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J Santos

Publications and source records attributed to J Santos.

At least 109 records · Page 6Linked to original sources
PubMed1996

The recombinant alpha isoform of protein kinase CK1 from Xenopus laevis can phosphorylate tyrosine in synthetic substrates.

The cDNA coding for protein kinase CK1 alpha has been cloned from a Xenopus laevis cDNA library. The derived amino acid sequence of the protein contains 337 amino acids and has a calculated molecular mass of 38874 Da. The sequence is identical to that of the human CK1 alpha and to the bovine CK1 alpha, except that it is 12 amino acids longer than the latter protein. Southern blotting with a 264-bp probe demonstrates that four or more fragments are obtained upon digestion of genomic DNA with EcoR1 and Hind3, suggesting that X. laevis possesses a family of related CK1 genes. CK1 alpha was expressed in Escherichia coli as a glutathione transferase fusion protein (GT-CK1 alpha) and certain of its characteristics were determined. The recombinant GT-CK1 alpha fusion protein was found to have apparent Km values for ATP (12 microM), casein (1.5 mg/ml) and the specific peptide substrate RRKDLHDDEEDEAMSITA (180 microM) which are similar to those of the rat liver CK1 enzyme. The recombinant CK1 alpha activity is weakly inhibited by heparin, but strongly inhibited by poly(Glu80:Tyr20). This inhibition is competitive and shows an approximate K1 of 5 microM. CK1 alpha can phosphorylate the tyrosine residues of poly(Glu80:Tyr20) and the tyrosine residue in the synthetic peptide RRREEEYEEEE. This kinase preparation also autophosphorylates in serine, threonine and weakly in tyrosine.

Amino Acid Sequence↗
PubMed1996

Allelic losses on chromosome 4 suggest the existence of a candidate tumor suppressor gene region of about 0.6 cM in gamma-radiation-induced mouse primary thymic lymphomas.

Mouse chromosome 4 was investigated to assess the involvement of tumor suppressor genes in primary thymic lymphomas induced by gamma-irradiation. PCR analysis using microsatellite DNA polymorphic markers was performed in F1 animals generated from a cross between the strains C57BL/6J and RF/J. Microsatellite markers were selected with focus on chromosome 4 around the region containing the interferon alpha gene cluster (D4Mit17, D4Wsm1, D4Mit9, and D4Mit205 and a more distal region (D4Mit12, D4Mit54, and D4Mit13). Allelic losses were detected in 21/47 (44.7%) gamma-radiation-induced thymic lymphomas. Analysis of markers located on six other chromosomes as well as on the proximal region of chromosome 4 illustrates the specificity of the occurrences of LOH appearing on the former markers. This analysis clearly suggests the existence of a candidate tumor suppressor gene region on mouse chromosome 4 of about 0.6 cM between the markers D4Wsm1 and D4Mit9 (TLSR1, Thymic Lymphoma Suppressor Region 1). In addition, another more distal region centered at the marker D4Mit54 could be also exist (TLSR2). In most tumors, allelic losses on these chromosome regions involved the paternal RF/J allele (19 of 20).

Alleles↗
PubMed1996

Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats.

BACKGROUND & AIMS: Intestinal mast cell activity is modulated by the central nervous system, but the mechanisms are not well established. The aim of this study was to investigate whether cerebral thyrotropin-releasing hormone (TRH) activates intestinal mast cells and to elucidate the mechanisms involved, specifically, the contribution of mast cells to vagally stimulated luminal protein release. METHODS: In anesthetized rats, mast cell activation was assessed by measuring the release of the specific mucosal rat mast cell protease II (RMCP II) and prostaglandin (PG) D2 into the intestinal lumen. Luminal protein release was measured as an index of epithelial permeability to macromolecules. RESULTS: Intracisternal injection of the TRH analogue RX 77368 (30 ng) induced a transient increase in intestinal release of RMCP II and PGD2 that was abolished by dox-antrazole. RX 77368-stimulated RMCP II release was also abolished by vagotomy and reduced by atropine by 65%. However, both systemic capsaicin and indo-methacin enhanced RMCP II release. RX 77368-stimulated luminal protein release was abolished by vagotomy and reduced by doxantrazole. CONCLUSIONS: Central vagal activation by TRH stimulates intestinal mast cell secretion, in part via peripheral muscarinic receptors, and is modulated by PGs and capsaicin-sensitive afferent innervation. Intestinal mast cell activation contributes to the TRH analogue-stimulated luminal protein release.

Animals↗
PubMed1995

Familial cosegregation of manic-depressive illness and a form of hereditary cerebellar ataxia.

