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Biomedical subjects

G H Smith

Publications and source records attributed to G H Smith.

At least 19 recordsLinked to original sources
PubMed1992

The effect of parity, tumor latency and transplantation on the activation of int loci in MMTV-induced, transplanted C3H mammary pre-neoplasias and their tumors.

Mouse mammary tumor virus (MMTV) infection of mammary glands results in proviral insertion into host DNA and activation of cellular genes. Clonal expansion of cells bearing insertional mutations results in hyperplastic alveolar nodules (HAN) and tumors. HAN, transplanted into epithelium-cleared mammary fat pads, form hyperplastic alveolar outgrowths (HOGs). Previous work indicates the commonly MMTV-activated genes wnt-1 and int-2 are rarely affected in HOGs and HOG-derived tumors. To determine the basis of the dichotomy between the frequency of wnt/int gene activation in HOG-derived tumors and tumors from breeders of the identical inbred mouse strain, we compared the activation of wnt-1, int-2 and int-3 in tumors from virgin and breeding C3H mice, in consecutive primary tumors arising in individual C3H breeders and in C3H HOGs at early passages. Activation of wnt-1 or int-2 was rare in HOG-derived tumors (6% and 0%) compared with primary tumors in breeders (52% and 14%). int-3 was never found to be activated. wnt-1 was activated in the same percentage of primary tumors from virgins as from breeders. int-2 was activated only in tumors from breeders. wnt-1 activation also did not correlate with shorter tumor latency in multiple tumors from individual breeders. wnt-1 RNA was not detected in HOGs at early transplant generations, however, low levels of wnt-1 RNA were variably found in the epithelium of virgin mammary glands. We cannot explain why C3H HOGs and their derivative tumors develop without wnt-1 expression when the majority of C3H primary mammary tumors possess an MMTV-activated wnt-1 gene.

Animals↗
PubMed1992

Adverse hemodynamic effects of pericardial closure soon after open heart operation.

The short-term hemodynamic effects of pericardial closure on cardiac function were studied during steady-state anesthesia and ventilation in 10 patients (6 men) (mean age, 59 +/- 9 years) who underwent an open-heart valve operation. Observations were made after the heart was decannulated, both while the pericardium was open and after it had been closed, and then after closure of the chest after the pericardium had been reopened by removing the pericardial suture through the chest wall. The effect of closing the pericardium before closing the chest was an immediate reduction in cardiac output (thermodilution) of 1.39 +/- 0.24 L/min from 5.09 +/- 0.40 L/min (p less than 0.001). The heart rate remained stable, but there was a decrease in stroke volume of 29% and an increase in systemic vascular resistance of 34% (both, p less than 0.01). The mean arterial pressure increased slightly by 2% (not significant). Opening the pericardium (1.5 to 2 hours after the end of the operation) while the chest remained closed was followed by an increase in cardiac output of 1.33 +/- 0.15 L/min from 4.12 +/- 0.62 L/min (p less than 0.001). As the heart rate and the mean blood pressure changed insignificantly, there was an increase in stroke volume of 15 +/- 3 mL from 53 +/- 5 mL and a reduction in systemic vascular resistance of 473 +/- 83 dyne . s . cm-5 from 1,721 +/- 181 dyne.s.cm-5 (both, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands.

Expression of the int-3 locus is activated in mouse mammary tumors as a consequence of insertional mutagenesis by the mouse mammary tumor virus (MMTV). Integration of the MMTV provirus into the int-3 locus promotes the transcription and translation of flanking cellular int-3 sequences sharing significant homology with the intracellular domain of the neurogenic Notch gene of Drosophila, and with the yeast cell cycle regulatory genes cdc10 and SWI6. To determine the in vivo consequences of activated int-3 expression, transgenic mice were generated harboring a genomic tumor DNA fragment consisting of the MMTV LTR and the flanking cellular int-3 sequences. All six int-3 founder transgenic mice and the progeny of one established line exhibited similar dramatic phenotypic abnormalities in tissues in which the transgene was expressed. Focal and often multiple poorly differentiated mammary and salivary adenocarcinomas appeared in the majority of transgenic mice between 2 and 7 months of age. Significantly, mammary glands were arrested in development and were lactation deficient in all female int-3 mice. The salivary glands, glands of the nasal mucosa and maxillary sinus, the extraorbital lacrimal glands, and the Harderian glands of juvenile and adult transgenic mice all contained proliferating immature ductule cells and were incompletely differentiated. In addition, all male int-3 transgenic mice were sterile, apparently the result of severe hyperplasia of the epididymis. These findings demonstrate in vivo that expression of the activated Notch-related int-3 gene causes deregulation of normal developmental controls and hyperproliferation of glandular epithelia.

