From a constellation to a continuum: policy and management implications for long-term care.
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Biomedical subjects
Publications and source records attributed to J L Martin.
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A Raman spectrometer that provides both subpicosecond resolution and independent, tunable pump and probe pulses is described. The spectrometer is employed to obtain time-resolved spectra of (carbonmonoxy)hemoglobin (HbCO) at times from 0.2 to 95 ps subsequent to ligand photodissociation. The spectra are interpreted in terms of a vibrationally hot heme that cools substantially in 10 ps. Concomitant with the proposed vibrational cooling is a slower relaxation, which we suggest results from a protein response to heme doming induced by ligand detachment. Results and interpretations are discussed in the context of current models of the heme photophysics and of hemoglobin reactivity.
Insulin-like growth factor (IGF) binding protein has been purified from adult rat serum by affinity chromatography on agarose-IGF-II and high performance reverse-phase chromatography. The final preparation contains two components, of apparent molecular mass 50 and 56 kDa nonreduced, or 44 and 48 kDa reduced, both of which specifically bind IGF-I and IGF-II. Competitive binding data indicate association constants of 5-10 X 10(10) l/mol for both IGFs, with a slightly higher affinity for IGF-II than IGF-I. Amino-terminal sequence analysis yields a unique sequence, identical in 11 of the first 15 amino acids with that of a human plasma IGF binding protein (Martin, J. L., and Baxter, R. C. (1986) J. Biol Chem. 261, 8754-8760), and with slight homology to other human and rat IGF binding proteins characterized to date. By analogy with the binding protein from human plasma, it is likely that the rat protein is part of the growth-hormone dependent complex which appears to carry most or all of the circulating IGFs.
To characterize the abnormal pattern of instantaneous left ventricular (LV) ejection in heart failure, proximal aortic pressure, flow, acceleration, power and dW/dt were measured at rest and during supine bicycle exercise using high-fidelity, catheter-mounted pressure and velocity sensors in 16 patients with idiopathic dilated cardiomyopathy (IDC) and 11 normal control subjects. In patients with IDC, peak flow was lower than normal both at rest (454 +/- 155 vs 649 +/- 168 ml/s, p less than 0.01) and during exercise (569 +/- 213 vs 916 +/- 329 ml/s, p less than 0.01). Peak acceleration, power and dW/dt were also significantly reduced in patients with IDC at rest and during exercise. Time to peak flow (as a fraction of LV ejection time) was consistently prolonged in patients with IDC (rest, 0.40 +/- 0.08 vs 0.29 +/- 0.04; exercise, 0.36 +/- 0.06 vs 0.28 +/- 0.04, both p less than 0.01). Exercise-induced increments in peak flow, power and dW/dt were significantly blunted in patients with IDC. Studies during pacing tachycardia and nitroprusside administration failed to reproduce the abnormalities during exercise in patients with IDC. Thus, the instantaneous flow pulse in heart failure is both diminished in magnitude (decreased stroke volume and peak flow) and abnormal in shape (decrease peak acceleration and delayed time to peak flow). Exercise stress in IDC results in abnormalities of LV performance that can be detected using instantaneous ejection information. These abnormalities are unlikely to be explained by changes in heart rate or loading conditions.
This is a progress report on some of the research that was planned and begun with Barbara Dohrenwend before she died in 1982. The main focus is on two of the studies. One was conducted in New York City; the other is still underway in Israel. The New York study is a retrospective case/control study of social and psychological factors that may put people at risk for developing schizophrenic episodes and episodes of major depression. The Israel research consists of epidemiological, case/control, and family studies of these two disorders together with other types of psychopathology that are inversely related to social class. Preliminary findings from both studies are reported, and their implications for primary prevention are discussed.
