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Biomedical subjects

R Mendoza

Publications and source records attributed to R Mendoza.

At least 37 records · Page 2Linked to original sources

Unexpected familial recurrence of iris coloboma. A delayed mutation mechanism?

Typical isolated ocular coloboma is a congenital abnormality caused by a defective closure of the embryonic fissure of the optic cup. Although an irregular autosomal dominant mechanism of inheritance has been proposed, there is some evidence of other modes of transmission and etiologies. This report shows an unexpected recurrence of iris coloboma, occurring in three sibships of the same family, that could be explained by a "delayed mutation" or "premutation" mechanism.

Child↗

E1 recognition sequences in the bovine papillomavirus type 1 origin of DNA replication: interaction between half sites of the inverted repeats.

The E1 protein encoded by bovine papillomavirus type 1 (BPV-1) is required for viral DNA replication, and it binds site specifically to an A/T-rich palindromic sequence within the viral origin of replication. The protein is targeted to this site through cooperative interactions and binding with the virus-encoded E2 protein. To explore the nature of the E1 binding site, we inserted a series of homologous DNA linkers at the center of dyad symmetry within the E1 recognition palindrome. The effects of these modifications indicated that the E1 recognition palindrome can be separated into functional half sites. The series of insertions manifest a phasing relationship with respect to the wild-type BPV-1 genome in that greater biological activity was measured when full integral turns of the DNA helix separated the palindrome than when the separations were half-turns. This phasing pattern of activity was observed to occur in a variety of biological phenotypes, including transformation efficiency, stable plasmid copy number in cell lines established from pooled foci, and transient replication of full-length viral genomes. For replication reporter constructs where E1 and E2 are supplied in trans by the respective expression vectors, distance between the half sites seems to play a major role, yet the phasing relationships are measurable. DNase I protection studies showed that E1 bound very poorly to the construct containing a 5-bp linker, and binding was close to the wild-type level for the 10-bp insertion, consistent with a requirement for a phasing function between half sites with a modulus of 10 bp. Binding to the 15- and 20-bp insertion mutants was weak, but only for the 20-bp insertions was protection over both halves of the palindrome measurable. As it had been previously reported that the 18-bp palindrome contains sufficient nucleotide sequence information for E1 binding, we speculate that a minimal E1 recognition motif is presented in each half site. A comparison between this sequence and that of an upstream region that also binds E1 (the E2RE1 region) revealed a common pentanucleotide motif of APyAAPy. Mutants with substitutions of the ATAAT elements within E2RE1 failed to bind E1 protein. We present models for how repeats of the pentanucleotide sequence may coordinate E1 binding at the dyad symmetry axis of the origin and compare the DNA sequence organization of BPV-1 with those of the simian virus 40 and polyomaviruses at their origins of DNA replication.

Base Sequence↗

The effects of imidazole on pulmonary damage induced by bleomycin.

Bleomycin may produce diffuse pulmonary damage. Our objective was to evaluate the effect of imidazole, a thromboxane-synthetase inhibitor, on pulmonary damage induced by endotracheal instillation of bleomycin in rats. Bleomycin 1 U/100 g body weight produced diffuse pulmonary damage and increased number of inflammatory cells after 3 days, hemorrhage and focal fibrosis after 7 days, and diffuse fibrosis and pneumocyte hyperplasia after 14 to 30 days. Imidazole 5 mg/100 g body weight, given intraperitoneally 30 min before bleomycin, decreased the 3rd day lesions without altering the histopathology in subsequent periods. Imidazole reduced (p < 0.05) the increases in cell number (3rd and 14th days) as well as in proteins in bronchoalveolar lavage (3rd day), without modifying the increase in phospholipids observed in rats treated with bleomycin. We conclude that imidazole decreases initial bleomycin-induced pulmonary damage, but it does not interfere with fibrosis and late development of epithelial hyperplasia.

Animals↗

Prospective evaluation of emergency department medical clearance.

