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Biomedical subjects

M Gross

Publications and source records attributed to M Gross.

At least 253 records · Page 14Linked to original sources
PubMed1997

The ethical allocation of scarce resources in surgery: implants and cost.

This paper is a discussion of the factors involved in instituting a bulk purchasing program for surgical supplies. An improved understanding of the surgical procedure of joint arthroplasty must relate to the variability in surgical methods that achieve patient outcomes. An understanding of the outcomes in relation to the expected duration of the success of an implant and the high costs associated with a revision earlier than expected must be factored into the budget and costs of implants. The ethical implications of choosing one implant over another are considered. A more uniform outcome assessment with respect to surgical activities is needed and potential savings related to other operating-room costs must be examined. Optimizing the implant to patient requirements is the goal within the framework of current fiscal constraints.

Canada↗
PubMed1996

Interest among gay/bisexual men in greater Boston in participating in clinical trials of preventive HIV vaccines.

To estimate interest in HIV preventive vaccine trials, we administered questionnaires to two otherwise demographically similar cohorts of older (mean 40 years) and younger (mean 23 years) gay men in Boston. Questionnaire responses were linked to concurrent behavioral and demographic data. Univariate analyses, performed separately for older and younger cohorts, identified factors that distinguished participants who were "very interested" from those who were "not at all interested". Multivariate logistic regression analyses were used to adjust for confounding. Among all 630 participants, 215 (34%) were "not at all" interested in participating, 306 (49%) were "somewhat" interested, and 102 (16%) were "very" interested. Older men were significantly more likely than younger men to be "very" interested and less likely to be "not at all interested." Among both older and younger men, perceived peer willingness to enroll in vaccine trials predicted interest after adjusting for confounding. Among older men, optimism about success in vaccine development also predicted interest. In the younger cohort, men recruited in community settings (e.g., bars, nightclubs) were more interested in vaccine trial participation than were those recruited by outreach workers and word of mouth on college campuses. Vaccine-induced seroconversion evoked significant concern.

AIDS Vaccines↗
PubMed1996

Linguistic analysis of protein folding.

Folding of nascent chains resembles the decoding of spoken language in that information is emitted as a unidirectional, one-dimensional string of elements, with higher structures and long-distance interactions emerging with time. Applying a "pseudolinguistic' analysis of structure to a set of all 36 possible six-stranded antiparallel beta-sandwich topologies reveals new order principles and reduces the complexity of this family significantly. The simple connectivity diagrams ("linguistic trees') proposed here allow predictions of the speed and cooperativity of beta-sheet folding and help understanding the cotranslational folding from the N-terminus.

Kinetics↗
PubMed1996

Purification and characterization of a 66-kDa protein from rabbit reticulocyte lysate which promotes the recycling of hsp 70.

We have purified to apparent homogeneity a 66-kDa protein from rabbit reticulocyte lysate which is associated with hsp 70. Our characterization of this 66-kDa protein demonstrates that its physiological role is to promote the recycling of hsp 70 by catalyzing the dissociation of hsp 70-bound ADP in exchange for ATP. We have therefore termed the 66-kDa protein RF-hsp 70, a recycling factor for hsp 70. RF-hsp 70 promotes stoichiometric binding of ATP to hsp 70, and it increases about 5-fold the rate of dissociation of hsp 70.ADP in the presence of ATP. This process represents adenine nucleotide exchange, since dissociation of ADP does not occur unless ATP is added; dATP, GTP, and ITP cannot substitute for ATP. The mechanism of action of RF-hsp 70 is to lower the KD of hsp 70 for ATP about 6-7-fold to a value that is close to the KDof hsp 70 for ADP. RF-hsp 70 also stimulates the ATPase activity of hsp 70, including the 42-kDa amino-terminal portion of hsp 70 generated by chymotrypsin, demonstrating that RF-hsp 70 interacts with that part of hsp 70 known to contain the ATP/ADP binding site. Confirming its recycling function, RF-hsp 70 stimulates about 7-10-fold the ability of hsp 70 to reactivate heat-denatured firefly luciferase. In addition, RF-hsp 70 acts catalytically to recycle hsp 70, since, at 0.2 times the molar concentration of hsp 70, RF-hsp 70 increases the rate of renaturation of luciferase by hsp 70 about 3-4-fold. The action of RF-hsp 70 is also partially species-specific since it is most effective with rabbit reticulocyte hsp 70, less effective with bovine brain hsp 70, even less effective with human hsp 70, and ineffective with broad bean hsp 70.

