Biomedical subjects
Publications and source records attributed to R Goldberg.
Managed care organizations are monitoring asthma to decrease costs relating to health care utilization. Comparisons between primary care providers and asthma specialists reflect better outcomes, treatment programs, and higher patient satisfaction and outcomes for less cost.
Xyloglucan polymers have been isolated from cyclamen seeds and characterized by both liquid and CP-MAS 13C NMR spectroscopy. Treatment of the polysaccharides with cellulase from Trichoderma viride afforded XG oligomers which have been studied with both mass spectrometry and NMR spectroscopy. The repeating unit in the intact polymers and the most abundant hydrolysis product correspond to the Gal1 Xyl3 Glc4 (XXLG) fragment. However, detection of notable amounts of Xyl3 Glc4 (XXXG) and Gal2 Xyl3 Glc4 (XLLG) indicates that the galactose distribution in xyloglucan from cyclamen is irregular. FAB-MS analysis of a new derivative, prepared by forming the glycosamine of m-tetrafluoroethoxy aniline, has led to unambiguous sequence information for the XXLG oligomer.
We report the results of two studies examining the genetic overlap between schizophrenia and velocardiofacial syndrome. In study A, we characterize two interstitial deletions identified on chromosome 22q11 in a sample of schizophrenic patients. The size of the deletions was estimated to be between 1.5 and 2 megabases. In study B, we examine whether variations in deletion size are associated with the schizophrenic phenotype in velocardiofacial syndrome patients. Our results show that a region of the genome that has been previously implicated by genetic linkage analysis can harbor genetic lesions that increase the susceptibility to schizophrenia. Our findings should facilitate identification and cloning of the schizophrenia susceptibility gene(s) in this region and identification of more homogeneous subgroups of patients.
Velo-cardio-facial (VCFS) or Shprintzen syndrome is associated with deletions in a region of chromosome 22q11.2 also deleted in DiGeorge anomaly and some forms of congenital heart disease. Due to the variability of phenotype, the evaluation of the incidence of deletions has been hampered by uncertainty of diagnosis. In this study, 54 patients were diagnosed with VCFS by a single group of clinicians using homogeneous clinical criteria independent of the deletion status. Cell lines of these patients were established and the deletion status evaluated for three loci within the commonly deleted region at 22q11.2 using fluorescence in situ hybridization (FISH). In 81% of the patients all three loci were hemizygous. In one patient we observed a smaller interstitial deletion than that defined by the three loci. The phenotype of this patient was not different from that observed in patients with larger deletions.
PURPOSE: Pigmented villonodular synovitis (PVNS) is a rare proliferative process involving synovial membranes. It has a variable course, and while usually benign, may be destructive, resulting in major symptoms and loss of function leading to amputation. Optimum treatment is not always clear, and little information exists with respect to the role of radiotherapy. The purpose was to review our experience with radiotherapy in cases at high risk for recurrence with functional loss including instances where amputation was the sole alternative for symptomatic disease. METHODS AND MATERIALS: The records of all patients registered between 1972 and 1992 with a diagnosis of PVNS were identified (21 cases). The records of 14 cases who received radiotherapy after referral were reviewed retrospectively for demographic information, radiotherapy treatment parameters, and tumor outcome. RESULTS: All cases had confirmation of pathologic diagnosis. Six patients had primary and eight had recurrent disease (with a mean of 2.5 prior surgical procedures). All cases had both intra- and extraarticular disease and, without exception, the poorer prognosis diffuse subtype of the disease. The majority had one or more additional risk factors including skin, bone, tendon, neurovascular, or muscle group extension. With a mean follow-up time of 69 months (range 13-250 months), only one patient has shown persistence of disease. With the exception of that single case, all those with measurable disease had obvious disease until at least 12 months and, subsequently, manifested complete responses. The single case was lost from the clinic after 8 months from the initiation of radiotherapy to a dose of 30 Gy in 15 fractions and had a palpable mass at the time. He subsequently was noted to have a persisting mass and an excisional biopsy 9 years later showed PVNS. He remains well 21 years after treatment with good function. Eleven patients enjoyed excellent or good function from the affected limb and three had fair function. All patients had greater use of limb than at the time of treatment. No patient required amputation, and none had evidence of serious radiotherapy complications. CONCLUSIONS: These results demonstrate that moderate dose radiotherapy is an effective modality in the treatment of a subset of cases with this rare condition. Its use has permitted avoidance of amputation in very advanced cases with acceptable function preservation. When treatment is indicated we currently recommend gross total removal of PVNS. This is followed by moderate dose radiotherapy (35 Gy in 15 fractions) for residual disease where salvage of subsequent recurrence may compromise function.
