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Biomedical subjects

C Dominguez

Publications and source records attributed to C Dominguez.

At least 55 records · Page 3Linked to original sources
PubMed1992

Synthesis and biological evaluation of conformationally restricted 2-(1-pyrrolidinyl)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methylethylenediam ines as sigma receptor ligands. 1. Pyrrolidine, piperidine, homopiperidine, and tetrahydroisoquinoline classes.

The synthesis and sigma receptor affinity of a series of conformationally restricted derivatives of 2-(1-pyrrolidinyl)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methylethylenedi amine (1) is described. The pyrrolidinyl (or N,N-dialkyl),ethylenediamine,N-alkyl, and phenylethyl portions of this sigma receptor pharmacophore were restricted by its incorporation into 1,2-cyclohexanediamine-, pyrrolidine-, piperidine-, homopiperidine-, and tetrahydroisoquinoline-containing ligands. The sigma receptor binding affinities of these compounds were determined using [3H](+)-pentazocine in guinea pig brain homogenates. The synthesis of all but one class was achieved by acylation and alane reduction of the appropriate diamine precursors whose synthesis is also reported. sigma receptor affinities ranged from 1.34 nM for 6,7-dichloro-2-[2-(1-pyrrolidinyl)ethyl]tetrahydroisoquinoline (12) to 455 nM for (1R,2R)-trans-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2- (1-pyrrolidinyl)cyclohexylamine [(-)-4]. In this displacement assay, (+)-pentazocine exhibited a Ki of 3.1 nM while DTG and haloperidol showed Ki values of 27.7 and 3.7 nM, respectively. The conformationally free parent compound 1 exhibited a Ki value of 2.1 nM. Comparison of both the sigma receptor affinities and nitrogen atom geometry of the compounds revealed that a gauche relation of the nitrogen atoms of cis-1,2-cyclohexanediamines is not imperative for high affinity as we had previously thought. It is highly likely that nitrogen lone pair orientations and steric factors on the aliphatic portions of these ligands play a major role in the sigma receptor binding of this pharmacophore.

Animals↗
PubMed1992

Synthesis and receptor binding properties of fluoro- and iodo-substituted high affinity sigma receptor ligands: identification of potential PET and SPECT sigma receptor imaging agents.

Unlabeled fluoro- and iodo-substituted ligands exhibiting very high affinity and selectivity for sigma receptors were synthesized based on three different structural classes of sigma receptor ligands. These compounds were evaluated for sigma receptor affinity and specificity in order to assess their potential as PET/SPECT imaging agents. Thus, (+)- and (-)-N-(5-fluoro-1-pentyl)normetazocines [(+)- and (-)-4] based on the (+)-benzomorphan class of sigma ligands were synthesized via N-alkylation of optically pure (+)- and (-)-normetazocine with 5-[(methylsulfonyl)oxy]-1-pentyl fluoride (11). (+)- and (-)-4 displaced [3H](+)-3-PPP with Ki values of 0.29 and 73.6 nM and [3H](+)-pentazocine with Ki values of 10.5 and 38.9 nM, respectively. The second class of PET/SPECT ligands was based upon the N-(arylethyl)-N-alkyl-2-(1-pyrrolidinyl)ethylamine class of sigma ligands; N-[2-(3,4-dichlorophenyl)-1-ethyl]-N-(3-fluoro-1-propyl)-2-(1- pyrrolidinyl)ethylamine (5) was obtained via N-alkylation of N-[2-(3,4-dichlorophenyl)-1-ethyl]-2-(1-pyrrolidinyl)ethylamine (14) with 3-fluoropropyl p-toluenesulfonate. 5 exhibited Ki values of 4.22 and 5.07 nM for displacement of [3H](+)-3-PPP and [3H](+)-pentazocine, respectively, comparable with the parent N-propyl compound. Attempts to synthesize N-[2-(3,4-dichlorophenyl)-1-ethyl]-N-[3- [(methylsulfonyl)oxy]-1-propyl]-2-(1-pyrrolidinyl)ethylamine (26), a precursor to 5 that could conceivably be converted to [18F]-5 by treatment with 18F-, proved unsuccessful. The sequence of regioselective nitration, catalytic hydrogenation, and diazotization followed by NaI quench of N-[2-(3,4-dichlorophenyl)-1-ethyl]-N-methyl-2-(1- pyrrolidinyl)ethylamine (2) afforded the iodinated ethylenediamine N-[2-(2-iodo-4,5-dichlorophenyl)-1-ethyl]-N-methyl-2-(1- pyrrolidinyl)ethylamine (8), a potential SPECT ligand for sigma receptors. This compound showed an affinity of 0.54 nM ([3H](+)-3-PPP) comparable with the parent compound 2 (Ki = 0.34 nM, [3H](+)-3-PPP). Ligand 8 exhibited a similar potency against [3H](+)-pentazocine. The third class of high-affinity sigma receptor ligands was rationalized based on rearrangement of the bonds in ethylenediamine 2 to give 1-[2-(3,4-dichlorophenyl)-1-ethyl]-4-(1-propyl)piperazine (3). This compound exhibited very high affinity (Ki = 0.31 nM, [3H](+)-3-PPP) and selectivity for sigma receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

[Abdominal echography to determine the weight of the prostate].

