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Biomedical subjects

M E Baser

Publications and source records attributed to M E Baser.

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

Identification of NF2 germ-line mutations and comparison with neurofibromatosis 2 phenotypes.

Neurofibromatosis 2 (NF2) is an autosomal inherited disorder that predisposes carriers to nervous system tumors. To examine genotype-phenotype correlations in NF2, we performed mutation analyses and gadolinium-enhanced magnetic resonance imaging of the head and full spine in 59 unrelated NF2 patients. In patients with vestibular schwannomas (VSs) or identified NF2 mutations, the mild phenotype was defined as < 2 other intracranial tumors and < or = 4 spinal tumors, and the severe phenotype as either > or = 2 other intracranial tumors of > 4 spinal tumors. Nineteen mutations were found in 20 (34%) of the patients and were distributed in 12 of the 17 exons of the NF2 gene, including intron-exon boundaries. Seven mutations were frameshift, six were nonsense, four were splice site, two were missense, and one was a 3-bp in frame deletion. The nonsense mutations included one codon 57 and two codon 262 C-->T transition in CpG dinucleotides. The frameshift and nonsense NF2 mutations occurred primarily in patients with severe phenotypes. The two missense mutations occurred in patients with mild phenotypes, and three of the four splice site mutations occurred in families with both mild and severe phenotypes. Truncating NF2 mutations are usually associated with severe phenotypes, but the association of some mutations with mild and severe phenotypes indicates that NF2 expression is influenced by stochastic, epigenetic, or environmental factors.

DNA Mutational Analysis↗
PubMed1996

The neuroimaging and clinical spectrum of neurofibromatosis 2.

Neurofibromatosis 2 (NF2) is an autosomal dominant disease predisposing to multiple tumors of the central and peripheral nervous system. Bilateral vestibular schwannomas are the hallmark of the disease. To define the clinical spectrum of the disease, we performed gadolinium-enhanced magnetic resonance imaging of the brain and spine as well as neurological, dermatological, and ocular examinations in 48 patients with NF2 diagnosed with the National Institutes of Health diagnostic criteria. Patients were ascertained from patient workshops and publications and from referral as a result of vestibular schwannoma surgery. Vestibular schwannomas were found in 46 patients (96%, 43 bilateral and 3 unilateral), spinal tumors were found in 43 (90%), posterior subcapsular cataracts were found in 30 (63%), meningiomas were found in 28 (58%), and trigeminal schwannomas were found in 14 (29%). The presenting symptoms included hearing loss or tinnitus in 15 patients (31%), multiple or nonspecific symptoms in 15 (31%), skin tumors in 12 (25%), and ocular symptoms in 6 (13%). When the complete spine was imaged, spinal tumors were more common in patients with NF2 than has previously been reported. This is a noteworthy finding, because spinal tumors are a major cause of NF2 morbidity and mortality.

Adolescent↗
PubMed1996

Presymptomatic diagnosis of neurofibromatosis 2 using linked genetic markers, neuroimaging, and ocular examinations.

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder that causes nervous system tumors and ocular abnormalities such as early-onset lenticular opacities. We assessed the clinical spectrum of NF2 at the time of presymptomatic DNA diagnosis in at-risk first-degree relatives. We studied five multigeneration NF2 families with short tandem repeat markers near the NF2 gene (NF2); gadolinium-enhanced high-resolution magnetic resonance imaging (GE-MRI); and ocular, dermatologic, and neurologic examinations. Eleven of 31 asymptomatic at-risk first-degree relatives were predicted by segregation analysis to be NF2 mutation carriers. Nine of the 11 NF2 mutation carriers were clinically evaluated. Four mutation carriers, including a 7-year-old, had vestibular schwannomas, early-onset cataracts, or both. However, five mutation carriers did not have clinical abnormalities, including a 38-year-old with normal cranial and spinal GE-MRIs and a normal ocular examination. These results indicate that clinical abnormalities can be present in young, but absent in middle-aged, presymptomatic NF2 mutation carriers. By identifying presymptomatic NF2 mutation carriers, DNA diagnosis of NF2 can improve genetic counseling and clinical management, and possibly reduce psychosocial difficulties in at-risk individuals.

