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C J Smith

Publications and source records attributed to C J Smith.

At least 145 records · Page 8Linked to original sources
PubMed1995

Age at onset and familial risk in Alzheimer's disease.

OBJECTIVE: The authors investigated the relationship between probands' age at onset of Alzheimer's disease with the risk of primary progressive dementia in the probands' first-degree relatives. METHOD: Two hundred probands with clinically diagnosed Alzheimer's disease and 179 nondemented elderly probands were recruited from the Mount Sinai Alzheimer's Disease Research Center, located at Mount Sinai Hospital and the Bronx Veterans Affairs Medical Center. Demographic and diagnostic data were collected on 1,398 of the first-degree relatives of the probands with Alzheimer's disease and 955 first-degree relatives of the nondemented probands. RESULTS: Cox proportional hazards regression analysis showed a significant inverse relationship between age at onset of Alzheimer's disease in probands and greater familial risk in their relatives. Follow-up analyses indicated that the most commonly used age at onset cutoff point--65 years--was one of the points where an association with familial aggregation is least likely to be revealed; other onset cutoff ages (e.g., 55, 70, and 75) better identified Alzheimer's disease groups with differing familial/genetic risks. CONCLUSIONS: The authors conclude that patients with an earlier age at onset of Alzheimer's disease are more likely to have relatives with Alzheimer's disease than are patients with a later age at onset of the disease. An onset age of 70 best differentiated probands whose relatives were at higher risk from those whose relatives were at lower risk.

Age of Onset↗
PubMed1995

Blood parameters associated with atherogenic and thrombogenic risk in smokers and nonsmokers with similar life-styles.

Current evidence indicates that life-style factors can affect the risk of developing cardiovascular disease. The life-style of cigarette smokers, as a group, differs in many ways from that of nonsmokers. Most studies that compare clinical pathologic findings related to atherogenic and thrombogenic risk in smokers and nonsmokers do not adequately control for most of the life-style differences between these two groups. In this study, a number of atherogenic risk factors (cholesterol, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, high-density lipoprotein/cholesterol, triglycerides, and glucose) and thrombogenic risk factors (total white blood cell count, total red blood cell count; percent of monocytes, lymphocytes, neutrophils, basophils, and eosinophils; interleukin-1, leukotriene B4, hematocrit, hemoglobin, bilirubin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, platelet count, prothrombin time, partial thromboplastin time, and fibrinogen) were compared in male and female cigarette smokers and non-smokers who were selected to have approximately similar self-reported life-styles (i.e., food, alcohol, and vitamin consumption and exercise level). However, the smokers (male and female) consumed more coffee (P < 0.05) than the nonsmokers. A trend toward blue-collar versus white collar occupational status was also observed in the male smokers relative to male nonsmokers. Cigarette consumption and urinary cotinine and carboxyhemoglobin levels did not differ between male and female smokers. Atherogenic and thrombogenic values were determined from venous blood samples. No statistically significant (P > 0.05) differences in clinical pathologic findings related to atherogenic risk were observed between the smokers and nonsmokers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Enhanced responses to L-arginine in aortic rings from rats with angiotensin-dependent hypertension.

We contrasted, in normotensive and hypertensive rats, the effect of L-arginine on isometric tension of phenylephrine-contracted rings of aorta bathed in Krebs' bicarbonate buffer on cyclic guanosine monophosphate content of aortic rings and on blood pressure. L-Arginine had no effect on isometric tension or cyclic guanosine monophosphate content of aortic rings from normotensive controls. Conversely, L-arginine (10(-5)-10(-3) mol/l) induced concentration-dependent relaxation of unrubbed and rubbed rings of thoracic and abdominal aorta and, as well, L-arginine (10(-3) mol/l) increased cyclic guanosine monophosphate in unrubbed and rubbed rings of thoracic aorta taken from hypertensive rats 7 to 14 days after aortic coarctation. Similar relaxations to L-arginine were seen in rings of thoracic and abdominal aorta from rats made hypertensive by infusion of angiotensin II for 7 to 8 days but not in rings of thoracic aorta from rats with aortic coarctation-induced hypertension of 28 to 42 days. Relaxant responses to L-arginine in rings of thoracic aorta from hypertensive rats 7 to 14 days after aortic coarctation were unaffected by pretreatment of rings with dexamethasone (10(-7) mol/l) or L-arginine (10(-4) mol/l) but were blunted by NG-nitro-L-arginine methylester (3 x 10(-4) mol/l) or methylene blue (10(-5) mol/l). Our results suggest that the vasorelaxant effects of L-arginine in aortic rings from hypertensive rats 7 to 14 days after aortic coarctation and 7 to 8 days after commencing angiotensin II infusion are mediated by nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Fast stress and rest acquisitions for technetium-99m-sestamibi separate-day SPECT.