The relationship of post-operatively determined prostatic gland weight and that calculated prior the procedure, by means of abdominal ultrasound techniques using the "ellipsoid method", has been studied in 88 patients undergoing retropubic adenectomy. The regression line was nearly optimal, Y = 0.946 X + 2.295, and the correlation coefficient between both weight measures was r = 0.915. Abdominal ultrasound examinations are a simple, quick and safe means to evaluate prostate weight, prior to deciding the type of surgery (open adenectomy or transurethral resection) for prostate adenoma.

Abdomen↗
PubMed1991

Bone marrow transplant in a case of mucopolysaccharidosis I Scheie phenotype: skin ultrastructure before and after transplantation.

An 11-year-old girl with mucopolysaccharidosis I Scheie phenotype (MPS I-S) received a bone marrow transplant (BMT) from her heterozygous HLA-identical LMC-non-reactive mother. Multidisciplinary studies were carried out and results evaluated 21 months after transplantation. Herein we report the ultrastructural findings pre- and post-BMT in skin. Multidisciplinary studies are commonly used to evaluate the benefits of metabolic correction following BMT in some MPS and other inherited metabolic disorders, and changes in morphology have been described in liver and few other tissues. In this case, we elected skin, since connective tissue is universally involved in MPS and is safely and easily obtainable. Comparison of skin biopsy specimens taken before and after BMT showed a considerable change in dermal fibroblast morphology, with marked reduction in cell size and the number and size of abnormal lysosomes, thus indicating the clearance of storage. Our results demonstrate that dermal cells respond to enzyme replacement therapy in MPS I-S, with the clearance of glycosaminoglycan lysosomal accumulation in connective tissue fibroblasts, which had near-normal morphology 21 months after BMT. Therefore, the practice of skin biopsy after BMT in MPS and other metabolic disorders in which dermal cells are involved should be encouraged.

Bone Marrow Transplantation↗
PubMed1991

Agenesis of seminal vesicles in infertile males: ultrasonic diagnosis.

We present the incidence of seminal vesicle agenesis and its association with deferens ductus agenesis in 141 males presenting with infertility. Transrectal ultrasonography was performed in every patient. Ten presented seminal vesicle agenesis (8 unilateral and 2 bilateral). Three had absence of the vas deferens on physical examination (3 of 7 with unilateral seminal vesicle agenesis and 1 of 2 with bilateral). Computed tomography confirmed the ultrasound findings. We emphasize the importance of the anomalies as a cause of infertility and the association with other genitourinary anomalies. Moreover, we state the necessity of transrectal ultrasound in the diagnosis.

Adult↗
PubMed1989

CEA in colonic adenocarcinomas and precancerous lesions. An immunohistochemical study with a novel monoclonal antibody.

Using a new anti-CEA (CB-CEA-1) murine monoclonal antibody, the expression of carcinoembryonic antigen (CEA) was studied in normal, premalignant and malignant human adult tissues with particular emphasis on colorectal mucosa. The CB-CEA-1 epitope was poorly expressed in normal adult tissues but was consistently found in colon cancers and adenomas in distinctive immunohistochemical patterns. Some apical staining was found with CB-CEA-1 in cells of normal colon mucosa whereas colon adenocarcinomas had a predominantly cytoplasmic staining pattern. Colonic adenomas presented a varied staining pattern. Some showed apical staining, others a CEA distribution pattern similar to that of adenocarcinomas, particularly those with a villous component. Our findings indicate a differential expression of CB-CEA-1 in adenoma cells in relation to their potential for malignant transformation. The possible usefulness of this Mab defined epitope for diagnostic and therapeutic purposes is indicated.

Adenocarcinoma↗
PubMed1985

Relation between arterial intimal thickening and the vasa-vasorum.

The histopathological data presented support a new concept for the origin of the cells which cause intimal thickening of arteries. Arterial segments, isolated between ligatures, when examined by intravascular contrast techniques, showed penetration of vasa-vasora and formation of intra-arterial granulation tissue which produced myointimal thickening. Transitional forms between pericytes and myointimal cells were found. In autoradiographic studies on the incorporation of 3H-thymidine, DNA synthesis was first seen in the adventitia, fundamentally in the vasa-vasora pericytes, and in the adjacent media, and later in the intimal thickening. In arterial segments between ligatures typical intimal thickening was produced when intra-arterial granulation tissue was formed and the ligatures were removed thus restoring the circulation. These results were not produced when the arterial segment was sectioned lengthways between ligatures. It is suggested that this intimal thickening originates in cells from the vasa-vasora, in particular from pericytes.