Adult↗
PubMed1995

Ocular abnormalities in neurofibromatosis 2.

PURPOSE: To evaluate the ocular abnormalities in patients with clinically diagnosed neurofibromatosis 2 and asymptomatic gene carriers. METHODS: Probands were ascertained through a surgical otolaryngology practice. In a cross-sectional study, we examined 49 patients with neurofibromatosis 2, 30 offspring of patients, and, as a comparison group, 18 parents and siblings of patients with sporadic neurofibromatosis 2. The examination included a complete neuro-ophthalmic assessment, physical examination, and, for patients and first-degree relatives at risk, cranial and spinal magnetic resonance imaging with gadolinium enhancement, if not previously performed. RESULTS: The most common ocular abnormalities were posterior subcapsular or capsular, cortical, or mixed lens opacities in 33 (67%) of 49 patients with neurofibromatosis 2 and retinal hamartomas in 11 (22%). We used segregation analysis to determine the mutation carrier status of six at-risk offspring who were 30 years old or younger in two multigeneration families. Three asymptomatic mutation carriers had cataracts, whereas those who were predicted not to carry the mutation did not have cataracts. Asymptomatic mutation carriers may have developmental abnormalities of the eye that are detectable in childhood or adolescence, a finding that may assist in early diagnosis of the disease. CONCLUSIONS: A variety of ocular abnormalities are present in neurofibromatosis 2, including cataracts, retinal hamartomas, and ocular motor deficits. Many of these are developmental or acquired early in life and may assist in presymptomatic diagnosis. For screening at-risk relatives of patients with neurofibromatosis 2, the types of cataract that are most suggestive of neurofibromatosis 2 are plaque-like posterior subcapsular or capsular cataract and cortical cataract with onset under the age of 30 years.

Adolescent↗
PubMed1995

Interindividual differences in the concentration of 1-hydroxypyrene-glucuronide in urine and polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells after charbroiled beef consumption.

Biological markers of internal dose and macromolecular dose from PAHs provide a potential means of assessing environmental exposure to PAHs through inhalation, ingestion and percutaneous absorption. In this study we examined the time course and interindividual variation of 1-hydroxypyrene-glucuronide (1-OHP-gluc) excretion in urine and PAH-DNA adduct formation in peripheral white blood cells (WBCs) after charbroiled (CB) beef consumption. As a marker of internal dose, 1-OHP-gluc was measured in human urine using immunoaffinity chromatography and synchronous fluorescence spectroscopy. PAH-DNA adducts were measured in WBCs by enzyme-linked immunosorbent assay (ELISA) in order to assess macromolecular dose. Ten healthy non-smoking males consumed identical amounts of CB beef on five consecutive days. Multiple blood and urine samples were collected before, during, and after the feeding period. The morning after the first day of CB beef consumption, individual urinary concentrations of 1-OHP-gluc increased 10- to 80-fold (range: 2.0-16.6 pmol/ml urine) above pre-feed baseline concentrations (0.23 +/- 0.11 pmol/ml) in the 10 subjects. 1-OHP-gluc concentration decreased to near baseline levels by 24-72 h after CB beef consumption ended. In contrast, PAH-DNA adducts in WBCs increased markedly in only four of 10 subjects during or after CB beef consumption. Significant interindividual variation was observed for both urinary 1-OHP-gluc concentration (P < 0.001 by Kruskal-Wallis) and PAH-DNA adduct levels (P < 0.005) during the feeding period. The mean urinary 1-OHP-gluc concentration for each subject during and immediately after (days 2-8) the feeding period was significantly correlated with their mean PAH-DNA adduct level in WBCs during the same time period (Spearman r = 0.79, P < 0.01). Evidence of segregation of the subjects into separate response groups based on level of urinary 1-OHP-gluc was observed, suggesting that discrete determinants may regulate the absorption, metabolism and/or excretion of ingested pyrene.