Adenosine Diphosphate↗
PubMed1996

Extensive sequencing of tryptic peptides of a rabbit reticulocyte 66-kDa protein that promotes recycling of Hsp 70. Homology To stress-related proteins.

Trypsinization and sequence analysis of the 66-kDa rabbit reticulocyte protein (RF-hsp 70), shown in the preceding article to function as a recycling protein for hsp 70, demonstrates striking similarity to the transformation-sensitive human protein IEF SSP 3521 (Honoré, B., Leffers, H., Madsen, P., Rasmussen, H. H., Vandekerckhove, J., and Celis, J. E.(1992) J. Biol. Chem. 267, 8485-8491) and mouse extendin (Blatch, G. L., Lassle, M., Takatori, T., Gandhi, T., Kundra, V., and Zetter, B. R.(1995) Proc. Am. Assoc. Cancer Res. 36, 68). The human and mouse proteins share 97% sequence identity, and sequencing of 20 polypeptides (225 residues) from RF-hsp 70 reveals only 10 differences between the rabbit and human proteins and 13 differences between the rabbit and mouse proteins (96 and 94% identity, respectively). In addition, all three proteins are of similar size, and each contains 11 cysteines. These findings strongly suggest that these three proteins are homologs of the same activity. All differences (but one) between the human and mouse proteins occur within the amino-terminal half of the protein, and there is only one difference among 121 sequenced residues between RF-hsp 70 and the human or mouse protein which occurs within the carboxyl-terminal 70% of the molecule. In addition, where partial sequences of RF-hsp 70 and p60, a chick oviduct protein that shows 70% identity to the human protein (Smith, D. F., Sullivan, W. P., Marion, T. N., Zaitsu, K., Madden, B., McCormick, D. J., and Toft, D. O. (1993) Mol. Cell. Biol. 13, 869-876), overlap (a total of 54 residues), RF-hsp 70 and chick p60 show 78% sequence identity. Studies of the initial digestion of RF-hsp 70 by trypsin indicate that it is first converted to 58- and 54-kDa components, each of which is then converted to a 43-kDa polypeptide. This 43-kDa component is located in the human and mouse proteins at position 124 to about 470. It is converted subsequently to a 31-kDa polypeptide by trypsin hydrolysis at position 207. This 31-kDa component is finally split into 17- and 14-kDa polypeptides that are located at positions 208 to approximately 351 and 352 to approximately 470, respectively. The 14-kDa polypeptide is relatively resistant to further digestion with trypsin, and seven tryptic peptides from other parts of RF-hsp 70 contain internal lysine and/or arginine residues (as do several tryptic peptides produced from IEF SSP 3521 and chick p60). Both features may be due to interference with trypsin action by secondary structure in the protein, since trypsinization of reduced and carboxymethylated RF-hsp 70 results in hydrolysis of the 14-kDa polypeptide and reduces the level of peptides that contain internal lysine and/or arginine, although it does not eliminate them.

Amino Acid Sequence↗
PubMed1996

Beta-blockers for prophylaxis of bleeding from esophageal varices in cirrhotic portal hypertension. Review of the literature.

