Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 361 records · Page 20Linked to original sources

PubMed1993

The Kallmann's syndrome variant (KSV) model of the schizophrenias.

The KSV model of the schizophrenias proposes that up to 70% of schizophrenics have a pathogenic allele, or abnormal expression, of the KALIG-1 gene which is located at Xp22.3. This gene encodes a nerve-cell adhesion molecule (N-CAM) like protein, and is deleted in 66% of patients with Kallmann's syndrome, anosmia with secondary hypogonadism. Although superficially distinct, the schizophrenias and Kallmann's syndrome show numerous parallel trait defects which occur with a similar sex distribution. These defects are usually more profound in Kallmann's syndrome. Occasionally, Kallmann's patients exhibit additional defects, such as ichthyosis, which are due to the further deletion or translocation of adjacent genes. Since schizophrenics exhibit virtually all known trait defects in Kallmann's except these, it suggests that the aberrant genes are defective, but not deleted in schizophrenia. It also appears that compensatory mechanisms, involving serine proteases, are active in schizophrenia, which largely preserve fertility, but at the expense of an increased vulnerability to develop a psychosis by an episodic disruption of the blood-CSF barrier. Consequently, schizophrenia is rare in Kallmann's patients, while most schizophrenics are capable of reproduction.

Alleles↗

PubMed1993

Re-examining handedness in schizophrenia: now you see it--now you don't.

The present study was designed to examine patterns of handedness across tasks (i.e., those requiring less vs. greater skill) and over time (initially and 1 month later) in 72 schizophrenic patients and 105 normal controls. Two important methodologic advances were introduced: (1) two handedness tasks, varying in skill level (simple vs. complex); and (2) the addition of a retest on both tasks, 1 month later. Results show a higher incidence (43%) of mixed handedness in the schizophrenic sample than in normal controls (14.3%) on tasks requiring less precision in performance. Similar results were obtained when schizophrenic patients were retested 1 month later, RI = .88. When the more demanding set of tasks was presented, the frequency of mixed handed schizophrenics dropped by 50% at initial testing. Despite these findings, there was no evidence for stability of change over time. For example, each of the most extreme shifters at Time 1 was fully lateralized 1 month later.

Adult↗

PubMed1993

Identification of genomic sequences that mediate the induction of the endoplasmic reticulum stress protein, ERp72, by protein traffic.

ERp72, a resident protein of the endoplasmic reticulum (ER) is both a stress protein and a member of the protein disulfide isomerase family of proteins. Analysis of the murine ERp72 promoter region revealed the presence of potential transcriptional control elements characteristic of the promoters of mammalian ER proteins. These include multiple CCAAT elements and Sp1 and AP-2 consensus sequences. Functional analysis of mutations in the ERp72 promoter and 5'-flanking region revealed an 82-bp fragment that is sufficient to mediate the stimulation observed for ERp72 either by stress or by the expression of incompletely assembled immunoglobulin mu heavy chain in the ER. This 82-bp fragment contains two CCAAT elements but little additional homology to protein traffic-responsive sequences of other members of the ER stress family. This suggests that the ERp72 gene contains a novel element that is the target of an intracellular signaling pathway initiated by protein traffic in the ER.

3T3 Cells↗

PubMed1993

Physician satisfaction with primary care office visits. Collaborative Study Group of the American Academy on Physician and Patient.

To study encounter-specific physician satisfaction we collected exit questionnaires from patients and physicians following 550 primary care office visits. The physicians' questionnaire included 20 items pertaining to satisfaction with the visit, one of which was an assessment of global satisfaction. Using a boot-strap technique, we factor analyzed the satisfaction questions in 10 repeated samples. Four distinct dimensions of physician satisfaction emerged: satisfaction with the patient-physician relationship, with the data collection process, with the appropriateness of the use of time, and with the absence of excessive demands on the part of the patient. Each scale was found to be reliable; global satisfaction was most closely related to the relationship factor. Satisfaction with use of time and the adequacy of data collection tended to be stable for individual physicians across a range of patients whereas global satisfaction and satisfaction with the relationship and the demanding nature of the patient and were more variable, hence most unique to each encounter. This study of physician satisfaction represents an effort to incorporate knowledge about physicians' subjective experiences into a systematic understanding of the dynamics of the medical interview.

Attitude of Health Personnel↗

PubMed1993

Parvovirus B19 infection in pediatric transplant patients.

