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Biomedical subjects

R G Smith

Publications and source records attributed to R G Smith.

At least 271 records · Page 15Linked to original sources

The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3',5'-monophosphate accumulation in rat primary pituitary cell culture.

His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) stimulated GH release from rat primary pituitary cells in a time- and dose-dependent manner. Stimulation was observed after a 15-min, but not a 4-h, incubation. The concentrations of GHRP-6 required for half-maximal and maximal stimulation were 7 x 10(-9) and 10(-7) M, respectively. GH release induced by GHRP-6 was not affected by the addition of either naloxone or the GRF antagonist [N-Ac-Tyr1,D-Arg2]GRF-(1-29)-NH2. The latter inhibited GRF-stimulated GH release by shifting the dose-response curve to the right. His-D-Trp-D-Lys-Trp-D-Phe-Lys-NH2, an analog of GHRP-6, inhibited GH release stimulated by GHRP-6 without affecting that induced by GRF. When present together at maximal concentrations, GHRP-6 and GRF produced a synergistic effect on GH release. GHRP-6 had no effect on intracellular cAMP levels, whereas GRF increased intracellular cAMP concentrations by 3-fold. Combined treatment of pituitary cells with GRF and GHRP-6 resulted in a potentiation of the GRF-induced increase in cAMP levels. Basal GH release was reduced by 30% after pretreatment with GHRP-6 (10(-7) M) for 1 h. Pretreatment with GHRP-6 also decreased the subsequent response to GHRP-6, but not GRF. In contrast, pretreatment with GRF for 1 h had no effect on the subsequent action of GHRP-6 or GRF on GH release. The desensitization induced by GHRP-6 was completely reversed within 1 h after removal of the peptide. Results from this study indicate that GHRP-6 and GRF stimulated GH release from somatotrophs via different receptors and through discrete mechanisms.

Animals↗

Androgens and glucocorticoids modulate heparin-binding growth factor I mRNA accumulation in DDT1 cells as analyzed by in situ hybridization.

The ductus deferens smooth muscle tumor cell line (DDT1-MF-2) is very sensitive to steroids. Treatment with 10 nM testosterone accelerates the growth of DDT1 cells in the absence of serum. Glucocorticoids in the presence or absence of androgens inhibits growth. Stimulation of growth of DDT1 cells by testosterone can be replaced by the addition of heparin-binding growth factor I and II (HBGF). Addition of testosterone plus HBGF growth factors results in a further increase in cell number. By in situ hybridization, accumulation of HBGF-I mRNA is significantly increased by testosterone treatment of low density cultures. Testosterone treatment of high density cultures results in no stimulation of HBGF-I mRNA accumulation. Glucocorticoids alone, which block growth of DDT1 cells, have no effect of HBGF-I mRNA accumulation. However, the simultaneous addition of glucocorticoid and androgens to DDT1 cells results in a rapid accumulation of HBGF-I mRNA by 12 h, although growth is inhibited by the presence of both steroid analogs.

Animals↗

Phenotypic heterogeneity of TDT+ cells in the blood and bone marrow: implications for surveillance of residual leukemia.

Terminal deoxynucleotidyl transferase (TdT) is a useful marker for normal lymphocyte precursors and acute lymphoblastic leukemia (ALL). Our previous studies, however, have shown that for monitoring minimal residual disease in the circulation, assay for TdT alone is not sufficiently specific to distinguish leukemia cells from the background of rare normal blood TdT+ cells. In an attempt to increase specificity for leukemic cells, we have used double and triple immunophenotypic analysis to characterize normal circulating and bone marrow TdT+ cells. Overall, normal TdT+ cells were about 1000-fold more frequent in the marrow than in the blood. More than 75% of TdT+ cells in both the blood and marrow expressed the CD34, CD22, and HLA-DR antigens. However, circulating TdT+ cells infrequently expressed CD19 (4.5%) and CD9 (2.3%), compared with their marrow counterparts (74% and 47%, respectively). The brightly staining CD10+ phenotype, frequently associated with ALL blasts, was significantly less common among normal blood (5.7%) than marrow (31%) TdT+ cells. Although T-lineage markers were rarely expressed on TdT+ cells in either site, CD7+ cells were far more prevalent within the circulating TdT+ subset (4%) than among the marrow population (less than 0.2%). The results suggest a selective release of lineage-uncommitted and/or thymus-destined TdT+ cells from the marrow into the circulation. Moreover, since CD19, CD9, and high-density CD10 are frequently found on ALL blasts, staining for these markers on TdT+ cells in the circulation should improve the specificity of assay for residual common ALL cells. Likewise, assay for CD5+ and possibly CD7+ TdT+ cells in either marrow or blood should provide a very sensitive method of detection of T-ALL blasts.

Antigens, CD↗

The effects of conservative treatment on temporomandibular joint sounds and mandibular deviation during opening and closing movement of the mandible.