Hemorrhage from esophageal varices is a life-threatening event in patients with liver cirrhosis. About 40% to 80% of the patients surviving the first bleeding suffer from a recurrence of variceal bleeding within one year. This high recurrence rate substantially contributes to the mortality in patients with liver cirrhosis. Therefore, various treatment regimens both in primary and secondary prophylaxis were studied. Most experience in medical primary prophylaxis was collected with beta-blockers, mainly propranolol. Treating patients with esophageal varices with propranolol significantly reduces the incidence of first variceal bleeding. However, the effect on mortality is marginal, and primary prophylaxis is generally not recommended in these patients. Several studies support the hypothesis, that medical prophylaxis with beta-blockers is more effective in reducing the rate of first esophageal bleeding in patients with a high risk of hemorrhage, such as the presence of very large varices with red spots. A score to assess the individual risk of a given patient to suffer a variceal bleeding would be helpful. As long as such a score is not validated, no general rule for this treatment decision can be given. In secondary prophylaxis, both administration of beta-blockers and endoscopic therapy (sclerotherapy or ligation of the varices) are effective in significantly lowering the rate of re-bleeding. However, the effect on mortality was not significant in most studies. Several studies comparing the efficacy of medical prophylaxis and endoscopic treatment showed advantages of the endoscopic therapy with a greater reduction in recurrent bleeding episodes. However, medical prophylaxis with beta-blockers has the important advantage of being immediately effective whereas endoscopic procedures provide the best protection against recurrent bleeding after complete obliteration of the varices. Therefore, in the first weeks and months of endoscopic therapy, the additional treatment with beta-blockers may further reduce the risk of re-bleeding. Only half of all studies on this topic reported a significant advantage of such a combined therapy. Therefore, it seems reasonable to restrict this approach to patients with a high risk of re-bleeding such as patients with large sclerotherapy-derived esophageal ulcers.

Adrenergic beta-Antagonists↗
PubMed1996

When and how to eradicate Helicobacter pylori: role of histamine receptor antagonists.

Peptic ulcer is today frequently considered to be an infectious disease. The bacteria assumed to be the cause of gastric or duodenal ulcer was first called Campylobacter pyloridis and later C. pylori because of its structural similarity to other Campylobacter species. Later, unique characteristics were reported, and it was renamed Helicobacter pylori (Hp). In retrospect, it was presumably first described in man in 1938 (Doenges 1938), although the clinical significance was not established until 1983 (Warren 1983, Warren and Marshall 1983). It is a spiral-shaped, gram-negative bacteria with four to six flagella and dimensions of 0.5 x 3.0 micron. . With the help of these flagella, it moves into the mucous layer overlying the gastric epithelium where it colonizes at the interface of the mucous layer and the surface epithelial cells. It can be found in any part of the gastrointestinal tract demonstrating gastric epithelium, i.e. the stomach and metaplastic areas of the esophagus or the duodenum. One characteristic of this bacteria is the production of a urease enzyme that catalyzes urea to ammonium and bicarbonate. The production of ammonium causes the development of an alkaline microenvironment that protects it from the gastric acid. In the presence of urea, the organism will therefore replicate to a pH as low as 4.3 and survive without replication to a pH as low as 2.3. In Western countries, an increase in the prevalence of Hp infection is observed in the population with progressing age. In childhood, infection before the age of 20 years is rare. At the age of 60 years or older, however, the prevalence rate is on the order of 40% to 60% (Dooley et al. 1989, Perez-Perez et al. 1988, Marshall 1994). The seroconversion rate in adults is lower than 1% per year (Parsonnet et al. 1992). The infection seems to be stable, probably persisting for many years or even a lifetime.

Adolescent↗
PubMed1996

Reconstitution of active octameric mitochondrial creatine kinase from two genetically engineered fragments.

