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Biomedical subjects

P K Reddy

Publications and source records attributed to P K Reddy.

At least 19 recordsLinked to original sources

Ratio of cathepsin B to stefin A identifies heterogeneity within Gleason histologic scores for human prostate cancer.

BACKGROUND: Cathepsin B (CB), a lysosomal cysteine protease, is involved in degradation of extracellular matrix proteins and progression of tumor cells from one biological compartment to another in many solid organ cancers, including prostate cancer. Our objective was to identify patterns of distribution of CB and its endogenous cellular inhibitor stefin A in cryostat sections of frozen BPH and prostate cancer tissue samples and to define these patterns in relation to Gleason histologic scores, clinical stages, and serum total PSA levels. METHODS: We localized CB and stefin A in the same sections using polyclonal and monoclonal antibody immunoglobulin G (IgGs) against CB and stefin A using immunofluorescence and confocal microscopic techniques. Only cryostat sections of frozen prostates were used in localizations of CB and stefin A. RESULTS: Benign prostatic hyperplasia (BPH) showed similar localization patterns for CB and stefin A and a ratio of 1 was indicated by CB = stefin A. Confocal studies indicated that most CB and stefin A sites in BPH glandular cells overlapped as shown by the yellow fluorescence of their co-localization. We found considerable variability in individual localization of CB and stefin A within and between Gleason histologic scores for prostate cancers. This variability was also found in Gleason score 6 tumors that are otherwise considered similar histologically and morphologically. Negative control sections did not show localization of CB by FITC, stefin A by Cy3 or yellow fluorescence for co-localization. Our analysis of the ratio of CB to stefin A showed three patterns, namely CB = stefin A, CB > stefin A, and CB < stefin A, within each Gleason score evaluated by us. Confocal microscopy showed more sites of yellow fluorescence when the ratio was CB = stefin A than those found in CB > stefin A or CB < stefin A. Statistical analyses showed prostate cancer cases with ratios of CB > stefin A (P < 0.05) and CB < stefin A (P < 0.05) significantly different from normal prostate and BPH which had ratios of CB = stefin A. Regression analysis did not show any specific relationship between the ratio of CB to stefin A and Gleason scores, clinical stages, and serum total prostate specific antigen (PSA) levels in prostate cancers. Analysis of our data indicates that the homeostatic balance between the enzyme and inhibitor was altered even in Gleason histologic score 6 tumors that are usually considered histologically similar by glandular differentiation. CONCLUSIONS: We have shown that prostate cancer is a heterogeneous tumor within each Gleason histological score regardless of the progression indicated by lower to higher Gleason score tumors. The ratio of CB > stefin A would indicate a preponderance of enzyme that would favor degradation of extracellular matrix proteins and progression of tumor cells in biological compartments. These tumors are expected to be aggressive prostate cancers. In contrast, prostate tumors showing ratios of CB < stefin A and CB = stefin A are expected to be less aggressive prostate cancers. This is the first report to define heterogeneity within any Gleason score for prostate cancers by the ratios of CB to stefin A.

Aged↗

Eosinophilic granuloma of spine in adults: a case report and review of literature.

A rare case of eosinophilic granuloma in an adult is reported. Eosinophilic granuloma (EG) is a lesion observed more frequently in adults. CT and MRI showed a lytic lesion of the T11 vertebral body. A transpedicular excisional biopsy of the lesion revealed EG. Spinal EG in adults is rare and differs from the childhood disease by the spinal level involvement. Vertebra plana, a condition of spondylitis in which the body of the vertebra is reduced to a sclerotic disc, is not a roentgenographic feature in the 14 cases reported in literature. It should be included in the differential diagnosis of the solitary lytic lesion of vertebrae in adults.

Eosinophilic Granuloma↗

Synovial chondromatosis of the temporomandibular joint with intracranial extension.

We present a rare case of synovial chondromatosis of the left temporomandibular joint with intracranial extension and review the relevant literature. This is the sixth published report of such a skull base tumour. We discuss imaging characteristics and the differential diagnosis with regards to a curative surgical resection.

Chondromatosis, Synovial↗

Effect of 17beta-estradiol on the expression of somatostatin genes in rainbow trout (Oncorhynchus mykiss).