Evidence of recent parvovirus virus infection (as determined by the presence of a positive IgM antibody titer) without other identified causes of anemia was found in 5 of 26 pediatric solid-organ transplant recipients evaluated for moderate-to-severe anemia between June 1990 and July 1991. Anemia tended to be chronic (median duration of anemia at the time of diagnosis was 12 weeks) and was associated with normal red blood cell indices in the absence of reticulocytes. The median age of the children at the time of presentation with anemia due to parvovirus was 1.8 years at a median time of 8 months after transplantation. Four of the 5 children were treated with i.v. immunoglobulin because of persistence of anemia requiring blood transfusions. A response characterized by an increase in reticulocyte count and normalization of hemoglobin was seen in each of these patients 2-4 weeks after treatment. The remaining patient experienced a spontaneous recovery from her anemia. Parvovirus infection should be included in the differential diagnosis of solid-organ transplant recipients presenting with severe anemia associated with low or absent reticulocytes.

Anemia↗

PubMed1993

Multiple functional domains of human transcription factor IIB: distinct interactions with two general transcription factors and RNA polymerase II.

Transcription factor IIB (TFIIB) plays a pivotal role in the formation of transcription-competent initiation complexes. TFIIB was found to interact with the TATA-binding protein, the small subunit of TFIIF, and RNA polymerase II. These interactions require distinct domains in TFIIB. Using the gel mobility-shift assay, it was found that the amino terminus of TFIIB was necessary for the formation of complexes containing RNA polymerase II and TFIIF, whereas the carboxy-terminal domain, which is composed of two imperfect direct repeats and includes a putative amphipathic alpha-helix, was sufficient for the formation of complexes containing the TATA-binding protein and TFIIB (DB complex). Protein-protein interaction analyses demonstrate that the amphipathic alpha-helix in TFIIB is important for the interaction with the TATA-binding protein. Specific residues mapping to the carboxyl terminus of the second direct repeat were found to be crucial for the interaction of TFIIB and RNA polymerase II. The interaction with the small subunit of TFIIF was mapped to the amino terminus of TFIIB, which includes a zinc finger.

Base Sequence↗

PubMed1993

Proinsulin, proinsulin intermediate and insulin in cystic fibrosis.

OBJECTIVE: We determined the changes in insulin, intact proinsulin and 32-33 split proinsulin as markers of beta cell damage in assessing the state of carbohydrate intolerance in patients with cystic fibrosis. DESIGN: Measurements of insulin, proinsulin and 32-33 proinsulin concentrations in cystic fibrosis following oral glucose tolerance test (OGTT). SUBJECTS: Sixteen cystic fibrosis patients attending the chest outpatient clinic for follow-up, age range 14-42 years, and 14 healthy controls matched for age and body mass index. MEASUREMENTS: Insulin, intact proinsulin and 32-33 split proinsulin were measured immunoradiometrically at 0, 30, 60, 90 and 120 minutes after an OGTT. Glucose and HbA1 were also measured. RESULTS: Cystic fibrosis patients were divided into two groups according to their OGTT results: those with diabetes mellitus or impaired glucose tolerance and those with normal glucose tolerance. Insulin concentrations and insulin/glucose ratios at 30 minutes were lower in both cystic fibrosis groups in comparison with the control. There was also a significant increase in the time to reach peak insulin levels in both cystic fibrosis groups. Fasting intact proinsulin concentrations and the proportion of proinsulin-like molecules were significantly higher in cystic fibrosis with diabetes mellitus or impaired glucose tolerance than in the control group, but not in the normal glucose tolerance cystic fibrosis group. There was no significant difference in the plasma concentrations of 32-33 split proinsulin amongst the three groups. CONCLUSIONS: Abnormal beta cell function in cystic fibrosis patients was reflected initially in a diminished 30-minute insulin response to oral glucose. A significant rise in fasting intact proinsulin and the proportion of proinsulin-like molecules was seen only in cystic fibrosis patients who had progressed to impaired glucose tolerance or diabetes mellitus. Cystic fibrosis patients with normal glucose tolerance showed changes intermediate between the control and the other group.

Adolescent↗

PubMed1993

Peptide alpha-amidation activity in human plasma: relationship to gastrin processing.

