Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 73 records · Page 4Linked to original sources

PubMed2001

Bi-site catalysis in F1-ATPase: does it exist?

The mechanism of action of F(1)F(0)-ATP synthase is controversial. Some favor a tri-site mechanism, where substrate must fill all three catalytic sites for activity, others a bi-site mechanism, where one of the three sites is always unoccupied. New approaches were applied to examine this question. First, ITP was used as hydrolysis substrate; lower binding affinities of ITP versus ATP enable more accurate assessment of sites occupancy. Second, distributions of all eight possible enzyme species (with zero, one, two or three sites filled) as fraction of total enzyme population at each ITP concentration were calculated, and compared with measured ITPase activity. Confirming data were obtained with ATP as substrate. Third, we performed a theoretical analysis of possible bi-site mechanisms. The results argue convincingly that bi-site hydrolysis activity is negligible, and may not even exist. Effectively, tri-site hydrolysis is the only mechanism. We argue that only tri-site hydrolysis drives subunit rotation. Theoretical analyses of possible bi-site mechanisms reveal serious flaws, not previously recognized. One is that, in bi-site catalysis, the predicted direction of subunit rotation is the same for both ATP synthesis and hydrolysis; a second is that infrequently occurring enzyme species are required.

Adenosine Triphosphate↗

PubMed2001

An HIV type 1 subtype A strain of low genetic diversity continues to spread among injecting drug users in Russia: study of the new local outbreaks in Moscow and Irkutsk.

An explosive epidemic of human immunodeficiency virus type 1 (HIV-1) has been documented among injecting drug users (IDUs) in the former Soviet Union republics. In 1999, the two largest local IDU outbreaks of HIV-1 infection in the Russian Federation were registered in the Moscow and Irkutsk regions, where 13,004 HIV-1 cases were identified (44% of the total number of HIV-1 infections in Russia in 1999). To study the prevailing genetic variants and to estimate the genetic diversity of HIV-1 in these outbreaks, 60 samples from Moscow (n = 36) and from Irkutsk (n = 24) were analyzed using the gag/env heteroduplex mobility assay, and the env gp120 V3 encoding regions obtained from 23 individuals were sequenced. Both virus populations were highly homogeneous (the means of pairwise nucleotide distance were 1.75 +/- 0.83 and 2.35 +/- 1.59 for Irkutsk and Moscow, respectively), and similar to the subtype A viruses obtained earlier from IDUs in the former Soviet Union. The subtype A HIV-1 variant thus dominates in the largest HIV-1 outbreaks among IDUs in the Russian Federation.

Adolescent↗

PubMed2001

Children in food-insufficient, low-income families: prevalence, health, and nutrition status.

OBJECTIVE: To examine characteristics of US children living in food-insufficient households and to compare food and nutrient intakes, physical inactivity, and overweight and underweight status of children in food-insufficient households with those in food-sufficient households. DESIGN: Cross-sectional, nationally representative sample of children and households from the Continuing Survey of Food Intakes by Individuals, from 1994 to 1996. PARTICIPANTS: A group of 3790 households, including 5669 children (ages 0-17 years). MAIN OUTCOME MEASURE(S): Estimates of food insufficiency for children were based on the reported adequacy of their households, described as "often don't have enough to eat" or "sometimes don't have enough to eat." Nutrient consumption was based on two 24-hour dietary recalls from in-person interviews. RESULTS: Three percent of all households with children, and 7.5% of low-income families with children experienced food insufficiency. Several demographic and characteristic differences were observed between the food-sufficient and food-insufficient low-income groups. Children of low-income families, either food-sufficient or food-insufficient, had similar macronutrient and micronutrient intake, reported exercise, television watching, and percentage of overweight and underweight. When compared with the higher-income food-sufficient households, children in the low-income food-insufficient households consumed fewer calories (P =.05) and total carbohydrates (P =.004), but had a higher cholesterol intake (P =.02). The low-income food-insufficient group included more overweight children (P =.04), consumed less fruits (P =.04), and spent more time watching television (P =.02). CONCLUSIONS: While not different from low-income families who do not report food insufficiency, low-income families with food insufficiency had children who differed from high-income families in several nutrition and anthropometric measures. Clinicians should be aware of the possible effects of poverty and lack of access to food on child health and nutrition status. The long-term effects of these are not yet known.