UNLABELLED: Abbreviated acquisition protocols were designed for stress and rest to decrease stress and rest SPECT image acquisition times but maintain the high count density of 99mTc-sestamibi separate-day cardiac images. METHODS: Scan findings were compared visually and quantitatively with standard SPECT for 12 rest and 32 stress patient studies. RESULTS: Of 29 stress defects detected by standard SPECT, 27 were present with the fast technique; of 8 resting SPECT defects, all were detected with fast SPECT. Two stress and no resting false-positive defects occurred with fast SPECT. Linear correlations (r) between standard and fast quantitative defect extent and severity were 0.76 and 0.86, respectively for stress SPECT, and 0.88 and 0.96 for rest SPECT. Stress fast defects were slightly less severe (p = 0.02) than those observed using standard acquisition. CONCLUSION: We conclude that these fast protocols for separate-day 99mTc-MIBI SPECT accurately detect and characterize perfusion defects and provide a means to improve patient tolerance and increase laboratory throughput.

Coronary Disease↗
PubMed1995

Management of the hypertensive patient: a case report.

Hypertension is a potentially life-threatening condition that can lead to heart failure, stroke, and kidney disease. Most patients with hypertension can be treated and controlled if they are diagnosed in a timely manner. This case report exemplifies how the dentist can play a key role in the detection of hypertension by simply taking vital signs on all patients. It is incumbent upon us as health-care professionals to understand the causes of hypertension, the therapeutic drugs used and associated side effects, and the potential for drug interactions. The dentist's ability to recognize and appropriately manage hypertension will greatly enhance the health and safety of our patients.

Adult↗
PubMed1994

Investigation of the role of cysteines in catalysis by prostaglandin endoperoxide synthase.

The importance of cysteine residues in the cyclooxygenase activity of prostaglandin endoperoxide synthase (PGHS) was investigated using cysteine-specific reagents and site-directed mutagenesis. N-(7-Dimethyl-amino-4-methyl-3-coumarinyl)maleimide (DACM), a hydrophobic maleimide, inactivated both cyclooxygenase and peroxidase activities of apoPGHS in a time-dependent manner but did not affect holoPGHS. Heme titration experiments indicated that modification of apoPGHS with DACM prevented heme binding. Peptide mapping revealed that DACM modified Cys313, Cys512, and Cys540. N-Ethylmaleimide inactivated cyclooxygenase and peroxidase activities of holoPGHS in a time-dependent manner but did not affect apoPGHS. Peptide mapping demonstrated that N-ethylmaleimide reacted primarily with Cys313 in holoPGHS and with Cys540 in apoPGHS. Each of the 3 cysteines was changed to serine by site-directed mutagenesis, and the mutant proteins were expressed in COS-1 cells. The C512S mutant converted arachidonic acid to products to the same extent as wild-type PGHS. In contrast, the C313S and C540S mutants converted arachidonic acid to products to the extent of 10% of wild-type PGHS. These results indicate that Cys313, Cys512, and Cys540 are not essential for cyclooxygenase activity but that alteration of Cys540 or Cys313 dramatically decreases enzyme activity. Both residues are well removed from the cyclooxygenase and peroxidase active sites so our findings reveal that subtle changes, such as substitution of a single oxygen for sulfur atom as far as 30 A from the heme prosthetic group, can significantly alter enzyme activity.

Animals↗
PubMed1994

Prion protein is necessary for normal synaptic function.