Adenocarcinoma↗
PubMed1992

Diagnosis of cytomegalovirus infection in heart transplant recipients.

In a prospective study eight (47%) heart transplant recipients had recurrent cytomegalovirus (CMV) infection. Of these, five had received hearts from seropositive donors. Neither serology nor virus isolation from urine was reliably associated with clinical CMV infection, but a high CMV IgM index correlated with CMV infection.

Antibodies, Viral↗
PubMed1992

Practical guidelines for preparing and administering amphotericin B.

Current practices used in the preparation and administration of amphotericin B are evaluated, and updated guidelines are presented. Intravenous admixtures of amphotericin B 0.25 and 1.4 mg/mL in 5% dextrose injection have an expiration date of 35 days and 36 hours, respectively. Since commercial formulations of amphotericin B lack a bacteriostatic agent, admixtures should be stored at 4-8 degrees C. Protection from fluorescent light is unnecessary. Admixtures may be prepared in polyolefin, glass, or polyvinyl chloride intravenous containers; certain evacuated intravenous containers contain buffers that can cause precipitation of amphotericin B. The addition of a buffering agent to the intravenous admixture is unnecessary when the initial pH of the 5% dextrose injection exceeds 4.2. The usual daily maintenance dose of amphotericin B is 0.5-1 mg/kg i.v. The manufacturer recommends beginning intravenous therapy with a 1-mg test dose. The initiation of therapy with incrementally increased doses may be detrimental if it delays the delivery of a therapeutic dose. Amphotericin B can be infused over one to two hours (less than or equal to 50 mg/hr) in patients with adequate renal function. Bladder instillation of amphotericin B 50 mg in 1 L of sterile water has been used to treat fungal cystitis. Ancillary medications administered to treat infusion-related adverse events should be used as prophylaxis in patients with a history of hypersensitivity or unacceptable reactions and as needed for relief of symptoms. Sodium supplementation should be implemented cautiously, on a patient-specific basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B↗
PubMed1991

Over-expression of an endogenous milk protein gene in transgenic mice is associated with impaired mammary alveolar development and a milchlos phenotype.

The whey acidic protein (WAP) gene is expressed in mammary epithelial cells at late pregnancy and throughout lactation. We have generated transgenic mice in which a mouse WAP transgene is expressed precociously in pregnancy. From 13 founder mice bearing WAP transgenes, two female founders and the daughters from a male founder failed to lactate and nurture their offspring. We named this phenotype milchlos. Mammary tissue from postpartum milchlos mice was underdeveloped, contained too few alveoli and resembled the glands of non-transgenic mid-pregnant mice. The hypothesis that alveolar development in milchlos mice was functionally arrested in a prelactational state is consistent with low levels of alpha-lactalbumin mRNA, and an unidentified keratin RNA in mammary tissue from postpartum mice. Defects in alveolar function in milchlos mice were detected at mid-pregnancy; in non-transgenic mice, WAP was secreted into the alveolar lumen but remained preferentially in the cytoplasm of the alveolar epithelial cells in the milchlos mice. Since deregulated WAP expression resulted in impaired mammary development, it is possible that WAP plays a regulatory role in the terminal differentiation and development of mammary alveolar cells.

Animals↗
PubMed1991

Long-term in vivo expression of genes introduced by retrovirus-mediated transfer into mammary epithelial cells.

Nonimmortalized mouse mammary epithelial cells expressing Escherichia coli beta-galactosidase from a murine amphotropic packaged retroviral vector were injected into the epithelium-divested mammary fat pads of syngeneic mice. Mammary glands formed from the injected mammary epithelial cells contained ductal and lobular cells, both of which expressed beta-galactosidase when examined in situ more than 12 months later. These results indicate that stable recombinant gene expression can be achieved in vivo in the mammary gland without altering the growth properties of normal mammary epithelium.

3T3 Cells↗
PubMed1991

Mitral valve repair: a valuable procedure with good long term results even when performed infrequently.