Adolescent↗

PubMed2001

Brief communication: neurotraumatological aspects of head injuries resulting from sharp and blunt force in the early medieval period of southwestern Germany.

Approximately 10% (33 of 304) of the predominantly male skulls from the 6th through 8th centuries in southwestern Germany exhibit cranial fractures derived from blunt or sharp force trauma. No evidence of fracture healing characterizes 24% (n = 8) of these individuals. All nonhealed fractures were caused by sharp force, and four of these wounds cross the sagittal sinus. The lengths of these straight-edged wounds, produced exclusively by sword blows, measure around 8.0 cm for fatal, and about 5.0 cm for nonfatal wounds. Seventy-six percent (n = 25) of these skulls exhibit some healing, which indicates that these injuries did not lead to immediate death. In this group are all depressed fractures resulting from blunt force blows. Two thirds of the 45 cranial injuries noted on these 33 skulls are located on the left side of these individuals, with a concentration in the frontoparietal region. Bony indications of wound infection occur in four cases (12%). Three crania exhibit circular trepanations in association with fractures. These phenomena are discussed in the context of modern neurotraumatological knowledge.

Adult↗

PubMed2001

Laparoscopic-assisted coloscopic polypectomy.

PURPOSE: Patients with colorectal polyps often display a large kink or distinct mucosal fold in the area where the polypectomy is to take place. As a result, there is a higher risk of perforation or partial ablation during an endoscopic polypectomy. Is it safer to perform an endoscopic polypectomy using the control and assistance of a laparoscope? Can a segment resection of the colon that would otherwise be necessary be avoided? METHODS: An endoscopic polypectomy using a laparoscope was conducted on six patients whose colorectal polyps were in an anatomically unfavorable location. The need for an open or laparoscopic segment resection or colotomy was indicated in all cases. The growth was located in the rectosigmoidal transition in five patients and in the region of the left flexure in one patient. We decided that an endoscopic polypectomy using the assistance of a laparoscope would be the most comfortable and technically elegant method, as well as easy. Except the well-known risks of laparoscopy and endoscopic polypectomy, no other risks have been seen in our patients. The affected area of the colon, the sigma, and the left flexure were mobilized and stretched as much as possible to enable a simultaneous and low-risk endoscopic polypectomy. In one case, we had to conduct a fractionated ablation because of a very wide-based finding. RESULTS: The operation averaged 57 minutes, and no operation-specific complications were observed. Postoperative recovery in the hospital was very short and averaged 2.5 days. The histopathologic findings were benign in all cases, but a serious dysplasia was diagnosed in one patient. CONCLUSIONS: The laparoscopic-assisted polypectomy is a safe method to remove even complicated polyps in anatomically unfavorable locations.

Colon↗

PubMed2001

Hepatic vein obstruction due to hypertrophy of right split-liver adult allograft.

The increasing shortage of liver allografts has led to the development of split liver transplantation. More frequent applications have permitted the resolution of most of its technical complications. A hitherto unreported complication of split liver transplantation, hepatic vein obstruction caused by hypertrophy of a right split-liver adult allograft, is discussed. As surgical correction was impossible, the outflow obstruction was treated successfully with interventional radiology.

Adult↗

PubMed2001

Hyperexcitatory activity in visual cortex in homonymous hemianopia after stroke.

OBJECTIVES: Damage to and destruction of neural afferents result in a disruption of sensory input, which causes reduced activity in the corresponding cortical areas. Conversely, there is also evidence that lesions in the sensory pathway induce changes in the intracortical connectivity resulting in augmented cortical activity due to disinhibition. As disinhibition is assumed to be involved in the reconfiguration of neural networks, its appearance after brain lesions might be relevant for the restitution of impaired brain functions. METHODS: The effects of lesions in the visual pathway on the activity in visual cortex were studied using magnetoencephalography. In order to compare the neural activity affected by the lesion with the activity associated with intact visual processing, only patients with unilateral, post-chiasmatic lesions resulting in homonymous hemianopia were examined. RESULTS: Stimulation within the scotoma resulted in reduced magnetic activity compared to the stimulation of the intact hemifield. Increased activity was observed when the border region of the scotoma was stimulated. CONCLUSIONS: It is concluded that the magnetic hyperactivity reflects cortical disinhibition induced by lesions in the visual system. Furthermore, the possible role of cortical disinhibition as a basis for cortical reorganization and as a precondition for the recovery of impaired visual functions is discussed.

