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Biomedical subjects

G Wolfe

Publications and source records attributed to G Wolfe.

At least 19 recordsLinked to original sources
PubMed2001

Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.

Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart.

Alleles↗
PubMed2001

Cervicobrachial involvement in diabetic radiculoplexopathy.

Diabetic radiculoplexopathy is commonly viewed as a condition affecting the lower extremities. However, other regions may also be affected and the presence of upper extremity involvement has rarely been emphasized. Our goal was to illustrate the clinical features of arm involvement in this condition. Of 60 patients with diabetic lumbosacral radiculoplexopathy, we identified 9 who also had upper extremity involvement. The study included 8 men and 1 woman, ranging in age from 36 to 71 years. Upper limb involvement developed simultaneously with the onset of lower limb disorder in 1 patient, preceded it by 2 months in another patient, and occurred between 3 weeks and 15 months later in the remaining 7. In 5 cases, arm involvement developed after symptoms in the legs began to improve. The upper extremity weakness affected the hands and forearms most severely. It was unilateral in 5 patients and bilateral but asymmetric in 4. Pain was often present, but it was not a prominent feature. In most patients, neurologic deficits in the arms improved spontaneously after 2-9 months. We conclude that diabetic radiculoplexopathy may involve the cervical region before, after, or simultaneously with the lumbosacral syndrome. The upper limb process is similar to that in the legs, with subacutely progressive weakness and pain followed by spontaneous recovery.

Adult↗
PubMed2000

NMR studies of the association of cytochrome b5 with cytochrome c.

In an effort to gain greater insight into the molecular mechanism of the electron-transfer reactions of cytochrome b(5), the bovine cytochrome b(5)-horse cytochrome c complex has been investigated by high-resolution multidimensional NMR spectroscopy using (13)C, (15)N-labeled cytochrome b(5) expressed from a synthetic gene. Chemical shifts of the backbone (15)N, (1)H, and (13)C resonances for 81 of the 82 residues of [U-90% (13)C,U-90% (15)N]-ferrous cytochrome b(5) in a 1:1 complex with ferrous cytochrome c were compared with those of ferrous cytochrome b(5) in the absence of cytochrome c. A total of 51% of these residues showed small, but significant, changes in chemical shifts (the largest shifts were 0.1 ppm for the amide (1)H, 1.15 for (13)C(alpha), 1.03 ppm for the amide (15)N, and 0.15 ppm for the (1)H(alpha) resonances). Some of the residues exhibiting chemical shift changes are located in a region that has been implicated as the binding surface to cyt c [Salemme, F. R. (1976) J. Mol. Biol. 10, 563-568]. Surprisingly, many of the residues with changes are not located on this surface. Instead, they are located within and around a cleft observed to form in a molecular dynamics study of cytochrome b(5) [Storch, E. M., and Daggett, V. (1995) Biochemistry 34, 9682-9693](.) The rim of this cleft can readily accommodate cytochrome c. Molecular dynamics simulations of the Salemme and cleft complexes were performed for 2 ns and both complexes were stable.

Amino Acid Sequence↗
PubMed2000

Fatigue: the most important consideration for the patient with cancer.

The Fatigue Coalition--a multidisciplinary group of medical practitioners, researchers, and patient advocates--conducted a study to determine the effects of fatigue on cancer patients. The study, published in September 1998, examined cancer patients, caregivers, and oncologists. This survey presents new information about how fatigue is perceived by the patient, caregiver, and oncologist. In response to the survey, the group developed a series of educational and research initiatives designed to help patients and physicians better understand chemotherapy-related fatigue and provide successful interventions.

Adult↗
PubMed1999

The effects of 4-nonylphenol in rats: a multigeneration reproduction study.

