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Biomedical subjects

R M Smith

Publications and source records attributed to R M Smith.

At least 487 records · Page 27Linked to original sources
PubMed1965

Metabolism of propionate by sheep liver. Stimulation of the mitochondrial rate by factors from the cell sap.

1. The rate of metabolism of propionate by aged sheep-liver mitochondria in the presence of oxygen + carbon dioxide (95:5) was 5.0 (+/- s.e.m. 0.8) mumoles/mg. of mitochondrial N/hr. 2. When aged in the presence of the mitochondrial supernatant the rate was increased. Mitochondria from 0.33g. of liver, when combined with the corresponding mitochondrial supernatant from 0.08g. of liver, metabolized propionate at a rate of 11.4 (+/- s.e.m. 1.2) mumoles/mg. of mitochondrial N/hr. This rate is comparable with rates previously obtained with aged nuclear-free homogenates. 3. Two factors in the mitochondrial supernatant were detected, which when combined reproduced the effect of the fresh supernatant and prevented loss of activity on aging. One of these was non-diffusible and was recovered by fractionation of the dialysed mitochondrial supernatant with ammonium sulphate. The second factor was present in an ultrafiltrate of fresh mitochondrial supernatant and in boiled mitochondrial supernatant; it was isolated and identified as l(+)-glutamate. 4. The effect of the non-diffusible factor was due to protection of the mitochondria from the aging process, whereas glutamate served both in this capacity and as a direct stimulant of propionate metabolism at low concentration.

Journal Article↗
PubMedDate not supplied

An approach to sequence-specific antibody proteases. The use of haptens mimicking both a transition state and a distorted ground state.

We describe here a novel strategy for the isolation of antibodies with sequence-specific protease activity: the synthesis of dipeptide haptens in which the targeted peptide bond has been replaced by a ring-strained or torsionally strained hydroxyethylene transition-state analog. Thus, the analogs mimic both a peptide bond in a distorted, reactive conformation and the transition state for peptide bond hydrolysis. In order to obtain sequence-specific antibody proteases, these analogs have been flanked with additional amino acid residues in preparation for immunization. In particular, we have synthesized peptides containing analogs such as 2-cis-amino-3-cis-hydroxycyclobutane carboxylic acid and endo-(3-amino-2-hydroxy)bicyclo[2.2.1]-heptane-7-anti-carboxylic acid. We have also prepared a series of peptide derivatives containing analogs, such as 2-[3-amino-2-oxo-1-azetidinyl]-3-methylbutanoic acid, in which the targeted peptide bond has been incorporated into a beta-lactam ring. Since the "peptide bond" has been left intact, these species mimic only a distorted ground state. At present, antibodies are being elicited against a number of the above peptide derivatives.

Antibodies, Catalytic↗
PubMedDate not supplied

Arterial gas embolism and hemoconcentration.

The charts of all patients with diving-related accidents presenting between 1983 and 1991 were reviewed. Individuals who sustained a neurologic deficit attributable to occlusion of part of the cerebral circulation within 10 minutes of surfacing from a dive and who had a depth time profile less than 80% of the U.S. Navy "no-stop" limits were considered to have had an arterial gas embolism. Their records were reviewed to determine the hematocrit upon first presentation and the final hematocrit prior to discharge or death. Twenty-three patients had hematocrit determinations on more than one occasion. There was a significant decrease from initial to final hematocrit for these patients. No source of significant blood loss was identified in any patient. A significant correlation was found between the magnitude of the fall in hematocrit and the eventual neurologic outcome. We conclude that gas embolism diagnosed using the above criteria produces hemoconcentration, and the degree of hemoconcentration correlates with the severity of the gas embolism. These observations suggest that the pathophysiology of gas embolism is more complex than previously thought and must include diffuse endothelial injury resulting in leak of fluid from the intravascular space.

Adolescent↗
PubMedDate not supplied

Cholesterol screening in children during office visits.

Elevated blood cholesterol levels, a major risk for coronary artery disease in adults, has been associated with atherosclerotic disease in children. More than 10% of North American children have blood cholesterol levels higher than the desirable levels for adults. Current guidelines recommend screening only in children who have a family history of hyperlipidemia or myocardial infarction at an early age; however, this method fails to identify most children with hypercholesterolemia. Office-based cholesterol screening is an effective means to identify children and family members for dietary assessment and counseling. Should these measures be insufficient to lower the child's cholesterol level, referral for pharmacologic treatment is indicated.

Adolescent↗
PubMedDate not supplied

Abnormal serum biochemistries in association with arterial gas embolism.

