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Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 181 records · Page 10Linked to original sources
PubMed1988

A prospective randomized trial of alpha 2B-interferon/gamma-interferon or the combination in advanced metastatic renal cell carcinoma.

Eighty-nine patients with advanced measurable metastatic renal cell carcinoma were entered into a prospective randomized trial comparing alpha-interferon to gamma-interferon and to the combination. The trial was performed in order to confirm the activity of gamma-interferon and assess the potential clinical synergism. Response rates were 5, 10, and 5%, respectively. The low response rate may have been due to the inability to raise the doses of the interferons to higher levels. Clinical synergy at this dose, route, and schedule of administration in renal cell carcinoma does not exist.

Carcinoma, Renal Cell↗
PubMed1987

Priming of influenza mRNA transcription is inhibited in CHO cells treated with the methylation inhibitor, neplanocin A.

Chinese hamster ovary cells were pretreated with Neplanocin A, a potent inhibitor of RNA methylation. Analysis of polyadenylated RNA from treated cells by high-pressure liquid chromatography revealed marked decreases of 2'-O-methylation within mRNA cap structures and of internal N6-methyladenosine residues. In these Neplanocin A-treated cells, influenza viral mRNA accumulation was virtually abolished. Cellular RNA from Neplanocin A-treated cells was substantially less efficient than RNA from control cells in priming cell-free influenza transcription reactions. These results suggest that the observed inhibition of influenza virus replication is due at least in part to impaired recognition of undermethylated cellular mRNA cap structures by the influenza polymerase complex.

Adenosine↗
PubMed1987

Unequal distribution of N6-methyladenosine in influenza virus mRNAs.

Influenza virus mRNA is posttranscriptionally methylated at internal adenosine residues to form N6-methyladenosine (m6A). It has been previously shown that there is an average of three m6A residues per influenza virus mRNA (R. M. Krug, M. A. Morgan, and A. J. Shatkin, J. Virol. 20:45-53, 1976). To determine the distribution of m6A in the different influenza virus mRNAs, we purified six of the mRNAs by hybrid selection, digested them with nuclease, and determined their methylation patterns by high-pressure liquid chromatography. The amount of m6A in the different mRNAs varied from one in matrix to eight in hemagglutinin.

Adenosine↗
PubMed1987

Prostatic carcinoma: staging by clinical assessment, CT, and MR imaging.

The sensitivity, specificity, accuracy, and positive and negative predictive values of clinical assessment, computed tomography (CT), and magnetic resonance (MR) imaging were compared in the differentiation of stage B from stage C prostatic carcinoma. Forty-six patients who had undergone radical prostatectomy were included in the study. Surgical-pathologic staging was considered the "truth measure." Clinical staging had an accuracy of 61%, and CT, 65%. Accuracy for MR imaging depended on the instrument parameters and plane of section used. When only transverse T1-weighted images were analyzed, MR accuracy was 61%. However, when transverse T1- and T2-weighted images supplemented by additional T2-weighted coronal or sagittal images were studied, accuracy increased to 83%. At present, MR imaging is the most accurate diagnostic modality for the local staging of carcinoma of the prostate, but for optimal results, multiple sequences and two orthogonal planes of imaging are needed.

Aged↗
PubMed1986

Radiation therapy as adjuvant treatment after radical prostatectomy: patient tolerance and preliminary results.

For the last 7 years we administered therapeutic doses of radiation therapy as adjuvant treatment after radical prostatectomy in 45 patients at high risk for recurrence, that is patients with pathological stage C (seminal vesicle invasion) or stage D1a (microscopic involvement of the resected pelvic lymph nodes) disease. All of the patients have been followed for at least 2 years. Short-term and long-term complications were minimal; only 2 patients had significant sequelae that were managed satisfactorily. There has been no local recurrence after mean followups of 62 and 48 months for patients with stages C and D1a disease, respectively. The actuarial 5-year survival rate free of disease was 79 per cent for patients with stage C and 72 per cent with stage D1a cancer.

Carcinoma↗
PubMed1986

Transurethral resection of the prostate with local anesthesia in 100 patients.

We performed transurethral resections of the prostate in 100 patients under local anesthesia supplemented when appropriate by intravenous medication. In the first part of the study (40 patients) local anesthesia was infiltrated into the prostate transurethrally only, while in the second part (60 patients) infiltration was performed transurethrally and perineally. Prostate sizes ranged from 5 to 50 gm., and pain control was excellent in the majority of the patients, especially when perineal infiltration was added to the procedure. Of the patients 98 per cent said they would do it again, no patient required conversion to general anesthesia and there were no significant complications relating to the anesthesia. Local anesthesia with intravenous supplementation can be performed successfully in the majority of the patients with small to moderately sized prostate glands.

Aged↗
PubMed1986

Oral malignant melanoma (a case report and review of literature).

Oral malignant melanoma is rare and has a poor prognosis. We report a case of melanoma of the lower alveolus with rapid spread to the cervical lymph nodes and breast. Metastasis was diagnosed by fine needle aspiration cytology. The literature on oral melanoma is also reviewed.