OBJECTIVE AND DESIGN: C-terminal amidation is an essential processing step towards bioactivation of many peptides including gastrin. This reaction is catalysed by peptidylglycine alpha-amidating mono-oxygenase (PAM, EC 1.14.17.3) which converts the glycine extended precursors on their carboxyl termini to the des-glycine amidated peptide products. In the case of gastrin, most of the amidation is thought to occur in the antrum. However substantial quantities of glycine extended gastrin and PAM are present in plasma. It is unclear whether circulating PAM reflects the secretory activity of the gastrin secreting cell or whether PAM is involved in the postsecretory processing of gastrin. The aim of the present study was to relate the circulating amidation activity to the plasma concentrations of glycine extended and amidated gastrins. PATIENTS AND MEASUREMENTS: Plasma PAM, gastrin-amide and gastrin-gly were measured in subjects with different gastrin secretory status: healthy subjects basally and following a meal, members of families with multiple endocrine neoplasia type 1 (MEN-1) with normal and high plasma gastrin, and patients with hypergastrinaemic atrophic gastritis. RESULTS: Patients with MEN-1 and hypergastrinaemia tended to have a higher plasma PAM activity than MEN-1 subjects with normal circulating G-NH2 indicating a cosecretion of hormone and PAM. However in contradistinction to patients with medullary thyroid carcinoma, PAM activity does not appear to be a useful tumour marker of gastrinoma. Hypergastrinaemia from a non-tumour source (hypergastrinaemic non-atrophic gastritis) was associated with a lower plasma PAM activity than in normal subjects and may reflect the secretion of a greater proportion of already amidated gastrin. In general, there was no relationship between plasma PAM activity and the ratio of amidated to non-amidated gastrin suggesting that circulating PAM was not involved in the amidation of gastrin. Feeding increased circulating gastrin but had no effect on plasma PAM activity. CONCLUSION: The results support the view that gastrin is amidated at the site of its synthesis and that hypergastrinaemia is associated with elevated plasma amidating enzyme activity only when the gastrin originates from tumour sources.

Anemia, Pernicious↗

PubMed1993

Genotype analysis in cystic fibrosis in relation to the occurrence of diabetes mellitus.

Carbohydrate intolerance and frank diabetes mellitus (DM) are recognised features of cystic fibrosis (CF), but their cause has not been established. Damage to the islet cells due to pancreatic fibrosis is the most common explanation. The relationship between the genotype and the occurrence of diabetes mellitus has been examined in 21 cystic fibrosis patients attending our out-patient chest clinics. DNA samples were tested for the presence of the most common mutation (delta F508) and the results related to the degree of carbohydrate intolerance. We found that in CF patients over 18 years of age diabetes is more frequent among those homozygous for the delta F508 allele than the heterozygotes (P < 0.05). Those homozygous for delta F508 were diagnosed as CF at an earlier age than the heterozygotes (P < 0.05). Both the mean age and the female/male ratio were similar in the diabetic and non-diabetic groups. The prevalence of the delta F508 allele was similar to that expected in a random sample of East Anglian cystic fibrosis patients. These data suggest that the occurrence of diabetes mellitus in patients with cystic fibrosis is related to the genotype, which could be secondary to the way the genetic factors influence the degree of pancreatic disease and its rate of progression.

Adolescent↗

PubMed1993

Zeneca ZD7114 acts as an antagonist at beta 3-adrenoceptors in rat isolated ileum.

1. The relaxant effects of Zeneca ZD7114, BRL37344 (putative beta 3-adrenoceptor agonists) and various phenylethylamine-based agonists were studied in isolated ileum of the rat where tone was increased with carbachol (0.5 microM). Agonist-induced relaxation.was measured under equilibrium conditions with alpha-, beta 1- and beta 2-adrenoceptors inhibited. 2. Relaxant responses were obtained to isoprenaline, noradrenaline, and BRL37344, although, the efficacy of this latter agent was significantly.lower than that of isoprenaline. Salbutamol caused weak relaxation (< 20%) at high concentrations (10 microM) and ZD7114 was without significant relaxant effect even at high concentrations (10 microM). 3. Relaxant responses to isoprenaline and BRL37344 were weakly antagonized by high concentrations of (+/-)-propranolol (10 and 100 microM) yielding pKB values of 5.7 with isoprenaline as the agonist and 5.5 with BRL37344 as the agonist. 4. The non-selective beta-adrenoceptor antagonist, (+/-)-alprenolol (1-100 microM) caused competitive antagonism of the relaxant responses to isoprenaline (pA2 value = 6.5). A similar pKB value was obtained when BRL37344 was used as the agonist (6.4). 5. Relaxant effects of isoprenaline and BRL37344 were also antagonized by ZD7114 (1-100 microM) yielding pA2 and pKB values of 6.3 and 6.7 respectively. 6. The low potencies of (+/-)-propranolol and (+/-)-alprenolol as antagonists of the relaxant responses to isoprenaline and BRL37344 indicate that both the agonists and antagonists employed in the current study may interact with beta 3-adrenoceptors in the rat isolated ileum. Contrary to the previous findings in guinea-pig ileum, where BRL37344 and ZD7114 were full agonists, in the current study, BRL37344 was a partial agonist and ZD7114 an antagonist at the beta 3-adrenoceptor in rat ileum.