This study was undertaken to examine changes in temporomandibular joint (TMJ) sounds and mandibular deviations on opening and closing movements subsequent to conservative treatment of twelve patients presenting with mandibular dysfunction. A comparison of synchronous records indicated that two thirds of TMJ sounds were directly related to minor deviations in the path of movement of the mandible on opening and closing. TMJ sounds decreased significantly following flat plane splint therapy in all types, qualities and positions of sounds with the exception of those occurring near occlusal contact and those of a soft character. TMJ sounds related to minor mandibular deviations decreased significantly in all types, qualities and position of sounds except those of a soft nature. Fast Fourier Transform analysis of joint sounds consistently present before and after treatment revealed that the dominant frequencies were at the lower end of the acoustic range and that hard clicks have dominant frequencies higher than soft clicks.

Auscultation↗

The functional status of elderly people admitted to a local authority residential home.

One hundred and forty-one consecutive admissions to a large local authority residential home were studied to assess their functional level. Both panel (71) and emergency (70) admissions were assessed. Forty-seven per cent of the panel admissions came from hospital and 39% from home compared with 4% and 83% of the emergency admissions. Severe mental impairment was found in 22% panel admissions and 34% of emergencies. Dementia was the commonest underlying condition. Inability to cope at home was the most common reason for referral in both groups. The activities of daily living (ADL) were assessed where possible on admission and after two to four weeks. No statistically significant change was found in any aspect of ADL between the two assessments although 9% of the panel and 19% of the emergency group were assessed as being unacceptable for residential care in one function. Residents initially showed a high level of negative attitude to the concept of residential care but this lessened over the four weeks. This study has shown that although new residents are suitable on admission to residential care, they are marginally so and are likely to become more dependent. This has future implications for staff levels and training in residential homes.

Activities of Daily Living↗

The circulatory assist device program at University Medical Center. Clinical training and technical support.

A great deal of preparation and coordination is necessary for participation in the investigational use of temporary circulatory assist devices. The use of engineers for technical support as well as for programs coordination has been very useful in the ongoing evaluation of our device performance. It is hoped that the early studies conducted today will lead to improvements in the devices and the eventual production of permanent, totally implantable circulatory assist devices. As these devices continue to develop, it is expected that the biomedical engineer will be able to continue to participate significantly in the development process.

Academic Medical Centers↗

Constipation in the elderly. A physiologic study.

Colorectal motility was studied in 25 elderly patients with chronic constipation and compared with an asymptomatic control group (N = 17). Proctometrograms were performed to measure rectal volumes at sensory threshold and maximal tolerance, and rectal compliance. Anal sphincter pressures and reflexes were measured by conventional techniques. Indices of colonic motility were also assessed. Significant impairment of rectal sensory threshold was apparent in constipation. Six patients presenting with impaction demonstrated functional megarectums. The remaining 19 showed a significant reduction in maximal rectal volume and rectal compliance and 14 extruded the balloon. There were no differences in sphincter length or presence of the rectosphincteric reflex. Four patients had an absent pudendoanal reflex and the remainder significant prolongation. Total gastrointestinal transit times were prolonged in the constipation group, mainly distally due to rectal stasis. In two patients bisacodyl failed to elicit a sigmoid motor response. Constipation in the elderly is not merely due to delayed transit. Neurogenic deficits of sacral spinal cord function may be responsible for abnormalities in rectal motor and sensory function.

Adult↗

ATP mediated receptor interconversion as a model of estrogen action: isolation of the factor which converts the non-estrogen binding form of the receptor to the lower affinity binding form.

Two steroid binding states of an estrogen receptor each with different equilibrium constants (Kd values) Rx (Kd = 0.06 nM) and Ry (Kd = 0.8 nM) have been identified and characterized in the hen and estrogen-stimulated chick oviduct. A third non-estrogen binding form of the receptor, designated Rnb, has also been identified. These three forms of the receptor are interconvertible and appear to have a common molecular weight of approx. 66,000 under denaturing conditions. Hydroxytamoxifen binds preferentially and with high affinity to Rx (Kd 0.03 nM) and the conversion of Rx to Ry which is mediated by gamma phosphoryl group of ATP is also inhibitable by hydroxytamoxifen. Thus receptor interconversion, which may have general application to hormone action, potentially explains agonist/antagonist activity. The conversion of the non-estrogen binding form of the receptor (Rnb) to the lower affinity receptor (Ry) in chick oviduct cytosol is catalyzed by a reaction requiring the loss of the terminal phosphoryl moiety from ATP. There is a specific requirement for Mg2+. We now describe that ammonium sulfate fractionation of the cytosol allows the separation of the receptor entities from the "activating factor" (Fy) that catalyzes the conversion of Rnb to Ry. In the presence of gamma [32P]-ATP at 30 degrees C the purified non-steroid binding form of the receptor is phosphorylated. Phosphoamino acid analysis using Partisil-10 SAX anion exchange resin demonstrates that a serine is phosphorylated; and quantitation of the phosphorylation is indicative of one phosphoserine/receptor molecule. Treatment of the receptor with the partially purified activating factor to induce estradiol binding causes a dramatic reduction in phosphorylation.