Adult↗
PubMed1985

Surgical treatment of patients with stages I and II nonseminomatous testicular cancer.

We analyzed treatment outcomes for 98 consecutive patients who underwent retroperitoneal lymphadenectomy for nonseminomatous germ cell testicular cancer between 1972 and early 1979. There were no surgical deaths. Major and minor complications occurred in 8 and 15 patients, respectively. Of the 57 patients with pathological stage I tumors 9 (16 per cent) had recurrences and were given chemotherapy, and all 57 are well 2 or more years after completion of treatment. Of the 12 patients with stage IIA disease who received no adjuvant treatment 5 had relapse, 2 of whom died. Relapse occurred in 13 of 14 patients with stage IIB disease who received no adjuvant treatment and 2 of 4 who received adjuvant radiation. All 3 patients with stage IIC tumor who received no adjuvant treatment had relapse. In contrast, none of the 7 patients with stage II disease who received adjuvant vinblastine and bleomycin with or without cisplatin had relapse. Our long-term survival rates are 100 per cent for patients with stage I and 88 per cent with stage II disease, and all of the patients who died either were treated before the introduction of cisplatin-based chemotherapy or did not complete the treatment protocol as recommended. In experienced hands retroperitoneal lymphadenectomy with chemotherapy, either as adjuvant or as needed for patients with stage I, IIA and IIB disease, remains the most cost-effective treatment for nonseminomatous testicular cancer and has the least short-term and long-term morbidity.

Adolescent↗
PubMed1985

Stabilization of a specific nuclear mRNA precursor by thyroid hormone.

The regulation of a thyroid hormone-responsive gene in rats, designated spot 14, was explored. The expression of this gene in liver is rapidly (less than 10 min) and markedly (greater than 10-fold) altered by the administration of 3,5,3'-triiodo-L-thyronine (T3) to hypothyroid rats (P. Narayan, C. W. Liaw, and H. C. Towle, Proc. Natl. Acad. Sci. USA 81:4687-4691, 1984). To investigate the cellular site at which T3 acts to induce this hepatic mRNA, we made parallel measurements of the relative levels of spot 14 mRNA and nuclear precursor RNA and of the rate of gene transcription after treatments designed to alter the thyroid status of rats. The relative levels of both the mRNA and nuclear precursor were elevated roughly 5- to 6-fold in euthyroid animals and 9- to 12-fold in hyperthyroid animals over those in hypothyroid controls. However, only a small difference of approximately 1.5-fold was detected in the rate of spot 14 gene transcription. After a single injection of T3 into hypothyroid animals, a small and transient rise in the transcription rate was detected at 30 min. However, the levels of spot 14 mRNA and nuclear precursor RNA increased much more dramatically throughout the first 4 h of treatment. In both cases, changes in the rate of gene transcription were not capable of accounting for the alterations observed in mRNA levels. Thus, the major site of spot 14 gene regulation by T3 is at a posttranscriptional level. The proportional changes observed in the nuclear precursor and mRNA levels suggest that the site of control is at the level of stability of the nuclear precursor RNA for spot 14 mRNA.

Animals↗
PubMed1984

Rapid effects of triiodothyronine on hepatic gene expression. Hybridization analysis of tissue-specific triiodothyronine regulation of mRNAS14.

We recently reported that 3,5,3'-triiodothyronine (T3) causes a rapid increase in the translational activity of a specific mRNA (mRNAS14) coding for a protein designated "Spot 14" (Mr = 18,000; 4.9 pI) using two-dimensional gel electrophoresis of in vitro translated proteins. The current studies suggest that Spot 14 is a cytosolic protein. Using a plasmid-derived cDNAS14 and dot hybridization, we have directly measured changes in hepatic mRNAS14 levels in response to T3 and other physiologic stimuli. Following injection of hypothyroid rats with a receptor-saturating dose of T3, a 20-min lag preceded the induction of hepatic mRNAS14 to levels 16-fold above basal values within 4 h. This is the most rapid effect of T3 on hepatic gene expression documented to date. Both during time course studies in hypothyroid animals injected with T3 as well as in the intact euthyroid rat, hepatic mRNAS14 levels varied up to 3-fold over a 24-h period in a pattern consistent with circadian variation. A lipogenic diet also significantly elevated hepatic mRNAS14. Thus, T3, dietary, and the unknown factors responsible for circadian variation influence hepatic mRNAS14 expression. Blot and dot hybridization analysis indicated that mRNAS14 expression in nonhepatic tissues was significantly below euthyroid hepatic values. Responsivity of mRNAS14 in nonhepatic tissue to in vivo T3 administration was also either substantially diminished or totally absent. Thus, expression and regulation of mRNAS14 is tissue specific.

Animals↗
PubMed1984

Rapid induction of a specific nuclear mRNA precursor by thyroid hormone.

