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Biomedical subjects

M Havenith

Publications and source records attributed to M Havenith.

18 recordsLinked to original sources
PubMed2006

Solute-induced retardation of water dynamics probed directly by terahertz spectroscopy.

The dynamics of water surrounding a solute is of fundamental importance in chemistry and biology. The properties of water molecules near the surface of a bio-molecule have been the subject of numerous, sometimes controversial experimental and theoretical studies, with some suggesting the existence of rather rigid water structures around carbohydrates and proteins [Pal, S. K., Peon, J., Bagchi, B. and Zewail A. H. (2002) J. Phys. Chem. B 106, 12376-12395]. Hydrogen bond rearrangement in water occurs on the picosecond time scale, so relevant experiments must access these times. Here, we show that terahertz spectroscopy can directly investigate hydration layers. By a precise measurement of absorption coefficients between 2.3 THz and 2.9 THz we could determine the size and the characteristics of the hydration shell. The hydration layer around a carbohydrate (lactose) is determined to extend to 5.13 +/- 0.24 A from the surface corresponding to approximately 123 water molecules beyond the first solvation shell. Accompanying molecular modeling calculations support this result and provide a microscopic visualization. Terahertz spectroscopy is shown to probe the collective modes in the water network. The observed increase of the terahertz absorption of the water in the hydration layer is explained in terms of coherent oscillations of the hydration water and solute. Simulations also reveal a slowing down of the hydrogen bond rearrangement dynamics for water molecules near lactose, which occur on the picosecond time scale. The present study demonstrates that terahertz spectroscopy is a sensitive tool to detect solute-induced changes in the water network.

Carbohydrates↗
PubMed2005

High-resolution spectroscopy of NO in helium droplets: a prototype for open shell molecular interactions in a quantum solvent.

We have measured the high-resolution infrared spectrum of the radical NO in the (2)Pi(1/2) state in superfluid helium nanodroplets. The features are attributed to the -doubling splitting and the hyperfine structure. The hyperfine interaction is found to be unaffected by the He solvation. For the Lambda-doubling splitting, we find a considerable increase by 55% compared to the gas phase. This is explained by a confinement of the electronically excited NO states by the surrounding He. The rotational level spacing is decreased to 76% of the gas phase value. The IR transition to the J=1.5 state is found to be homogeneously broadened. We attribute both observations to the coupling between the molecular rotation and phonon/roton excitations in superfluid (4)He droplets.

Journal Article↗
PubMed2005

Comparison of pregnancy course and outcome with color and radiographic angiography of the placenta in a monochorionic triplet pregnancy.

A patient with spontaneous monochorionic (MC) triamniotic triplet pregnancy developed symptoms of feto-fetal-transfusion-syndrome (FFTS) at 18 weeks of gestation with one donor (oligohydramnios) and one receptor (polyhydramnios) triplet. The patient "received" a diet enriched with proteins. Amniotic-fluid volume returned to normal after 24 weeks. At 32 weeks, a Cesarean section was performed due to intra-uterine growth restriction of the donor triplet. Post partum color injection and computer angiograms showed arterio-arterial (AA) anastomoses between all triplets. Deep arterio-venous (AV) anastomoses between the two triplets who had demonstrated with oligo- and polyhydramnios between 18 and 26 weeks were revealed by computer angiography that were not seen by placental color angiogram. Detailed analysis of placental vascular communications by use of color injection angiogram of the chorionic plate and computer angiogram demonstrating deep anastomoses beneath the chorionic plate helps to understand the individual pathophysiology and clinical course in patients with FFTS, which is even more complex in MC triplet compared to MC twin pregnancies.

Adult↗
PubMed1998

Faraday Laser Magnetic Resonance Spectroscopy of Vibrationally Excited C2D.

We studied the gas phase spectrum of the deuterated ethynyl radical C2D in the region between 3196 and 3243 cm-1 using a Faraday LMR spectrometer in combination with a CO overtone laser. The C2D radicals were generated in a dc glow discharge containing helium, deuterium, and acetylene. We observed a hot band between two vibronic 2Pi states with an origin at 3225 cm-1. The lower level is assigned to the first excited bending level of the electronic X ground state. The upper level corresponds to the first excited electronic state A at 3513 cm-1, which was observed previously [J. Mol. Struct. 190, 41-60 (1988)]. This region is subject to strong vibronic interaction, caused by mixing of the electronic X ground state with the A state at 3513 cm-1. From the analysis of the spectra we could determine the orbital g factor of the upper level, which gave important information about the mixing ratios. In addition we were able to derive a precise term value for the first excited bending level of the electronic X ground state. The experimentally derived molecular parameters are compared with theoretically calculated values, obtained by ab initio calculations. Copyright 1998 Academic Press.