In the present study, the effects of 17beta-estradiol (E(2)) treatment on the expression of preprosomatostatin (PPSS) I, PPSS II', and PPSS II" mRNA in the hypothalamus and endocrine pancreas (Brockmann body), as well as the effects of E(2) treatment on plasma somatostatin (SS)-14 and -25 concentrations in sexually immature rainbow trout (Oncorhynchus mykiss), were investigated. E(2) treatment significantly (P < 0.001) depressed both plasma SS-14 and SS-25. In the hypothalamus, E(2) treatment significantly (P < 0.001) decreased the levels of PPSS I and PPSS II" mRNA. However, there was no effect of E(2) treatment on PPSS II' mRNA levels. In the pancreas, E(2) treatment had no significant effect on the levels of either PPSS II' mRNA or PPSS II" mRNA. However, E(2) treatment significantly (P < 0.005) decreased levels of PPSS I mRNA. These data suggest that E(2) acts, in part, to increase plasma growth hormone levels in rainbow trout by decreasing the endogenous inhibitory somatostatinergic tone by inhibiting plasma levels of both SS-14 and SS-25 and hypothalamic levels of mRNA encoding these proteins.

Animals↗

Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy.

Cathepsin B (CB) is involved in invasion and metastasis of a variety of solid organ tumors, including human prostate cancer. The tertiary structures of the proenzyme and mature forms of CB are related closely, as revealed by crystallographic studies. However, the cellular distributions of the CB forms have not been defined in human prostate and its tumors. Our objective was to investigate the distribution and codistribution of CB and procathepsin B (proCB) in human prostate tumors. Human prostate tissue samples that were obtained from 21 prostatectomy and/or cystectomy patients were collected immediately after surgery and processed for this study. We used a rabbit antihuman liver CB immunoglobulin G (IgG) that recognizes both mature CB and proCB and a mouse antipropeptide monoclonal antibody IgG that recognizes only proCB. Fluorescein isothiocyanate (FITC)-conjugated donkey antirabbit IgG and indocarbocyanine (Cy3; rhodamine)-conjugated donkey antimouse IgG were used to differentiate localization of the enzyme forms. Immunofluorescence of FITC and Cy3 was examined in prostate sections by using epifluorescence and confocal laser-scanning microscopy. Because fluorescence is dependent on section thickness, time needed for study and photography, and the antigenic sites of proCB and mature CB localized by antibodies and by fluorescent markers (Cy3 vs. FITC), the cellular distributions and the relative intensity of fluorescence on cryostat sections were assessed qualitatively. Immunofluorescence of Cy3 for localizing proCB and of FITC for localizing mature CB were observed in prostatic epithelial cells and their tumors and in stromal connective tissue cells. By using confocal microscopy, colocalization of the enzyme forms in the same cells was indicated by yellow fluorescence. In stromal cells (such as smooth muscles, fibroblast, and macrophages), the distribution of proCB and relative fluorescence intensity was moderate to predominant in human prostate and its tumors. In neoplastic prostate, the cellular distributions of CB ranged from low to predominant levels. In some neoplastic glands, Cy3 fluorescence for proCB was absent, whereas the mature form of CB localized in cancer cells and in the subjacent extracellular matrix. Confocal microscopy showed a close association of CB with extracellular matrix surrounding neoplastic acini and invasive cells, indicating that the enzyme form was probably involved in degradation of the matrix proteins. The negative control study showed no specific immunofluorescence for proCB or CB in prostate cancer cases. We have shown a differential distribution of proenzyme and mature forms of CB in normal prostate, benign prostatic hyperplasia, and neoplastic prostate. The enzyme forms were assessed by determining the cellular distributions of CB and proCB. Our study indicates that the differential distribution of proCB and CB might provide clues into aggressiveness of prostate cancers within Gleason grades. However, we emphasize that our observation should be evaluated in a larger series of prostate samples before a definitive conclusion can be reached. This is the first report to show codistribution of proenzyme and mature forms of CB by using confocal microscopy.

Animals↗

Technique of removal of an impacted sharp object in a penetrating head injury using the lever principle.

Penetrating head injuries can be difficult to manage as the extensive surgery which may be required can result in severe morbidity and mortality in some patients. A conservative surgical approach with a "pull and see" policy was adopted successfully in a described case. Extraction can be achieved by using the mechanical advantage of the lever principle. By this method while removing the object any movements of sharp edges which will cause secondary damage can be reduced to a minimum.

Brain Injuries↗

Bladder stone causing renal failure.

We describe a 62-year-old man with a large bladder calculus causing bilateral ureteral obstruction. Diagnosis was delayed despite the patient's history of recurrent urinary infections. This case report illustrates the importance of radiological evaluation of patients presenting with recurrent urinary infections. To our knowledge, only three previous reports of bladder stone causing renal failure have been published.

Diagnosis, Differential↗

Delayed/salvage radiation therapy in patients with elevated prostate specific antigen levels after radical prostatectomy. A long term follow-up.