An acetyl esterase was purified from cell walls isolated from mung bean hypocotyls. The purified enzyme had an apparent Mr of 43,300 and an apparent pI > 9. It rapidly deesterified triacetin and p-nitrophenylacetate and slowly released acetate from beet and flax pectins, the deesterification rate being increased by previous demethylation of the pectins. No significant peptide sequence identity between the acetyl esterase and any known protein could be found in protein data bases.
This study investigated the possibility that overexpression of transforming growth factor alpha (TGF alpha) changes those neurotransmitter systems that have been associated with behaviors found to be altered in the transgenic TGF alpha CD-1 mice. The female TGF alpha mice showed elevated levels of norepinephrine (NE) in the hypothalamus and serotonin (5-HT) in the cortex and brain stem when compared with nontransgenic CD-1 females. The concentrations of monoamines were not altered in the male transgenic brain. The 5-hydroxyindoleacitic acid (5-HIAA)/5-HT ratio was significantly reduced in the brain stem of the male TGF alpha mice and frontal cortex in the female transgenics. The binding of the [3H]GBR 12935-labeled DA transporter was lower in the frontal cortex in the transgenic male TGF alpha mice than in the female TGF alpha mice. No gender difference in dopamine (DA) transporter binding was noted between the nontransgenic male and female mice. Serotonin and GABAA receptors were measured only in males. No differences in the number of 5-HT1A and 5-HT2 receptors were found in the cortex or hippocampus. Maximal GABA stimulation of [3H]flunitrazepam binding in the forebrain hemispheres and cerebellar binding of an imidazobenzodiazepine, [3H]Ro 15-4513, were not different between transgenic and nontransgenic male mice. However, forebrain [35S]TBPS binding in male TGF alpha mice was less affected by the blockade of the GABA agonist sites by the specific GABAA antagonists SR 95531 and bicuculline than the binding of the controls, suggesting either altered endogenous GABA concentrations or a change in receptor populations.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to study changes in the cell-wall composition of growing poplar cambium during the seasonal cycle, cell walls were isolated from the cambium and newly formed vascular tissues of poplar branches at three times during the year (winter, beginning of spring, end of summer). Polysaccharide material was isolated by sequential extraction of the cell walls and analysed. The principal polysaccharides identified were pectins and xylose- and glucose-containing polysaccharides, possibly xylans and (xylo)glucans. Our results indicate changes in the relative quantities of these polysaccharides during the seasonal cycle.
We have characterized a new transgenic mouse model that offers the unique opportunity to study the biological mechanisms linking aggression to alcohol. In contrast to all other aggressive animal models, the male transgenic mice that overexpress transforming growth factor-alpha (TGF-alpha) maintain their highly elevated aggressive behavior following an alcohol administration. The transgenic mice also exhibit elevated plasma levels of 17 beta-estradiol (E2). Animal data support the role of E2 in aggression and alcohol intake in males. Further, type 2 alcoholism is male-limited, suggesting that gonadal hormones are important. We examined whether gonadal hormones play a role in the resistance to respond to alcohol in the resident-intruder test of aggression among the male transgenic TGF-alpha mice. As previously reported, alcohol had a biphasic effect on sham-operated, nontransgenic controls: 0.6 g/kg increased and 2.0 g/kg inhibited their aggressiveness. Alcohol did not significantly reduce the high levels of aggression in the sham-operated TGF-alpha mice. Castration abolished the difference in aggressive behavior between the transgenic and nontransgenic male mice by reducing aggression. Alcohol did not increase aggressive behavior in these mice. Treatment with pellets releasing 0.25 mg E2 over a 60-day period increased aggression in the castrated male TGF-alpha mice and nontransgenic controls to the levels seen in intact male transgenic mice. Alcohol did not significantly alter aggressive behavior in the E2-treated castrated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
