were determined and compared to CM-tropomyosin and sequential polyheptapeptides. The stabilizing effect of the disulfide bridge in the synthetic dimer was indicated by the shift in the transition of the thermal unfolding profile (t 1/2) of +6.5 degrees C from 72.5 degrees C for the reduced sample to 79 degrees C for the oxidized sample. The 86-residue disulfide-linked dimer maintains 65% of the original helicity at 65 degrees C, and the polyheptapeptide [Leu-Glu-Serr-Leu-Glu-Ser-Lys]n of 9,500 daltons in denaturant maintains 75% helicity at 65 degrees C, whereas CM-tropomyosin is completely denatured at this temperature. These results show a shift in the transition of the thermal unfolding profile (t 1/2) of greater than 39 degrees C for the above two synthetic peptides relative to CM-tropomyosin. The polyheptapeptide [Leu-Glu-Ser-Leu-Glu-Ser-Lys]n maintains 95% of the original helicity in 3 M urea, whereas 50% remains in CM-tropomyosin. Comparison of the CD spectra of three polyheptapeptides, [Leu-Glu-Ser-Leu-Glu-Ser-Lys]n, [Ala-Glu-Ser-Leu-Glu-Ser-Lys]n, and [Ala-Glu-Ser-Ala-Glu-Ser-Lys]n showed that the ellipticities increased as the size of the hydrophobic side chains increased in the positions responsible for the formation and stabilization of the coiled-coil. That substituting residues in the outer positions of the coiled-coil can affect alpha-helix stabilization is shown by comparing the CD spectra of three polymers [Leu-Glu-Ser-Leu-Glu-Ser-Lys]n, [Leu-Glu-Ser(Ac)-Leu-Glu-Ser(Ac)-Lys]n, and [Leu-Glu-Ala-Leu-Glu-Ala-Lys]n.
A simplified ileovesical anastomosis is herein described. It prevents vesicoileal reflux and allows for unimpeded efflux of urine into the bladder. The technique involves implanting 3 inches of distal ileum into a denuded muscular bed in the bladder. Vesical mucosa grows over the ileum creating an effective valvular mechanism. Experimental work done on the canine bladder and the use of this technique in 2 patients is described.
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A 21-residue peptide analog of the Ca2+ binding Site 3 in rabbit skeletal troponin C has been synthesized by the solid phase method. CD studies as well as uv difference spectroscopy did not show any changes upon addition of Ca2+ to this peptide in aqueous solution. Acetylation of the NH2-terminal residue of the analog resulted in Ca2+-induced CD and uv difference spectral changes and these changes could be accentuated upon increasing the hydrophobicity of the solvent system. It was also found that the nonacetylated peptide showed Ca2+-induced changes in CD and uv difference spectroscopy when the studies were carried out in the hydrophobic solvent system. These results indicate that the complete helix-loop-helix unit is not required for Ca2+ binding to the loop region of the unit and that synthetic analogs can be prepared to determine the molecular requirements of the unit for metal ion affinity and selectivity. We describe the folding of this peptide about a calcium cation based on these preliminary results.
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During a 2-year period continent vesicostomy has been attempted in 17 adults and a continent stoma has been achieved in all but 4 patients. Operative morbidity is low and there has been no operative mortality. Definition of precise indications and contraindications must await further experience but this operative procedure seems to be a useful alternative in the management of neurogenic bladder and incontinence.