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Biomedical subjects

C Santos

Publications and source records attributed to C Santos.

At least 19 recordsLinked to original sources

Stable binding of the eukaryotic acidic phosphoproteins to the ribosome is not an absolute requirement for in vivo protein synthesis.

The genes encoding the four acidic ribosomal phosphoproteins have been inactivated in Saccharomyces cerevisae by recombination with truncated genes carrying different genetic markers. By crossing single haploid disruptants, strains harboring two simultaneously inactivated acidic protein genes were constructed. None of the six possible double disruptions was lethal, but the simultaneous inactivation of either YP1 alpha and YP1 beta(L44') or YP2 alpha(L44) and YP2 beta(L45) caused an important decrease in the cell growth rate. Ribosomes isolated from these slow-growing strains did not contain acidic proteins, not even the two polypeptides whose genes were still intact, although these proteins were present in the cell extracts and they seem to be able to form high-molecular weight protein complexes. Transformation of a slow-growing double transformant with a plasmid containing one of the disrupted genes restored the presence of the acidic proteins in the ribosomes and normal growth rates. The particles of the slow-growing strains were active in an in vitro amino acid polymerizing system, although their activity could be stimulated by the exogenous addition of the missing proteins. These results indicate that in the absence of either YP1 alpha and YP1 beta(L44') or YP2 alpha (L44) and YP2 beta(L45), the remaining acidic proteins are unable to interact with the ribosome in a stable manner, but that a strong interaction of these ribosomal components with the particle is not an absolute requirement for in vivo and in vitro protein synthesis.

Blotting, Southern

Leukonychia due to cytostatic agents.

Chromonychia induced by antineoplastic agents has been known for several years. The most frequent of these is melanonychia, either diffuse or in tranverse or longitudinal bands, that may co-exist with diffuse pigmentation of the skin. Although any cytostatic agent may be involved in melanonychia, this condition appears most commonly after treatment with adriamycin and cyclophosphamide or in polychemotherapy. Leukonychia, either true or apparent, seems to be less frequent and is the reason for our reporting two patients with this colour change.

Adult

Identification of human papillomavirus type 16 in primary and recurrent cervical cancer following radiation therapy.

Formalin-fixed, paraffin-embedded tissue blocks from 13 women with cervical carcinoma that recurred following radiation therapy were evaluated for the presence of human papillomavirus (HPV) by in situ hybridization using ribonucleic acid 35S-labeled probes for HPV types 6, 11, 16, and 18. Ten of thirteen patients also had pretreatment biopsies from their primary tumors available for analysis. HPV 16 was detected in both primary and recurrent lesions in 4 women. In 1 case, HPV was detected in the primary tumor and not in the recurrence. HPV 16 was also present in three recurrent cancers from which primary lesions were not available for probing. Radiation therapy did not alter the hybridization signal strength or pattern, suggesting that the HPV genome copy number was not significantly affected. The persistence of HPV 16 in recurrent cervical carcinoma is consistent with the theory that HPV plays a role in maintaining the malignant state.

Adult

[Trials of acute treatment with SMS 201-995 in acromegalics].

The results of two acute treatment tests using SMS 201-995 (SMS), over a 24 hour period in acromegalic patients are presented. Test number 1: Seventeen cases with a mean age of 44.3 +/- 11.9 (21/71) years with an evolution of 9.2 +/- 6.5 (2/20) years and GH of 30.1 +/- 21.1 (5.2/96.4) ng/ml were treated with 50 micrograms/8 hours (8, 16, and 24 hours) of subcutaneous SMS. Test number 2: 26 cases with a mean age of 45.5 +/- 15.5 (21/71) years with an evolution of 9.1 +/- 7.9 (2/35) years and GH of 28.6 +/- 22.2 (5.2/96.4) ng/ml were treated with 100 micrograms/8 hours (8, 16, and 24 hours) of subcutaneous SMS. Ten point GH profile in 24 hours is evaluated in both tests and in number 2 insulin and blood sugar levels are measured at the same time points. In both tests GH is significantly reduced being the 100 micrograms/8 hour treatment schedule more efficient. The results in the decrease of GH in test number two are related to those obtained using SMS in prolonged treatments. Inspire of the reducing effect that SMS has on insulin levels, its influence on the blood sugar profile is scare.

Acromegaly

[Results of trans-sphenoidal surgery for the treatment of acromegaly].

UNLABELLED: During the past 17 years (1972-89) 55 transsphenoidal surgery (TSS) interventions were performed in our Hospital in 53 cases of acromagaly (2 cases underwent surgery twice). RESULTS: 22 were cured (40%); 15 partial efficacy (27%) and 18 negative efficacy (33%). Mean GH values (ngr/ml) before surgery were: Cured cases 15.8 + 12.9 (p = 0.0015). Basal GH values above 40 ngr/ml obscure the prognosis of TSS in acromegaly. Cure was perfectly achieved in smaller size hypophysis adenomas (Hardy Grade land 11 in CT scan). The complications in the early post-surgery were rare and transient. Chronic sequelae due to TSS occurred in 7 cases (13.5%), as complete or partial anterior hypophysis failure. TSS is the treatment of choice of acromegaly in our environment, however a significant number of cases do not achieve cure and need to complete treatment with hypophyseal radiotherapy.

Acromegaly

[Treatment of macroprolactinomas with delayed bromocriptine. Effectiveness of a single intramuscular injection].

