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Biomedical subjects

G Smith

Publications and source records attributed to G Smith.

At least 433 records · Page 24Linked to original sources
PubMed1994

Prone position for ventilation in patients with severe adult respiratory distress syndrome.

We report 3 cases of severe adult respiratory distress syndrome. The patients were very difficult to oxygenate, even with the most advanced conventional mechanical ventilation techniques. In all cases oxygenation improved dramatically when the patient was turned to the prone position. Reports of the use of the prone position for ventilation are scanty, and this is the first time it has been reported in this country. The proposed mechanisms for its effectiveness are reviewed.

Adolescent↗
PubMed1993

[Cor triatriatum with atrial fibrillation as initial symptom in adults].

Cor triatriatum is a rare congenital heart disease. In its classic form its consists of a fibromuscular perforated membrane which divides the left atrium and obstructs blood flow from pulmonary veins to mitral orifice. Clinical symptoms and signs resemble those of mitral stenosis. Traditionally cor triatriatum was encountered most often in infancy and childhood. We describe the case of a young man with cor triatriatum and atrial fibrillation, with syncope. He was operated on with total resection of the obstructing membrane. Modern echocardiography has made diagnosis more easy. Thus, an increasing number of cases of cor triatriatum are diagnosed in adults with few or no symptoms. Symptoms, diagnosis and treatment are discussed, with emphasis on these patients.

Adult↗
PubMed1993

Poor survival of black patients in carcinoma of the endometrium.

PURPOSE: To compare the prognostic factors and survivals of black and white patients with endometrial carcinoma. METHODS AND MATERIALS: A retrospective study was undertaken of a total of 290 patients with endometrial carcinoma who were treated similarly at the Health Science Center at Brooklyn and Kings County Hospital Center from 1975 and 1990. One hundred and thirty-six of 290 (47.2%) were black and 135/290 (46.9%) were white. Well-known prognostic factors affecting endometrial carcinoma were studied in black and white group of patients. Their overall survival and comparison of survival in each prognostic group were also estimated using multi-variate analysis. RESULTS: Fifty-four percent of white patients had Stage I disease, compared to 45.9% in black patients. In Stage II, 51.6% were white and 48.4% were black, and in Stage III, 88.89% were black and 11.1% were white patients (p = 0.034). Fifty six percent Grade 1 patients were white and 44% were black. In Grade 2, 53.3% were white and 46.7% were black and in Grade 3 disease, 70.5% were black and 29.5% were white (p = 0.008). Up to the inner third of myometrial invasion had occurred in 60.6% of white patients and 39.4% in black patients. The middle third of the myometrium was invaded in 60.7% of white patients, and 39.3% of black patients. Thirty-seven percent of outer third of myometrial invasion was found in white patients and 63% in black patients (p = 0.038). Seventy-two percent of positive lymph nodes were found in black patients and 28.0% in white patients (p = 0.01). Sixty-one percent of patients with positive peritoneal cytology were black as compared to 38.7% in white patients (p = 0.017). The overall ten-year corrected survival for white and black patients was 72% and 40%, respectively (p = 0.0003). Survivals comparisons, when stratified by race and each prognostic group, showed statistically significant overall survival differences in favor of white patients. CONCLUSION: Black patients with endometrial carcinoma have poor survival. Low socio-economic status (SES) would not explain these findings. More research is required to determine the cause of poor survival in black patients with endometrial carcinoma.

Adult↗
PubMed1993

Both a ubiquitous factor mTEF-1 and a distinct muscle-specific factor bind to the M-CAT motif of the myosin heavy chain beta gene.

The A element, a fourteen base pair sequence in the rabbit myosin heavy chain (HC) beta promoter (-276/-263), contains the M-CAT motif, a cis-acting element found in several muscle-specific genes. The A element is essential for muscle-specific transcription of the myosin HC beta gene. Recently, we have identified both muscle-specific and ubiquitous factors (A1 and A2 factors, respectively) that bind to the A element. Since the sequence of the A element is very similar to the GTIIC motif in the SV40 enhancer, we examined the relationship between A-element-binding factors and a GTIIC binding factor TEF-1, recently isolated from HeLa cells. The GTIIC motif was bound by the A1 and A2 factors in muscle nuclear extracts and competed with the A element for DNA-protein complex formation. Antibody against human TEF-1 'supershifted' the ubiquitous A2 factor-DNA complex, but did not alter the mobility of the muscle-specific A1 factor-DNA complex. We isolated a murine cDNA clone (mTEF-1) from a cardiac cDNA library. The clone is highly homologous to Hela cell TEF-1. The in vitro transcription/translation product of mTEF-1 cDNA bound to the A element, and the DNA binding property of mTEF-1 was identical to that of the A2 factor. Transfection of mTEF-1 cDNA into muscle and non-muscle cells confirmed that mTEF-1 corresponds to A2, but not to A1 factors. The mTEF-1 mRNA is expressed abundantly in skeletal and cardiac muscles, kidney and lung, but it is also expressed at lower levels in other tissues. These results suggest that the M-CAT binding factors consist of two different factors; the ubiquitous A2 is encoded by mTEF-1, but the muscle-specific A1 factor is distinct from mTEF-1.