Adult↗
PubMed1995

Spinal tumors in patients with neurofibromatosis type 2: MR imaging study of frequency, multiplicity, and variety.

OBJECTIVE: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder leading to various tumors of the CNS, with vestibular schwannomas being the hallmark of the disease. We have observed multiple asymptomatic spinal lesions in patients who have a single symptomatic spinal tumor. Accordingly, we studied the frequency, multiplicity, and variety of spinal tumors in all patients with NF2 to determine what is characteristic of the disease. SUBJECTS AND METHODS: MR images of the entire spinal canal were made in 73 patients aged 4-69 years with NF2. The number, location, morphology, signal characteristics, and contrast medium uptake of the spinal tumors as seen on MR images were recorded and analyzed. Histopathologic proof of 22 spinal tumors was obtained in 19 patients. RESULTS: Spinal tumors were found on MR images in 89% of the patients studied. No location in any part of the spine was preferred. MR imaging showed intramedullary tumors in 24 patients (33%) (three ependymomas pathologically proven). Extradural and intradural extramedullary tumors were found on MR imaging in the cervical spine of 36 patients, the thoracic spine of 40 patients, and the lumbar spine of 49 patients. These tumors were meningiomas, schwannomas, or neurofibromas, three categories that could not be differentiated on the basis of the neuroradiologic findings, with ten schwannomas, seven meningiomas, and two neurofibromas pathologically proven. Extradural extramedullary tumors were found on MR imaging in the cervical spine of 12 patients, the thoracic spine of five patients, and the lumbar spine of 18 patients. A syrinx associated with a tumor was found in two patients. In 19 patients the variety of tumor types was confirmed by histologic examination. CONCLUSION: Patients with NF2 frequently have spinal tumors, which are often multiple and of various histologic types. The presence of multiple and different pathologic types of spinal tumors is highly suggestive of NF2.

Adolescent↗
PubMed1994

Comprehensive management of bilateral acoustic neuromas. Current perspectives.

Bilateral acoustic neuromas are pathognomonic for neurofibromatosis 2. Patients with neurofibromatosis 2 present complex and challenging management problems, because growth or surgical removal of the acoustic neuroma may result in total hearing loss. Early diagnosis with gadolinium-enhanced magnetic resonance imaging and refinements in hearing preservation surgery have improved our ability to prevent total hearing loss. For patients with larger tumors or no useful hearing, the auditory brain-stem implant allows restoration of some auditory function when the tumor is removed. We describe our management strategy for patients with bilateral acoustic neuromas, and present case reports to show their diversity. We also discuss the newly identified neurofibromatosis 2 tumor suppressor gene.

Adolescent↗
PubMed1994

Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas.

Schwannomas are common tumors of the nervous system and are frequently found in patients with neurofibromatosis (NF) 2. Although loss of heterozygosity in NF2 tumors suggests that the NF2 gene functions as a tumor suppressor gene, the NF2 gene shows amino acid sequence homology to structural proteins in one of which dominantly acting mutations have been described. We performed a mutational analysis in 30 vestibular schwannomas and examined the effect of mutations on the NF2 protein. We detected 18 mutations in 30 vestibular schwannomas of which seven contained loss or mutation of both NF2 alleles. Most mutations were predicted to result in a truncated protein. Mutational hot spots were not identified. Immunocytochemical studies using antibodies to the NF2 protein showed complete absence of staining in tumor Schwann cells, whereas staining was observed in normal vestibular nerve. These data indicate that loss of NF2 protein function is a necessary step in schwannoma pathogenesis and that the NF2 gene functions as a recessive tumor suppressor gene.