Hemianopsia↗

PubMed2001

Dolastatin-10 in metastatic melanoma: a phase II and pharmokinetic trial of the California Cancer Consortium.

Dolastatin-10 is a novel pentapeptide agent originally isolated from the marine mollusk Dolabella auricularia with a mechanism of antitumor activity that involves the inhibition of microtubule assembly. We performed a Phase II trial of Dolastatin-10, 400 microg/m2 in patients with advanced melanoma who had received no prior chemotherapy. Dolastatin-10 pharmokinetics were evaluated in a subset of patients following courses 1 and 2. Twelve patients were treated with a median of 2 cycles of Dolastatin-10, and no patient experienced an objective response. The only grade >2 toxicities were grade 3 neutropenia uncomplicated by infection, occurring in 4 patients following the first treatment cycle. The total systemic clearance and volume of distribution at steady-state were 2.61 +/- 1.9 L/h/m2 and 28.4 +/- 13 L/m2, respectively. Due to prolonged terminal elimination. Dolastatin-10 plasma concentrations of greater than 1 nM were sustained for 24 h in all patients studied. Dolastatin-10 is unlikely to have substantial activity in the treatment of melanoma.

Adult↗

PubMed2001

Varicosis of the accessorial lateral saphenous vein: evidence of recirculation shown by pre-operative phlebography.

BACKGROUND: The incidence of varicosis of the anterior side branch of the long saphenous vein clinically ranges about 8 to 10% of descending venous decompensation, originating at the level of the thigh. Its incidence in women showing significant overweight is clearly pronounced. Mostly torturous and enlarged varicosed segments of the accessorial lateral saphenous vein can be seen clinically crossing the anterior middle of the thigh. The indications for surgical radical extirpation of the entire varicosed side branch depends from pain, phlebitic complications, peripheral venous dysfunction including cosmetic aspects. PATIENTS: In a clientele of 138 patients (females: 114, males: 24) the phlebographic demonstration of the entire recirculation pathways was performed prior to surgery. RESULTS: Ascending leg phlebography was found sufficient in 7.7% of cases only. Combined with varicography however, in further 90.7% of patients a clear demonstration of the upper and lower points of venous insufficiency was possible. The extent of functional disorders was calculated by additional peripheral venous pressure measurements. CONCLUSIONS: This clientele clearly shows that long-term reflux via the varicosed side branch increases the tendency of peripheral functional decompensation along the lower leg. Adequate surgical therapy depends from a clear demonstration of the varicosed veins being involved, and this can be realized by combined phlebography and varicography.

Female↗

PubMed2001

Does age play a role in mylohyoideus muscle function?

Because swallowing disorders are frequent in the elderly, we assessed the relationship between age and mylohyoideus muscle contraction, which is an important component of the initial step in swallowing. In a prospective study, 120 subjects without any personal history of diseases associated with swallowing disorders underwent electromyographic recording (EMG) of mylohyoideus muscle activity. Four groups of equal size (n = 30) were defined according to age (< or = 50, 51-70, 71-85, >85 years). The frequency and duration of mylohyoideus muscle asynchronisms were compared among the four groups. The comparison of mylohyoideus muscle EMG among groups did not show a significant difference in the mean number of asynchronisms, in duration per subject or in the frequency of long-lasting asynchronisms. Asynchronisms were a very frequent event, observed in 98% of subjects, and were mostly short, lasting less than 0.1 s in 90% of subjects. In healthy elderly patients, there was no linear relationship between the mean duration of asynchronisms and ageing. The occurrence of one or more long-lasting asynchronisms or of at least six asynchronisms during a sequence of 10 successive swallows should be considered to be abnormal.

Aged↗

PubMed2001

Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors.

The frequency of Candida infections has increased in recent years and it has been accompanied by a significant rise in morbidity and mortality. The secretion of aspartic proteases by Candida spp. was demonstrated to be one of the virulence determinants. Candida albicans is classified as the major human pathogen in the genus Candida. However, other species of this genus have been found to cause an increasing number of candidiases. We isolated secreted aspartic proteases (Saps) of C. albicans (Sap2p), C. tropicalis (Sapt1p), C. parapsilosis (Sapp1p), and C. lusitaniae (Saplp) from culture media. All the isolated proteases were N-terminally sequenced. Their specific proteolytic activities and sensitivity to series of peptidomimetic inhibitors modified in the type of scissile bond replacement as well as in the N- and C-termini were analyzed. The most divergent substrate specificity was observed for the Sap of C. tropicalis. The specificity of Sap of C. lusitaniae is most closely related to that of Sap of C. parapsilosis. We designed and prepared an inhibitor containing phenylstatine isoster that was equipotent towards all four proteases within the range of 10-10-10-9 M. The HIV-1 protease inhibitors ritonavir, saquinavir, indinavir, and nelfinavir were also tested for the inhibition of four Saps. Only ritonavir and saquinavir inhibited Sap2p, Sapt1p, Sapp1p, and Saplp in micromolar concentrations.