The distribution of vasoactive intestinal peptide binding sites in the rat brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of vasoactive intestinal peptide (M-[125I]VIP) previously shown to maintain in the central nervous system the full biological activity of native vasoactive intestinal peptide was used for this study. In initial kinetic and pharmacological experiments the binding of M-[125I]vasoactive intestinal peptide to slide-mounted sections was shown to be time-dependent, saturable and reversible. Association of M-[125I]VIP specific binding was maximal within 90-120 minutes. Specific binding, corresponding to approximately 50% of total binding was saturable, of high affinity (Kd of 76.6 pM) and low capacity (fmol/mg prot range). Dissociation of M-[125I]VIP was maximal at 10 minutes. Unlabeled vasoactive intestinal peptide and the two structurally related peptides "peptide-histidine-isoleucine" (PHI) and secretin competed in a concentration-dependent manner for sites labeled by M-[125I]vasoactive intestinal peptide with the following rank order of potencies: vasoactive intestinal peptide greater than PHI greater than secretin. Vasoactive intestinal peptide receptors, as revealed by quantitative autoradiography, are present at various levels of the neuraxis. High densities were observed in olfactory bulb, cerebral cortex (highest in layers I, II, IV and VI), dentate gyrus, subiculum, various thalamic and hypothalamic nuclei, superior colliculus, locus coeruleus, area postrema, subependymal layer and pineal gland. Intermediate densities were found in the amygdala, nucleus accumbens, caudate-putamen, septum, bed nucleus of the stria terminalis, CA1 to CA4 fields of the hippocampus and central gray. No specific binding of M-[125I]vasoactive intestinal peptide was observed in white matter tracts such as corpus callosum, anterior commissure, medial forebrain bundle and fornix. The mapping of M-[125I]vasoactive intestinal peptide binding sites as revealed by autoradiography on slide-mounted sections indicates an association, although not exclusive, of vasoactive intestinal peptide receptors with brain regions involved in the processing of specific sensory inputs.
In vitro and in vivo studies were done on a herpes simplex virus type 2 strain recovered from a patient on acyclovir (ACV) which was ACV resistant but expressed thymidine (dThd) kinase (EC 2.7.1.21) activity. Plaque-purified clones derived from the original clinical sample were heterogeneous with respect to plaque size and drug susceptibility. The heterogeneity of this viral mixture was also evident from varied 125I-labeled 5-iodo-2'-deoxycytidine autoradiographic patterns and from varied expression of dThd kinase-associated phosphorylating activities. Four clones from this mixture were 1-beta-D-arabinofuranosylthymine (ara-T) susceptible and ACV resistant. Extracts of cells infected with these clones catalyzed the phosphorylation of ara-T but little of ACV. The virus-coded dThd kinase was purified from one of these clones to determine whether its substrate specificity was altered. The amount of virus-coded dThd phosphorylating activity with the cell extracts was estimated to be sevenfold lower with the resistant clone than with the MS strain of herpes simplex virus type 2. The dThd kinase eluted from a dThd-agarose affinity column under the same conditions with extracts from both sources and substrate saturations of both enzymes by acyclic nucleoside analog phosphate acceptors were classical hyperbolic functions. However, there were significant differences in the kinetic parameters of substrates between the two enzymes. Apparent Km (Km') values for dThd, deoxycytidine, ara-T, ACV, and the acyclic guanosine analog 9-[[2-hydroxyl-1-(hydroxymethyl)ethoxy]methyl]guaine (BW B759U) were 2- to 60-fold higher with the variant enzyme than with the enzyme from laboratory strain MS. Comparing these two enzymes, relative maximal phosphorylation rates (Vm) were eightfold lower for ACV but unchanged for BW B759U. In contrast, the relative rates for deoxycytidine and ara-T were eight- and twofold higher, respectively. The surprisingly good substrate activity with BW B759U compared with that of ACV (Vm/Km' = 0.39 versus 0.01) coincided with susceptibility of the ACV-resistant virus to BW B759U. This clinical variant retained its pathogenicity for mice and was only moderately less neurovirulent than wild-type virus. Although such mutants have the potential to induce illness less responsive to therapy, the recurrence from which the isolate was obtained was typical for this patient in severity and duration. Since this episode, the patient has been treated successfully with ACV.