Amino Acid Sequence↗
PubMed1993

Human anti-endoplasmic reticulum autoantibodies produced in aromatic anticonvulsant hypersensitivity reactions recognise rodent CYP3A proteins and a similarly regulated human P450 enzyme(s)

Hypersensitivity reactions to aromatic anticonvulsants are associated with anti-liver microsomal antibodies which recognise rodent proteins. The reactivity of these antibodies, the regulation of the rodent antigens and the identity of the human autoantigen have been investigated. Dexamethasone elevated markedly the levels of an immunoreactive mouse protein(s) which exhibited a Mr (53 kDa) and inducibility consistent with the major Cyp3a product. Immunoblots conducted with hepatic microsomes from control and induced rats and purified rat P450s confirmed that these antibodies also recognised constitutive (3A2) and inducible (3A1) rat CYP3A products. Negligible reactivity was observed with microsomes from human B-lymphoblastoid cell lines expressing CYP1A1, 1A2, 2A6, 2D6, 2E1, 3A4 or epoxide hydrolase. Analysis of a phenotyped human liver bank revealed that the antibodies recognised a 52.5 kDa microsomal protein which exhibited marked heterogeneity in its expression and appeared to be regulated co-ordinately with human CYP2C8 and 3A3/4. The inter-individual variation in the expression of this protein(s) and its potential induction by anticonvulsant therapy together with an inherited deficiency in drug detoxification capacity may explain predisposition to these immunoallergic reactions.

Adult↗
PubMed1993

Genetic counselling in Noonan syndrome.

A clinical and echocardiographic study is presented of 117 families with Noonan syndrome. The 117 families contained 144 individuals with typical Noonan syndrome. The age range of these individuals was from one week to 45 years (mean 12.0 years). One parent was definitely affected with Noonan syndrome in only 14% of the 117 families (mother 11%, father 3%). In a further 31% of families, one parent had possible signs of Noonan syndrome, based on facial appearance only. Within the apparently sporadic group of probands there was no evidence of increased parental age. Echocardiography demonstrated no cases of subclinical cardiac disease in all first degree relatives examined, and clinical examination alone missed no case of cardiac disease. Segregation analysis of affected pedigrees confirmed autosomal dominant inheritance. If both parents had only possible or no signs of Noonan syndrome, subsequent to the birth of the first child with Noonan syndrome in a family, an empiric recurrence risk of 5% was obtained.

Adult↗
PubMed1993

1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene, an extremely potent modulator of mouse hepatic cytochrome P-450 gene expression.

We have investigated the effects of TCPOBOP (1,4-bis[2-(3,5- dichloropyridyloxy)]benzene), a potent cytochrome P-450-inducing agent [Poland, Mak, Glover, Boatman, Ebetino and Kende (1980) Mol. Pharmacol. 18, 571-580], on cytochrome P-450 isoenzyme expression in the mouse. Hepatic cytochrome P-450s from several distinct gene families were strikingly induced by a single dose of 75 micrograms of the compound. Northern-blot analysis demonstrated that this induction was almost certainly due to transcriptional activation of the cytochrome P-450 genes. The potency of this inductive effect was further reflected in the finding that cytochrome P-450 levels were still increased 12 weeks after a single injection of 75 micrograms of this compound. Interestingly, the mRNA levels of certain other genes, including those of metallothionein and the mouse major urinary proteins, were also induced. In view of the similarity in the effects of TCPOBOP and the synthetic glucocorticoid dexamethasone on mouse hepatic gene expression, we determined whether TCPOBOP acts through the glucocorticoid receptor. This did not, however, appear to be the case. Experiments with hypophysectomized animals demonstrated that TCPOBOP action was not regulated indirectly via the pituitary. In addition, induction of mouse Cyp2b protein by TCPOBOP in a primary culture of mouse hepatocytes suggests that the compound has a direct action on mouse liver. The above findings demonstrate that TCPOBOP is one of the most potent modulators of cytochrome P-450 gene expression described to date. It is not inconceivable that a single dose of this compound may alter hepatic gene expression for the majority of the lifespan of a mouse.

Animals↗
PubMed1993

Mathematical models for the population biology of Ostertagia ostertagi and the significance of aggregated parasite distributions.

Parasite frequency distributions are frequently aggregated. Such distributions are conveniently described using the negative binomial frequency distribution. This distribution is completely characterized by two parameters: the mean of the distribution and an exponent, k. The degree of aggregation is inversely proportional to the value of k. Aggregated parasite distributions enhance the ability of regulatory processes to maintain parasite populations at or near their equilibrium level but incorporating parasite frequency distributions in realistic models of parasite population biology is fraught with difficulty (several simplified examples are given). Indeed, it is not always possible to incorporate parasite frequency distributions and the question arises whether this compromises model performance. Trichostronglyid nematodes, including Ostertagia ostertagi, are aggregated but the estimated value of k for such populations is usually greater than 1. This is typical of populations with high population means (tens of thousands). It is shown that when the degree of aggregation is such that k > 1, the results of a model which recognizes parasite frequency distribution is not much different from the results of a model which assumes all hosts contain exactly the same number of parasites.