The aim of the present study was to evaluate the effectiveness and tolerance of a new pharmaceutical preparation of long acting bromocryptine (bromocryptine depot of L.A.), characterized by the slow release of bromocryptine during 4 or 6 weeks after a deep intramuscular injection. It was administered to 9 patients with macroprolactinoma, 7 of which had visual abnormalities. The tolerance of the drug was excellent, and only one patient had nausea within the first 24 hours. In all cases, PRL values fell between 40% and 97%. All patients with visual abnormalities, including 2 patients with cranial nerve palsy (IIIth and VIIth pairs) returned to normal or improved. In the CT controls carried out after 4 weeks of therapy a reduction in tumor size was observed in 7 of 9 patients. Two patients were operated through the transesphenoidal route, PRL being demonstrated in the immunohistochemical study of the resected specimen. Subsequently, all patients received oral bromocryptine therapy with perfect tolerance. The results show that parenteral long acting bromocryptine is an effective, well tolerated and convenient way to start the therapy of macroprolactinoma, even when severe visual abnormalities are present.

Adolescent

Disruption of single-copy genes encoding acidic ribosomal proteins in Saccharomyces cerevisiae.

Using the cloned genes coding for the ribosomal acidic proteins L44 and L45, constructions were made which deleted part of the coding sequence and inserted a DNA fragment at that site carrying either the URA3 or HIS3 gene. By gene disruption techniques with linearized DNA from these constructions, strains of Saccharomyces cerevisiae were obtained which lacked a functional gene for either protein L44 or protein L45. The disrupted genes in the transformants were characterized by Southern blots. The absence of the proteins was verified by electrofocusing and immunological techniques, but a compensating increase of the other acidic ribosomal proteins was not detected. The mutant lacking L44 grew at a rate identical to the parental strain in complex as well as in minimal medium. The L45-disrupted strain also grew well in both media but at a slower rate than the parental culture. A diploid strain was obtained by crossing both transformants, and by tetrad analysis it was shown that the double transformant lacking both genes is not viable. These results indicated that proteins L44 and L45 are independently dispensable for cell growth and that the ribosome is functional in the absence of either of them.

Blotting, Southern

Size changes of a growth hormone- and prolactin-producing adenoma during and after sandostatin treatment.

A 46-year-old woman with acromegaly and marked hyperprolactinemia was treated chronically with sandostatin (50 micrograms b.i.d. up to 100 micrograms t.i.d.). Plasma growth hormone (GH) was reduced by 90% of basal values and prolactin (PRL) dropped from initially 204 to 74 ng/ml. Serial CAT scans detected a volume reduction of the pituitary adenoma of 46.7%, but discontinuation of therapy was followed by re-expansion of the tumor. Tissue collected at transsphenoidal adenomectomy was examined by immunohistology and found positive for both GH and PRL. This characteristic would explain the dual hormonal response to the specific GH inhibitor sandostatin.

Adenoma

Yohimbine reduces morphine tolerance in guinea-pig ileum.

Opiates are known to inhibit electrically-evoked twitches of longitudinal muscle-myenteric plexus strips from guinea-pig ileum. When this preparation was incubated with morphine for 1 h tolerance developed to the inhibitory effect, since dose-response curves were shifted to the right. In the present study, the effects of alpha-2 adrenergic agents on the tolerance induced by morphine in this preparation was investigated. Addition of yohimbine 10 microM (but not 0.1 or 1 microM) to the incubating medium reduced the magnitude of opiate tolerance. This effect did not appear in the presence of the alpha-2 agonists clonidine or guanfacine (10 microM). Our results provide evidence of the longitudinal muscle-myenteric plexus as a useful model for the study of the relationship between morphine tolerance and alpha-2 adrenergic mechanisms.

Animals

Peripheral adrenergic stimulation and indomethacin in experimental ocular shedding of HSV.

The application of 6-hydroxydopamine to the cornea by iontophoresis, followed by topical epinephrine, effectively induces herpes simplex virus (HSV) shedding from the external eye of latently infected rabbits. In this study the beta adrenergic blocker, Timolol, reduced virus shedding when applied immediately before the epinephrine, but continued administration resulted in increased viral shedding. While indomethacin, a prostaglandin synthesis inhibitor decreased HSV replication in cell culture, it failed to decrease virus shedding when applied topically to the eye in adrenergically stimulated animals. Timolol may act then by its effect on the peripheral cells of the eye rather than by stimulation of virus production in ganglionic neurons. These same animals were subsequently tested for latent infection of the trigeminal and superior cervical ganglia and corneas 14 months after primary infection. Only 2 of 14 animals had virus in the trigeminal ganglia, a finding which suggests that latent virus may be depleted by repeated reactivations. Virus was recovered from corneas of five rabbits by co-cultivation so it is possible that corneal latency occurs in this rabbit model as it does in humans.

Animals

Human papillomavirus deoxyribonucleic acid in cervical carcinoma from primary and metastatic sites.

Tissue from 13 cervical cancers and pelvic or para-aortic lymph nodes from the same patient were evaluated by deoxyribonucleic acid hybridization with a human papillomavirus type 16 deoxyribonucleic acid probe for the presence of human papillomavirus-related deoxyribonucleic acid sequences. Twelve of the primary malignancies were squamous cancers and one was an adenocarcinoma. Eight of the primary tumors contained human papillomavirus type 16 deoxyribonucleic acid sequences, and five contained viral sequences closely related to human papillomavirus type 16. Histopathologic diagnosis confirmed malignant cells in six of 13 lymph nodes; three of these specimens contained human papillomavirus type 16 sequences while three had human papillomavirus type 16-related sequences. One lymph node that failed to show malignant cells also contained human papillomavirus type 16 deoxyribonucleic acid. The remaining lymph nodes did not contain malignant cells by either histologic examination or deoxyribonucleic acid hybridization. The human papillomavirus deoxyribonucleic acid sequences in the lymph nodes were similar to those in the matched primary cancer in all cases. These data provide further evidence implicating human papillomavirus in the etiology of cervical cancer.

Adenocarcinoma