To investigate possible alterations of myocardial performance in young rats, cardiac hypertrophy was induced by stenosis of the ascending aorta (AS) in three groups of 25-day-old rats that were compared with three groups of sham-operated controls (C). The cardiac overload duration was 8-10 days, 1 mo, and 2 mo in groups 1, 2, and 3, respectively. Mechanics and energetics were studied in left ventricular papillary muscles, and determination of the V1 and V3 isomyosin pattern was achieved in the same papillary muscle. The majority of quantitative changes concerning the cardiac growth process, contractility, and isomyosin shifts occurred within 8-10 days of stenosis. At this point, the degree of left ventricular hypertrophy relative to C was 53 +/- 6%, whereas maximum unloaded shortening velocity (Vmax) decreased significantly (2.8 +/- 0.1 in C vs. 1.9 +/- 0.1 Lmax/s in AS), peak power output (Emax) decreased (1.8 +/- 0.3 in C vs. 0.6 +/- 0.1 in AS), and the curvature of Hill's hyperbola increased (1.3 +/- 0.4 in C vs. 2.0 +/- 0.7 in AS); moreover, the percent V1 isomyosin decreased significantly (98 +/- 1 in C vs. 51 +/- 3% in AS) and the percent V3 isomyosin increased significantly (2 +/- 1 in C vs. 26 +/- 2% in AS). Beyond 8-10 days of AS, additional changes in cardiac hypertrophy and in mechanical and biochemical parameters were less marked.(ABSTRACT TRUNCATED AT 250 WORDS)
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Aortic insufficiency was induced in rats. Left ventricular papillary muscle function was studied after 5, 12, and 40 wk and compared with the papillary muscles from sham-operated animals. The maximum unloaded velocity of shortening, Vmax, was decreased in the rats with aortic insufficiency relative to controls by 15, 20, and 34% at 5, 12, and 40 wk, respectively. The decrease in Vmax occurred concomitantly with a change in the myosin isoenzyme composition such that the V1 isoform content decreased and the V3 isoform increased. Relative to age-matched controls, the V3 content in the hearts with aortic insufficiency had increased by 80, 180, and 125% at 5, 12, and 40 wk, respectively. The decrease in Vmax in the aortic insufficiency group muscles correlated with the change in myosin isozyme composition and could not be explained by changes in collagen content. Thus aortic insufficiency induced changes in myosin isozyme content and Vmax similar to those previously observed with aortic stenosis, thus suggesting a common mechanism of myocardial adaptation to different types of mechanical overload.
In Boolarra virus infected Drosophila line 1 cells five virus-induced proteins were readily detected 20 h postinfection. These were A (103,500), alpha (46,000), beta (40,000), B (9,600), and gamma (6,600) and are similar in molecular weight to those induced in vivo by other nodaviruses. The addition of actinomycin D for the 1st h before the labeling period resulted in the production of all five proteins; but when actinomycin D was introduced for the entire labeling period, the synthesis of the products of RNA1 was greatly reduced. Host functions inhibited by actinomycin D may play a major role in the replication of this virus.
Left ventricular hypertrophy (LVH) was produced in guinea pigs after aortic stenosis (AS). The percentage of LVH in AS was determined by normalizing left ventricular (LV) weight by the mean LV weight of sham-operated controls (n = 12). After 3 weeks of cardiac overload, a mild LVH (30 +/- 3%) was induced in 17 animals and a relatively severe LVH (56 +/- 3%) was induced in 7 animals. LV papillary muscles were rapidly excised for mechanical studies. No significant differences were observed between control and mild hypertrophy groups. In contrast, a marked decrease in myocardial performance was seen in the more severe cardiac hypertrophy group and was expressed as a percentage of sham-operated levels (Vmax, 22%; active isometric force/mm2, 23%; +dF/dt max/mm2, 26%). Relaxation in this group was still more impaired than contraction (peak lengthening velocity, 14%; -dF/dt max/mm2, 19%). Moreover, the load sensitivity of relaxation was present in both sham-operated controls and mild hypertrophy but almost disappeared in more severe hypertrophy. Isometric relaxation was delayed in the latter group, as shown by the 15% increase of the half-time of the decline of isometric relaxation (t 1/2). On the other hand, acute hypoxia (95% N2-5% CO2 for 20 minutes) also induced a fall in contractility and the disappearance of the load sensitivity of relaxation but with a 67% decrease of t 1/2. Thus, the mechanical analysis of relaxation allows the effects of chronic overload in relatively severe cardiac hypertrophy to be separated from those of acute hypoxia. Moreover, in severe cardiac hypertrophy, the impairment of the load sensitivity of relaxation with increased t 1/2 strongly suggests alterations of the sarcoplasmic reticulum, especially since the moderate decrease in the myofibrillar ATPase activity, which has been observed previously in guinea pig pressure overload, cannot account completely for the marked fall in myocardial performance.
