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Biomedical subjects

S C Hopkins

Publications and source records attributed to S C Hopkins.

12 recordsLinked to original sources

Electric field and conformational effects of cytochrome c and solvent on cytochrome c peroxidase studied by high-resolution fluorescence spectroscopy.

Electronic spectra of mesoporphyrin-substituted yeast cytochrome c peroxidase (MP-CcP) were measured as a function of pH, ionic strength, and binding of cytochrome c (cyt c) by fluorescence line narrowing (FLN) spectroscopy at 5 K. The FLN spectra provided information about the vibrational structure of the first excited singlet state of MP-CcP, the various tautomeric forms of mesoporphyrin, and the positions and widths of their 0,0 bands. The composite 0,0 band of MP-CcP at pH 6 could be resolved into three components with peak positions at 16,046, 16,103, and 16,203 cm-1. MP-CcP at pH 8 could be analyzed using two components with peak positions at 16,048 and 16,193 cm-1. The disappearance of the 16,103-cm-1 component at alkaline pH suggests that it is due to a "chemical substate" arising from protonation of His52 in the distal side of the porphyrin. Computer simulations of the electrostatic field that CcP imposes on its porphyrin show that, in the presence of charged axial histidines His52 and His175, the electrostatic field at porphyrin nitrogens increases, especially along the normal to the heme by about 200 mV/A. Electric field effects may account for pH-dependent spectral shifts of the 0,0 positions of the resolved components, although hydrogen bonding may also affect these positions. On the other hand, the peak position of the components was not affected by ionic strength or binding of cyt c, implying that the electrostatic field of the heme pocket of MP-CcP remains unchanged. Indeed, computed changes in ionic strength of the solvent show no modification of the electrostatic field at the porphyrin. The only detectable effect of ionic strength and binding of cyt c to MP-CcP is on the relative contributions of the components, suggesting some rearrangements in the vicinity of the heme. Finally, shifts in the position of the vibrational lines for MP-CcP components indicate either that the tautomers have different vibrational frequencies due to the nonsymmetry of the porphyrin and/or that tautomers experience various distortions. Comparison of the vibrational spectrum of the first excited singlet state of mesoporphyrin in CcP and horseradish peroxidase also suggests that the heme pocket in the two peroxidases provides different steric restrictions.

Binding Sites

Postoperative complication from hemostatic clips.

Hemostatic clips were found in a patient's bladder four months after radical retropubic prostatectomy. A calculus, which had formed on one clip, caused acute urinary retention. Inadvertent enclosure of the hemoclips within the bladder intraoperatively and early intraurethral migration of the hemoclips are possible causes of this complication. Although this problem is rarely reported, hemoclips should be used sparingly, if at all, around the vesicourethral anastomosis.

Aged

The stability and antitumor activity of recycled (intravesical) mitomycin C.

Although intravesical mitomycin C (MMC) is effective in the treatment of superficial bladder cancer, its expense is a major factor limiting its use. These authors have analyzed the antitumor activity and stability of MMC following 2-hour intravesical instillation in consideration of recycling the drug or using a smaller dose over a longer retention time. The first voided urine samples from 11 patients who received 40 mg MMC intravesically were measured for MMC content by high performance liquid chromatography (HPLC). An average of 50% of the parent drug was recovered. MMC from the urine samples inhibited the growth of a transplantable murine transitional cell carcinoma as effectively as stock drug. Moreover, MMC is relatively stable in human urine at body temperature. These findings suggest that recovery and reuse of the intravesically administered drug is possible and if sterility and appropriate concentrations can be established for the initial and subsequent doses, the drug may be able to be recycled.

Animals

Total and nondialyzable hydroxyproline excretion in Stage D2 prostate cancer.

Hydroxyproline is excreted in urine as a breakdown product of normal bone turnover: A dialyzable (D) fraction (90% of total) reflects active bone destruction and a nondialyzable (ND) fraction reflects bone growth/regrowth. In metastatic prostate cancer where blastic osseous metastases predominate, disease progression on bone scan correlated with elevation of both total hydroxyproline excretion (7.84 + 1.28, P less than 0.001) and the ND urinary level (0.94 +/- 0.20, P less than 0.01). In patients with a serially stable/improving scan, urinary excretion of each fraction (2.18 + 0.27 and 0.27 +/- 0.01) was similar to that of men with no evidence of disease. For Stage D2 prostate cancer, these two markers satisfactorily monitor osseous activity in the intervals between serial bone scintigraphy.

