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Biomedical subjects

J F Collins

Publications and source records attributed to J F Collins.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effect of valproate on cognitive functioning. Comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group.

OBJECTIVE: To assess the effects of carbamazepine vs valproate sodium on cognitive functioning in patients with epilepsy compared with normal control subjects. DESIGN: Patients with recently diagnosed, previously unmedicated seizures participated in a prospective randomized double-blind Department of Veterans Affairs multicenter study of the efficacy and toxicity of carbamazepine vs valproate. MAIN OUTCOME MEASURE: A behavioral toxicity battery was administered prior to treatment and again 6 and 12 months after the initiation of antiepileptic medication. RESULTS: There were no significant differences in the effect of carbamazepine vs valproate on motor speed and coordination, memory, or concentration and mental flexibility, and there was no significant decline in neuropsychological performance from pretreatment baseline levels for either drug. No significant differences in performance were found between patients with low (mean, 52.8 micrograms/mL) vs high (mean, 94.4 micrograms/mL) serum valproate levels within the therapeutic range. Patients treated with either carbamazepine or valproate did not show practice effects experienced by normal controls, a finding that may reflect a subtle compromise in cognitive functioning. CONCLUSION: The impact of carbamazepine and valproate monotherapy on cognitive functioning is similar: both drugs produce minimal negative effects compared with pretreatment baseline performance.

Adult↗
PubMed1996

The role of the cytoskeleton in left ventricular pressure overload hypertrophy and failure.

To characterize alterations in gene expression which may occur during the development of compensated left ventricular pressure overload hypertrophy (CH) and the transition to decompensated congestive heart failure (DH), differential RNA display was used to compare mRNA transcripts from sham operated, 4-week, and 8-week thoracic aorta banded guinea-pigs. Of several regulated transcripts chosen for analysis, one was identified by nucleotide sequence homology as titin, a sarcomeric cytoskeletal protein. By differential display and comparative PCR, titin transcripts were increased in CH and then declined in DH. Comparative PCR of desmin and tubulin demonstrated increased mRNA levels for these cytoskeletal proteins in CH and DH. Western analysis showed associated increases in titin (DH) and desmin (CH and DH) protein expression but no increase in tubulin protein. Isolated Langendorff cardiac mechanics failed to reveal functional differences in either hypertrophy phenotype when microtubules were depolymerized (colchicine 10(-6)M). In summary, the major cytoskeletal proteins are differentially regulated in LV pressure overload hypertrophy and failure. Neither the level of beta-tubulin or its polymerization state appear to affect LV function in this model of cardiac hypertrophy.

Animals↗
PubMed1996

The molecular defect in the renal sodium-phosphate transporter expression pathway of Gyro (Gy) mice is distinct from that of hypophosphatemic (Hyp) mice.

Two animal models of the human disorder hypophosphatemic vitamin D-resistant rickets exist, the Hyp and Gy mice. Affected mice and humans both manifest an X-linked phenotype, and show decreased Na+/Pi transport activity in the renal proximal tubules, which is characterized by a decreased maximal velocity (Vmax). The defect in Hyp mice is most likely due to a decreased transcription rate of the renal Na+/Pi transporter gene. The current studies were designed to define the molecular defect in the Gy mice. Sodium-dependent uptake of phosphate (Pi) in renal BBMV showed uptake levels of 170.58 +/- 25 and 66.00 +/- 11 pmol x mg protein-1 x 6 s-1 in normal and Gy mice, respectively (n=3, P=0.0102). Glucose uptake levels in the BBMV were 1.94 +/- 0.87 and 1.91 +/- 0.35 pmol x mg protein-1 x 6 s-1 in normal and Gy mice, respectively (n=3). Northern blot analysis of kidney cortex in both mice revealed nearly equivalent message levels (normal/Gy=1.01 +/- 0.12, n=3). In situ hybridization localized the mRNA to the renal cortex in both mice and confirmed equal message levels. Western blot analysis of renal BBM proteins, using a polyclonal antiserum, showed one predominant band at 87 kDa in both mouse samples, with intensities being decreased in the Gy mice (normal/Gy=4.129 +/- 0.70, n=4, P< 0.04). Immunohistochemical analysis localized the protein to the apical membrane of proximal tubules in both mice. These results suggest that the molecular defect in the Gy mice is distinct from that in the Hyp mice, and furthermore, that the manifestation of the diseased phenotype in Gy mice is related to a different defect in the renal Na+/Pi transporter expression pathway. The molecular mechanism of the defect likely relates to protein processing, metabolic turnover rate, or translocation to the brush-border membrane. These results further suggest that two distinct X-linked factors modulate different steps in the expression pathway of the Na+/Pi transporter gene.