The alkylphenol breakdown products of alkylphenol ethoxylates have been shown in in vitro studies to be weakly estrogenic, but few in vivo data address this issue in mammals. Because estrogens have been found to be most potent during developmental/perinatal exposures, this study maximized developmental exposure to nonylphenol (NP) by treating 3.5 generations of Sprague-Dawley rats to NP in diet at 200, 650, and 2000 ppm to determine the range and severity of any toxicity. Dose rate was higher for younger rats; calculated dose ranges were 9-35, 30-100, and 100-350 mg/kg/d for the low (200NP), middle (650NP), and high (2000NP) dose groups, respectively. There were adult (F0, F1, F2) and postnatal day (pnd) 21 (F1, F2, F3) necropsies; the oldest F3 rats were killed on pnd 55-58. Body weight gain was reduced by 8-10% in the 650NP and 2000NP groups. Vaginal opening was accelerated by approximately 2 days (650NP) and approximately 6 days (2000NP) in F1, F2, and F3 generations. Uterine weights at pnd 21 were increased in 650NP (14%) and 2000NP (50%) F1 females, but not in other generations. Testis descent, anogenital distance, and preputial separation were not consistently changed. No consistent changes were seen in pup number, weight or viability, litter indices, or other functional reproductive measures. Relative ovary weight in F2 adults was decreased at 650NP and 2000NP by 12%; relative ovary was unchanged in other generations. Follicle counts were unchanged in F2 adults. Sperm indices, including CASA measures, were unchanged in F0 and F1 males. In F2 rats, epididymal sperm density was reduced by 8% and 13% at 650NP and 2000NP, respectively. Testicular spermatid count was reduced by 13% in 2000NP F2 males; testis and epididymis weights were unchanged. Erosion of gastric and duodenal mucosa was monitored grossly and microscopically, and never found. Kidney weights were increased in 650NP and 2000NP males, and renal medullary tubular dilatation and cyst formation were noted in all generations of males, and often at the lowest dose tested. These data show that NP had limited effects on the reproductive system in the presence of measurable nephrotoxicity. The F2 sperm effects are either statistical/biological "noise," or imply heretofore unknown pharmacokinetics or toxicodynamics. These sperm data should be interpreted cautiously until the findings are repeated.

Animals↗
PubMed1995

Radiation-induced malignant fibrous histiocytoma of the brachial plexus.

Brachial plexopathy is a common and disabling complication in cancer patients most often attributed to metastasis or radiation-induced fibrosis. Occasionally, other rare but potentially treatable causes are found. A 73 year old woman had a left radical mastectomy followed by radiation to the chest wall and axilla 24 years ago. She recently presented with left arm pain, chronic, nonprogressive lymphedema, profound distal arm sensory loss and progressive severe hand weakness. There was moderate atrophy of all intrinsic hand muscles, anesthesia of the hypothenar eminence and 4th and 5th digits, and no adenopathy or palpable mass in the axilla. EMG confirmed a brachial plexopathy. MRI showed loss of tissue planes consistent with radiation fibrosis, but CT showed a discrete mass in the brachial plexus. Open biopsy showed pleomorphic spindle shaped cells with immunoperoxidase stains consistent with malignant fibrous histiocytoma. Radiation-induced malignant fibrous histiocytoma may present with a brachial plexopathy in the absence of a palpable mass and should be considered in the differential diagnosis of brachial plexus lesions in cancer patients. CT scanning through the plexus may be useful when MRI is normal or equivocal.

Aged↗
PubMed1995

Lipopolysaccharide-induced hypotension and vascular hyporeactivity in the rat: tissue analysis of nitric oxide synthase mRNA and protein expression in the presence and absence of dexamethasone, NG-monomethyl-L-arginine or indomethacin.

The role of inducible nitric oxide synthase (iNOS) was examined in the hypotension and vascular hyporesponsiveness to norepinephrine (NE) invoked by lipopolysaccharide (LPS) in pentobarbital-anesthetized rats. Saline, dexamethasone (DEX), NG-monomethyl-L-arginine (LNMMA) or indomethacin (IND) were administered either pre-LPS (0.5 hr) or post-LPS (4.5 hr) treatment. Rats were then challenged with NE 10 min before LPS injection and 1, 4, and 5 hr after LPS. Administration of LPS produced a biphasic hypotension: an immediate hypotension, which partially recovered within 15 min and was unaffected by any of the pretreatments; and a secondary, more prolonged hypotension which was attenuated by DEX, LNMMA and IND. The NE-induced pressor effects were significantly attenuated 1, 4 and 5 hr post LPS. Pretreatment with LNMMA or DEX significantly attenuated the LPS-induced NE hyporesponsiveness 4 and 5 hr post LPS. LNMMA was the only post-LPS treatment able to reverse the NE hyporesponsiveness. The LPS-induced iNOS mRNA and protein expression was demonstrated in the liver, lung, spleen, heart, kidney and brain by Northern hybridization and Western blot analyses. Low levels of neuronal constitutive NOS mRNA and endothelial cell constitutive NOS mRNA were only detected in brain or myocardial tissue, respectively. Significant induction of iNOS mRNA and protein expression was also observed in the liver, lung and spleen of rats pretreated with DEX, LNMMA or IND. The continued expression of iNOS in the presence of a pharmacologically relevant dose of DEX suggests that DEX may not be an optimal pharmacological agent for defining the in vivo roles of iNOS.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Combined use of behavior modification and very low-calorie diet in weight loss and weight maintenance.