STUDY OBJECTIVE: To analyze a standardized medical evaluation of alert, adult emergency department patients with new psychiatric symptoms. DESIGN: Prospective, descriptive case series. SETTING: Urban, county hospital. PARTICIPANTS: One hundred consecutive, alert patients, aged 16 to 65 years, seen over 9 months, with new psychiatric symptoms. Excluded patients included those with obvious alcohol or drug intoxication, psychiatric patients with previously diagnosed abnormal behavior, psychiatric patients with medical complaints, and overdose or suicide patients. INTERVENTIONS: The following evaluation was performed: medical history, physical examination, complete blood count, SMA-7 (electrolytes, blood urea nitrogen, creatinine, and glucose), prothrombin time, calcium, oxygen saturation, creatine phosphokinase (CPK) if there was possible myoglobulinuria, alcohol level, urine drug screen (for cocaine, amphetamine, and phencyclidine), cranial computed tomography, lumbar puncture if febrile, and psychiatric evaluation when appropriate. Results were considered significant when they diagnosed the cause of the symptoms or resulted in medical admission. RESULTS: Sixty-three of the 100 patients had an organic etiology of their symptoms. The medical history was significant in 27, physical examination in 6, CBC in 5, SMA-7 in 10, CPK in 6, alcohol and drug screen in 28, computed tomography scan in 8, and lumbar puncture in 3. CONCLUSION: Most alert, adult patients with new psychiatric symptoms have an organic etiology. We recommend performing a medical history, physical examination, SMA-7, calcium, CPK if there is possible myoglobinuria, alcohol and drug screens, computed tomography scan, and lumbar puncture as part of the medical clearance of these patients.

Adolescent↗

Emergency room evaluation of cocaine-associated neuropsychiatric disorders.

The widespread abuse of cocaine has produced an alarming number of cocaine-related emergency room visits in the last several years. The authors discuss the various issues involved in emergency rom evaluation of patients who abuse cocaine and manifest signs and symptoms suggesting neuropsychiatric disease. Appropriate triage is emphasized, and a discussion of impediments to the accurate assessment of these patients ensues. The unique features of cocaine-induced mood, psychotic, and organic disorders are then detailed and contrasted with other functional and organic disorders. Strategies for the emergency room treatment of patients exhibiting symptomatology consistent with cocaine intoxication and withdrawal are outlined. The issues of psychiatric comorbidity and dual diagnosis in the cocaine-abusing population are examined. In addition, the neurological complications associated with the use of cocaine are reviewed. Finally, emerging data from single photon emission computerized tomography (SPECT) analysis of cocaine abusers is reported.

Brain Damage, Chronic↗

Rhabdoid tumor of the skin.

A tumor in the skin of a 42-year-old man was analyzed by light and electron microscopic study and immunohistochemistry. The tumor cells were large and contained eosinophilic, periodic acid-Schiff (PAS)-positive inclusions in the cytoplasm. Immunohistochemically, the neoplasm was positive for intermediate filaments, cytokeratin, vimentin, desmin, and alpha-1-antichimotrypsin, and negative for S-100 and leukocyte common antigen (LCA). Ultrastructurally, the cytoplasm and cellular processes of the cells were inundated with intermediate filaments, some of which were tightly bundled. Junctional complexes and secretory granules were absent. These features suggest a rhabdoid tumor: a malignant tumor of uncertain origin.

Adult↗

Effects of G-6-PD deficiency, experimentally induced or genetically transmitted, on the sorbitol pathway activity. In vitro and in vivo studies.

Aldose reductase catalyzes the NADPH-linked reduction of hexoses to their respective sugar-alcohols, which are involved in the pathogenesis of "sugar-cataracts". In the lenses, the reaction catalyzed by G-6-PD is the source of NADPH supply blocking sugar-alcohol formation and consequently prevents or delays the onset of "sugar-cataracts". We have investigated the effect of G-6-PD deficiency, either experimentally induced or genetically transmitted, on the sorbitol accumulation in whole cells incubated in high glucose media and on the "sugar-cataracts" formation in a galactosemic rat model. We also screened 31 Negro male adults with diabetes mellitus for red cell G-6-PD deficiency. G-6-PD deficiency produced a significant inhibition on sorbitol accumulation in rat lenses and human red cells incubated in 50 mM glucose. In the galactosemic rat model G-6-PD deficiency experimentally induced with acetaminophen delayed the development of cataracts. Finally, two diabetic individuals were G-6-PD deficient and did not show cataracts whereas cataracts were identified in six other diabetic patients.

Acetaminophen↗

Removal of DNA curving by DNA ligands: gel electrophoresis study.

