Report of the Third International Workshop on Human Chromosome 15 Mapping 1996. October 25-27, 1996 in Vancouver B.C., Canada.
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Biomedical subjects
Publications and source records attributed to R Schultz.
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This Grand Rounds is concerned with the classification of Asperger's syndrome and its continuity/discontinuity with autism. Information on a 15-year-old with the condition is presented as are data on other family members. The proband exhibited a longstanding pattern of marked deficits in social interaction, motor awkwardness, and unusual, circumscribed interest consistent with a diagnosis of Asperger's syndrome. Both the proband and his father exhibited unusual discrepancies between verbal and performance (nonverbal) cognitive abilities favoring the former. Deficits were observed in the social use of language. Father and son had similar abnormalities on magnetic resonance imaging examination. Potential differences between higher-functioning autism and Asperger's syndrome are important areas for future research.
Cytomegalovirus is the main agent of congenital viral infections. The aim of this study was to compare the incidence of congenital cytomegalovirus infections of two groups of newborns of differing socioeconomic status. Cytomegalovirus was isolated from urine or oropharingeal secretions in 218 children born in a private clinic and 471 born in a public hospital. Positive viral isolates were confirmed with indirect immunofluorescence using monoclonal antibodies. Infection was detected in 12 children (1.82%), four coming from the private clinic (1.86%) and 8 coming from the public hospital (1.81%). Ninety two percent of infected children were asymptomatic. Urine and oropharingeal secretion samples had the same yield for viral isolation. It is concluded that the incidence of congenital cytomegalovirus infection is similar to that described in developed countries.
UNLABELLED: A strong association between interatrial septal aneurysm (IASA) and stroke has recently led many authors to consider IASA as a potential cardiac source of embolism. We studied the morphological characteristics and main associations of IASA in a large cooperative study based on transoesophageal echocardiographic examinations; 259 IASA were studied in 134 men and 125 women with a mean age of 59 +/- 15 years. Fifty-five percent of IASA were found to overlap the commonly described fossa ovalis region. IASA protruded into the right atrium in 90% of the cases. They appeared thin in 81% of the patients and highly mobile in 79%. Fifty-eight percent of patients had a history of systemic embolic events, while an atrial septal shunt was detected in 61% of the patients. In patients with an embolic event, only the mobility of IASA was significantly higher than in those with no embolic event. In nine cases a pulmonary embolism was associated with arterial embolism. Furthermore, we reported three cases of paradoxical embolism. However, the true demonstration of a thrombus within the IASA was quite rare. CONCLUSION: IASA is probably an important risk factor for stroke. In patients with IASA and a history of embolic events, IASA may enhance migration of a thrombus constituted in situ or transiting through it. Marked mobility of IASA may also increase the risk of peripheral embolus.
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A series of novel distamycin-related polyanionic compounds were compared for their anti-HIV activity. Several were highly potent inhibitors of HIV virus-induced cell killing and viral replication of a wide variety of laboratory isolates, as well as a monocytotropic virus and a clinical isolate in human peripheral blood lymphocytes. These compounds are structurally different from other sulfonic acid containing compounds reported to be potent inhibitors of the human immunodeficiency virus (HIV) in two respects: (1) they are structurally related to the non-toxic minor groove DNA binder distamycin; and (2) a number of them contain the aromatic phosphonic acid group. The compounds that were evaluated can be categorized into monomeric or dimeric ureido structural classes incorporating the bisamido-N-methylpyrrolenaphthalene-sulfonic acid group, with differences in the number and position of the sulfonic acids on the naphthalene rings. Broader structure-activity studies were made possible through the synthesis and evaluation of the compounds containing only a single N-methylpyrrole unit, those incorporating the N-methylpyrazole structure, and compounds having the isosteric phosphonic acid group substituted for the sulfonic acid group. One of the most potent of the inhibitors was 2,2'[4,4'[[aminocarbonyl]amino]bis[N,4'-di[pyrrole-2-carboxamide- 1,1'-dimethyl]]-4,6,8 naphthalenetrisulfonic acid] hexasodium salt, NSC 651015. This compound, the phosphonic acid analog NSC 662162, and the monomeric compound NSC 651018 were studied to determine the mechanism of their inhibitory activity. Mechanistic studies revealed that inhibition was due to the disruption of virus attachment to CD(4+)-susceptible cells and a further restraint on fusion of virus and cell membranes. The relative tolerance of these compounds in mice suggests that sufficient antiviral concentrations could be reached in vivo and thus may prove valuable in the treatment of AIDS patients.