Administration of thyroid hormone to the thyroidectomized rat results in a rapid and dramatic increase in the relative amount of hepatic mRNA coding for spot 14--a translational product with an approximate Mr of 17,500 and isoelectric point of 4.9. We have now isolated a cDNA clone containing sequences homologous to this thyroid hormone-responsive mRNA. Two distinct mRNA species that differed by 200 nucleotides in length were found to be capable of hybridizing to the cDNA probe. Both mRNA species were proportionally elevated in relative concentration in rats with increasing plasma levels of thyroid hormone. The earliest change in the levels of mature mRNA occurred at 20 minutes following thyroid hormone treatment of the thyroidectomized rat. Analysis of nuclear RNA revealed a single higher molecular weight species that was homologous to spot 14 mRNA. An increase in the nuclear level of this putative precursor occurred by 10 minutes following thyroid hormone administration, a time preceding the earliest change in mature mRNA. Thus, thyroid hormone appears to act at least in part at a nuclear level in altering the cellular concentration of this mRNA species. The rapidity of this change suggests that it may reflect a direct response to the binding of thyroid hormone to its nuclear receptor.

Animals↗
PubMed1983

Understaging and undergrading of prostate cancer. Argument for postoperative radiation as adjuvant therapy.

This report reviews the staging and grading errors that occurred in a consecutive series of 14 patients treated for prostate cancer by radical prostatectomy and of 58 patients treated by both radical prostatectomy and pelvic lymphadenectomy. Almost half of the patients who were in Stages A2, B1, or B2 by clinical criteria were in pathologic Stage C when both capsular perforation and seminal vesicle invasion were used as the criteria for Stage C disease. Seminal vesicle invasion was the more important prognostic factor. Moreover, the pathologic grade of cancer, as determined by needle or transurethral biopsy, was underestimated in 39 per cent of the cases; when the grade was corrected, the patient often was in a worse prognostic group than the one originally assigned. Thus, in this series, more than 40 per cent of the patients were at high risk of persistent or recurrent disease after radical prostatectomy. Radiation was given after operation to 22 such high-risk patients and was well tolerated.

Biopsy, Needle↗
PubMed1983

Comparison of Doppler examination and retrograde spermatic venography in the diagnosis of varicocele.

The accuracy of the Doppler stethoscope is compared with that of retrograde spermatic venography in the diagnosis of varicocele in 39 subfertile men. In the 38 cases in which left-sided venography was successful, there was a good correlation between the radiographic and Doppler results in 33 cases (87%). The five failures were all false-negative results in patients without clinically diagnosed varicoceles. In the 33 cases in which right-sided venography was successful, there was a good correlation between the radiographic and Doppler results in 17 patients (52%). This low sensitivity on the right side appears to be a minor drawback, because right-sided reflux almost always occurs in conjunction with left-sided reflux, and therefore varicocele would be diagnosed in these patients despite the false-negative Doppler finding. Unlike venography, the Doppler study is noninvasive, inexpensive, and easy to perform. We conclude that it should be part of all studies of varicocele and infertility and that it may prove sufficiently accurate for use in controlled studies of the effectiveness of varicocelectomy and the role of subclinical varicocele in the pathogenesis of infertility.

Humans↗
PubMed1983

Return of fertility after treatment for nonseminomatous testicular cancer: changing concepts.

We studied the return of ejaculation in 31 patients who had undergone retroperitoneal lymphadenectomy for stage I or II nonseminomatous germ cell testicular cancer. Ejaculation returned spontaneously in 13 patients and was restored by sympathomimetic drugs in 5 of 8 patients treated. Both patients known to have tried to father a child succeeded. We also studied the effects of chemotherapy (vinblastine and bleomycin with or without cisplatin) in 34 patients, 24 of whom also had undergone retroperitoneal lymphadenectomy. Although chemotherapy profoundly depressed spermatogenesis during treatment 75 per cent of the patients tested 18 months or more after completion of treatment had some return of function, as evidenced by normal follicle-stimulating hormone levels and/or the presence of live sperm in the ejaculate. We concluded that it is possible to perform a therapeutically sound retroperitoneal lymphadenectomy for low stage nonseminomatous testicular cancer that permits return of ejaculation in many patients and that spermatogenesis recovers in a significant number of patients treated for this cancer with modern chemotherapy. Thus, traditional beliefs that operative and drug treatment of nonseminomatous testicular cancer invariably causes infertility must be revised.

Antineoplastic Agents↗
PubMed1982

Ejaculation and fertility after extended retroperitoneal lymph node dissection for testicular cancer.

We studied ejaculation and fertility in 55 men who had undergone suprahilar extended retroperitoneal lymphadenectomy for nonseminomatous testicular cancer between 1972 and 1980. Antegrade ejaculation had returned spontaneously in 25 patients, with sperm counts of 35 to 190 million per ml., and normal morphology and motility in 20. The other 5 men either refused to provide semen for analysis or had had vasectomies but all had fathered children postoperatively. Ten men in whom antegrade ejaculation had not returned spontaneously were treated wih sympathomimetic drugs. Antegrade ejaculation was induced in 5 patients, 1 of whom fathered a child while taking the drugs. Two other patients who had only small volumes of ejaculate also responded well to sympathomimetic drugs. A therapeutically sound retroperitoneal node dissection can be performed for testicular cancer without impairing fertility permanently in a significant number of patients.

Adolescent↗