The prion diseases are neurodegenerative conditions, transmissible by inoculation, and in some cases inherited as an autosomal dominant disorder. They include Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. The prion consists principally of a post-translationally modified form of a host-encoded glycoprotein (PrPC), designated PrPSc (ref. 1); the normal cellular function of PrPC is, however, unknown. Although PrP is highly conserved among mammals and widely expressed in early embryogenesis, mice homozygous for disrupted PrP genes appear developmentally and behaviourally normal. PrP is a protein anchored to the neuronal surface by glycosylphosphatidylinositol, suggesting a role in cell signalling or adhesion. Here we report that hippocampal slices from PrP null mice have weakened GABAA (gamma-aminobutyric acid type A) receptor-mediated fast inhibition and impaired long-term potentiation. This impaired synaptic inhibition may be involved in the epileptiform activity seen in Creutzfeldt-Jakob disease and we argue that loss of function of PrPC may contribute to the early synaptic loss and neuronal degeneration seen in these diseases.

Action Potentials↗
PubMed1994

Identification of the phosphorylation site in vitro for cAMP-dependent protein kinase on the rat adipocyte cGMP-inhibited cAMP phosphodiesterase.

Rat adipocyte cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) appears to be dually regulated in intact cells by serine phosphorylations induced by isoprenaline and insulin, respectively (Degerman, E., Smith, C. J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V. C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 533-537; Smith, C. J., Vasta, V., Degerman, E., Belfrage, P., and Manganiello, V. C. (1991) J. Biol. Chem. 266, 13385-13390). Since cAMP-dependent protein kinase (cAMP-PK) catalyzes the beta-adrenergic effects, the site in the isolated cGI-PDE phosphorylated by this kinase was explored. A peptide, LRRSSGASGLLTSEHHSR (P18), corresponding to the amino acid sequence Leu423-Arg440 in the putative regulatory domain of the rat adipocyte cGI-PDE was synthesized. It contains a consensus substrate sequence -RRXS- for cAMP-PK within two tryptic cleavage sites and was readily phosphorylated by cAMP-PK. Two phosphopeptides, identified as RS-[32P]SGASGLLTSEHHSR and S-[32P]SGASGLLTSEHHSR, were obtained after stoichiometric phosphorylation and trypsinization of the peptide. These two peptides and the two main tryptic phosphopeptides obtained from immunoisolated [32P]cGI-PDE phosphorylated with cAMP-PK in a solubilized crude adipocyte membrane fraction were immuno-precipitated by an affinity-purified polyclonal antibody raised against P18 and exhibited the same chromatographic and electrophoretic profiles in three different separation systems. Similar radiosequencing profiles indicated that the second most N-terminal serine, corresponding to Ser-427 in the intact cGI-PDE, was phosphorylated by cAMP-PK in both P18 and authentic cGI-PDE. It is concluded that serine 427 is the target for cAMP-PK phosphorylation of the rat adipocyte cGI-PDE in vitro.

Adipocytes↗
PubMed1994

Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase.

The human platelet cilostamide- and cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) was rapidly purified approximately 19,000-fold to apparent homogeneity using single step affinity chromatography on the isothiocyanate derivative of cilostamide coupled to aminoethyl agarose. Within 24 h, 30 micrograms of enzyme protein was obtained from 20 ml of packed platelets. Vmax for cAMP and cGMP was 6.1 and 0.9 mumol/min per mg protein, respectively. Several polypeptides (110/105, 79, 62, 55/53 kDa) were identified after SDS-PAGE, all of which were immunologically related to cGI-PDE and represented approx. 5, 20, 50 and 20% of the total protein, respectively. Limited proteolysis of the cGI-PDE with chymotrypsin produced a major fragment of approximately 47 kDa (and at least two smaller peptides) with catalytic activity and sensitivity to cGMP and OPC 3911 similar to controls. Phosphorylation of the cGI-PDE by cAMP-dependent protein kinase (A-kinase) resulted in maximal incorporation of 0.6-1.8 mol of 32P/mol 110/105 and 79 kDa polypeptides; much lower and variable amounts of phosphate were incorporated into the 62 and 55/53 kDa polypeptides. After digestion of cGI-PDE with several proteinases a number of peptides were isolated and sequenced. Most of the peptide sequences obtained could be aligned within the carboxy terminal domain of the deduced sequence of the human cardiac cGI-PDE. These and other results suggest that the subunit size of the intact platelet cGI-PDE is 110 kDa and that proteolytic fragments of 79, 62 and 55/53 kDa are produced during purification. The smaller fragments (62 and 55/53 kDa) contain the catalytic domain; the larger fragments (110 and 79 kDa) also contain the regulatory domain with phosphorylation sites for A-kinase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Patterns of risk in first-degree relatives of patients with Alzheimer's disease.