We report on a Spanish family with cooccurrence of manic-depression and a form of hereditary cerebellar ataxia. All affected individuals in the second generation showed cerebellar ataxia and manic-depression simultaneously. Since anticipation has been described in both disorders and the pattern of segregation may be autosomal as well as X-linked, we have searched for a possible involvement of two candidate genes which are located either on an autosome (SCA1) or on the X-chromosome (GABRA3). We concluded that expansion of trinucleotide repeats at SCA1 gene cannot be considered as a disease-causing mutation, and this gene should be initially discarded.

Adolescent↗
PubMed1995

Association between hepatitis C virus seroreactivity and HIV infection in non-intravenous drug abusing prostitutes.

Two hundred and ninety-four non-transfused prostitutes from Spain, who denied intravenous drug abuse, were tested for hepatitis C virus (HCV) antibodies. Seventeen (5.78%) of them were seropositive. Both in univariate and correspondence analyses, serological results for hepatitis C were associated with the HIV-1 serostatus (p < 0.001), number of sex partners (p < 0.05) and a history of genital ulcers (p < 0.05). In logistic regression analysis, hepatitis C seropositivity was associated only with HIV-1 infection (adjusted odds ratio = 13.6; 95% confidence interval = 3.3-55.2). These results show that hepatitis C seropositivity is associated with HIV-1 infection in female non-intravenous drug abusing prostitutes. These findings are also consistent with the hypothesis that HCV can be sexually transmitted with low efficiency.

Adult↗
PubMed1995

Incidence and recurrence rates of colorectal adenomas: a prospective study.

BACKGROUND/AIMS: The frequency of colorectal adenomas, the precursor lesions for most cases of colorectal carcinoma, has been generally measured as prevalence rates of adenomas at autopsy or colonoscopy. The aim of this study was to estimate the incidence rate of adenomas and compare it with the adenoma recurrence rate. METHODS: Data on colonoscopies performed in three New York City practices were collected prospectively. The cumulative rate of adenoma diagnosis on repeat colonoscopy was calculated for patients with no abnormalities on index colonoscopy ("incidence" rate) and for patients with adenomas on the index colonoscopy ("recurrence" rate). RESULTS: The cumulative incidence rate of adenomas at 36 months was 16%, and the cumulative recurrence rate at 36 months was 42% (P < 0.004). The recurrence rate was higher in patients with multiple adenomas than in those with a single adenoma on index colonoscopy, although the increase was not statistically significant. CONCLUSIONS: Although the recurrence rate has always been assumed to be elevated, this study is the first to compare the recurrence rate of adenomas with the incidence rate directly and to show that the recurrence rate is indeed elevated.

Adenoma↗
PubMed1995

Efficacy of intravenous cyclosporine for steroid refractory attacks of ulcerative colitis.

The use of cyclosporine in refractory ulcerative colitis (UC) is still controversial. An 8-year-long retrospective review open-label treatment with intravenous cyclosporine in 21 patients with steroid-refractory UC is therefore in order. Intravenous cyclosporine, 5 mg/kg-1 day, was added to ongoing drug therapy. Those who responded were switched to oral cyclosporine for a mean 8.4-month period, and steroids were discontinued when possible. Sixteen out of 21 patients improved (76%). Mean latency time to onset of improvement was 9 days. Five did not improve: three underwent urgent surgery, one was switched to methotrexate, and the remainder died. While on oral cyclosporine, 10 out of 16 maintained remission and seven could discontinue steroids, five relapsed, and one went on continuous mild activity. One patient died of a Pneumocystis carinii pneumonia, while in remission. Five reversible episodes of hepatobiliary toxicity were recorded. Intravenous cyclosporine effectively and rapidly induces improvement of acute steroid-refractory flare-ups of UC and helps to prevent urgent surgery. However, major adverse events may limit its usefulness.

Adolescent↗
PubMed1995

Ameloblastic fibroma: report of two cases.

The ameloblastic fibroma is an odontogenic tumour with an unusual presentation. It is considered to have both epithelial and mesenchymal elements, but it lacks any calcified dental structures. Two new cases are presented. The first of these began as a mandibular tumour whereas the second was discovered by chance. The radiographic finding in each case was a unilocular cystic radiolucency. Treatment consisted of excisional biopsy by enucleation in both patients. Histopathological findings were consistent with ameloblastic fibroma.

Child↗
PubMed1995

A weak association between TH and DRD2 genes and bipolar affective disorder in a Spanish sample.