Creatine kinase (CK) has been postulated to consist of two flexibly hinged domains. A previously demonstrated protease-sensitive site in M-CK (Morris & Jackson, 1991) has directed our attempts to dissect mitochondrial CK (Mi-CK) into two protein fragments encompassing amino acids [1-167] and [168-380]. When expressed separately in Escherichia coli, the two fragments yielded large amounts of insoluble inclusion bodies, from which the respective polypeptides could be purified by a simple two-step procedure. In contrast, co-expression of the two fragments yielded a soluble, active, and correctly oligomerizing enzyme. This discontinuous CK showed nearly full specific activity and was virtually indistinguishable from native Mi-CK by far- and near-UV CD. However, the positive cooperativity of substrate binding was abolished, suggesting a role of the covalent domain linkage in the crosstalk between the substrate binding sites for ATP and creatine. The isolated C-terminal fragment refolded into a native-like conformation in vitro, whereas the N-terminal fragment was largely unfolded. Prefolded [168-380] interacted in vitro with [1-167] to form an active enzyme. Kinetic analysis indicated that the fragments associate rapidly and with high affinity (1/K1 = 17 microM) and then isomerize slowly to an active enzyme (k2 = 0.12 min-1; k-2 = 0.03 min-1). Our data suggest that the C-terminal fragment of Mi-CK represents an autonomous folding unit, and that the folding of the C-terminal part might precede the conformational stabilization of the N-terminal moiety in vivo.

Adenosine Triphosphate↗
PubMed1996

Significant hydrogen exchange protection in GroEL-bound DHFR is maintained during iterative rounds of substrate cycling.

An unresolved key issue in the mechanism of protein folding assisted by the molecular chaperone GroEL is the nature of the substrate protein bound to the chaperonin at different stages of its reaction cycle. Here we describe the conformational properties of human dihydrofolate reductase (DHFR) bound to GroEL at different stages of its ATP-driven folding reaction, determined by hydrogen exchange labeling and electrospray ionization mass spectrometry. Considerable protection involving about 20 hydrogens is observed in DHFR bound to GroEL in the absence of ATP. Analysis of the line width of peaks in the mass spectra, together with fluorescence quenching and ANS binding studies, suggest that the bound DHFR is partially folded, but contains stable structure in a small region of the polypeptide chain. DHFR rebound to GroEL 3 min after initiating its folding by the addition of MgATP was also examined by hydrogen exchange, fluorescence quenching, and ANS binding. The results indicate that the extent of protection of the substrate protein rebound to GroEL is indistinguishable from that of the initial bound state. Despite this, small differences in the quenching coefficient and ANS binding properties are observed in the rebound state. On the basis of these results, we suggest that GroEL-assisted folding of DHFR occurs by minor structural adjustments to the partially folded substrate protein during iterative cycling, rather than by complete unfolding of this protein substrate on the chaperonin surface.

Humans↗
PubMed1996

The effect of saline iontophoresis on skin integrity in human volunteers. I. Methodology and reproducibility.

This study, conducted in 36 human volunteers, was an evaluation of the effects of saline iontophoresis on skin temperature, irritation, and barrier function. The major objectives were to assess the effects of low-level ionic currents, to validate the proposed methodology of assessment, and to establish reproducibility in repeated saline iontophoresis applications. This was the first of a multistage study designed to assess the safety of 24-hr saline iontophoresis episodes at selected currents and current densities. Since an iontophoresis patch challenges the skin barrier both by occluding the skin surface and by passing ionic current through the skin, the experimental protocol was designed to permit measurement of the contribution of each of these processes to the overall response. In this first stage we investigated the effect of 10 min of current delivery, at 0.1 mA/cm2 on a 1-cm2 area patch and 0.2 mA/cm2 on a 6.5-cm2 area patch compared to unpowered control patches. Twelve subjects were tested under each condition on two separate occasions to examine reproducibility of the response variable measurements. A further 12 subjects were tested once under the 0.2 mA/cm2, 6.5-cm2 condition. Skin irritation was evaluated via repeated measurements of transepidermal water loss, capacitance, skin temperature, skin color, and a visual scoring system, before the iontophoresis episode and after patch removal. No damage to skin barrier function in terms of skin-water loss or skin-water content was detected. Slight, subclinical, short-lasting erythema was observed for both conditions. Assessment of correlation coefficients showed highly statistically significant indications of reproducibility for all five response variables measured. The experimental design, in combination with a repeated measures analysis, provided clear separation of the occlusion and ionic current components of the iontophoretic patch challenge. Further, the repeated measures analysis gave a highly sensitive assessment of skin irritation and resolution after patch removal. We conclude that the experimental methodology is appropriate for assessing possible changes in skin integrity resulting from saline iontophoresis under similar operating conditions for longer durations and for other skin challenges from which a subclinical response is expected.