Amino Acid Sequence↗
PubMed1992

The development of registries for surveillance of adult lead exposure, 1981 to 1992.

OBJECTIVES: Since 1981, 15 states have established registries for surveillance of adult lead absorption, primarily based on reports of elevated blood lead levels from clinical laboratories. I review the status of the registries and recommend steps for further development. METHODS: Companies reported to the New York registry are compared with those cited by the Occupational Safety and Health Administration (OSHA). I present data on US workers and plants with potential lead exposures and blood tests, as well as review registries' reporting requirements. RESULTS: Registries identify many companies not cited by the Occupational Safety and Health Administration, but underreporting occurs because (1) reporting is usually not required from laboratories outside the state, (2) most registries use a blood lead reporting level of 1.21 mumol/L, which excludes many exposed workers, and (3) many companies with potential exposures do not have routine monitoring programs. CONCLUSIONS: Registries' reporting requirements and procedures should be standardized, including a blood lead reporting level of 0.72 mumol/L. Elevated blood lead levels should be a reportable condition nationwide, and a comprehensive national surveillance system should be established: clinical laboratories should be required to report cases to those states with lead registries or directly to the national adult lead registry.

Adult↗
PubMed1991

Pulmonary function and respiratory symptoms in wildland firefighters.

We studied cross-seasonal changes in pulmonary function and respiratory symptoms in 52 wildland firefighters in Northern California. The mean cross-seasonal change in forced expiratory volume in 1 second (FEV1) was -1.2% (95% confidence interval [CI] -0.5%, -2.0%) with a corresponding mean change in forced expiratory volume (FVC) of -0.3% (95% CI 0.4%, -1.0%). Decreases in FEV1 and FVC were most strongly associated with hours of recent fire-fighting activity (P = .002 and .01, respectively). When the study group was divided into three categories based on recent fire-fighting activity, firefighters in the high activity category (mean +/- SE, 73 +/- 7 hours of fire-fighting in previous week) had a -2.9% (130 mL) change in FEV1 and a -1.9% (102 mL) change in forced vital capacity (FVC). There was a significant cross-seasonal increase in most respiratory symptoms evaluated. Several symptoms (eye irritation, nose irritation, and wheezing) were associated with recent fire-fighting. These findings suggest that wildland firefighters experience a small cross-seasonal decline in pulmonary function and an increase in several respiratory symptoms. Research is under way to identify the fire conditions and specific components of exposure that produce pulmonary irritants, and to examine the potential reversibility of acute pulmonary change.

Adolescent↗
PubMed1990

Hydroxyl radical generating activity of hydrous but not calcined kaolin is prevented by surface modification with dipalmitoyl lecithin.

The catalytic activity of kaolin, an aluminum silicate, for generating hydroxyl radicals (.OH) from hydrogen peroxide (H2O2) was studied in a chemical system that measured .OH as evolution of methane (CH4) from dimethyl sulfoxide. In the presence of a reducing agent and 10 mM H2O2, hydrous and calcined kaolin generated mean +/- SE CH4 concentrations of 1634 +/- 328 and 1395 +/- 29 ppm, respectively. Surface modification with dipalmitoyl lecithin, the lipid of pulmonary surfactant, blocked generation of .OH in hydrous kaolin (38 +/- 38 ppm CH4) but not in calcined kaolin (875 +/- 262 ppm CH4). The catalytic activity of kaolin for producing .OH from H2O2 may be important in the pathogenesis of kaolin toxicity, and calcined kaolin may be more toxic than hydrous kaolin because the calcined form is resistant to surface modification by lipids of pulmonary surfactant.

Humans↗
PubMed1990

Formation of polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells during consumption of charcoal-broiled beef.