Genetic factors play an important role in the aetiology of bipolar affective disorder (BP). So far, results of linkage studies have been largely disappointing. We have searched for a possible association between polymorphic DNA markers of two candidate genes (tyrosine hydroxylase, TH; dopamine D2 receptor gene, DRD2) and BP in a population from central Spain. Our results are consistent with the existence of a weak association between these two genes and BP, in such a way that TH and DRD2 could be considered as minor genes contributing to susceptibility.

Adult↗
PubMed1995

Role of vagal and splanchnic capsaicin-sensitive afferents in enterogastric inhibition of acid secretion in rats.

The role of capsaicin-sensitive afferent innervation and neural pathways involved in the enterogastric inhibition of gastric acid secretion by luminal acid was investigated in urethan-anesthetized rats. Intestinal perfusion with graded concentrations of HCl (50, 75, and 100 mM) for 1 h dose dependently inhibited both thyrotropin-releasing hormone (TRH) analogue- and pentagastrin-stimulated acid output (P < 0.01). The inhibitory effect of intestinal perfusion with HCl (100 mM) on pentagastrin-stimulated acid secretion was blocked by bilateral vagotomy, whereas celiac ganglionectomy had no effect. Systemic capsaicin pretreatment (125 mg/kg sc) reduced the antisecretory effects of luminal acid on both TRH analogue- and pentagastrin-stimulated acid secretion. Neither selective perivagal nor selective periceliac capsaicin treatments (1% solution) modified the antisecretory effect of intestinal perfusion with HCl (75 mM) on TRH analogue-stimulated acid secretion. However, combined selective perivagal plus periceliac capsaicin treatment reduced it to the same extent as systemic capsaicin treatment. We conclude that enterogastric inhibition of acid secretion by luminal acid in urethan-anesthetized rats is mediated by extrinsic reflexes involving both vagal and splanchnic capsaicin-sensitive afferent fibers.

Animals↗
PubMed1995

Central vagal activation by an analogue of TRH stimulates gastric nitric oxide release in rats.

In the stomach nitric oxide (NO) appears to be involved in vagally induced cholinergic vasodilation and nonadrenergic, noncholinergic relaxation of the fundus. We investigated whether central vagal activation by intracisternal injection of a thyrotropin-releasing hormone (TRH) analogue stimulates gastric NO release in anesthetized rats. To quantitate gastric NO production, the luminal release of NO breakdown products, nitrite (NO2-) and nitrate (NO3-), were measured by the Griess method. Intracisternal injection of RX-77368 (30-300 ng) dose dependently stimulated gastric NO2- and NO3- release (P < 0.05) along with a significant acid secretory response (P < 0.05). The specific inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (10 mg/kg ip), completely blocked gastric luminal NO2- and NO3- release without affecting the acid secretory response to the highest dose of RX-77368. Either bilateral cervical vagotomy, hexamethonium (15 mg/kg ip), or atropine (1 mg/kg ip) abolished both gastric luminal release of NO-derived metabolites and the acid secretory responses to RX-77368. These results indicate that intracisternal injection of RX-77368 stimulates gastric release of NO through vagal nicotinic pathways and peripheral activation of muscarinic receptors. These findings provide evidence for central nervous system regulation of NO-mediated functions in the rat stomach through TRH-sensitive vagal pathways.

Amino Acid Oxidoreductases↗
PubMed1995

Molecular and cytological evidence of S-adenosyl-L-homocysteine as an innocuous undermethylating agent in vivo.

Undermethylating agents are frequently used in the study of DNA methylation. However, the drugs of choice to induce experimental DNA undermethylation, 5-azacytidine and 5-aza-2'-deoxycytidine, are known to be cytotoxic. We report on S-adenosyl-L-homocysteine (SAH) as an alternative agent for inducing undermethylation of human DNA in vivo. The molecular and cytological evidence presented in this paper clearly suggests that SAH could be even more efficient than the cytidine analogs; in addition, SAH does not exhibit the secondary toxic effects that cripple the usefulness of cytidine analogs.

Base Sequence↗
PubMed1995

Eight new polymorphic microsatellites in mouse gene loci.

Eight mouse gene loci (Atp1b2, Epo, Kit, Krt2, Mor1, Ren1, Pdgfb, and Wnt1) that contain unidentified microsatellites were selected to detect simple sequence-length polymorphisms on genomic DNAs from two laboratory strains (C57BL/6J and RF/J) and strains recently derived from the Mus musculus species complex (CAST/Ei, MOLF/Ei, CZECH II, and M. m. domesticus) and from M. spretus (SPRET/Ei). All microsatellite DNA sequences varied in size among some of the seven mouse strains tested. These new polymorphisms might be useful in the search for tumor suppressor genes involved in specific cancers.

Animals↗
PubMed1995

[Estrogen and progestagen treatment in digestive hemorrhage caused by vascular malformations].