BACKGROUND: Although an increased cumulative risk for primary progressive dementia (PPD) has been repeatedly demonstrated in relatives of probands with Alzheimer's disease (AD), an examination of their rates of illness at different ages has not been previously undertaken. Such an examination might reveal possible age-related characteristics associated with a more familial variety of AD. METHODS: Using family history interviews and survival analysis, the cumulative risk for and 5-year age-specific hazard rates of PPD were assessed in the first-degree relatives of 200 probands with AD and two nondemented control groups--179 elderly ascertained through the Alzheimer's Disease Research Center (ADRC-derived controls) and 427 elderly ascertained from community senior centers (community controls). RESULTS: The PPD risk curve for the relatives of probands with AD rose to about 30% and was significantly higher than the curves for the relatives of the ADRC-derived and community controls, where comparable rates were observed (approximately 12%). The age-specific hazard rates of PPD were calculated in three groups of relatives for each 5-year interval from ages 45 to 49 years through ages 85 to 89 years. The age-specific relative risk (RRi) for PPD in the relatives of probands with AD began to steadily diminish from the 75- to 79-year age interval (RRi = 13.49) through the 85- to 89-year age interval (RRi = 0.96) compared with the relatives of ADRC-derived controls and from the 60- to 64-year age interval (RRi = 16.15) through the 85- to 89-year age interval (RRi = 2.03) compared with the relatives of the community controls. CONCLUSIONS: These data indicate that, for relatives of probands with AD, while the lifetime risk for PPD is greater than in relatives of controls, the familial contribution to the risk for PPD decreases with increasing age. The higher risk for PPD in relatives of probands with AD may be substantially diminished or even eliminated by the latter half of the ninth decade.

Age Factors↗
PubMed1994

Energy intake and physical activity in Pima Indians: comparison with energy expenditure measured by doubly-labeled water.

To test the validity of survey techniques for measuring diet and activity patterns of Pima Indians, sequential 24-hour recalls, a food frequency questionnaire (FFQ), and an activity questionnaire were compared to free-living energy expenditure. Total energy expenditure (TEE) measured by doubly labeled water was 13.27 +/- 2.95 MJ/d for the 12 males (mean +/- SD: 35 +/- 14 yr; 97 +/- 35 kg; 32 +/- 9% body fat) and 11.67 +/- 1.85 MJ/d for the 9 females (31 +/- 13 yr; 106 +/- 32 kg; 49 +/- 6% body fat). Energy intake assessed by 24-hour recall was 13.59 +/- 7.81 MJ/d for men and 9.29 +/- 2.77 MJ/d for women, compared to 12.84 + 2.85 and 9.40 + 2.61 MJ/d for men and women, respectively, by FFQ. Both dietary methods indicated significant underreporting by women when compared to TEE. Energy intake assessed by FFQ was significantly correlated with TEE (r=0.48, p=0.03). This was true with 24-hour recall energy intake only when data from two extremely large alcohol consumers were eliminated (r=0.64, p=0.03, N=19). Although a low level of activity was apparent, the activity questionnaire produced significant correlations with measurements of energy expenditure and therefore represents an important tool for examining the relationship between physical activity and diseases.

Adult↗
PubMed1994

The effect of intraperitoneal N-methyl-N-nitrosourea on hamster palatal gingiva and intermolar mucosa.