Animals↗
PubMed1993

Cardiologic abnormalities in Noonan syndrome: phenotypic diagnosis and echocardiographic assessment of 118 patients.

OBJECTIVES: The purpose of this study was to determine the incidence of cardiologic abnormalities in Noonan syndrome. BACKGROUND: The incidence of cardiac abnormalities in Noonan syndrome remains unknown, largely because of such difficulties as assembling a substantial cohort, ensuring a correct phenotypic diagnosis and providing accurate definitions of the most frequent abnormalities--pulmonary stenosis and left ventricular hypertrophy. METHODS: A cohort of 145 patients was assembled, and before cardiologic assessment two independent geneticists scrutinized the phenotype. The diagnosis was confirmed in 118 patients, and they were studied by two-dimensional and Doppler echocardiography. RESULTS: A dysplastic pulmonary valve was present in eight patients (7%) and was associated with significant stenosis in six (75%) of the eight. Significant stenosis was present in 22 (20%) of 110 patients without dysplasia. Left ventricular hypertrophy was present in 29 patients (25%) without significant pulmonary stenosis. Localized anterior septal hypertrophy was the most common pattern in 12 (41%) of 29 patients. Diffuse hypertrophy involving the entire septum and the free wall was present in nine patients (31%) and was severe (> 1.7 cm) in five. Other abnormalities included secundum atrial septal defects (10%). CONCLUSIONS: The high incidence of cardiac abnormalities suggests that echocardiographic and Doppler evaluation of patients with the Noonan phenotype is important because it will aid in genetic counseling and in the assessment of the natural history of--and, ultimately, identification of the gene(s) responsible for--Noonan syndrome.

Adolescent↗
PubMed1993

Comparison between colposcopic, cytologic, and histologic findings in women positive and negative for human papillomavirus DNA.

Little is known about the role of detection of human papillomavirus (HPV) DNA in exfoliated cells of the cervix in aiding the colposcopic diagnosis of cervical lesions. The purpose of our study was to compare the colposcopic findings of young women who were positive and negative for HPV DNA. Eighty-four women aged 13-22 years attending family planning clinics were examined colposcopically with the aide of acetic acid and Lugol's solution and without knowledge of HPV DNA status. Lesions identified were given scores based on the severity of observed colposcopic changes. Samples for cytology and HPV DNA testing, which included types 6, 11, 16, 18, 31, 33, and 35, were obtained at the time of the examination. Biopsies were performed on women with significant lesions identified on examination or with cytology suggestive of neoplasia. Students t-test and chi 2 analysis were performed to compare colposcopic variables and HPV DNA type. Of the 84 women examined, 17 were positive for HPV DNA; 9 had type 16/18. The average length of sexual activity was 2.7 years. Women with HPV 16/18 had a mean of 1.7 lesions visible at colposcopy compared to 0.7 lesions visible in those negative for HPV 16/18 (this included HPV DNA negative women and women positive for HPV types 6, 11, 31, 33, and 35) (p < 0.001). Women who were positive for HPV 16/18 also had higher lesional scores than the HPV 16/18-negative group (3.4 versus 1.0, respectively, p < 0.001). All four women who had dysplasia either on cytology or histology were positive for type 16/18.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Regulation of cytochrome P450 gene expression in human colon and breast tumour xenografts.

It is extremely difficult to identify the factors which regulate the expression of drug-metabolising enzymes in man. To address this problem, we have developed a model involving the use of human tumours grown as xenografts in immune deficient mice. Mice bearing human colon or breast tumours as xenografts were challenged with a range of compounds, known from animal studies to be inducers of cytochrome P450s from a variety of gene families. Almost all of the compounds tested could induce human tumour P450 expression, measured either by Western blot or immunohistochemical analysis. Indeed, the levels of P450s from several distinct gene families or subfamilies including CYP2A, CYP2B, CYP2C, CYP3A and CYP4A were induced. Of particular interest was the profound induction of human P450s by 1,4 bis 2-(3,5dichloro-pyridyloxybenzene)(TCPOBOP), a compound which exhibits a marked species specificity in its ability to induce P450 expression in experimental animals. Induction of a human CYP2B protein by this compound was confirmed by Northern blot analysis and in situ hybridisation for mRNA, indicating that induction occurred at the level of transcription. These studies have a variety of implications: they provide a method for approaching the previously intractable problem of how environmental, hormonal and metabolic factors regulate human P450 genes and other genes involved in drug metabolism; they demonstrate that human tumours express P450s constitutively and that the levels of these proteins can be modulated by exogenous agents.

Animals↗