The efficacy of an association of estrogens and progestagens in the treatment of gastrointestinal bleeding by angiodysplasia was analyzed. Thirty-three patients with gastrointestinal bleeding due to vascular malformations were admitted from January 1986 to December 1993. Fifteen of the 33 patients were submitted to surgical or endoscopic treatment. The remaining 18 patients underwent daily oral treatment with a combination of estrogens-progestagens containing 2.5 mg of lynestrenol and 0.075 mg of mestranol. One patient presented a venous thrombosis leading to suppression of treatment at one month of initiation. The 17 remaining patients were treated for a mean of 22 +/- 4 months (range: 3-60). During treatment 13 of the 17 patients (76%) did not present evidence of hemorrhage. Likewise, the number of hemorrhagic episodes per year decreased from 4.4 +/- 1.2 prior to treatment to 0.7 +/- 0.5 during treatment (p < 0.05) with transfusional requirements decreasing from 7.9 +/- 2.8 erythrocyte concentrates per year prior to treatment to 1.2 +/- 1.0 during treatment (p < 0.05). In conclusion, the combined treatment with estrogens and progestagens prevents recurrence of gastrointestinal bleeding by angiodysplasia.

Aged↗
PubMed1995

Eosinophilic gastroenteritis presenting as ascites and splenomegaly.

A 25-year-old man with a 1 year history of episodic abdominal pain presented with splenomegaly, eosinophilic ascites and peripheral eosinophilia. Full-thickness biopsies from his gastrointestinal tract revealed intense eosinophilic infiltration involving both muscular and serosal layers and extending from his stomach to his ileum. When given oral steroids, the patient's condition improved and he was discharged without symptoms. Eighteen months later, he remains asymptomatic and without recurrence of ascites or splenomegaly. This report adds to the scarce data on extraintestinal involvement in eosinophilic gastroenteritis. Special attention is drawn to the differential diagnosis of eosinophilic ascites and to the optimal approach to its management.

Adult↗
PubMed1994

[Cardiac tamponade and Kaposi's sarcoma].

The case of a 31 year-old intravenous drug addict female patient with infection by the human immunodeficiency virus who had recurrent cardiac tamponade and who was diagnosed by pericardic biopsy as Kaposi's sarcoma is reported. The patient demonstrated involvement by cutaneous, mucosal, lymph node and probably pleuropulmonary Kaposi's sarcoma. Thoracic radiography, computerized tomography and echocardiography only showed the presence of pericardic effusion. Neither did the pericardic fluid obtained by pericardiocentesis provide any significant ethiologic data. Only the pericardic biopsy showed the typical lesions of Kaposi's sarcoma in this localization confirming diagnosis. This is the first case of pericardic Kaposi's sarcoma described in an alive patient and the difficulties of achieving the diagnosis of the cardiac involvement by Kaposi's sarcoma in AIDS patients are commented upon.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Increased risk of lung cancer after breast cancer radiation therapy in cigarette smokers.

BACKGROUND: Ionizing radiation is a lung carcinogen in a variety of settings, including after breast cancer radiation therapy. The authors explored whether cigarette smoking and breast cancer radiation therapy have a multiplicative effect on the risk of subsequent lung cancer. METHODS: This case-control study investigated women registered with primary breast cancer in the Connecticut Tumor Registry who developed a second malignancy between 1986 and 1989. Those diagnosed with a subsequent primary lung cancer were compared with those diagnosed with a subsequent nonsmoking, nonradiation-related second malignancy, and age-adjusted odds ratios were calculated with logistic regression. RESULTS: No radiation effects were observed within 10 years of initial primary breast cancer. Among both smokers and nonsmokers diagnosed with second primary cancers more than 10 years after an initial primary breast cancer, radiation therapy was associated with a 3-fold increased risk of lung cancer. A multiplicative effect was observed, with women exposed to both cigarette smoking and breast cancer radiation therapy having a relative risk of 32.7 (95% confidence interval [CI], 6.9-154). The radiation carcinogenic effect was observed only for the ipsilateral lung and not for the contralateral lung both in smokers and nonsmokers. CONCLUSIONS: Breast cancer radiation therapy, as delivered before 1980, increased the risk of lung cancer after ten years in nonsmokers, and a multiplicative effect was observed in smokers. For both smokers and nonsmokers, this effect was observed only for the ipsilateral lung and not the contralateral lung. Modern techniques, however, significantly decrease the radiation dose to the lungs, which may decrease the risk of lung cancer. Nonetheless, due to the available choices in early-stage breast cancer treatment, current practices may need to be revised for young breast cancer patients who smoke.

Breast Neoplasms↗