Fifty 4- to 6-week-old male random-bred golden hamsters were injected intraperitoneally with a weight-related dose (12.5 mg/kg body weight) of N-methyl-N-nitrosourea (NMU) three times a week for 4 weeks. Groups of seven animals were killed 10, 16 and 22 weeks after the first injection. The palatal gingiva from six animals and the intermolar mucosa from 21 animals was examined. Seven male age-matched untreated control animals were killed at each period. Although all NMU-treated hamsters showed dysplastic and neoplastic changes similar to those in human oral squamous-cell carcinoma, other changes such as acantholytic dyskeratosis, invading cysts, duct-like structures and basaloid islands and cords were not. The extent and severity of the changes increased with time so that by 22 weeks there was extensive involvement of the palatal bone and marrow spaces, the molar periodontal ligament and the greater palatine neurovascular bundle by neoplastic epithelium. The invading epithelium was derived from the junctional, crevicular and palatal gingival and intermolar epithelium. The latent period for the crevicular and junctional epithelia was shorter than that for the palatal gingival and intermolar epithelium. The invasive changes from the latter epithelium were often preceded by exophytic changes such as epithelial projections, papillae and papillomas. Such changes were infrequent for the gingival, crevicular and junctional epithelia. The study shows that intraperitoneal NMU acts as a complete carcinogen on the palatal gingival and intermolar epithelium in hamsters.

Animals↗
PubMed1994

Restraint inhibits luteinizing hormone secretion in the follicular phase of the menstrual cycle in rhesus macaques.

The present study investigated the question of how restraint affects the hypothalamo-pituitary adrenocortical axis and the hypothalamo-pituitary gonadal axis in intact, adult female rhesus macaques in both the follicular and luteal phases of the menstrual cycle. Restraint was chosen because it is not physically harmful to the animal but rather serves primarily as a psychological stressor. Blood samples were collected from a remote site at 15-min intervals beginning at 0700 h from tethered adult female rhesus macaques. Each animal was subjected to 6 h of chair restraint after a 3-h control period in the animal's home cage. Samples were collected for an additional 6 h after the end of the restraint period, when each animal was returned to its home cage. Brief anesthesia with ketamine (administered through indwelling catheter) facilitated transfer of the animals to and from the chair. Blood samples were also collected from undisturbed females in both the follicular and luteal phases to document LH, cortisol, and progesterone secretion throughout the day. Plasma ACTH and cortisol, measured as indices of stress, were elevated within 15 min after initiation of restraint and remained elevated after the animals were returned to their cages. In animals sampled in the follicular phase, mean plasma LH levels were lower during restraint and remained suppressed for several hours after the animals were removed from restraint. LH levels were not significantly inhibited by restraint in the luteal phase. When the opiate receptor antagonist naloxone (Nx; 5 mg bolus plus 5 mg/h) was given beginning 2 h after the initiation of restraint, LH levels were elevated compared to prerestraint levels in both phases of the menstrual cycle. These data indicate that restraint is a potent activator of the pituitary-adrenal axis and that at least in the follicular phase of the menstrual cycle, restraint inhibits pituitary LH release. This inhibition of gonadotropin release may involve endogenous opiate suppression of GnRH release, since Nx reversed the effect of restraint.

Adrenocorticotropic Hormone↗
PubMed1994

Molecular and genetic analysis of the Bacteroides uniformis cephalosporinase gene, cblA, encoding the species-specific beta-lactamase.

The gene, cblA, encoding the species-specific, clavulanate-susceptible, endogenous cephalosporinase was cloned from Bacteroides uniformis WAL-7088. The nucleotide sequence was determined, and the cblA structural gene was found to be 891 nucleotides, with a 48% G+C composition, which is similar to that of the B. uniformis genome. The cblA open reading frame encoded an Ambler class A beta-lactamase polypeptide precursor of 296 amino acid residues with a predicted molecular weight of 33,450. A beta-lactamase-deficient B. uniformis mutant with increased beta-lactam susceptibility was constructed by insertional inactivation of the chromosomal gene. This mutant was complemented by plasmids bearing the cblA gene, and the resulting strains were resistant to cephaloridine and had a beta-lactamase that comigrated with the parental beta-lactamase on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (30,500 Da) and in isoelectric focusing gels (pI 4.6), confirming a role for this beta-lactamase in resistance.

Amino Acid Sequence↗