Adrenergic beta-Agonists↗

PubMed1993

Constitutively vancomycin-resistant Enterococcus faecium resistant to synergistic beta-lactam combinations.

Vancomycin resistance among enterococci has recently been recognized. Synergy between vancomycin and penicillin has been shown in vitro for isolates of Enterococcus faecium resistant to both of these antibiotics. We describe three isolates of vancomycin-resistant E. faecium which demonstrate unique phenotypic characteristics. The isolates exhibited high-level resistance to both vancomycin and teicoplanin, consistent with the VanA phenotype. However, resistance in these isolates could not be induced or cured, and mating experiments failed to detect a transfer of resistance. The combination of vancomycin and penicillin did not significantly change the MIC of penicillin for any of the three isolates. Immunoblotting with polyclonal anti-VanB antibody showed no reaction with the cellular proteins of these strains. Probing with a vanA oligonucleotide revealed hybridization with chromosomal but not plasmid DNA. The mechanism of constitutive resistance of those strains remains unclear. A second mutational change, perhaps involving PBP 5, may explain the presence of resistance to synergistic combination penicillin-vancomycin therapy. In vitro evaluation of penicillin-vancomycin should be carried out in all clinical cases where this therapeutic regimen is being considered.

Adult↗

PubMed1993

Comparison of two antigen assays for rapid intrapartum detection of vaginal group B streptococcal colonization.

As part of a clinical investigation evaluating the efficacy of intrapartum antigen detection for screening for heavy vaginal colonization with group B streptococci (GBS), we compared the performance of modified Bactigen and Directigen GBS latex particle agglutination (LPA) kits. Paired vaginal swabs obtained from women in labor were rapidly transported to the laboratory and used for culturing (both swabs) and LPA testing (one swab by each method). GBS growth was estimated semiquantitatively and further designated as light or heavy growth. Performance specifications for each method were determined by comparing LPA and culture results from the same swab. A total of 4,251 paired swabs were evaluated during the study period. The performance specifications for detecting GBS growth of any degree for Bactigen and Directigen, respectively, were as follows: sensitivity, 20 and 24%; specificity, 99 and 99%. The performance specifications for heavy colonization for Bactigen and Directigen, respectively, were as follows: sensitivity, 57 and 62%; specificity, 99 and 99%. Neither LPA kit was a sensitive indicator of vaginal colonization with GBS or neonatal infection.

Antigens, Bacterial↗

PubMed1993

Clonal spread of vancomycin-resistant Enterococcus faecium between patients in three hospitals in two states.

The DNAs of 3* vancomycin-resistant Enterococcus faecium isolates from five hospitals in three states were analyzed by contour-clamped homogeneous electric field electrophoresis and plasmid analysis. There were 22 strain types. One strain type was common to patients in three hospitals in two states. These results suggest the apparent intra- and interhospital spread of vancomycin-resistant E. faecium.

Bacterial Typing Techniques↗

PubMed1993

The E1A products of oncogenic adenovirus serotype 12 include amino-terminally modified forms able to bind the retinoblastoma protein but not p300.

The cell growth-regulating properties of the adenovirus type 5 (Ad5) E1A oncogene correlate closely with the binding of the E1A products to specific cellular proteins. These proteins include the products of the retinoblastoma tumor susceptibility gene and a 300-kDa product, p300. pRB binds to E1A sequences that are highly conserved among the E1A products of various serotypes, while p300 binding requires sequences in the E1A amino terminus, a region that is not highly conserved. To help evaluate the roles of the E1A-associated proteins in cell growth control, we have compared the p300-binding abilities of the E1A products of Ad5 and of the more oncogenic Ad12 serotype. We show here that despite encoding a sequence that varies somewhat from the p300-binding sequences of Ad5 E1A, the Ad12 E1A products associate with p300 with an affinity similar to that of the Ad5 E1A products. Both the 12S and 13S splice products of Ad12 E1A, like those of Ad5 E1A, encode proteins able to associate with p300. Interestingly, though, both also give rise to prominent forms that are amino terminally modified and unable to associate with p300. This modification, at least in the 13S product, does not appear to diminish the affinity of this product for the retinoblastoma protein.

Adenovirus E1A Proteins↗

PubMed1993

Pharmacokinetics of morphine infusion in premature neonates.