The removal of inherent curving in Crithidia fasciculata kinetoplast DNA by various small DNA ligands, groove binders and mono- and bisintercalators, has been studied by gel retardation and electron microscopy. The migration of the kinetoplast DNA fragment is highly retarded during gel electrophoresis. We demonstrate that this retardation is suppressed by DNA ligands such as distamycin and ditercalinium, which have different modes of binding and sequence specificities. Observation by electron microscopy confirms that the effect of ditercalinium on gel migration of curved DNA is linked to DNA uncurving. As the drug is progressively added to DNA, a large broadening of the retarded band is observed during gel electrophoresis for distamycin and ditercalinium. In the case of distamycin, the retarded DNA band splits into two broad bands, whereas the noncurved DNA bands remain homogeneous. This indicates that the drug-DNA exchange is extremely slow in the gel and that a limited number of specific sites on DNA are critical for the removal of bending. GC-specific quinomycin, monointercalators, and bisintercalators act in a manner similar to that of AT-specific distamycin. This indicates that direct drug binding at the dAn tracts is not required for DNA uncurving. We propose that the uncurving of kinetoplast DNA by drugs is caused by a global alteration of DNA structure; subsequent increased flexibility leads to the suppression of rigid bending at the AT tract junctions.

Animals↗

Chromosome studies in human unfertilized oocytes and uncleaved zygotes after treatment with gonadotropin-releasing hormone analogs.

OBJECTIVE: To determine the frequency of the anomalies from the cytogenetic point of view in the oocytes remaining from our in vitro fertilization (IVF) program. Two gonadotropin-releasing hormone analogs (GnRH-a) were used (buserelin acetate and leuprolide acetate) in the superovulation treatment. DESIGN: A prospective study was planned in January 1989. Deadline for data and quantitative analysis was to be July 1990. SETTING: Hospital de Cruces, a public and tertiary institute. PATIENTS: One hundred thirty-nine IVF patients, yielding 433 oocytes. Selected on the basis of availability of oocytes and staff. RESULTS: Two hundred thirty-eight oocytes (71.25%) exhibited the normal number of metaphase II chromosomes; 64 (19.16%) exhibited aneuploidy; 13 (3.89%) were diploid, hyperdiploid, or hypodiploid; and 19 (5.68%) showed parthenogenetic activation. Of the 99 zygotes, 17 were polyploid and 48 showed prematurely condensed chromosomes, whereas in 31 cases the male and female pronuclei remained separate. CONCLUSIONS: It would not appear that the rate of chromosomal anomalies is affected after pituitary suppression with GnRH-a.

Adult↗

Pharmacokinetic and other related factors affecting psychotropic responses in Asians.

The last decade has witnessed substantial progress in our understanding of ethnic differences and similarities between Asians and other ethnic groups in response to various psychotropics. Capitalizing on recent advances in cross-cultural and psychobiological research methodology, a number of recent studies have suggested a special sensitivity of Asians to various psychotropic medications. Whereas pharmacokinetic differences have been consistently found with haloperidol and some benzodiazepines, results of studies focusing on tricyclic antidepressants (TCAs) have remained inconclusive. In addition, ethnic differences in protein binding and in the pharmacodynamics of some of these drugs have also been reported. Future studies should explore newer assay methods and imaging techniques capable of measuring receptor-drug interactions, in addition to utilizing existing research methodologies to more systematically scrutinize the nature and extent of such differences. They should be designed not only to ascertain differences in drug responses, but also to examine genetic and environmental (e.g., diet, exposure to enzyme inducers) factors that may contribute to these differences. Pharmacogenetic probes could be used in combination with studies examining pharmacokinetic and pharmacodynamic issues for such purposes.

Asian↗

Psychopharmacologic considerations in the treatment of black American populations.

Although striking ethnic differences in pharmacologic responses to various medications have been documented in the general medical literature, there is a paucity of such information in the psychopharmacologic literature. Recent work has provided a number of studies that illustrate interesting inter-ethnic pharmacogenetic, pharmacokinetic, and pharmacodynamic differences. In general, however, such studies have reported inconsistent findings relative to dose response relationships with various psychotropics. Results of our literature review, with a particular focus on black Americans, suggest that the lack of consistency in these investigations is largely attributable to various methodological and design problems. Prominent among these problems are: diagnostic misclassification, treatment of various ethnic groups in a homogeneous undifferentiated manner, lack of appropriate control for age and gender, and minimal consideration for chronicity of illness. As a result, though there exist some interesting data suggesting inter-ethnic genetic and kinetic differences, the extant literature on black Americans and other ethnic groups should be evaluated with some caution. The purpose of this article is to provide a systematic review of the existing psychopharmacologic literature on the black American population.

Black or African American↗

Ethnic psychopharmacology: the Hispanic and Native American perspective.