Although diving-associated arterial gas emboli have been thought to embolize the cerebral circulation preferentially, more recent evidence suggests that gas bubbles disseminate widely and may cause dysfunction in multiple organ systems. We performed a retrospective survey of the records of patients presenting with diving-associated gas embolism over a 10-yr period to determine the maximal levels of serum transaminases and lactate dehydrogenase after a diving accident. Twenty-nine subjects with arterial gas embolism were identified whose dive profiles suggested that decompression sickness was unlikely. Maximal transaminase levels (aspartate amino transaminase = 442 +/- 187 IU/L; alanine amino transaminase = 315 +/- 205 IU/L) and lactate dehydrogenase level (800 +/- 227 IU/L) were significantly greater in the gas embolism patients than those levels measured in a group of normal individuals undergoing training dives of similar depth and duration. These preliminary studies suggest that arterial gas embolism frequently produces significant abnormalities in serum enzyme activity in sport divers whose dives would not be expected to produce decompression sickness. Arterialized gas bubbles may circulate widely, causing injury outside of the cerebral circulation.

Adolescent↗
PubMedDate not supplied

Isolated cervical recurrence of squamous cell carcinoma in the previously treated neck.

PURPOSE: Our study goal was to identify clinical factors associated with, and that might predict, treatment outcome for patients with an isolated cervical recurrence of squamous cell carcinoma in the previously treated neck (ICR-PTN). MATERIALS AND METHODS: We reviewed all patients with noncutaneous head and neck squamous cell carcinoma treated at our tertiary care center between 1987 and 1997, and identified 17 patients (2%) who later developed an isolated recurrence in a previously treated neck. These patients made up our study group, and their charts were thoroughly reviewed. Outcome of salvage therapy (surgery, radiation, or combined therapy) for these patients was compared with pooled clinicopathologic data using the Fisher exact test (one tail). RESULTS: Fifteen such ICR-PTN patients consented to salvage therapy. Six patients were without disease at last follow-up, and 3 were successfully palliated. A statistically significant association between the side of ICR-PTN relative to the primary tumor and outcome of salvage therapy (P =.026) was noted, with ipsilateral neck recurrence being a favorable prognostic factor. Trends that did not meet the standard for statistical significance were observed between a better outcome of salvage therapy and the following parameters: age of less than 60, nonsurgical initial treatment of the neck, and lack of a history of a recurrence before they developed the ICR-PTN. CONCLUSIONS: The current study showed that only the side of the ICR-PTN relative to the primary site is associated with outcome of salvage therapy. Based on our findings and a review of the literature, we have developed a summary of factors that might predict which patients with an ICR-PTN are most likely to benefit from aggressive salvage therapy.

Adult↗
PubMedDate not supplied

Prolongation of heterotopic heart allograft survival by portal venous injection of alloantigen: the role of hepatic nonparenchymal cells.

The induction of immune hyporesponsiveness in transplantation is a complex interaction between the immune system and the alloantigen. The route by which an antigen is introduced to the immune system plays an important role in the immune response. Antigen delivered via the portal circulation has the ability to induce T-cell hyporesponsiveness. In this study we examined the mechanism responsible for the induction of hyporesponsiveness by assessing immune response following portal vein (pv) injection of donor alloantigen. C57B1/6 mice were immunized via pv with splenic mononuclear cells (SMNC) from BALB/c mice. The recipient immune response was assessed in vivo by murine heterotopic heart transplant survival. SMNC and hepatic nonparenchymal cells (NPC) were isolated from pv immunized animals and used as regulatory cells in a one-way mixed lymphocyte culture (MLC) as a measure of in vitro recipient responder SMNC proliferation. Survival of murine heterotopic heart transplants was prolonged following pv injection of alloantigen (p < .04 compared to nonimmunized or systemically immunized mice). Stimulation of responder SMNCs isolated from pv immunized mice resulted in an antigen-specific hyporesponsiveness (p < .05 compared with nonimmunized or systemically immunized mice). Cocultures of responder SMNCs from nonimmunized (naive) mice with hepatic NPC from previously pv immunized mice resulted in attenuation of T-cell proliferation in MLR following stimulation with donor alloantigen (p < .05 compared to coculture with NPC from nonimmunized mice or SMNC from pv immunized mice). These data would suggest that the hepatic NPC plays an important role in the regulation of the immune response. With further identification of cell subtypes responsible for induction of hyporesponsiveness, future therapies may be directed at these specific targets, thereby minimizing the harmful side effects of current immunosuppressive therapies.

Animals↗
PubMedDate not supplied

Hydroxymethoxybenzoylmethylecgonines: new metabolites of cocaine from human urine.

4'-Hydroxy-3'-methoxybenzoylecgonine methyl ester (IIIe) and 3'-hydroxy-4'-methoxybenzoylecgonine methyl ester (IIId) were identified as cocaine metabolites in the urine of an admitted habitual polydrug user. The mass spectra and relative gas-liquid chromatography retention times of these metabolites were compared with those of five synthesized hydroxymethoxycocaine positional isomers. IIIe was also identified by mass chromatography in the urine of three patients who received emergency treatment for cocaine abuse.

Adult↗