The effect of ingesting charcoal-broiled (CB) beef on polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels in nucleated peripheral white blood cells (WBCs) was examined in four healthy, non-smoking males who consumed an average of 280 g CB beef daily for 7 days. PAH-DNA adducts were quantitated by enzyme-linked immunosorbent assay. During the week of CB beef consumption, two individuals exhibited a 3- to 6-fold increase in PAH-DNA adducts above baseline levels observed during the month prior to CB beef consumption. In contrast, PAH-DNA adduct levels in the two other subjects did not increase. Thus, dietary sources of PAH can contribute to the PAH-DNA adduct load in peripheral WBCs in some individuals.

Adult↗
PubMed1990

A statewide case registry for surveillance of occupational heavy metals absorption.

The New York State Heavy Metals Registry is a legislatively mandated program through which clinical laboratories, physicians, and health facilities report state residents 18 years of age and older with elevated levels of lead, mercury, arsenic, or cadmium in blood or urine. From 1982-86, the current employer was determined for 95.9 percent of 3,309 cases. Occupational exposures in 328 companies accounted for 82.8 percent of cases. The majority of companies were reported for lead (247 companies, 75.3 percent of total) or mercury (47 companies, 14.3 percent of total). Of the 247 companies reported to the Registry for lead, the Occupational Safety and Health Administration (OSHA) inspected 18 of 98 companies (18.4 percent) in the manufacturing sector, but only one of 149 companies (0.6 percent) outside the manufacturing sector. We conclude that the Registry effectively detects companies with heavy metals exposures, and is an especially useful adjunct to OSHA inspections outside the manufacturing sector.

Adolescent↗
PubMed1989

Differences in lung function and prevalence of pneumoconiosis between two kaolin plants.

To investigate the origin of differences in previously published pulmonary function studies of workers in kaolin plants in Georgia, spirometric and radiographic data collected in a cross sectional survey of two large plants were analysed. As compared with workers in plant 2, workers in plant 1 had a 2.7-fold greater prevalence of pneumoconiosis and a mean 0.361 decrement in adjusted forced vital capacity. Our previous finding that exposure to kaolin was not associated with a decrement in lung function may have resulted from failure to consider differences between the plants.

Adolescent↗
PubMed1988

Eosinophilia, respiratory symptoms and pulmonary infiltrates in rubber workers.

This report describes a spectrum of respiratory illnesses associated with eosinophilia which occurred in a group of workers exposed to fumes from a synthetic rubber-based curing operation. Respiratory syndromes induced by this exposure included an acute sensitizing illness with dyspnea and wheezing in some workers and pulmonary infiltrates with eosinophilia in others. Another worker developed chronic obstruction of the airways with recurrent bronchitic illnesses. Mild to marked peripheral eosinophilia, up to 3,000/cu mm, was usually present in the symptomatic workers and in 11 of 30 asymptomatic workers. These cases illustrate the diversity of respiratory illnesses which may result from a common workplace exposure and reinforce the importance of considering occupational exposures in the differential diagnosis of peripheral eosinophilia.

Acute Disease↗
PubMed1986

Peripheral eosinophilia and respiratory symptoms in rubber injection press operators: a case-control study.

To evaluate a suspected association between an outbreak of acute respiratory illness and eosinophilia and employment as a rubber worker, we performed a retrospective review of medical records of rubber workers employed from September 1983 to July 1984 in a plant housing a thermoinjection process. Twenty-five workers met the case definition of a respiratory illness requiring a physician visit. The predominant respiratory illness was acute in onset with cough, chest tightness, and dyspnea. Peripheral eosinophilia, up to 40% of white blood cells in a peripheral smear, was seen in 10 of 18 (56%) cases. Twenty-one of 25 white males with respiratory symptoms were employed in the thermoinjection process (odds ratio = 22, p less than .001). Smoking and employment in this process contributed independently to an increased risk of being a case as determined by a logistic regression analysis. Return to the plant building caused recurrence of symptoms in most cases, and these workers have been transferred or left the company. We conclude that a strong previously unrecognized association exists between employment in this neoprene rubber thermoinjection process and the development of an acute respiratory illness.

Adult↗