Phase II of the Trials of Hypertension Prevention is a multicenter, randomized, controlled trial designed to determine the efficacy of weight loss and reduction of sodium intake for lowering blood pressure and incidence of hypertension among persons with high-normal levels of blood pressure. The 2 x 2 factorial study design includes weight loss alone, restricted sodium intake alone, the combination of weight loss and sodium restriction, and a control group. Nine clinical centers used a variety of recruitment strategies to enroll 2382 participants over 17 months, which exceeded the sample size goal of 2250. Among randomized participants, 21% were minorities and 34% were women. Overall, direct mail generated the most randomized participants (73%), followed by community screening (12%) and media advertisement (11%). Referrals from community health care providers yielded few participants. Prescreening improved overall efficiency and reduced costs. Participants who were more likely to drop out voluntarily during the three-visit screening regimen tended to be younger, single, male, smokers, and less educated.
In this study we investigated the expression of the immediate early genes (IEGs) c-fos, c-jun, and junD on mRNA and protein levels during the spermatogenic cycle of the rat using Northern blotting, in situ hybridization, and immunocytochemistry. The expression of these IEG mRNAs and proteins exhibited stage-specific variations. The results suggest that IEGs take part in transcriptional events that are involved in regulating the proliferation and differentiation of spermatogenic cells during specific stages of the cycle of the seminiferous epithelium.
OBJECTIVE: Many children with Tourette's syndrome (TS) are handicapped more by difficulties with inattention, impulsivity, and hyperactivity than by their tics. However, stimulant medications used to treat attention-deficit hyperactivity disorder (ADHD) can exacerbate tics. Guanfacine is an alpha 2-adrenergic agonist that may have beneficial effects on attention, without the hypotensive or sedative effects of clonidine, which is often used as an alternative to stimulants. METHOD: An open-label study of guanfacine was performed in 10 children with TS+ADHD, aged 8 to 16 years. The duration of follow-up was 4 to 20 weeks, and the majority of subjects were treated with 1.5 mg/day. Ratings of tic severity and ADHD symptoms were obtained using the Yale Global Tic Severity Scale (YGTSS), the Tic Symptom Self Report (TSSR), and the Conners Parent Rating Scale. In addition, blind Continuous Performance Tests (CPTs) were performed at baseline and at two follow-up intervals in eight subjects. RESULTS: Guanfacine was associated with significant decreases in both commission errors (p < .02) and omission errors (p < .01) on the CPT. In addition, guanfacine caused a significant decrease in severity of motor (p < .02) and phonic (p < .02) tics as measured by the TSSR and the YGTSS, respectively. The most common side effects were transient sedation and headaches. CONCLUSION: Guanfacine may provide a safe alternative therapy for children with ADHD in the presence of tics. Future double-blind, controlled trials should be undertaken.
Five fresh-frozen cadaver feet obtained from traumatic amputations were tested during hyperdorsiflexion stress of the first metatarsophalangeal joint. Three different types of injury were observed: (1) rupture of the capsule proximal to the sesamoids, (2) rupture of the plantar plate distal to the sesamoids, and (3) rupture of the capsular structures medially, allowing a lateral swing of the sesamoids around the metatarsal head. Incomplete dislocation can be associated with significant damage to the plantar plate and other soft tissues of the foot.
In the present study we have investigated the induction of immediate early gene (IEG) c-fos, c-jun, junB and junD mRNAs and proteins in interstitial cells of rat testis after hCG treatment in vivo using in situ hybridization and immunocytochemistry. The basal levels of all IEGs were barely detectable with our methods. A prominent induction of c-fos, c-jun and junB mRNAs and proteins in Leydig cells was seen after hCG treatment. The induction of these IEG mRNAs and proteins demonstrates that their expression is an early transcriptional response to the extracellular stimulus of hCG and that they are involved in transcriptional processes which may mediate the effects of LH on cellular adaptive responses or steroid biosynthesis.