BACKGROUND: In this article the authors report an analysis and long term results of delayed/salvage radiation therapy administered to asymptomatic patients who had an elevated prostate specific antigen (PSA) level, many months to many years after radical prostatectomy. METHODS: During 1987 to 1990, 40 asymptomatic patients were found to have an elevated PSA level 9 to 96 months after radical prostatectomy. The patients underwent transrectal needle aspiration biopsy of the urethrovesicle junction anastomosis (uvj); 28 patients had a positive biopsy and 12 patients had a negative biopsy. Delayed/salvage radiation therapy was administered to the pelvis (45 Gray [Gy]) and prostate bed (59.5 Gy), including the uvj. RESULTS: Twenty-four of 37 patients (65%) were free of clinical disease. In 10 patients (27%), the radiation therapy resulted in a durable decrease in the elevated PSA level below a detectable level for a minimum 5-year follow-up. Five patients were alive with clinical disease. Eight died of disease. Three patients were lost to follow-up. CONCLUSIONS: This experience shows that delayed/salvage radiation therapy to the pelvis (45 Gy) and prostate bed (59.5 Gy), even many years after radical prostatectomy for pathologic stage pB, pC, and pD1 carcinoma of the prostate, was well tolerated and provided freedom from clinical disease in 24 of 37 patients (65%), and a decrease in elevated PSA level in 10 patients (27%). Delayed/salvage radiation therapy appears to be beneficial for patients who had undergone radical prostatectomy only and then developed rising PSA levels during the follow-up period.

Anastomosis, Surgical↗

Retrograde ureteral intussusception: a rare complication.

A 45-year-old man with a history of cyclophosphamide exposure underwent repeated ureteroscopy for positive urine cytology findings after resection of a Grade 2 papillary transitional-cell carcinoma of the bladder. Despite careful technique, an intussusception developed in the left ureter, which was repaired by resection and construction of a Boari flap. To our knowledge, this is the first report of retrograde ureteral intussusception caused by ureteroscopy.

Carcinoma, Transitional Cell↗

Report of a multicenter clinical evaluation of the Dura-II penile prosthesis.

PURPOSE: Information was collected during the first 2 years of an ongoing, prospective, multi-institutional evaluation of the Dura-II penile prosthesis. Evaluation included data on clinical outcomes and a patient satisfaction survey, and will continue for 5 years after implantation for each patient. MATERIALS AND METHODS: To date 196 patients have been evaluated. Surgical data, adverse events and information from satisfaction surveys are reported. RESULTS: At a followup of 13.4 +/- 8.4 months postoperatively, adverse events occurred in 8.2% of the patients, resulting in reoperation in 5.1%. There have been no mechanical failures. Overall satisfaction rates were 85% at 3 months, 83% at 1 year and 91% at 2 years after implantation, and levels of sexual functioning were correspondingly high. A majority of patients assigned high scores to rigidity, concealability, ability to have intercourse and erection size, although satisfaction with erection size ranked lower than the other measures. CONCLUSIONS: The Dura-II penile prosthesis provides a satisfactory result and has an acceptable level of complications associated with its use. Further followup will assess temporal changes in satisfaction rates and sexual functioning for these patients.

Adult↗

Cyclophosphamide associated bladder cancer--a highly aggressive disease: analysis of 12 cases.

PURPOSE: We gained knowledge of the etiology, treatment and prevention of cyclophosphamide associated urothelial cancer. MATERIALS AND METHODS: The medical records of 6 men and 6 women (mean age 55 years) with cyclophosphamide associated bladder cancer were reviewed. RESULTS: All tumors were grade 3 or 4 transitional cell carcinoma. Of the 5 patients initially treated with endoscopic resection alone only 1 is alive without disease. Of the 6 patients who underwent early cystectomy 4 were alive at 24 to 111 months. The remaining patient with extensive cancer underwent partial cystectomy for palliation and died 3 months later. CONCLUSIONS: Cyclophosphamide associated bladder tumor is an aggressive disease. However, long-term survival is possible when radical cystectomy is performed for bladder tumors with any sign of invasion and for recurrent high grade disease, even when noninvasive.

Adult↗

Immunohistochemical localization of cathepsin B in neoplastic human prostate.