Body Temperature↗
PubMed1996

[Endoscopic imaging of vocal cord vibrations. Digital high speed recording with various systems].

Vocal fold vibration patterns during phonation are presented with different digital imaging systems. With newly developed technical equipment color images up to 1000 digital images/s were obtained without light intensifying enhancement techniques via rigid and flexible endoscopy. With this color high-speed system, morphologic structures, such as small blood vessels, were visualized in high-resolution quality as a result of additional color information. In another system, zooming of endoscopic pictures via pixel interpolation algorithms provided full-monitor presentation of vocal fold vibratory patterns. This system allows PC-based synchronization with microphone and electroglottographic signals in a frame-by-frame technique. Although only processing gray scale images, analyses of dynamic changes in modes of vibration were facilitated by the higher frame rate recording of up to 2000 frames/s and, in addition, they display corresponding analog signals. Both methods provide clinically important information. Furthermore, we demonstrated irregular vocal fold vibration patterns in a healthy adult volunteer. In this experiment, the irregular vibratory modes were induced by voluntarily applying asymmetric vocal fold tension. The asymmetric vocal fold vibration pattern resulted in (functionally induced) roughness of the voice as predicted by computer models of asymmetric vocal fold vibration. Digital high-speed cinematography proved to be a highly promising technique in the analysis of dysphonia and provided physiological examples that could be compared with models of coupled nonlinear oscillators.

Adult↗
PubMed1996

Plasmodium falciparum circumsporozoite vaccine immunogenicity and efficacy trial with natural challenge quantitation in an area of endemic human malaria of Kenya.

It has been hypothesized that antibody induced by Plasmodium falciparum circumsporozoite protein vaccine would be effective against endemic human malaria. In a malaria endemic region of Kenya, 76 volunteers, in 38 pairs sleeping adjacently, were immunized with subunit circumsporozoite protein Asn-Ala-Asn-Pro tetrapeptide repeat-pseudomonas toxin A, or hepatitis B vaccine. After quinine and doxcycycline, volunteers were followed for illness daily, parasitemia weekly, antibody, T-lymphocyte responses, and treated if indicated. Anopheles mosquitoes resting in houses were collected, and tested for P. falciparum antigen, or dissected for sporozoites and tested for blood meal ABO type and P. falciparum antigen. Vaccine was safe, with side-effects similar in both groups, and immunogenic, engendering IgG antibody as high as 600 micrograms ml-1, but did not increase the proportion of volunteers with T-lymphocyte responses. Estimation of P. falciparum challenge averaged 0.194 potentially infective Anopheles bites/volunteer/ day. Mosquito blood meals showed no difference in biting intensity between vaccine and control groups. Both groups had similar malaria-free survival curves, cumulative positive blood slides, cumulative parasites mm-3, and numbers of parasites mm-3 on first positive blood slide, during three post-vaccination observation periods. Every volunteer had P. falciparum parastemia at least once. Vaccinees had 82% and controls 89% incidences of symptomatic parasitemia (P = 0.514, efficacy 9%, statistical power 95% probability of efficacy < 50%). Vaccine-induced anti-sporozoite antibody was not protective in this study. Within designed statistical precisions the present study is in agreement with efficacy studies in Colombia, Venezuela and Tanzania.

Animals↗
PubMed1996

[Intubation trauma of the larynx--a literature review with special reference to arytenoid cartilage dislocation].