The authors assessed the long-term efficacy of a weight-loss program combining the use of a very low-calorie diet and behavior modification. This program involved medical supervision as well as group behavior modification classes, which emphasized long-term lifestyle changes, along with nutrition education. A study was conducted in 1984 and again in 1991, of unselected consecutive patients who had completed this hospital-based, weight-control program 12 to 18 months earlier. Patients were asked to return to the medical center to be weighed and complete a questionnaire regarding biobehavioral factors. The results of both the 1984 and 1991 follow-up studies were very similar. The patients' initial body mass index was 34.6 kg/m2 +/- 0.57 kg/m2 (mean +/- standard error of the mean, n = 109) and average weight loss was 23.2 kg +/- 1.1 kg, resulting in a body mass index of 26.2 kg/m2 +/- 0.42 kg/m2 upon completion of the program. At 12 to 18 months of follow-up, mean body mass index was 29.6 kg/m2 +/- 0.54 kg/m2. There was a wide spectrum of long-term compliance and recidivism. On average, 61% of patients kept off at least 50% of the weight they had originally lost. In addition, medication usage for hypertension, hyperlipidemia, and diabetes was reduced among the patients with reduced obesity. A retrospective analysis of patient characteristics and habits did not accurately predict which patients would be successful long-term.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavior Therapy↗
PubMed1991

Distribution and activity of alternatively spliced Alzheimer amyloid peptide precursor and scrapie PrP mRNAs on rat brain polysomes.

Mammalian brains contain low levels of the Alzheimer amyloid precursor variants (AAPPs) and the normal form of the scrapie agent protease-resistant protein (PrPc); however, their mRNAs are readily detectable. To understand these discrepancies we have investigated some aspects of the translational regulation of these mRNAs. An accurate blot-hybridization procedure was developed to measure absolute amounts of mRNA. Rat brain contains the following mRNA levels (ng/g tissue) AAPP(695), 170; AAPP(751/770), 63; PrPc, 144; actin, 615; glyceraldehyde-3-phosphate dehydrogenase (G3PDH), 359; ferritin, 148. The method was also used to determine the distribution of mRNAs between translationally active polysomes and translationally inactive ribonucleoprotein protein particles (mRNPs). More than 90% of G3PDH and actin mRNAs were associated with polysomal RNA; whereas, ferritin light chain mRNA was predominantly (90%) in mRNP RNA. The degree of cross-contamination of mRNPs with polysomes was less than 10%. Probes specific for the scrapie PrP protein and the AAPP(695) splice junction revealed that 70% of these mRNAs were associated with polysomes. One-half of AAPP(751/770) mRNAs (which comprise 20-30% of all AAPP mRNA in brain) were found in polysomes. We conclude therefore that both scrapie and AAPP mRNAs are subject to translational regulation in rat brain. Evidence from in vitro translational experiments confirm the message distribution determined by blot hybridization and corroborate the hypothesis that AAPP is subject to partial post-transcriptional regulation. Nevertheless, the low tissue levels of AAPP and PrPc must result primarily from their relatively rapid turnover.

Amyloid beta-Peptides↗
PubMed1988

Fine mapping of an Alzheimer disease-associated gene encoding beta-amyloid protein.

We have sublocalized an Alzheimer Disease-associated gene, which encodes for cerebrovascular beta-amyloid protein, to the region from the centromere through the proximal half of band 21q21 using both somatic cell and in situ mapping techniques. In addition we found repeatedly significant but weaker hybridization of the beta-amyloid protein probe to the short arm of chromosome 20. 794 cells were analyzed from whole blood, lymphoblastoid and skin cultures. The latter two types of cultures had parts of the 21st chromosome translocated to other chromosomes facilitating sublocalization.

Alzheimer Disease↗
PubMed1988

Upper extremity dysfunction in children with myelomeningocele.

