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Biomedical subjects

J M Friedman

Publications and source records attributed to J M Friedman.

339 records · Page 19Linked to original sources
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Inheritance of fragile X syndrome: an hypothesis.

The fragile X (fra(X), or Martin Bell-MB) syndrome is considered an X-linked recessive trait. However, clinically normal male transmitters of the condition have been observed occasionally. The occurrence of "carrier" males and the observation of other unusual genetic characteristics in the MBS suggest that this condition is not a standard X-linked recessive trait. We propose that the MBS is due to a transposable genetic element which can exist in 3 different chromosomal states and effect 2 different extrachromosomal environments. This model can account for the peculiar genetic behavior of the fragile X syndrome.

DNA Transposable Elements↗
PubMedDate not supplied

Anatomic correlates of ultrasonographic prenatal diagnosis.

In utero sonographic diagnoses from forty-five malformed infants were correlated with their autopsy findings. Fifty-two malformations were diagnosed prenatally in 42 of the patients but 90 additional malformations were not. Nine sonographically diagnosed abnormalities were not confirmed at autopsy. Factors compromising sonographic diagnosis included: limited examinations, small fetal size, timing of examination, oligohydramnios, fetal position, nature of the malformation and unfamiliarity of the ultrasonographer with specific malformation syndromes. In utero ultrasonography is an invaluable tool of diagnosing congenital malformations but has limitations.

Abnormalities, Multiple↗
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Plasma dexamethasone and cortisol levels in depressed outpatients.

We investigated the 1-mg dexamethasone suppression test (DST) in 41 outpatients with major depressive disorder assessing the role of dexamethasone blood level, age and basal cortisol on DST results. Non-suppressors (approximately 25% of patients) had lower dexamethasone levels, and post-dexamethasone cortisol was negatively correlated with plasma dexamethasone; these findings were more significant after covarying out age and basal cortisol, factors that were also significantly associated to non-suppressors. A subgroup of patients (n = 19) also had 0.75-mg and 2.0-mg DST to evaluate whether a threshold dexamethasone blood level existed; a dexamethasone blood level greater than 1.5 ng/ml converted all non-suppressors to suppressors. Implications of these findings are discussed.

Adult↗
PubMedDate not supplied

Site-specific PEGylation of hemoglobin at Cys-93(beta): correlation between the colligative properties of the PEGylated protein and the length of the conjugated PEG chain.

Increasing the molecular size of acellular hemoglobin (Hb) has been proposed as an approach to reduce its undesirable vasoactive properties. The finding that bovine Hb surface decorated with about 10 copies of PEG5K per tetramer is vasoactive provides support for this concept. The PEGylated bovine Hb has a strikingly larger molecular radius than HbA (1). The colligative properties of the PEGylated bovine Hb are distinct from those of HbA and even polymerized Hb, suggesting a role for the colligative properties of PEGylated Hb in neutralizing the vasoactivity of acellular Hb. To correlate the colligative properties of surface-decorated Hb with the mass of the PEG attached and also its vasoactivity, we have developed a new maleimide-based protocol for the site-specific conjugation of PEG to Hb, taking advantage of the unusually high reactivity of Cys-93(beta) of oxy HbA and the high reactivity of the maleimide to protein thiols. PEG chains of 5, 10, and 20 kDa have been functionalized at one of their hydroxyl groups with a maleidophenyl moiety through a carbamate linkage and used to conjugate the PEG chains at the beta-93 Cys of HbA to generate PEGylated Hbs carrying two copies of PEG (of varying chain length) per tetramer. Homogeneous preparations of (SP-PEG5K)(2)-HbA, (SP-PEG10K)(2)-HbA, and (SP-PEG20K)(2)-HbA have been isolated by ion exchange chromatography. The oxygen affinity of Hb is increased slightly on PEGylation, but the length of the PEG-chain had very little additional influence on the O(2) affinity. Both the hydrodynamic volume and the molecular radius of the Hb increased on surface decoration with PEG and exhibited a linear correlation with the mass of the PEG chain attached. On the other hand, both the viscosity and the colloidal osmotic pressure (COP) of the PEGylated Hbs exhibited an exponential increase with the increase in PEG chain length. In contrast to the molecular volume, viscosity, and COP, the vasoactivity of the PEGylated Hbs was not a direct correlate of the PEG chain length. There appeared to be a threshold for the PEG chain length beyond which the protection against vasoactivity is decreased. These results suggest that the modulation of the vasoactivity of Hb by PEG could be a function of the surface shielding afforded by the PEG, the latter being a function of the disposition of the PEG chain on the protein surface, which in turn is a function of the length of the PEG chain. Thus, the biochemically homogeneous PEGylated Hbs described in the present study, surface-decorated with PEG chains of appropriate size, could serve as potential candidates for Hb-based oxygen carriers.

Animals↗
PubMedDate not supplied

Cardiovascular disease in neurofibromatosis 1: report of the NF1 Cardiovascular Task Force.

PURPOSE: Patients with neurofibromatosis 1 (NF1) are at increased risk for a variety of cardiovascular disorders, but the natural history and pathogenesis of these abnormalities are poorly understood. METHODS: The National Neurofibromatosis Foundation convened an expert task force to review current knowledge about cardiovascular manifestations of NF1 and to make recommendations regarding clinical management and research priorities related to these features of the disease. RESULTS: This report summarizes the NF1 Cardiovascular Task Force's current understanding of vasculopathy, hypertension, and congenital heart defects that occur in association with NF1. Recommendations are made regarding routine surveillance for cardiovascular disease and diagnostic evaluation and management of cardiovascular disorders in individuals with NF1. CONCLUSION: Our understanding of the natural history and pathogenesis of cardiovascular disease in NF1 has improved substantially in the past few years, but many clinically important questions remain unanswered.

Advisory Committees↗