Trauma to the cricoarytenoid joint represents a rare but serious complication of endotracheal intubation. Subluxation and luxation of the arytenoid cartilage may occur during difficult but also following uncomplicated intubation. Forces on the arytenoid cartilage exerted by the laryngoscope blade or by the distal part of the endotracheal tube may cause anterior and inferior displacement of the arytenoid cartilage. Due to the conventional intubation technique the left arytenoid cartilage is affected most frequently. Posterolateral subluxation is attributed to the pressure exerted on the posterior glottis by the convex part of the shaft of the tube. Systemic diseases (e.g. terminal renal insufficiency, bowel diseases, acromegaly) may cause degeneration of the cricoarytenoid ligaments, thus making the cricoarytenoid joint more susceptible to traumatic dislocation. Persisting alterations of voice, sore throat and pain on swallowing may hint to the diagnosis of arytenoid dislocation. However, stridor and shortness of breath have also been observed. If pharyngo-laryngeal complaints persist, evaluation by laryngologists is mandatory. In addition to indirect and direct laryngoscopy, computerised tomography and electromyography of the larynx play an important role in differentiating arytenoid dislocation from true vocal cord paralysis due to nerve damage. Early operative reposition results in fair prognosis, whereas delayed diagnosis may lead to ankylosis of the cricoarytenoid joint with permanent impairment of the voice and possibly compromised airway protection.

Anesthesia, Endotracheal↗
PubMed1996

Safety, immunogenicity, and efficacy of Plasmodium falciparum repeatless circumsporozoite protein vaccine encapsulated in liposomes.

Seventeen malaria-naive volunteers received a recombinant Plasmodium falciparum vaccine (RLF) containing the carboxy- and the amino-terminal of the circumsporozoite protein (CSP) antigen without the central tetrapeptide repeats. The vaccine was formulated in liposomes with either a low or high dose of 3-deacylated monophosphoryl lipid A (MPL) and administered with alum by intramuscular injection. Both formulations were well tolerated and immunogenic. MPL increased sporozoite antibody titers measured by ELISA, Western blot, and immunofluorescence assay. One high-dose MPL vaccine formulation recipient developed a CSP-specific cytotoxic T lymphocyte response. After homologous sporozoite challenge, immunized volunteers developed patent malaria. There was no correlation between prepatent period and antibody titers to the amino- or carboxy-terminal. The absence of delay in patency argues against inclusion of the amino-terminal in future vaccines. A significant cytotoxic T lymphocyte response may have been suppressed by the inclusion of alum as an adjuvant.

Adolescent↗
PubMed1996

High-speed imaging of vocal fold vibrations and larynx movements within vocalizations of different vowels.

Theoretic investigations of the "source-filter" model have indicated a pronounced acoustic interaction of glottal source and vocal tract. Empirical investigations of formant pattern variations apart from changes in vowel identity have demonstrated a direct relationship between the fundamental frequency and the patterns. As a consequence of both findings, independence of phonation and articulation may be limited in the speech process. Within the present study, possible interdependence of phonation and phoneme was investigated: vocal fold vibrations and larynx position for vocalizations of different vowels in a healthy man and woman were examined by high-speed light-intensified digital imaging. We found 1) different movements of the vocal folds for vocalizations of different vowel identities within one speaker and at similar fundamental frequency, and 2) constant larynx position within vocalization of one vowel identity, but different positions for vocalizations of different vowel identities. A possible relationship between the vocal fold vibrations and the phoneme is discussed.

Adult↗
PubMed1996

Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells.

The totipotent stem cells of the pregastrulation mouse embryo which give rise to all embryonic somatic tissues and germ cells express Oct-4. The expression is downregulated during gastrulation and is thereafter only maintained in the germline lineage. Oct-4/lacZ transgenes were used to determine how this pattern of expression was achieved, and resulted in the identification of two separate regulatory elements. The distal element drives Oct-4 expression in preimplantation embryos, in migratory and postmigratory primordial germ cells but is inactive in cells of the epiblast. In cell lines this element is specifically active in embryonic stem and embryonic germ cells. The proximal element directs the epiblast-specific expression pattern, including downregulation during gastrulation; in cell lines its activity is restricted to epiblast-derived cells. Thus, Oct-4 expression in the germline is regulated separately from epiblast expression. This provides the first marker for the identification of totipotent cells in the embryo, and suggests that expression of Oct-4 in the totipotent cycle is dependent on a set of factors unique to the germline.

Animals↗