OBJECTIVE: To assess the results of mitral valve repair in a series with a low frequency of repair despite a policy to conserve the valve whenever possible. DESIGN: Retrospective review of case notes with clinical and echocardiographic examination of survivors. SETTING: Cardiac surgery unit in a university teaching hospital. PATIENTS: 62 consecutive patients undergoing mitral valve repair by one surgeon between 1979 and 1989. INTERVENTIONS: Mitral valve repair according to the criteria and techniques of Carpentier. MAIN OUTCOME MEASURES: Frequency of repair, operative mortality, actuarial survival, freedom from reoperation and thromboembolism, clinical state, and echocardiographic state. RESULTS: The 62 patients, median age 58 years (interquartile range 51 to 64 years), represent 14% (70% confidence interval 12% to 15%) of the 454 mitral valve operations performed in the study period. Operative mortality was 8% (70% CI 5% to 13%). Actuarial survival was 62% (70% CI 43% to 81%) at nine years. At nine years actuarial freedom from reoperation was 91% (70% CI 79% to 102%) and freedom from thromboembolism 91% (70% CI 80% to 102%). At a median follow up of 33 months (interquartile range 21 to 74 months), 38 of 46 survivors had improved functional state. Of 21 patients who underwent echocardiography one had severe mitral regurgitation and one mitral stenosis. CONCLUSION: Although compared with other reports of mitral valve repair the prevalence of repair was low in this series the results are comparable and justify a positive approach to repair in all patients undergoing mitral valve surgery even if this can only be achieved in a small proportion of patients.

Female↗
PubMed1990

TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas.

To define the role of TGF alpha in normal tissue function and in pathogenesis, transgenic mice have been generated bearing a fusion gene consisting of the mouse metallothionein 1 promoter and a human TGF alpha cDNA. In these mice, human TGF alpha RNA and protein are abundant in many tissues and TGF alpha is detectable in blood and urine. The effects of TGF alpha overproduction in transgenic mice are pleiotropic and tissue specific. The liver frequently contains multifocal, well-differentiated hepatocellular carcinomas that express enhanced levels of human TGF alpha RNA. The mammary gland exhibits impeded morphogenetic penetration of epithelial duct cells into the stromal fat pad. The pancreas shows progressive interstitial fibrosis and a florid acinoductular metaplasia, during which acinar cells appear to degranulate, dedifferentiate, and assume characteristics of intercalated or centroacinar duct cells. TGF alpha therefore plays an important role in cellular proliferation, organogenesis, and neoplastic transformation.

Aging↗
PubMed1990

Transforming growth factor-alpha messenger RNA localization in the developing adult rat and human mammary gland by in situ hybridization.

Transforming growth factor-alpha (TGF alpha) has been implicated in the autocrine growth control of a number of different rodent and human tumor cells, including breast cancer cells. Although TGF alpha has been detected in a limited number of normal tissues, its distribution and physiological function in the mammary gland are relatively unknown. TGF alpha mRNA expression was detected by in situ hybridization with a labeled TGF alpha antisense RNA probe and quantitated by application of computer-assisted digital image processing in both the ductal and alveolar epithelial cells in the virgin rat and nulliparous and parous human mammary glands. During pregnancy and lactation, the level of TGF alpha mRNA expression in the ductal and alveolar epithelial cells increased two- to threefold, while a heterogeneous yet strong expression of TGF alpha mRNA could also be detected in approximately 10-15% of the surrounding stromal cells in the pregnant mammary gland.

Animals↗
PubMed1990

Factors influencing long-term implant success.

An implant quotient (IQ) has been proposed to help clinicians identify the 24 factors that can affect the potential long-term success of endosseous dental implants. Maximizing the positive factors and minimizing the negative factors will result in relatively high values for the theoretical IQ. Long-term success is directly proportional to the resultant value of the IQ. The greater the value of the IQ, the better the possibility for long-term success. The length of healing time and the necessity for submerged healing are indirectly proportional to the resultant value of the IQ. The greater the value of the IQ, the shorter the healing time before loading an endosseous implant may be. The greater the value of the IQ, the less necessary it becomes to submerge the healing implant.

Dental Implantation, Endosseous↗
PubMed1990

Mallory-Weiss syndrome after cardiopulmonary resuscitation.

We report hematemesis from Mallory-Weiss tears after successful cardiopulmonary resuscitation (CPR). A computer search of the English language literature disclosed only 3 similar cases, and we review them. This complication of CPR may occur more frequently than recognized and should be prevented by careful technique.

Aged↗
PubMed1990

Congenital labial cyst.

We present the case of a congenital labial cyst in an otherwise normal female infant. This condition is uncommon, with only 30 female congenital external genital cysts previously reported in the English literature. When recognized, these cysts can be treated conservatively with an expectation of spontaneous resolution.