Adenocarcinoma

Primary carcinoma of male urethra.

Carcinoma of the male urethra is infrequent. To date approximately 600 cases have been reported. We reviewed 16 cases of carcinoma of the male urethra seen at the University of Tennessee and the Memphis Veterans Administration Hospital. The mean patient age was sixty-three years (range 38 to 84). The most common presentation was a palpable mass followed by symptoms of urinary obstruction. Five urethral carcinomas arose distal to the suspensory ligament of the penis while 11 were of bulbar or bulbomembranous origin. The histology was squamous cell carcinoma in 8 patients (50%), mixed squamous and transitional cell carcinoma in 5 (31%), transitional cell carcinoma in 2 (13%), and adenocarcinoma in 1 (6%). The mean patient survival was fifteen months following diagnosis of a proximal urethral tumor and seventy-seven months for tumors arising distally. Neoplasms of the distal urethra can be surgically managed successfully even if regional lymph nodes are involved. The prognosis for proximal urethra tumors remains poor and is best treated by a combination of surgery and radiotherapy.

Adenocarcinoma

Invasive bladder cancer: support for screening.

Of 297 patients with bladder cancer treated between 1975 and 1981, 90 (30 per cent) had histologic documentation of muscle invasion, 82 of whom (91 per cent) had invasion into the muscle at the time of presentation. Of these 82 patients 51 (62 per cent) had tumor localized to the bladder after clinical staging. Of 36 patients undergoing radical cystectomy 9 (25 per cent) had microscopic pelvic lymph node involvement. Nine patients underwent urinary diversion alone and 31 presented with perivesical or pelvic nodal tumor extension, or distant metastases. Only 8 of the 90 patients (9 per cent) had prior superficial bladder cancer. The mean survival for patients with stage B to C disease at diagnosis was 23 months and for those with stage D tumor it was 11 months. This experience indicates that the majority of patients with advanced bladder cancer are not identified at a stage when definitive therapy offers an excellent prognosis. More resources must be devoted to earlier detection.

Adult

Serial spot hydroxyproline/creatinine ratios in metastatic prostatic cancer.

Analysis of urinary hydroxyproline levels offers a marker to monitor osseous involvement in patients with metastatic malignancies. Such a marker is needed in patients with prostatic cancer when bone metastases predominate. Thirty-two men with stage D2 prostatic cancer were monitored by bone scan, acid and alkaline phosphatase values, and urinary hydroxyproline, beginning from 4 to 36 months after initiation of hormonal manipulation and/or systemic chemotherapy. In patients with disease progression determined by bone scan serial urinary hydroxyproline values progressively increased and were significantly elevated compared to urinary values obtained from patients with a stable or improving scan (p less than 0.001). Simultaneous alkaline phosphatase determinations showed less significant differences between patient groups. Acid phosphatase did not reliably indicate osseous response to therapy. These data suggest that urinary hydroxyproline values are predictive as an early objective sign of osseous response in patients receiving therapy for stage D2 prostatic cancer.

Acid Phosphatase

Carcinoma of the female urethra: reassessment of modes of therapy.

Of 15 women with primary urethral carcinoma 2 had tumors confined to the urethra and were managed successfully by an operation. Of the 9 patients with tumor extending to the surrounding structures 6 (67 per cent) died of complications related to inadequate control of the primary tumor. The last 4 patients had stage D1 disease or greater at initial diagnosis and died of distant metastases. Our current approach for patients with locally advanced disease is combined brachytherapy and operation in an effort to eradicate the primary tumor, since morbidity and mortality result from failure to control the local tumor.

Adenocarcinoma

Total, dialyzable, and nondialyzable postabsorptive hydroxyproline. Values in patients with cancer.

The postabsorptive urinary total (T), dialyzable (D), and nondialyzable (ND) hydroxyproline (HYPRO) tests were evaluated to determine whether the patterns of excretion varied according to the predominance of osteoblastic v osteolytic bone involvement in 58 patients with neoplastic disease. In patients with osteolytic lesions from multiple myeloma, elevated T and D levels with normal ND HYPRO values were observed, along with elevated D/ND ratios. In prostate cancer, the T, D, and ND values were all elevated and the D/ND ratio was normal. Patients with Hodgkin's disease had elevated T, D, and ND HYPRO levels, and the D/ND ratio was in the range of patients with prostate cancer. The data suggest that these collagen markers may be useful in the long-term evaluation of these neoplasms in patients.

Bone Neoplasms