Adenosine Triphosphate↗

Oral squamous cell carcinoma in identical twins: report of a case.

This case report describes two middle-aged identical female twins with a mild to moderate history of tobacco and alcohol abuse who developed squamous cell carcinomas in the same anatomic sites. By exclusion of major factors, a correlation between heredity and the incidence of cancer in these cases appears likely; however, carcinogenic agents (tobacco and alcohol) must also be considered as contributing factors. Close observation of siblings (and certainly twins) is recommended when head and neck carcinoma occurs prior to middle age. Although no genetic population prone to oral cancer is known, the disease is rare enough in younger individuals to raise the question of a possible genetic predisposition.

Adult↗

Inorganic carbon transport in biological systems.

1. The flux of inorganic carbon (Ci) is an important biological process. 2. CO2 crosses membranes through passive diffusion and, perhaps active transport while HCO3- crosses membranes via facilitated diffusion and active transport mechanisms. 3. Carbonic anhydrase is ubiquitous and enhances the flux of Ci. 4. Generally, Ci crosses membranes through passive and facilitated diffusion when the flux of Ci, per se, is important and crosses membranes via active transport when cells are regulating their intracellular pH and/or ion levels.

Animals↗

Early experience with the total artificial heart as a bridge to cardiac transplantation.

There is no doubt that currently available biventricular pneumatic pulsatile devices placed orthotopically with transcutaneous drive lines can support life in patients who may then be successfully transplanted. For the most part, the world experience is with the Jarvik hearts. The current model of choice is the 70-cc device because it is smaller and may be implanted with less fear of "fit problems" than the 100-cc model. As Case 4 illustrates, a fit problem may cause a fatal outcome. But if special precautions in implantation are taken, these may be avoided (Case 6). The fears of excessive bleeding, hemolysis, embolism, and infection with the use of these devices are not as prohibitive as we suspected. Bleeding is always a threat in complex cardiac surgery with grafting. Hemolysis is not a problem if excessive transfusion can be avoided. Embolism and infection may be inevitable, but as our patient B.C. has proven, there is no need to rush immediately to transplantation. And if the implanted patient does not meet local transplant selection criteria, we have enough information now to recommend that they not be accepted for transplantation. Bleeding may be anticipated to be a major problem in any patient with dense reactive scar tissue. To avoid this, transplantation should be done within 3 weeks. We recommend patients who have previously been selected for orthotopic transplantation and begin an accelerated decompensation (our Cases 2 and 7) as the best candidates for temporary orthotopic mechanical support. In these patients, there is no question about whether recovery of the native heart is possible or whether a reversible myocardial insult is present. The plan to do an orthotopic transplant indicates that a cardiectomy is necessary. Case 5, who was in reasonable shape for transplantation, was also favorable. In cases of anticipated graft failure, early use of the Jarvik 7-70 is recommended. This type of device, when suitably placed, provides excellent control of the circulation. There is no requirement for intensive care of the native heart, since it is gone, along with toxic antiarrhythmic medications, risk of embolizing a mural thrombus, and the constant balancing of a univentricular device vis-á-vis the native heart. Further, if pulmonary edema is present with accompanying elevation in pulmonary vascular resistance, the biventricular device requires only an upward adjustment in right drive pressure. With a univentricular device one must worry not only about the pulmonary vascular resistance but also about the capacity of the right heart to pump at a normal output.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

A study of zinc status of elderly institutionalized patients.

In a study of zinc status in the elderly, the mean serum and leucocyte zinc concentrations were found to be significantly lower in continuing-care patients compared with elderly people living in the community. The mean daily dietary intakes of zinc, protein and fibre did not differ between the two groups. Serum zinc levels were found to correlate with serum albumin levels. No significant relationship was found between the mean serum or leucocyte zinc concentrations of patients and either their mental status or the presence of skin pressure damage, leg ulcers or unhealed wounds.

Aged↗

Undergraduate teaching of geriatric medicine in the United Kingdom: changes in the years 1981-1986.

A follow-up survey of undergraduate teaching of geriatric medicine was carried out in 1986. All 27 clinical medical schools responded. Geriatric medicine is taught to all medical students in 25 and to only a proportion of students in two. Fifty-nine per cent of schools have academic departments teaching for a mean of 89 hours compared with 33 hours in non-academic departments--an overall mean of 68 hours. The subject is taught by various methods with 70% of teaching time spent on bedside clinical instruction. Other aspects of institutional and community care are often covered. The subject is examined in 18 schools. New academic departments are planned at four schools, and an increase in teaching time planned in five. To meet the needs of the population of the next century, reconsideration of curricula in some of the medical schools is recommended.

Curriculum↗