Animals↗
PubMed1996

Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group.

BACKGROUND: Two prospective observations of adults with symptomatic, localization-related (partial) epilepsy included 1,102 patients in VA multicenter studies (VA-118 and VA-264). Analyses assessed the likelihood of remaining seizure free for 12 and 24 months after initiating adequate antiepileptic drug therapy. METHODS: Patients were grouped as having only secondarily generalized tonic-clonic seizures (GTC), only complex partial seizures (CPS), or both types (MIXED) at entry. The cumulative proportion of patients remaining seizure free with standard antiepileptic drug therapy was determined by actuarial life table methods. RESULTS: At 12 months, 70% and 61% of GTC patients (VA-118 and VA-264, respectively) had no further GTC; 53% and 50% of MIXED, predominantly GTC patients had no further GTC, 21% and 28% of CPS patients had no further CPS and 98% and 91% were seizure free for GTC; 32% and 35% of MIXED, predominantly CPS patients had no further CPS, and 62% and 51% of patients with MIXED seizure types remained seizure free for CPS for 12 months after enrollment. CONCLUSIONS: The overall prognosis for control of seizures of any type for 12 months was best for those who had only GTC at entry (55% and 48%), worst for those who had only CPS at entry (23% and 26%), and intermediate for those with MIXED seizures at entry (32% and 25%) (all p < 0.0001). Prognosis can be based on the predominant seizure type in patients with multiple types.

Adult↗
PubMed1995

Local and systemic phentolamine antagonism of norepinephrine-induced hand vein constriction.

The dorsal hand vein distention technique has been used to study the effects of alpha-adrenergic receptor antagonists on alpha-agonist-induced venoconstriction. Using this technique, we investigated the dose-effect relationships between different intravenous routes of phentolamine (an alpha-antagonist) administration on norepinephrine (an alpha-agonist)-induced hand vein constriction. Hand vein studies were done on healthy men; each man was studied on up to four occasions. On one occasion for each man, graded doses of phentolamine were infused into a hand vein preconstricted (submaximally) with norepinephrine. The dose of phentolamine producing a half maximal response (ED50) for reversal of venoconstriction, and the maximal reversal were calculated. On the other three occasions (randomly allocated) for each man, graded doses of norepinephrine were infused into a hand vein before and during intravenous infusions of (1) control (vehicle solutions); (2) systemic (other arm vein) phentolamine; and (3) local (hand vein) phentolamine. Systemic and local phentolamine dose ratios (ED50 of norepinephrine during phentolamine, divided by ED50 of norepinephrine before phentolamine; divided by the control dose ratio) were calculated. These studies show that phentolamine (administered directly into a preconstricted hand vein) can completely reverse norepinephrine-induced venoconstriction. Phentolamine, administered by either local or systemic intravenous infusion, induces a significant rightward shift (approximately 10-fold) in responsiveness to norepinephrine-induced venoconstriction. To achieve comparable degrees of alpha-antagonism, however, systemic phentolamine must be administered intravenously at a dose approximately 3,000-fold higher than that of local phentolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Finding flexible patterns in unaligned protein sequences.

We present a new method for the identification of conserved patterns in a set of unaligned related protein sequences. It is able to discover patterns of a quite general form, allowing for both ambiguous positions and for variable length wildcard regions. It allows the user to define a class of patterns (e.g., the degree of ambiguity allowed and the length and number of gaps), and the method is then guaranteed to find the conserved patterns in this class scoring highest according to a significance measure defined. Identified patterns may be refined using one of two new algorithms. We present a new (nonstatistical) significance measure for flexible patterns. The method is shown to recover known motifs for PROSITE families and is also applied to some recently described families from the literature.

Algorithms↗
PubMed1995

Validation of the Banff criteria for acute rejection in renal transplant biopsies.

BACKGROUND: The histological criteria for the diagnosis of mild acute rejection in renal transplant biopsies have not been well defined. AIM: To ascertain the value of the Banff criteria for transplant biopsy reporting, particularly for the diagnosis of acute rejection, and the 'borderline' category. METHODS: We compared two systems of histological assessment in 23 transplant biopsy specimens and compared histological diagnoses to separately defined clinical diagnoses. The histological criteria applied were those of the recently described Banff criteria which were compared with our traditional diagnostic method for each specimen. RESULTS: We found the Banff diagnoses more closely related to the clinical outcome than the system of histological diagnosis that we had previously been using. CONCLUSIONS: We conclude that the Banff criteria more accurately reflect the clinical situation.