Amino Acid Sequence↗

PubMed2001

Therapeutic vaccination (p24-VLP) of patients with advanced HIV-1 infection in the pre-HAART era does not alter CD4 cell decline.

In a randomized placebo controlled trial 304 HIV infected patients with CD4 cell counts below 350 cells/microL received therapeutic vaccination with: alum placebo (Group I, n = 102), p24-VLP 500 microg (Group II, n = 101) or p24-VLP 1000 microg (Group III, n = 101) p24-VLP monthly for six months. Over one year the average change in CD4 cell count did not differ significantly between groups (-32, -40 and -52 cells per microL respectively). There was also no difference between groups in progression to CDC category B or C events, or in adverse events. Therapeutic vaccination with p24-VLP does not affect CD4 cell decline in patients with advanced HIV infection.

AIDS Vaccines↗

PubMed2001

Role of contact system activation in hemodialyzer-induced thrombogenicity.

BACKGROUND: The contact system is generally believed to be the main trigger of the coagulation cascade during extracorporeal circulation. However, the extent of contact activation, its role for intradialytic thrombin generation as well as the influence of different dialyzer membranes have not been well established. METHODS: In a novel full-scale ex vivo recirculation dialysis model, we investigated the thrombogenicity of three widely used hemodialyzers (Cuprophan Renak RA15-U, Polysulfone F6HPS and AN69XT Nephral 200). The activation of the contact system was evaluated using a newly developed ELISA for factor XIIa-C1-inhibitor complexes. Additionally, we determined free FXIIa (ELISA), thrombin-antithrombin (TAT) complexes, platelet factor 4 (PF4), complement activation (C5a), granulocyte elastase and blood cell counts. The findings in blood from normal volunteers were compared with factor XII-deficient blood. RESULTS: With normal blood AN69 exhibited the highest thrombogenicity in comparison to Cuprophan and Polysulfone, as assessed by TAT generation and platelet consumption. AN69 caused a rapid increase of the FXIIa-C1-inhibitor complexes and of free FXIIa. Despite significant TAT generation with Cuprophan and Polysulfone free FXIIa remained unchanged and the FXIIa-C1-inhibitor complexes stayed below the detection limit. With factor XII-deficient blood Polysulfone exhibited the same TAT generation, whereas the thrombogenicity of AN69 was greatly reduced. CONCLUSIONS: Our data challenge the common assumption that activation of the contact system with generation of FXIIa is the main trigger for coagulation and thrombus formation in hemodialysis. Only the negatively charged AN69 membrane with enhanced thrombogenicity strongly induced contact activation.

Adult↗

PubMed2001

[Unilateral opacification of the paranasal sinuses in CT or MRI: an indication of an uncommon histological finding].