In the last decades several authors have observed a frequent association between diabetes mellitus and porphyria, mainly porphyria cutanea tarda. In previous studies, it has been demonstrated that both d delta d-aminolevulic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D), enzymes of the heme pathway, are inhibited by high concentrations of glucose in vitro in crude preparations of erythrocytes. The activity of these same enzymes was diminished in different tissues obtained from streptozotocin induced diabetic mice. Therefore, we decided to investigate the incidence of heme metabolism alterations in diabetes mellitus in a population of 100 non selected adult patients. The activities of erythrocytic ALA-D and PBG-D were measured. Rhodanese, an enzyme of the sulfocompounds pathway closely related to the regulation of heme biosynthesis, was also studied. Urine porphyrin content as well as the chromatographic pattern of esterified porphyrins were determined. ALA-D and PBG-D activities were diminished in diabetic patients (40% and 20% respectively), while rhodanese was only slightly increased (Fig. 1). ALA-D activity was subnormal in a 92% of the complete diabetic population, while PBG-D activity was less than normal in a 79% of the same population. No significative differences between enzymic activities were observed in the groups insulin and non-insulin dependent (Fig. 3). Urine porphyrin content was increased in 5% of the diabetic population. Chromatographic pattern of urinary porphyrins was notably altered in diabetic patients irrespectively of their porphyrin content (Fig. 4), suggesting an alteration in the enzyme uroporphyrinogen decarboxylase resembling the primary enzymic defect observed in porphyria cutanea tarda.(ABSTRACT TRUNCATED AT 250 WORDS)
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The authors report a prospective study of the correlation between histopathological alterations in the placenta and the umbilical cord and neonatal infection in 223 newborns. The pathological studies were specifically concerned with the presence of infection as shown by a polymorphonuclear infiltrate at these sites. Inflammatory lesions were demonstrated in 26.9% of specimens and were highest in those with prolonged premature rupture of membranes and in the least mature placentas. Among the cases of histological chorioamnionitis, only 23.3% of infants had documented infection. Neonatal infection was diagnosed in 7.2% of the newborns and was 10 times more frequent in preterm newborns. Among the cases of infected newborns, 87.5% of placentas had histological chorioamnionitis. Pneumonia and septicemia were the most frequent conditions found among infected newborns. There was a strong correlation between histological chorioamnionitis and neonatal infection. The data obtained in this investigation suggest that histological chorioamnionitis is an important indicator of neonatal infection.
A new approach to increase the selectivity of interaction between oligonucleotide probes and target nucleic acids is described. In place of a single, relatively long oligonucleotide probe, two or three short oligomers terminated by thiophosphoryl and bromoacetamido groups are employed. Fast and efficient autoligation takes place when the oligomers hybridize in a contiguous mode to the same complementary strand such that a thiophosphoryl group on one strand and a bromoacetamido group on another are brought into proximity. A single nucleotide mismatch for the short probes leads to marked reduction in the rate of autoligation. The binding affinity of the product is close to that for a natural probe of the same length. This approach could have potential in oligonucleotide-based diagnostics, chemical amplification systems, and therapeutic applications.
To determine whether alterations in energy balance account for growth failure in Rett syndrome, we measured dietary energy intakes, fecal fat losses, activity patterns, and sleeping as well as quietly and actively awake metabolic rates in Rett syndrome girls and healthy controls. Dietary energy intakes and fecal fat losses did not differ between the groups. Metabolic rates while sleeping and quietly awake were 23% lower (P < .05) in Rett syndrome girls than in controls; metabolic rates while actively awake did not differ between the groups. However, because of the 2.4-fold greater time (P < .001) spent in involuntary motor movement, energy expenditure associated with activity was twofold greater (P < .05) in Rett syndrome girls than in controls. Although total daily energy expenditure of the two groups did not differ significantly, energy balance was less positive in the Rett syndrome girls than in the controls. This small difference in energy balance, if sustained over months to years, is sufficient to account for growth failure in Rett syndrome girls.