Acute Disease↗
PubMed1995

Sodium-phosphate transporter adaptation to dietary phosphate deprivation in normal and hypophosphatemic mice.

The X-linked hypophosphatemic (Hyp) mouse is a model for hypophosphatemic vitamin D-resistant rickets and is a homologue of human X-linked hypophosphatemia. The defect in the Hyp mouse appears to be related to decreased renal tubular reabsorption of P(i) via the renal brush-border membrane (Na(+)-P(i)) transporter. Dietary P(i) deprivation upregulates Na(+)-P(i) transport activity in brush-border membrane vesicles (BBMV) isolated from both normal and Hyp mice; however, the molecular mechanisms underlying this phenomenon are not known. The current studies were designed to investigate the effect of P(i) deprivation on the renal Na(+)-P(i) transporter. Low P(i) diet upregulated Na(+)-P(i) transporter activity in isolated BBMV by 2.1-fold in normal and Hyp mice (n = 3, P = 0.01). Low P(i) diet also induced a 1.9 +/- 0.3-fold increase in normal mice and 2.9 +/- 0.4-fold increase in Hyp mice in Na(+)-P(i) transporter message levels (n = 3, P = 0.028). The increase in message level encoding the Na(+)-P(i) transporter stimulated increased Na(+)-dependent P(i) uptake by Xenopus laevis oocytes when poly(A)+ RNA was injected into them from mice on low P(i) diet (approximately 1.67-fold in normal mice and 1.33-fold in Hyp mice). Immunoreactive protein levels increased 2.3 +/- 0.4-fold in normal mice and 8.2 +/- 0.5 in the Hyp mouse kidney cortexes (n = 3, P = 0.0001) in response to dietary P(i) deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Decreased transcription of the sodium-phosphate transporter gene in the hypophosphatemic mouse.

Recently, it has been hypothesized that the proximal tubular Na(+)-Pi transporter may play a role in murine X-linked hypophosphatemic vitamin D-resistant rickets. In the present investigation, Western blot analysis of renal brush-border membrane proteins, utilizing polyclonal antisera raised against the mouse Na(+)-Pi transporter, revealed a predominant band at 87 kDa in normal and hypophosphatemic (Hyp) mice. The intensity of this band was reduced in the Hyp mouse by 4.5-fold (Hyp/normal = 0.22 +/- 0.04, n = 3, P < 0.05). Additionally, immunohistochemical analysis of kidney cortex in both mice localized the protein to the apical membrane of the proximal tubules. Relative transcription rates of the Na(+)-Pi transporter gene in the normal and Hyp mouse were then investigated. Nuclear run-on assays showed a 51 +/- 0.02% decreased rate of transcription of the Na(+)-Pi transporter gene in the Hyp mice (n = 3). Thus abnormal transcriptional control of this gene in the Hyp mouse likely plays a role in X-linked hypophosphatemia.

Animals↗
PubMed1995

Cancer risk assessment for crystalline silica to implement California's hot spots act.

Crystalline silica has been identified as a probable human carcinogen. To assess the potential for adverse health effects due to environmental exposures to respirable crystalline silica, a quantitative estimate of carcinogenicity has been made using incidence data from three studies in which long-term silica inhalation caused lung tumors in rats. The uncertainties in risk assessment in general and in the risk assessment for silica in particular are discussed.

Animals↗
PubMed1994

Assessing shade differences in acrylic resin denture and natural teeth.

Four experiments in this study assess shade differences in acrylic resin denture and natural teeth. The first two examine the perceptual errors made by experienced dentists in their use of a manufacturer-provided shade guide for acrylic resin denture teeth. In the first of four experiments, dentists examine whether the numbering of a selected shade guide corresponds to the arrangement of the tabs from light to dark. In the second experiment, a visual discrimination task determines whether dentists can distinguish shade guide tabs from one another. The results from these two experiments revealed that the numbered progression of the shade tabs does not correspond to a light-to-dark order, that dentists have difficulty discriminating between several shade tabs, and that the shade tabs can be rearranged on an empirical basis. The third experiment demonstrated how the shade of natural teeth varies by age, gender, and complexion. The Biotone shade guide, rearranged in the manner suggested by the second experiment, was used to make these assessments. The fourth experiment examined whether the shades used for complete dentures were similar to shades found in natural teeth. The results from the last two experiments showed that shade selection can be facilitated by use of a rearranged set of shade guide tabs. The results also reveal that natural teeth significantly and clinically darken with age; however, selections made for denture teeth tend to be relatively constant in color, despite the age of the patient. Differences for gender and complexion do not appear to be clinically significant.

Acrylic Resins↗
PubMed1994

Determinants of left ventricular hypertrophy and systolic dysfunction in chronic renal failure.