We used a noninvasive monitor of arterial pressure to determine whether respiratory changes in arterial pressure were closely correlated with airflow obstruction in asthmatic patients during bronchial challenge with methacholine. To validate the noninvasive measurement of respiratory changes in arterial pressure, a preliminary study in 6 subjects with normal cardiovascular and respiratory systems was done during cardiac catheterization for suspected coronary artery disease. There were no significant differences between inspiratory falls in systolic pressure measured noninvasively and those measured from intraaortic pressure. In 11 otherwise healthy asthmatic patients we measured finger arterial pressure, end-expiratory lung volume (FRC), and forced expired volume (FEV1) during baseline and bronchial challenge in the supine posture. Finger arterial pressure was also measured in 11 normal control subjects seated and supine. Normal subjects had an inspiratory fall in systolic pressure (IFSP) of 3.2 mm Hg supine and 5.1 mm Hg seated (p < 0.01). Asthmatic patients when bronchodilated (seated FEV1 = 83 +/- 7% of predicted) had an IFSP of 5.9 mm Hg supine (p < 0.01 compared with supine normal subjects). During bronchial challenge (average fall in FEV1 = 22%), IFSP increased to 16.1 mm Hg (p < 0.001 compared with baseline). In asthmatic subjects, there was a significant correlation between IFSP and FEV1 (mean r = -0.92 +/- 0.05, p < 0.01), and the average change in IFSP/change in FEV1 was -0.38 mm Hg per percentage change in FEV1. During subsequent bronchodilation, IFSP decreased with a similar time course as relaxation of airway smooth muscle, assessed by the breath-to-breath fall in FRC.(ABSTRACT TRUNCATED AT 250 WORDS)
Velo-cardio-facial syndrome (VCFS) is a common genetic disorder among individuals with cleft palate and is associated with hemizygous deletions in human chromosome 22q11. Toward the molecular definition of the deletions, we constructed a physical map of 22q11 in the form of overlapping YACs. The physical map covers > 9 cM of genetic distance, estimated to span 5 Mb of DNA, and contains a total of 64 markers. Eleven highly polymorphic short tandem-repeat polymorphic (STRP) markers were placed on the physical map, and 10 of these were unambiguously ordered. The 11 polymorphic markers were used to type the DNA from a total of 61 VCFS patients and 49 unaffected relatives. Comparison of levels of heterozygosity of these markers in VCFS patients and their unaffected relatives revealed that four of these markers are commonly hemizygous among VCFS patients. To confirm these results and to define further the breakpoints in VCFS patients, 15 VCFS individuals and their unaffected parents were genotyped for the 11 STRP markers. Haplotypes generated from this study revealed that 82% of the patients have deletions that can be defined by the STRP markers. The results revealed that all patients who have a deletion share a common proximal breakpoint, while there are two distinct distal breakpoints. Markers D22S941 and D22S944 appear to be consistently hemizygous in patients with deletions. Both of these markers are located on a single nonchimeric YAC that is 400 kb long. The results also show that the parental origin of the deleted chromosome does not have any effect on the phenotypic manifestation.
Pectin methylesterase (PME) is a cell wall enzyme that catalyses the de-esterification of pectins leading to fundamental changes which confer new properties to the micro-environment of each cell. In order to elucidate the meaning of PME-mediated changes of pectin in the time course of cell differentiation, we attempted to study the regulation of PME genes in Arabidopsis thaliana. In this report, the first full cDNA sequence showing sequence similarities with other PME genes characterised so far in other plant species has been isolated from an Arabidopsis shoot cDNA library. This ATPMEl cDNA is 1,970 bp long and contains an open reading frame encoding a protein of 64.1 kDa and a basic pI of 8.7 as predicted from the nucleotide sequence. Northern blot analyses denoted changes in the expression level of the ATPMEl mRNA according to plant organs. High mRNA levels were found in young developing organs such as cauline leaves while they were significantly lower in rosette leaves, stems and inflorescences, and almost undetectable in roots. Beside this molecular approach, isoelectrofocusing analyses revealed the occurrence of three PME isoforms in Arabidopsis. Two PME isoforms with pI values of 4.9 and 9.1 were found throughout the plant, but at a higher level in the root, while an other PME isoform with a pI of 5.7 was essentially detected in the inflorescence. The relationship between our observations and the data reported for other plant species is discussed.