There is ample evidence attesting to differences in drug response and disposition among certain ethnic groups. The existing body of knowledge concerning pharmacological issues in the Hispanic and Native American ethnic groups, however, is both meager and confusing. In this article, the authors first attempt to briefly characterize these increasingly important ethnic groups, citing recent population figures and epidemiological findings. This is followed by a review of several existing retrospective studies concerning the pharmacological treatment of patients belonging to these groups. Recent findings in the area of pharmacogenetics are critically appraised and other factors influencing drug responsiveness are also examined. The clinical significance of this research for the optimal treatment of patients in cross-cultural settings is highlighted. The need for further research that would both fortify and clarify the available information with respect to these issues and the Hispanic and Native American populations is obvious.

Ethnicity↗

Olfactory classical conditioning in neonates.

One-day-old, awake infants underwent an olfactory classical conditioning procedure to assess associative learning within the olfactory system of newborns. Experimental infants received ten 30-second pairings of a novel olfactory conditioned stimulus (a citrus odor of neutral value) and tactile stimulation provided by stroking as the reinforcing unconditioned stimulus (a stimulus with positive properties). Control babies received only the odor, only the stroking, or the stroking followed by the odor presentation. The next day, all infants, in either the awake or sleep state, were given five 30-second presentations of the odor. Results were analyzed from video tapes scored by an observer unaware of the infants' training condition. The results indicate that only those infants who received the forward pairings of the odor and stroking exhibited conditioned responding (head turning toward the odor) to the citrus odor. The performance of the conditioned response was not affected by the state of the baby during testing, because both awake and sleeping infants exhibited conditioned responses. Furthermore, the expression of the conditioned response was odor specific; a novel floral odor presented during testing did not elicit conditioned responses in the experimental babies. These results suggest that complex associative olfactory learning is seen in newborns within the first 48 hours of life. These baseline findings may serve as normative data against which observation from neonates at risk for neurological sequelae may be compared.

Conditioning, Classical↗

DNase I susceptibility of bent DNA and its alteration by ditercalinium and distamycin.

The bending of kinetoplast DNA from Crithidia fasciculata is thought to be related to the periodic distribution of AA or TT cluster sequences. The sensitivity to DNase I of the two strands of this DNA was analyzed at nucleotide resolution by sequencing gel electrophoresis. The effect on the DNase I cleavage pattern of two drugs, ditercalinium and distamycin, that are able to remove bending was analyzed. The same analysis was done on a pBR 322 DNA fragment of random sequence as a control. The periodic distribution of the AA or TT clusters in the bent DNA fragment was first analyzed by computing the autocorrelation function of the AA or TT clusters in the bent DNA fragment. It is shown that the AT tracts are on average 10.5 base pairs apart. This value is almost identical with that of the B-DNA helix pitch in solution [10.5 (Wang, 1979); 10.6 +/- 0.1 (Rhodes & Klug, 1980)]. To reveal the periodic pattern of DNase I cleavage on this bent DNA, alone or in presence of drugs, the cross correlation between the different bands obtained from DNAse I cleavage and the presence of AA or TT sequences was computed. This shows that GC and mixed sequences are the most sensitive regions. These data also suggest that there is a periodic fluctuation in the width of the minor groove in the bent fragment. Ditercalinium and distamycin alter the DNase I cutting pattern of the bent DNA fragment but in an inverse fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Deletion of chromosome 4: 46,XY, del(4) (q31.3) after gamete intrafallopian transfer and in vitro fertilization-embryo transfer.

It seems that assisted reproduction technology does not increase the rate of chromosome abnormalities, and up to now, a few cases have been reported. The case we describe here is the first one of monosomy 4q31 in a full-term liveborn after a combined GIFT-IVF procedure. Once more, this case raises the question of whether pregnancies resulting from IVF should be monitored for chromosome abnormalities or not.

Adult↗

[Long-term anatomic results of tympanic homografts. Apropos of 170 cases].

Long-term anatomic results of 170 tympanic homografts performed in the Necker-Enfants-Malades hospital, France between 1977 and 1983 showed high frequency of complications: early perforation (17.7%); late perforation (14%); myringitis (8.5%); recurrence of retraction (7.31%); lateralization (9.4%). These complications are of much higher frequency than after tympanoplasty with autograft, and indications for tympano-ossicular homografts are now limited to total tympanic destruction with absence of handle of malleus.

Adolescent↗