Cysts↗
PubMed1990

Oral cephalosporins in perspective.

Oral cephalosporins, after 25 years of use, continue to present the clinician with a therapeutic challenge. The older agents have been extensively prescribed for ambulatory adult and pediatric patients with a wide variety of infections caused by gram-positive and some gram-negative organisms. The newer agents, cefaclor, cefuroxime axetil, and cefixime, have increased in vitro activity against beta-lactamase-secreting strains of Haemophilus influenzae and Branhamella catarrhalis which has made them more popular for the treatment of otitis media and respiratory tract infections in children. The new agents are also more active against most gram-negative organisms. However, clinical trials have failed to show a clear-cut superiority over older, proven therapy when used to treat infections of the respiratory tract, middle ear, skin and soft tissue, urinary tract, and bone and joints when caused by sensitive organisms. Published reports of clinical trials continue to support the recommendation that oral cephalosporins, especially the newer and more expensive agents, be reserved for second- or third-line therapy when amoxicillin, penicillin V, or trimethoprim/sulfamethoxazole have either failed or produced patient intolerance. Erythromycin/sulfisoxazole and amoxicillin/clavulanate potassium are equally efficacious and also less expensive than cefaclor, cefuroxime axetil, and cefixime and could be considered second-line therapy prior to the use of the newer cephalosporins for infections in the ambulatory patient.

Cephalosporins↗
PubMed1990

Differential keratin gene expression in developing, differentiating, preneoplastic, and neoplastic mouse mammary epithelium.

Two keratins whose expression has been associated with proliferation (K14) and hyperproliferation (K6) in mouse epithelia were detected in normal, preneoplastic, and neoplastic mouse mammary tissues. K6 and K14 keratins were independently expressed in distinct epithelial cell populations in developing mammary anlage. K6 was confined to a small number of mammary epithelial cells associated with the growing end buds and among the proximal luminal epithelium, whereas K14 expression appeared in basally located fusiform cells that correspond to the location of mammary myoepithelial cells. This pattern was maintained in mature glands and through full functional differentiation with the exception that K6-positive cells were only rarely detectable. During lobuloalveolar growth in early pregnancy, K6 and K6/K14 coexpressing cells were observed among the luminal and suprabasal cells in the expanding lobular epithelium. This K6/K14 coexpressing epithelial subset persisted throughout pregnancy, lactation, and involution, albeit in much smaller numbers than observed in early pregnancy. Two patterns of K6 and K14 expression in preneoplastic and neoplastic lesions of mouse mammary glands were induced by various carcinogenic stimuli. In one, increased numbers of K6- or K14-positive cells were present in distinct cellular populations; in the other, coexpression of K6/K14 was found in a large subpopulation of both preneoplastic and neoplastic mammary epithelium. These observations suggest that expression of K6 and K14 keratins in the mouse mammary gland is associated with growth and expansion of specific mammary epithelial cell populations, and as such these keratins may be useful probes with which to identify mammary epithelium-specific primordial cells. In agreement with this possibility, K6/K14 expression was demonstrated within a distinct subset of morphologically distinct luminal mammary epithelial cells that have been reported to possess kinetic properties in vitro consistent with those expected of latent mammogenic stem cells.

Animals↗
PubMed1989

Intestinal atresia: factors affecting survival.

Eighty-four patients with congenital jejuno-ileal or colonic atresia treated at this hospital during the years 1961-86 were studied. There were 42 cases of jejunal atresia, seven cases of jejuno-ileal atresia, 33 cases of ileal atresia and two cases of colonic atresia. Multiple atresias occurred in 19 patients. During the first 15 years of the study the mortality rate was 56%. In the last 10 years it was 22%. Multivariate linear modelling techniques were used to determine the factors associated with a fatal outcome. In order of magnitude associations were found between death and year of treatment (P less than 0.01), the type of anastomosis performed to correct the atresis (P less than 0.05), the presence of other congenital abnormalities (P less than 0.01) and presence of a malrotation (P less than 0.02). The anastomoses associated with the highest mortality were those with a stoma. The mean length of bowel resected proximal to the anastomosis was 15 cm and the mean length resected distally 5 cm. Eleven patients had 60 cm or less of small bowel remaining after surgery and only three of these survived. The highest mortality rate can be expected in patients with other congenital abnormalities and those with a malrotation. A primary anastomosis without a stoma is recommended.

Analysis of Variance↗