Cathepsin B (CB) has been shown to degrade extracellular matrix (ECM) proteins, and has been reported to be involved in invasion and metastasis of several types of solid organ tumors in human and animals, but CB has not been studied in human prostate cancer (CAP). Our objective was to determine the CB protein immunostaining pattern in CAP and to correlate the immunostaining with the degree of malignancy as reflected in the Gleason grading system. We used two types of CB antibodies (namely, monospecific, polyclonal antibodies to human liver CB prepared in rabbits, and polyclonal antibody produced in sheep) to establish CB localization patterns in neoplastic prostate. Our analysis showed a heterogeneous CB immunostaining pattern in the neoplastic human prostate. CB immunostaining occurred in many, but not all, of the neoplastic columnar/cuboidal cells of acini and isolated cells, i.e., in small ragged glands and clusters (groups) of invasive cells in the prostatic stroma. We have shown that, in general, there was a positive correlation of the intensity of CB immunostaining with the Gleason histologic score (or Gleason grade sum) tumors, i.e., from the lowest scores through score 8, but many of the tumors with scores 9 and 10 showed little CB immunostaining. Our study indicated that the increased CB immunostaining in the Gleason grade sum 5-8 tumors may be associated with increased degradation of ECM, but not in 9 and 10 despite the fact that the latter tumors are more malignant clinically. In well-differentiated tumors, fewer CB immunostaining cells were present than the moderately-differentiated tumors. In other words, most of the stromal invasion of the prostatic ECM occurred in tumors of Gleason grade sums 5-8. We suggest that CB immunostaining might be a useful method to assess stromal invasion of prostatic carcinoma, especially in the higher grade tumors.

Animals↗

Laparoscopic pelvic lymph node dissection, laparoscopically assisted seminal vesicle mobilization, and total perineal prostatectomy versus radical retropubic prostatectomy for prostate cancer.

OBJECTIVES: The outcomes of patients with prostate cancer who were candidates for radical prostatectomy were compared with patients who underwent either: (1) radical retropubic prostatectomy (RRP); or (2) laparoscopic pelvic lymph node dissection, laparoscopically assisted seminal vesicle mobilization, and total perineal prostatectomy (LN-SV-TPP). METHODS: The staging, surgical, and early postoperative characteristics of 10 consecutive patients treated by RRP were compared with 12 consecutive patients who underwent LN-SV-TPP. RESULTS: Patients who underwent LN-SV-TPP versus RRP had respective median blood loss of 450 versus 1250 cc (P = 0.001), median anesthesia time of 330 versus 287.5 minutes (P = 0.05), median surgical time of 237.5 versus 237.5 minutes (P = 0.6), median units transfused of 0 versus 1 (P = 0.05), median time to ambulation of 1 versus 2 days (P = 0.002), median time to oral intake of 1 versus 3.5 days (P < 0.001), median hospital stay of 3 versus 6 days (P < 0.001), and median morphine requirements of 44 versus 119 mg (P < 0.001). CONCLUSIONS: LN-SV-TPP is less morbid than RRP concerning blood loss, blood transfusions, pain, and postoperative recovery. Compared with LN-SV-TPP, RRP is faster and is particularly indicated for ease of performing a nerve-sparing radical prostatectomy.

Aged↗

Paradoxical progression of tuberculous lesions during chemotherapy of central nervous system tuberculosis. Report of four cases.

The peculiar phenomenon of paradoxical progression during the treatment of central nervous system tuberculosis is discussed. A few cases with this phenomenon were reported in the past, and the authors have treated four such cases. During the treatment for tuberculous meningitis, the four patients developed new lesions, mainly in the form of tuberculomas, which progressed for some time and later regressed. In all these cases the initial drug regimen was not changed, except for the addition of steroids for a short period at the time of deterioration. All four patients underwent ventriculoperitoneal shunt insertion during the course of treatment. The authors discuss the significance of the changes in the lesions and management of such cases, and review the literature.

Adolescent↗

The effects of cortisol on hepatocyte metabolism in rainbow trout: a study using the steroid analogue RU486.

The objective of this study was to examine if RU486, a corticosteroid antagonist, modified hepatocyte metabolism and blocked the metabolic effects of exogenously administered cortisol in rainbow trout (Oncorhynchus mykiss). The fish were given a single intraperitoneal implant of either coconut oil alone or coconut oil containing RU486 (100 mg.kg-1), cortisol (100 mg.kg-1), or a combination of RU486 and cortisol and were sampled 7 days postimplantation. The RU486 implants had no effect on plasma cortisol and glucose concentrations, hepatocyte glycogen content, and total glucose production, but increased in vitro hepatocyte glycogen breakdown. Cortisol implantation had no effect on plasma glucose concentration, hepatocyte glycogen content, glycogen breakdown, or total glucose production, while it significantly increased alanine oxidation and gluconeogenesis in rainbow trout hepatocytes. Hepatocyte responsiveness to epinephrine and glucagon stimulation of total glucose production was not modified by either RU486 or cortisol treatment, whereas the insulin response on total glucose production was decreased with cortisol. RU486 treatment modified hepatocyte glycogen metabolism and blocked the cortisol-induced increases in alanine gluconeogenesis and glycogen mobilization for endogenous use by the hepatocytes. These results indicate that cortisol enhances the metabolic potential of hepatocytes, thereby adapting the fish to cope with stress. This study provides further validation of RU486 as a tool for studying metabolic actions of cortisol in fish.

Alanine↗