Journal Article↗
PubMed1994

De la Chapelle dysplasia (atelosteogenesis type II): case report and review of the literature [corrected].

We report a male infant with de la Chapelle dysplasia (atelosteogenesis type II), a skeletal dysplasia characterized by severe shortening of the long bones, deficient ossification of distinct parts of the skeleton, cleft palate and neonatal death from asphyxia. This is a rare condition with only 10 patients described in the literature. We report the clinical, radiographical and histopathological data and summarize the data on the total of 11 patients. Differential diagnosis with diastrophic dysplasia and atelosteogenesis (type I) is discussed. On clinical and histological grounds we hypothesize that de la Chapelle dysplasia and diastrophic dysplasia are closely related. The mode of inheritance is autosomal recessive.

Adult↗
PubMed1993

Long-term follow-up (12 to 35 weeks) after dynamic cardiomyoplasty.

OBJECTIVES: To obtain information on the long-term effects of dynamic cardiomyoplasty on hemodynamics and muscle histology, this surgical method was evaluated in goats. BACKGROUND: Dynamic cardiomyoplasty has been introduced as a new method to treat patients with severe cardiac failure. METHODS: In 24 goats, the left latissimus dorsi muscle was wrapped around the heart. The muscle was then subjected to progressive electrical stimulation. In 16 goats, invasive transesophageal Doppler echocardiographic measurements and histologic evaluation of the latissimus dorsi muscle were performed at > or = 12 weeks after the wrapping. RESULTS: Only two goats showed an increase in aortic and left and right ventricular pressures concomitant with increased aortic flow during latissimus dorsi muscle stimulation both before and after induction of cardiac failure using imipramine. This was accompanied by a preserved latissimus dorsi muscle structure and nearly complete transformation to type I muscle fibers. The remaining 14 goats showed extensive lipomatosis in the latissimus dorsi muscle, with severe intimal hyperplasia and proliferation of smooth muscle cells in the walls of the thoracodorsal artery and its branches. An increase in endoneural and endomysial connective tissue was observed, with some goats showing destroyed nerve branches near the electrodes. These findings differed from those observed after long-term electrical stimulation of goat latissimus dorsi muscle in situ. CONCLUSIONS: Dynamic cardiomyoplasty is of use in the treatment of severe heart failure if the histologic structure of the wrapped latissimus dorsi muscle remains intact. Long-term results in goats suggest that the current approach used in dynamic cardiomyoplasty may lead to deterioration of the wrapped muscle.

Animals↗
PubMed1993

A new stimulation protocol for cardiac assist using the latissimus dorsi muscle.

When treating severe cardiac failure with dynamic cardiomyoplasty, knowledge about the optimal way of stimulating the latissimus dorsi (LD) muscle is of obvious importance. We evaluated a new stimulation protocol in four goats using in situ electrical stimulation of the left LD muscle. Stimulation was started using a burst of two pulses with an interpulse interval of 100 msec for 50 bursts/min. The number of pulses was increased every 2 weeks concomitant with a decrease in interpulse interval. This resulted after 12 weeks in 60 bursts/min using bursts of six pulses with an interpulse interval of 20 msec after 12 weeks. Force measurements, which were done every 2 weeks, showed an early decrease in contraction and relaxation speed as reflected in the ripple (= interstimulus amplitude/peak force amplitude measured at 10 Hz). Fatigue resistance increased significantly within 4 weeks of conditioning as indicated by preservation of force, positive dF/dt, and negative dF/dt. Full preservation of these variables was seen even during a 1-hour fatigue test at the end of the conditioning period. Skeletal muscle enzyme activity as an indicator of muscle damage showed a significant rise in creatine kinase enzyme activity only on the first day following the start of LD stimulation. LD muscle biopsies revealed almost complete transformation to type I muscle fibers with a significant increase in capillary/fiber ratio when compared to the nonstimulated LD muscle. However, some biopsies, in particular near the electrodes, did show some signs of skeletal muscle damage. Contraction characteristics of the fully transformed LD muscles were tested by increasing the number of bursts of six pulses from 50/min to 100/min. Interpulse intervals of 20 and 33 msec were used. These tests revealed that maximal force, positive dF/dt, and negative dF/dt was reached with 50 bursts/min using a six pulse burst with interpulse intervals of 20 msec.

Animals↗
PubMed1993

Rat cytomegalovirus-induced pneumonitis after allogeneic bone marrow transplantation: effective treatment with (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine.