Animals↗
PubMed1984

Primary pedunculated fibrosarcoma of the peritoneum: a case report.

Fibrosarcoma is a primitive, mesenchymal tumor frequently arising from superficially located soft tissues. A case of a primary intraperitoneal, pedunculated fibrosarcoma is reported, initially presenting as an abdominal mass protruding into a large incisional hernia of the anterior abdominal wall. Despite total tumor resection, multiple intraperitoneal tumor nodules of varying sizes were found and resected six months and one year later. The patient died 18 months after the first surgical intervention. This case illustrates the highly malignant behavior and poor prognosis of fibrosarcomas of the peritoneum.

Aged↗
PubMed1982

Mechanisms of appearance of the Pasteur effect in Saccharomyces cerevisiae: inactivation of sugar transport systems.

Saccharomyces cerevisiae does not show a noticeable Pasteur effect (activation of sugar catabolism by anaerobiosis) when growing with an excess of sugar and nitrogen source, but it does do so after exhaustion of the nitrogen source in the medium (resting state). We have found that this different behavior of growing and resting S. cerevisiae seems due to differences in the contribution of respiration to catabolism under both states. Growing S. cerevisiae respired only 3 to 20% of the catabolized sugar, depending on the sugar present; the remainder was fermented. In contrast, resting S. cerevisiae respired as much as 25 to 100% of the catabolized sugar. These results suggest that a shift to anaerobiosis would have much greater energetic consequences in resting than in growing S. cerevisiae. In resting S. cerevisiae anaerobiosis would strongly decrease the formation of ATP; as a consequence, various regulatory mechanisms would switch on, producing the observed increase of the rate of glycolysis. The greater significance that respiration reached in resting cells was not due to an increase of the respiratory capacity itself, but to a loss of fermentation which turned respiration into the main catabolic pathway. The main mechanism involved in the loss of fermentation observed during nitrogen starvation was a progressive inactivation of the sugar transport systems that reduced the rate of fermentation to less than 10% of the value observed in growing cells. Inactivation of the sugar transports seems a consequence of the turnover of the sugar carriers whose apparent half-lives were 2 to 7 h.

Ammonium Chloride↗
PubMed1979

Inhibitory activity of alpha 1-antitrypsin in infants with idiopathic respiratory distress syndrome.

In two groups of neonates serum concentrations of alpha-1-antitrypsin (1-AT) were determined by means of radial immunodiffusion, and 1-AT inhibitory capacity determinations were made using benzoyl-1-arginine-p-nitroanilide as a substrate. There were 66 children in the first group of neonates with idiopathic respiratory distress syndrome (IRDS), and 82 healthy children in the second group with birth weight and gestational and post natal ages similar to those of neonates with IRDS. In the latter, 1-AT concentration and inhibitory activity levels were lower than those found in healthy children; these differences were statistically significant. These findings explain both the retardation in the lysis of the hyaline membrane and the fact that a decrease in serum 1-AT levels elicits lung tissue damage by the action of proteolytic enzymes contained in leucocytes.

Birth Weight↗
PubMed1978

Cutaneous involvement by IgD myeloma.

Multiple, firm, nontender, violaceous, cutaneous and subcutaneous nodules of the abdomen and thighs developed in a 53-year-old man with proven IgD myeloma. A biopsy specimen showed dermal infiltration by large atypical undifferentiated cells similar to those previously found on bone marrow aspiration. Despite intermittent improvement with radiotherapy and chemotherapy, the patient died and an autopsy showed multiple osteolytic lesions and massive involvement with tumors that encased the pelvic organs, infiltrated and replaced portions of the psoas muscles, infiltrated the kidneys and intestines, and replaced the bone marrow by small and intermediate-sized malignant lymphoid cells. IgD myeloma is a rare hematologic malignancy that occurs at a younger age than other forms of myeloma, has a high incidence of involvement of soft tissues, and is a particularly dedifferentiated and vicious form of myeloma.

Humans↗
PubMed1975

Natural history of pulmonary thromboemboli in dogs. Serial radiographic observation of clots labeled with powered tantalum.

Powdered tantalum was blown onto the surface of blood clots from 10 dogs. After autologous, tantalum-labeled clots were injected into a systemic vein in each dog, the dogs were sacrificed at varying times over a 5-week period. Microscopic sections showed the tantalum remained attached to the intraluminal clots throughout this period. No appreciable dispersion of label into extravascular parenchyma was observed. Serial roentgenograms demonstrated (a) initially, the labeled clots in the pulmonary arterial tree, (b) lysis of the clots, as indicated by progressive decrease in the breadth of the tantalum labels, (c) peripheral movement of the labeled clots, and (d) eventual fragmentation of the labels.

Animals↗