A retrospective chart review of 138 subjects with myelomeningocele was performed to determine factors affecting upper extremity function in this population. Upper extremity dysfunction was found in 62 subjects (46.6%). A relationship was found between upper extremity dysfunction and hydrocephalus. Subjects with hydrocephalus had a significantly greater incidence of upper extremity dysfunction than subjects without hydrocephalus. No significant relationship was found between surgically treated versus spontaneously arrested hydrocephalus or number of shunt revisions and upper extremity dysfunction. A relationship was found between level of lesion of the spinal cord and upper extremity dysfunction. High level lesions had a significantly higher incidence of upper extremity dysfunction. Of 62 patients with upper extremity dysfunction only 3 (3.2%) had normal development. This was statistically significant. Little attention has been given to general developmental status in myelomeningocele children with upper extremity dysfunction. This study suggests a strong correlation between these two variables. In conclusion, hydrocephalus, level of spinal cord lesion, and developmental status, appear to be significant factors affecting upper extremity dysfunction in children with myelomeningocele.

Adolescent↗
PubMed1987

The effects of intrauterine position on competition and behavior in the mouse.

The purpose of the present study was to examine the effect of intrauterine position on: (1) competition for limited food resources when the animals were previously deprived of food; (2) social preference for a male during various phases of the estrous cycle; and (3) social and sexual behavior when the animals were provided with like-treated females or receptive females, respectively. Females developing in utero between two males (2M females) and females developing between two females (0M females) were different on only one measure recorded during the competition for limited food, i.e., gaining control of the food pellet, with the 0M females outcompetiting the 2M females. When given a choice between a male or a female neither 2M or 0M females in estrus showed a preference for the male. The results also indicated that 2M females were significantly more aggressive and more likely to show male sexual behavior when compared to 0M females.

Animals↗
PubMed1987

Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides.

Deposits of amyloid fibers are found in large numbers in the walls of blood vessels and in neuritic plaques in the brains of patients with Alzheimer disease and adults with Down syndrome. We used the amino acid sequence of the amyloid peptide to synthesize oligonucleotide probes specific for the gene encoding this peptide. When a human brain cDNA library was screened with this probe, a clone was found with a 1.7-kilobase insert that contains a long open reading frame coding for 412 amino acid residues including the 28 amino acids of the amyloid peptide. RNA gel blots revealed that a 3.3-kilobase mRNA species was present in the brains of individuals with Alzheimer disease, with Down syndrome, or with no apparent neurological disorders. Southern blots showed that homologous genes are present in the genomic DNA of humans, rabbits, sheep, hamsters, and mice, suggesting that this gene has been conserved through mammalian evolution. Localization of the corresponding genomic sequences on human chromosome 21 suggests a genetic relationship between Alzheimer disease and Down syndrome, and it may explain the early appearance of large numbers of neuritic plaques in adult Down syndrome patients.

Alzheimer Disease↗
PubMed1982

Hematologic and serum chemical values of adult female Rocky Mountain elk from New Mexico and Oklahoma.

Hematologic and serum chemical values were determined for two groups of adult female Rocky Mountain elk (Cervus elaphus nelsoni) from New Mexico and Oklahoma. Although considerable variation in values was observed between elk from the same group, the mean values from 16 of the 20 blood parameters tested were significantly different between the two groups. Of these, the most significant variations were observed in values which were likely to be influenced by nutritional condition and health status. The results of this study indicate that when evaluating the health status of different herds kept under known conditions, hematologic and serum chemical values are of optimal significance when the mean values of the herds are compared.

Animal Population Groups↗
PubMed1980

Protection from extinction by a conditioned inhibitor.

The phenomenon of protection from extinction (PFE) of a conditioned stimulus (CS) by a conditioned inhibitor (CI) has not been yet unequivocally demonstrated for the CS-CI compound in which the CS precedes the onset of the CI. Preliminary data from a project addressed to this problem strongly indicate that PFE is a real and robust phenomenon. Moreover, the protection is demonstrated not only for the CS duration overlapping with the CI but also for the early part of the CS which is not prevented by the CI from eliciting a conditioned response. The review of a few theories of conditioning suggests that the phenomenon of PFE is theoretically acceptable and predicted within the framework of any hypothetical mechanism which allows for post-trial "processing" or "consolidation" of information acquired during the trial.

Animals↗