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STUDY OBJECTIVE: To determine the effects of standard spinal immobilization on a group of healthy volunteers with respect to induced pain and discomfort. DESIGN: Prospective study. SETTING: University teaching hospital. TYPE OF PARTICIPANTS: Twenty-one healthy volunteers with no history of back disease. INTERVENTIONS: Subjects were placed in standard backboard immobilization for a 30-minute period. Number and severity of immediate and delayed symptoms were determined. MEASUREMENTS AND MAIN RESULTS: One hundred percent of subjects developed pain within the immediate observation period. Occipital headache and sacral, lumbar, and mandibular pain were the most frequent symptoms. Fifty-five percent of subjects graded their symptoms as moderate to severe. Twenty-nine percent of subjects developed additional symptoms over the next 48 hours. CONCLUSION: Standard spinal immobilization may be a cause of pain in an otherwise healthy subject.
Sleep-disturbed breathing, which includes apneas, hypopneas, and oxygen desaturations, occurs in asymptomatic individuals and increases with age. Obstructive apnea is the most frequent type of respiratory disturbance documented by polysomonography, the gold standard test for assessing sleep-disturbed breathing. Many of the prevalence studies done to date have had one or more methodological weaknesses, including selection biases, varying definitions of obstructive sleep apnea, failure to distinguish types of apneas, failure to control for confounding variables, and small sample size. Although there is consensus on the definitions of sleep-disturbed breathing, the appropriate number of apneas and hypopneas for diagnosing clinically significant obstructive sleep apnea is uncertain. While the cutoff of five or more apneas and hypopneas per hour is historically considered abnormal, the origins of this number are vague, and the longevity of those who have this value on polysomnography is not necessarily reduced. This is particularly true among those without symptoms of obstructive sleep apnea syndrome, which include excessive daytime sleepiness, snoring, nocturnal awakenings, and morning headaches. Investigators should be careful to distinguish symptomatic study subjects from asymptomatic subjects, and to exclude central apneas in calculating their estimates. In addition, various studies have used different definitions of sleep apnea syndrome, making comparisons of point estimates difficult. It would be more appropriate for researchers to estimate morbidity and mortality indices with confidence intervals, using several different cutoff points. Subject selection in all studies should follow a two-stage sampling procedure. All subjects with symptoms compatible with obstructive sleep apnea syndrome and a subsample of asymptomatic individuals should be studied with all-night polysomnography. If portable monitoring is used, the validity and reproducibility of this diagnostic method should be assessed. Subjects with significant comorbidity should be excluded from prevalence studies. Factors that clearly increase the risk of sleep-disturbed breathing and obstructive sleep apnea and its related symptoms include age, structural abnormalities of the upper airway, sedatives and alcohol, and probably family history. Although endocrine changes such as growth hormone, thyroid hormone, and progesterone deficiency also have been suggested as risk factors for exacerbating obstructive sleep apnea syndrome, there is minimal epidemiologic evidence to support this. Case-control studies are recommended to assess the relation of endocrine factors to obstructive sleep apnea syndrome in a rigorous fashion. A limited number of mortality studies have suggested decreased survival in persons with the obstructive sleep apnea syndrome, possibly primarily due to vascular-related disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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A patient with adult acid maltase deficiency (AMD) developed severe obstructive sleep apnea (OSA) and respiratory insufficiency. Weaning failure was followed by diffuse pneumonia and death. At autopsy, profound muscle replacement by fibrofatty tissue was noted in the tongue and diaphragm, while the accessory and nonrespiratory muscles were variably preserved. To our knowledge, this case represents the first detailed clinical description of OSA associated with adult AMD. In addition, we suggest that severe tongue weakness due to fatty metamorphosis, in concert with macroglossia, provides a unique pathophysiologic mechanism for OSA.
We used perfluorophenanthrene as an aid during pars plana vitrectomy in removing lens fragments dislocated posteriorly into the vitreous cavity. We reviewed the records of all patients (nine patients, nine eyes) referred with dislocated lenses who underwent pars plana vitrectomy with perfluorophenanthrene for removal of the lens material at Wills Eye Hospital from July 1, 1991, through Nov. 30, 1991. The lens was dislocated during cataract extraction in eight eyes. One eye had a history of nonpenetrating trauma and lens dislocation. In one eye a retinal tear was noted intraoperatively and treated. Six eyes had postoperative visual acuity of 20/50 or better. In all eyes the lens was removed without further complications. Perfluorocarbon liquids such as perfluorophenanthrene may enhance current techniques by allowing easier and safer removal of displaced lens fragments through the pars plana.