Two antiviral compounds, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), were evaluated for their effects on rat cytomegalovirus (RCMV)-induced interstitial pneumonitis after allogeneic bone marrow transplantation (BMTx). Eight-week-old Brown Norway rats immunosuppressed by a lethal dose of total body irradiation were inoculated with RCMV and received allogeneic bone marrow cells from Lewis rats. Animals were treated with either HPMPC (20 mg/kg of body weight as a single dose) or DHPG (20 mg/kg as two daily doses for 5 days). The effect of antiviral therapy was monitored by measuring RCMV titers in different organs and the histopathologic changes in lungs at 8 to 10 days postinfection. In RCMV-infected allogeneic BMTx recipients, severe diffuse thickening of alveolar septa (6.02 microns) with a diffuse infiltration of mononuclear cells occurred, whereas in the noninfected allogeneic BMTx recipients, the septal width was on the order of 2 microns (P < 0.01). Treatment with DHPG (20 mg/kg in two daily doses for 5 days) resulted in a decrease in virus titers (log10 PFU per gram of tissue) in lungs and spleens from 3.81 +/- 0.34 and 4.29 +/- 1.07 (untreated animals) to 1.26 +/- 0.53 and 3.22 +/- 0.27 (treated animals), respectively. Treatment with HPMPC (20 mg/kg as a single dose) resulted in a complete reduction of virus titers in all organs to below the detection level (P < 0.01). Furthermore, antiviral treatment resulted in a reduction of the alveolar septal width from 6.02 +/- 1.59 microns (untreated animals) to 4.67 +/- 1.70 and 3.32 +/- 0.63 microns after DHPG and HPMPC treatment, respectively. Treatment with HPMPC (20 mg/kg as a single dose) resulted in a complete reduction of virus titers in all organs to below the detection level (P <0.01). Furthermore, antiviral treatment resulted in a reduction of the alveolar septal width from 6.02 +/- 1.59 micrometre (untreated animals) to 4.67 +/- 0.63 micrometre after DHPG and HPMPC treatment, respectively. Furthermore, the influx of mononuclear cells in the alveolar septa was significantly impaired after treatment with HPMPC (P <0.01). We conclude that in the described rat model, HPMPC is highly effective in suppressing RCMV-induced interstitial pneumonitis after allogeneic BMTx.

Animals↗
PubMed1993

The effect of hypocapnia and mechanical pulmonary stress on lung tissue in newborn lambs.

Positive pressure ventilation, using high inspiratory pressures, often causes lung damage. When associated with hypocapnia, it can produce severe focal alveolar alkalosis and can cause damage in areas of low blood flow. A vein-to-vein extracorporeal membrane oxygenator (ECMO) system was used to control blood gases independently of mechanical ventilation in 12 healthy newborn lambs. After connection to the ECMO system, ventilation was started with a peak inspiratory pressure of 35 cm H2O and a positive end-expiratory pressure of 5 cm H2O; the ventilator rate was 40/min with I:E = 1.5 and FiO2 = 1.0. In 6 of the 12 lambs sweep gases through the silicone membrane were regulated to assure arterial normocapnia. The other 6 were ventilated with the same settings and perfused with the same pump flow, but PaCO2 was allowed to fall to hypocapnic levels. The lambs were ventilated for 4 h. Average pH and PaCO2 were 7.62 +/- 0.14 and 2.11 +/- 0.54 kPa, respectively, in the hypocapnic group and 7.39 +/- 0.11 and 4.79 +/- 0.51 kPa in the normocapnic group. After sacrificing the lambs, the lungs were inspected macroscopically and microscopically by computer-assisted morphometry to assess atelectasis and lung edema. Macroscopically there were no hemorrhages, barotrauma or widespread atelectasis of the lungs in either group. The thickness of interlobular lung septa in the right upper lobe was 32.5 +/- 18.0 microns for the hypocapnic group and 29.7 +/- 12.5 microns for the normocapnic group. The parenchymal-alveolar area ratio in the right upper lobe was 28.4 +/- 5.04 and 24.6 +/- 3.75% in the hypocapnic and normocapnic groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Percutaneous implantation of a new intracoronary stent in pigs.

Sixty-two self-expanding parallel wire stainless steel stents were implanted in normal coronary arteries of 31 young pigs using a newly developed delivery system. In 57 of 62 procedures, the percutaneous coronary implant of the stent was successful; five stents were released in side branches. Implants remained in place for a few hours to 6 months. In spite of correct sizing, two stents migrated out of the coronary arteries. Seven pigs died prematurely; in six of them death might be stent-related. Although no anticoagulant and antiplatelet aggregation drugs were administered during the follow-up period, at autopsy thrombi were observed in only seven arteries (nonobstructive in four of seven arteries). All arteries except for three were patent; these three vessels occluded probably due to oversizing of the stent. Complete neointimal coverage was found within 3 weeks. Important hyperplasia was not seen. It was concluded that coronary implantation of this stent usually was easy. Obstructive thrombus formation was rather uncommon despite the absence of chronic anticoagulant and antiplatelet aggregation therapy. Hyperplasia was rare.

Angioplasty, Balloon, Coronary↗
PubMed1991

Characterization of Cobblestone mitral valve interstitial cells.