To evaluate determinants of left ventricular hypertrophy (LVH) and left ventricular (LV) systolic dysfunction in chronic renal failure (CRF), M-mode and two-dimensional echocardiography were performed in 38 undialyzed patients with CRF (serum creatinine > or = 3.4 mg/dL), 54 patients receiving continuous ambulatory peritoneal dialysis, 30 patients receiving hemodialysis, and 59 healthy age- and sex-matched volunteers. Left ventricular (LV) wall thickness and LV dimensions were greatest in dialysis patients, intermediate in CRF patients, and least in control subjects. LV mass index calculated from M-mode measurements was 78.7 g/m2 +/- 14.8 g/m2 in controls, 120.5 g/m2 +/- 28.7 g/m2 in CRF patients, and 136 +/- 45.0 g/m2 in dialysis patients (P < 0.0001). LV fractional shortening and LV velocity of circumferential shortening were lower in dialysis patients than in CRF patients and controls (fractional shortening 36.5% +/- 5.6% in controls, 36.2% +/- 7.2% in CRF patients, and 29.8% +/- 8.9% in dialysis patients; P < 0.0001). Echocardiography was normal in only 24 dialysis patients (29%) and 14 CRF patients (37%) (P = NS). Thirty-nine dialysis patients (46%) and 10 CRF patients (26%) had LVH (P = NS). Thirty dialysis patients (36%) and five CRF patients (13%) had LV systolic dysfunction (P < 0.05). LV hypertrophy with LV systolic dysfunction was present in 15 dialysis patients but no CRF patients (P < 0.05). There were no significant differences between hemodialysis patients and continuous ambulatory peritoneal dialysis patients in M-mode echocardiographic measurements or the frequency of LVH and LV systolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Prevention and Treatment of Hypertension Study (PATHS). Rationale and design.

Alcohol consumption has been recognized as an important correlate of blood pressure in many epidemiologic studies, but few interventional studies have been conducted to examine the effect of a reduction in alcohol intake on blood pressure. Because these studies have usually included few subjects and been of short duration, the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the Veterans Affairs (VA) Cooperative Studies Program have initiated a randomized, controlled, multicenter trial to determine whether blood pressure and left ventricular mass are lowered over 6 months of alcohol moderation in non-dependent moderate to heavy drinkers (three or more drinks per day average but not alcohol dependent) with above-average normal (80 to 89 mm Hg) and mildly hypertensive (90 to 99 mm Hg) levels of diastolic blood pressure, and whether a reduction in alcohol intake can be maintained for 2 years. Eligible veterans are randomized to either an alcohol reduction intervention or a control observation group at seven clinical sites. The projected sample size is 580 participants. Alcohol intake is assessed by self-report using a retrospective diary (Chronological Drinking Record) and by various biochemical markers, including apolipoproteins, HDL cholesterol (and subfractions), and carbohydrate deficient transferrin, analyzed at a central laboratory. The alcohol intervention technique is a cognitive-behavioral program, the intensive phase of which consists of six counseling sessions over 3 months. Echocardiograms are obtained at baseline and 6 months after randomization. This trial has important implications for both the prevention and treatment of hypertension.

Adult↗
PubMed1994

Molecular cloning, functional expression, tissue distribution, and in situ hybridization of the renal sodium phosphate (Na+/P(i)) transporter in the control and hypophosphatemic mouse.

The current studies were designed to isolate a cDNA encoding the control mouse renal sodium phosphate (Na+/P(i)) transporter and to determine mRNA levels encoding this transporter in control and (Hyp) mice. A 2.4 kb cDNA was isolated from a control mouse kidney cDNA library using a PCR-amplified 850 base pair (bp) fragment of rat cDNA. The cDNA encoding the mouse renal Na+/P(i) transporter shows sequence similarity to the rat and human Na+/P(i) transporters. The predicted protein exhibits 98% and 91% amino acid sequence identity with the rat and human proteins, respectively. A cRNA was synthesized from the cDNA and showed an expression of sodium-dependent phosphate transport in Xenopus laevis oocytes. Northern blot analysis of renal poly(A)+ RNA from (Hyp) and control mice showed a threefold decrease in mRNA level in the (Hyp) mice compared with control mice. In situ hybridization analysis localizes the Na+/P(i) transporter message to the renal proximal tubule, with message levels distinctly lower in the (Hyp) mouse. Also, genomic Southern blotting suggests that the gene encoding the sodium phosphate transporter is structurally identical in the control and (Hyp) mice. These studies suggest that we have cloned the cDNA encoding the renal Na+/P(i) transporter in the control [C57BL/6J+/ymale] mouse, localized the message to the renal proximal tubule, and shown that the mRNA level encoding the renal Na+/P(i) transporter is decreased in the hypophosphatemic mouse.