A binding protein for insulin-like growth factors (IGFs) has been purified from human amniotic fluid by IGF-I affinity chromatography and high performance reverse phase chromatography. This protein, with an apparent molecular mass of 28K nonreduced and 34K reduced, had an identical amino-terminus to a previously purified binding protein from amniotic fluid and to placental protein 12. The purified preparation (BP-28) bound both IGFs with high affinity [Ka, 6.55 +/- 2.24 (+/- SD) L/nmol for IGF-I and 3.23 +/- 1.05 L/nmol for IGF-II], with approximately 0.5 mol binding sites/mol BP-28 for either ligand. A 53K IGF-binding protein purified from human plasma (BP-53) did not cross-react in a RIA for BP-28, and BP-28 had less than 0.1% molar cross-reactivity in a RIA for BP-53. Human amniotic fluid reacted strongly in both assays. Fractionation of amniotic fluid samples by reverse phase chromatography showed that BP-28 and BP-53 immunoreactivities were present on separate proteins. In 40 third trimester amniotic fluid samples selected to cover a wide range of lecithin to sphingomyelin ratios, the mean concentrations of BP-28 and BP-53 were 37.6 +/- 17.6 (+/- SD) and 4.6 +/- 1.6 mg/L, respectively. Significant negative correlations were found between the levels of both BP-28 and BP-53 and the lecithin to sphingomyelin ratio, suggesting an association between the levels of both proteins and the degree of fetal maturity. A significant positive association was also found between the levels of BP-28 and BP-53. We conclude that the 28K IGF-binding protein from amniotic fluid, like the previously purified 53K binding protein, has high affinity for both IGF-I and IGF-II, that it coexists in amniotic fluid with BP-53 or a related protein, and that the levels of both proteins decline with increasing fetal maturity.
A sample of 745 gay men, ages 20 to 65, were interviewed in 1985 as part of an effort to determine the impact of the AIDS (acquired immunodeficiency syndrome) epidemic on the non-ill but at-risk community. Measured in terms of the number of different sexual partners, sexual activity was reported to have declined by 78 per cent since hearing about AIDS. The frequency of sexual episodes involving the exchange of body fluids and mucous membrane contact declined by 70 per cent, and condom use during anal intercourse increased from 1.5 to 20 per cent. Abstinence from gay sex did not change over time.
A case of delayed detection of esophageal intubation is described. Preoxygenation and pulse oximetry were used, and the first indication of tube misplacement was arterial desaturation indicated by the pulse oximeter. The combination of preoxygenation and pulse oximetry may contribute to delays in early detection of endotracheal tube misplacement for the following reasons: (1) preoxygenation results in a pulmonary reservoir of oxygen sufficient to maintain arterial hemoglobin saturation for an extended period of time; and (2) the maintenance of normal arterial saturations for an extended period after inadvertent esophageal tube placement may lead the practitioner to initially seek other causes of declining oxygen saturations. Although pulse oximetry is an acknowledged advance in patient monitoring, it must not be utilized as an early indication of correct endotracheal tube placement.
A growth hormone-dependent binding protein for insulin-like growth factors (IGF-I and IGF-II) has been isolated from human plasma. Analyzed on SDS gels, the preparation contained a major protein band of 53 kDa, and a minor band of 47 kDa. After transfer to nitrocellulose, both species bound iodinated IGF-I, and could be detected using an antibody raised against the purified preparation. In contrast, an IGF binding protein purified from human amniotic fluid bound IGF-I but was not detectable immunologically. The amino acid comparison of the plasma binding protein preparation was different from that reported for amniotic fluid and HEP G2 hepatoma proteins, and the unique amino-terminal sequence, Gly-Ala-Ser-Ser-Ala-Gly-Leu-Gly-Pro-Val-, was different from that of the amniotic fluid and hepatoma proteins. This study indicates that the growth hormone-dependent IGF binding protein of human plasma is structurally and immunologically distinct from other IGF binding proteins.