Mitral valve interstitial cells (MVICs) are important in the structure and function of the valve. In a cell culture system that used explants to harvest MVICs, we found that after several passages, some of the cultures at confluence formed a monolayer of cobblestone-shaped cells (CB type). The rest of the cultures were, however, different, consisting of elongated cells (EL type) that formed overlapping orthogonal patterns. When compared with the MVICs-EL, cells from cultures of MVICs-CB were less adherent to a plastic substratum initially than were MVICs-EL and were more sensitive to trypsinization following culture for 3 to 7 days. Ultrastructurally, the cultures of MVICs-CB showed prominent Golgi's complexes and endoplasmic reticulum and fewer microfilaments when compared with those of MVICs-EL. Most strikingly, the CB cells contained much less alpha-smooth-muscle cell actin compared with that of EL cells. The MVICs-CB were not endothelial cells as they did not show the characteristic dense peripheral band that was present in endothelial cells in a confluent monolayer and showed only trace amounts of fluorescence when incubated with 1,1-dioctadecyl 1-3,3,3,3 tetramethyl-indocarbocyanine-percholate (Dil-)--acetylated low-density lipoprotein compared with large amounts of fluorescence with endothelial cells. Cells that were morphologically similar to MVICs-CB were present in the in vivo valve as well and also formed small islands of cells even in the primary cultures that grew out of the explant. The findings supported the hypothesis that MVICs-CB represent a distinct phenotype of the MVICs that is different from that of the MVICs-EL and is not that of either endothelial or medial smooth-muscle cells.

Actin Cytoskeleton↗
PubMed1990

Double-wave reentry as a mechanism of acceleration of ventricular tachycardia.

By using a Langendorff-perfused ring of anisotropic rabbit epicardium, sustained reentrant ventricular tachycardia with a cycle length of 168 +/- 13 msec (n = 26) was induced by programmed electrical stimulation. Continuous left ventricular epicardial mapping with 256 simultaneously recorded unipolar electrograms demonstrated that the tachycardia was based on circuital movement of the impulse around a fixed obstacle. Because of the anisotropic properties of the myocardium, the circuit consisted of a ring with segments in which the circulating wave propagated slowly (20 +/- 2 cm/sec) or faster (62 +/- 4 cm/sec). This was related to transverse or longitudinal propagation in relation to fiber direction. In six of 26 experiments, sudden acceleration in rate of the tachycardia was observed during programmed electrical stimulation. This acceleration was caused by the occurrence of double-wave reentry (two successive waves traveling in the same direction and using the same circuit). In one of the experiments, induction of double-wave reentry was only possible at basal conditions but not after the administration of a class III antiarrhythmic drug. In a seventh experiment, induction of double-wave reentry became possible after the administration of a class IC antiarrhythmic drug. Because conduction velocity around the ring was depressed during acceleration, the total revolution time of the circuit during double-wave reentry was about 120% of that during single-wave reentry. Ventricular tachycardias in which double-wave reentry could be elicited had longer cycle lengths (197 +/- 11 vs. 156 +/- 8 msec, p less than 0.001) and larger excitable gaps (71 +/- 16 vs. 28 +/- 5 msec, p less than 0.001) than those not showing this phenomenon. Double-wave reentry might have important clinical implications in understanding ventricular tachycardia acceleration during programmed electrical stimulation, proarrhythmic effects of drugs, and pathophysiology of rapid ventricular tachycardias.

Animals↗
PubMed1985

Basement membranes in cancer.

Basement membranes are ubiquitous tissue constituents which occur as supportive structure adjacent to epithelium, endothelium, mesothelium and also around smooth as well as striated muscle cells, Schwann cells and fat cells. In various types of cancer, basement membranes have been extensively studied by electron microscopy. Often basement membrane interruptions were seen in invasive neoplasms but in some tumors the neoplastic cells were surrounded by a continuous basal lamina. Recent immunocytochemical studies have shown that in invasive carcinomas the neoplastic cells often lack a continuous basement membrane. This may be caused by catabolic activity of invasive tumor cells, which have been shown to produce specific collagenases, or by insufficient production and/or extracellular assembly of basement membrane components by the neoplastic epithelial cells. In diagnostic histopathology, immunocytochemical staining of basement membrane components such as type IV collagen and laminin may help to distinguish between noninvasive (benign or in situ) and invasive lesions. Furthermore, in carcinomas the extent of the expression of basement membrane components may be correlated with the degree of differentiation of the neoplastic cells. Finally, in soft tissue tumors, basement membrane staining may be helpful for the differentiation of basement membrane producing neoplasms (e.g. of vascular, neural, smooth muscle or striated muscle origin) from non-basement membrane producing neoplasms (e.g. of fibroblastic origin).

Basement Membrane↗