BACKGROUND: Clinical and radiological differentiation between subacute or chronic sinusitis and differential pathologies such as malignoma, inverted papilloma or mycosis can be very difficult. In some cases the CT- or MRI-scan shows a unilateral opacification of the paranasal sinuses. Which histological results can be found in patients with persisting sinusitis related problems and a unilateral opacification of the paranasal sinuses in the CT- or MRI-scan? There are only a few publications on this topic. PATIENTS: In a prospective study between June 1998 and November 1999 all patients who underwent surgery in our Department for subacute or chronic sinusitis problems were included into our study group if they had a unilateral opacification of the paranasal sinuses. Thereafter, the same neuroradiologist verified the unilateral radiological findings on CT or MRI, unaware of the clinical and histological findings. Cases with a pre-existing histological examination, previous operation or injury to the paranasal system were excluded from this study. Data on clinical symptoms, radiological and histological findings were analysed. RESULTS: 43 cases with unilateral opacified paranasal sinuses were diagnosed by means of CT or MRI. These were comprised of 24 males and 19 females with an average age of 43.6 years (range 6 to 88 years). The major findings of our study were as follows: Firstly unilateral opacification of the paranasal sinuses is often (19/43 cases or 43%) associated with diseases othe than simple chronic sinusitis (8 inverted papilloma, 5 malignoma, 3 mycoses and one brown tumor, one osteoidosteoma and one haemangioma). Secondly the incidence of significant pathology other than simple chronic sinusitis rises strikingly with increasing age of the patient. For instance pathologies other than simple chronic sinusitis were found in 14% (1/7) of cases in the under 16 years group, 27% (6/22) of cases in the 16-60 years group and in 86% (10/12) of cases in the over 60 years group. Concerning clinical signs of our patients with unilateral sinus opacity 7 of 11 patients (63%) with epistaxis and 3/5 with diplopia had histological findings other than simple chronic sinusitis. In contrast unilateral rhinorrhea, unilateral nasal congestion and cephalgia were not of predictive value. CONCLUSION: Unilateral opacification of paranasal sinuses in the CT or MRI is--especially at a higher age--an indice for a neoplasm or mycotic sinusitis and therefore an early histological diagnosis or operative treatment is always suggested.

Adolescent↗

PubMed2001

[Balloon dilatation and stent implantation in malignant and benign stenoses of the central venous system].

Compared with the excellent good results on the arterial side, venous angioplasty combined with stent-application was described relatively late in the literature, dealing in the majority of cases with palliative tumour stenoses of the superior and inferior vena cava. Recanalization of benign stenoses, especially of the pelvic venous spur (May/Thurner; syn. Pelvic compression syndrome, Cockett) was realized so far only in a limited number of cases. We have performed this interventional therapy since 1991 in 21 patients (female: 16, male: 5), with good long-term results in 18 cases. According to the special patho-anatomy of the "spur", developing intimal proliferation and progressive stenosis at the left-sided ilio-caval junction in about 20% of the average adult population, a restrictive indication is, however, mandatory. According to strong clinical symptoms (severe varicosis and leg oedema at the left-sided lower extremity), phlebographic and functional parameters (won by central venous blood pressure measurements) are indicating selected cases for this curative treatment.

Adult↗

PubMed2001

[Phlebological diagnosis. Phlebography of the veins of the lower extremity].

Phlebography should be weighed up against the current sonographic techniques (Doppler and Duplex) applied for visualization of venous disorder along the lower extremity veins, following a decision tree considering completeness and quality of documentation wanted, invasiveness and clinical consequences expected in the individual case. Ascending leg phlebography, incorporating Valsalva's manoeuvre, means the up-to-date standard technique, offering morphologic and functional information. Varicography and additional phlebographic techniques are considered to be additive, solving special problems, having not been visualized by the standard phlebography before. Combined phlebography and peripheral blood pressure measurements may improve the output of functional informations within one session. Quality standards of phlebography have to include standardized technique of phlebography, of documentation and interpretation, dealing with the special aspects of varicose syndrome, acute thrombosis and the post-thrombotic syndrome.

Humans↗

PubMed2001

Trepanations from the early medieval period of southwestern Germany--indications, complications and outcome.

Of the 384 skulls from the early medieval period, 8 (2.1%) exhibited trepanations. Three skulls showed trepanations in the proximity of fractures. One case of infection after borrhole trepanation that resulted in death is identifiable. Seven skulls showed clear evidence of healing and survival after trepanation. The mortality and infection rates for trepanation were low during the 6th to 8th centuries in southwestern Germany.

Adult↗

PubMed2001

The pathogenesis of HIV-1 infection.

Epidemiologists have long established beyond all reasonable doubt that infection by the human immunodeficiency virus type 1 (HIV-1) leads to the acquired immune deficiency syndrome (AIDS). Natural history cohorts have demonstrated that the median time from infection to development of AIDS is approximately 12 years, and that this long duration is broadly similar in all populations infected by HIV-1, in all risk groups, in all ethnic groups and in all geographical areas. These epidemiological observations suggest that HIV-1 causes AIDS largely independently of human major histocompatibility complex (MHC) and HIV-1 sequence polymorphisms, as great diversity of both these factors exist world-wide. This is not to say that HLA and HIV diversity do not affect the natural history of HIV disease, but these observations support a common mechanism of HIV-1 pathogenesis which is largely independent of human and viral diversity.

Acute Disease↗