Morphine pharmacokinetics were studied in 17 premature neonates (26-34 weeks' gestation) after intravenous infusion during the first 24 hours of life. Infants received either standard dose morphine that comprised of a 100 micrograms/kg/hour loading infusion for 2 hours followed by a maintenance infusion of 12.5 micrograms/kg/hour, or a high dose of 200 micrograms/kg/hour for 2 hours followed by 50 micrograms/kg/hour. Mean plasma concentrations of morphine (SD) after 2 and 24 hours were 99 (12.9) and 96.4 (3.2) ng/ml, and 184.2 (37.7) and 319 (71.2) ng/ml for the standard and high dose regimens, respectively. Morphine-3-glucuronide plasma concentrations achieved about 20% and 80% of morphine values at 2 and 24 hours respectively. Morphine-6-glucuronide could not be detected at 2 hours, but attained 20-25% of morphine plasma concentrations by 24 hours. The population mean morphine clearance was 2.4 ml/min/kg, the elimination half life was 8.75 hours and the volume of distribution was 1.82 1/kg. High plasma concentrations of morphine appeared to be well tolerated. Although mean arterial blood pressure decreased during the first six hours of treatment, this was not statistically significant; two infants experienced transient muscle rigidity, but no evidence of seizures was noted. There appears to be no clinical advantage in using the high dose regimen.

Blood Pressure↗

PubMed1993

Diaphragmatic dysfunction in neuralgic amyotrophy: an electrophysiologic evaluation of 16 patients presenting with dyspnea.

We report 16 adult men (age, 41 to 75 yr) with neuralgic amyotrophy (NA) who presented with dyspnea due to involvement of the diaphragm. All patients developed breathlessness after a prodrome of acute severe neck and shoulder pain. Bilateral diaphragm paralysis (BDP) was confirmed in 12 patients and unilateral diaphragm paralysis (UDP) in four by the absence of electrical and mechanical responses to percutaneous phrenic nerve stimulation. Global expiratory muscle strength was well preserved in all patients, but inspiratory muscle strength was reduced in proportion to the extent of diaphragmatic involvement. Lung function showed low lung volumes with preservation of carbon monoxide transfer coefficient in all patients. Two BDP patients were hypoxic (PaO2 = 67 and 54 mm Hg, respectively) on daytime arterial blood gas analysis; the latter patient with pre-existing chronic obstructive pulmonary disease and marked obesity also had borderline hypercapnia (PaO2 = 49 mm Hg). Overnight sleep studies in three BDP and two UDP patients showed frequent intermittent arterial oxygen desaturations apparently caused by obstructive sleep apneas, but there was no evidence of alveolar hypoventilation. Follow-up muscle studies in five BDP and four UDP patients between 2 and 4 yr after initial referral showed complete recovery of diaphragmatic function in only two UDP patients, one of whom relapsed a year later. We postulate that NA may be an important but underrecognized cause of diaphragmatic paralysis in otherwise normal patients. Diaphragmatic strength returns very slowly, if at all.

Action Potentials↗

PubMed1993

Management of alcohol abusing patients in accident and emergency departments.

A pilot study was undertaken in the Accident & Emergency (A & E) departments of two central London teaching hospitals to determine if patients who were abusing alcohol and had not received any prior medical treatment or counselling for their drinking problem were amenable to offers of help. During the 24-month study period 104 patients were identified as having a previously untreated alcohol problem, and of these 46% attended an appointment to discuss their drinking habits. The group identified was much smaller than would be expected from the number attending the A & E departments during the study period and the reasons for this are discussed. However, the important observation from the study is that almost half the patients identified as having an alcohol problem returned to the department the following day to seek advice. This suggests that A & E departments are an appropriate place to offer patients initial help about their drinking habits.

Adolescent↗

PubMed1993

Behavioral pediatrics: its past and its future.

What can one predict about the future of behavioral pediatrics? How can its present academic status be enhanced? What anticipatory guidance can be offered to behavioral pediatrics fellows? The evolution of ambulatory pediatrics and adolescent medicine as academic disciplines offers a historical perspective that helps answer these questions. The similarities between these sister disciplines and behavioral pediatrics are identified along with the principles that guided their development. Likewise, promoting factors and potential future initiatives for behavioral pediatrics are presented. A checklist of career success predictors is included. The establishment of Sections of Personal Health Promotion in departments of pediatrics is suggested as a means to augment the creativity, resources, and critical mass available to Sections of Behavioral Pediatrics.

Behavioral Medicine↗