Amino Acid Sequence↗
PubMed1994

A comparison of oral and intravenous alfacalcidol in the treatment of uremic hyperparathyroidism.

The i.v. bolus administration of 1 alpha hydroxylated vitamin D derivatives is effective in the treatment of uremic hyperparathyroidism. However, few of the published studies of this mode of treatment have been adequately controlled, and recent reports have suggested that p.o. bolus administration may be just as effective. In this study, 16 hemodialysis patients with mild to moderate hyperparathyroidism were assigned, after a 4-wk run-in period, to receive a 6-wk course of either thrice-weekly i.v. or p.o. alfacalcidol (initial dose, 4 micrograms). Then, after a further control period, they received a second 6-wk course, with either p.o. or i.v. alfacalcidol (whichever was not given in the first treatment period). Plasma parathyroid hormone (PTH) was measured weekly by the use of an intact hormone assay. Both routes of therapy resulted in a significant suppression of plasma PTH (P = 0.005) and an elevation in plasma ionized calcium (P = 0.01). The magnitude of the responses was similar for the two treatment phases, as was the relationship between the increment in calcium and the decrement in PTH. The most complete suppression of PTH was seen in those with the greatest increment in plasma calcium. The incidence of hypercalcemia and the mean dose reductions necessary were also similar in the two treatment phases. Oral bolus therapy and i.v. bolus therapy with alfacalcidol are equally effective in suppressing hyperparathyroidism. The postulated advantages of i.v. over p.o. therapy with 1 alpha hydroxylated vitamin D derivatives remain to be confirmed by controlled studies.

Administration, Oral↗
PubMed1993

Molecular cloning, sequencing, tissue distribution, and functional expression of a Na+/H+ exchanger (NHE-2).

The present studies demonstrate cloning, sequencing, tissue distribution, and functional expression of a Na+/H+ exchanger which was isolated from a rat intestinal cDNA library. The cloned cDNA recognizes two transcripts in poly(A)+ RNA from the stomach, jejunum, ileum, liver, large intestine, and uterus. Based on deduced amino acid sequences, this clone shares sequence homology with the other known Na+/H+ exchanger isoforms (NHE-1, NHE-3, and NHE-4) except for its 5' end. Overall, the protein exhibits 47.8%, 41.2%, and 56.2% amino acid sequence identity to NHE-1, NHE-3, and NHE-4, respectively. The hydropathy profile of the predicted protein shows 10 transmembrane domains, suggesting a protein with transport characteristics. The tissue distribution differs from that of the other Na+/H+ exchanger isoforms. The cDNA hybridizes to two closely related transcripts in the mRNA of these tissues, which suggests that the predominant transcript of this clone is alternatively spliced. Transfection of this cDNA into Na+/H+ exchanger-deficient mutant fibroblasts (PS120 cells) results in functional Na+/H+ exchange activity. These data suggest that we have cloned a member of the Na+/H+ exchanger family with tissue-specific expression. We suggest the designation of NHE-2 for this Na+/H+ exchanger.

Amino Acid Sequence↗
PubMed1993

TRAMP (tyrosine rich acidic matrix protein), a protein that co-purifies with lysyl oxidase from porcine skin. Identification of TRAMP as the dermatan sulphate proteoglycan-associated 22K extracellular matrix protein.

A protein (M(r)24 K) that co-purifies with porcine skin lysyl oxidase (M(r)34 K) has been isolated and characterised. Five variants of the 24 K protein were identified by Mono Q ion-exchange FPLC, as were four variants of lysyl oxidase. Amino acid analysis and partial sequencing revealed near identity of a 36-residue CNBr peptide from porcine skin lysyl oxidase to corresponding regions of the putative lysyl oxidase precursor derived from rat and human cDNA. The 24 K protein was found to be unrelated to lysyl oxidase, but comparison with a protein sequence database showed it to be the same as a recently described protein from bovine skin that is associated with dermatan sulphate proteoglycans. The 24 K protein is relatively rich in tyrosine, and isoelectric focussing shows it to be acidic, with pI's in the range 4.1 to 4.4. In view of these properties, we propose the name TRAMP (Tyrosine Rich Acidic Matrix Protein) to identify this protein. Though TRAMP appears not to be glycosylated, several experiments indicate the presence of sulphotyrosine residues. When assayed using an elastin substrate, the activity of lysyl oxidase is unaffected by TRAMP.

Alcian Blue↗