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Biomedical subjects

C Witte

Publications and source records attributed to C Witte.

At least 19 recordsLinked to original sources

Modelling high-resolution electron microscopy based on core-loss spectroscopy.

There are a number of factors affecting the formation of images based on core-loss spectroscopy in high-resolution electron microscopy. We demonstrate unambiguously the need to use a full nonlocal description of the effective core-loss interaction for experimental results obtained from high angular resolution electron channelling electron spectroscopy. The implications of this model are investigated for atomic resolution scanning transmission electron microscopy. Simulations are used to demonstrate that core-loss spectroscopy images formed using fine probes proposed for future microscopes can result in images that do not correspond visually with the structure that has led to their formation. In this context, we also examine the effect of varying detector geometries. The importance of the contribution to core-loss spectroscopy images by dechannelled or diffusely scattered electrons is reiterated here.

Journal Article↗

Limb volume reduction after physical treatment by compression and/or massage in a rodent model of peripheral lymphedema.

Lack of a standardized experimental counterpart of peripheral lymphedema (LE) in a small animal has hampered research into treatment of this debilitating condition. We recently refined a rodent model consisting of radical unilateral lymphatic/nodal groin excision in conjunction with a circumferential integumental gap, followed by regional irradiation of the groin to reproduce stable unilateral hindlimb LE (1). In the current study, Wistar-Fuzzy rats with established right hindlimb LE, were subdivided into five groups and subjected to one of the following daily physical regimens over a 5-day period: pneumatic compression pumping at 30 torr (PCP); low-stretch multi-layered compressive bandaging using Coban (CB); manual lymphedema drainage (MLD) or a light massage consisting of stationary circular motions using the fingertips; combined physiotherapy (CPT consisting of MLD + CB); and a no treatment or control group (CTRL). Hindlimb and LE volumes were serially measured before and after treatment. Whereas CTRL showed progressive worsening of hindlimb swelling, PCP, CB, CPT and MLD each produced similar and substantial edema reduction over the 5 day interval, PCP, CB and CPT induced vacillating edema reduction which, however, exceeded rebound swelling on a daily basis. MLD, on the other hand, showed a steady gradual daily decline in LE volume.

Animals↗

Reduction of trachoma in the absence of antibiotic treatment: evidence from a population-based survey in Malawi.

PURPOSE: A survey was conducted in Chikwawa District, Malawi in order to compare the current prevalence of trachoma with a similar survey in 1983. METHODS: Using random cluster household sampling, children aged 1 to 6 and adults aged 50 or older were enumerated and examined for the presence of trachoma. RESULTS: Among the 1313 children enumerated, 1249 (95.1%) were examined and among the 1431 adults enumerated, 1221 (85.3%) were examined. The prevalence of active trachoma among the children was 13.9% (11.9-15.9%), 10.0% in males and 14.4% in females. The prevalence of active trachoma varied significantly among the 25 clusters, ranging from 3.9% to 38.2% with 5 clusters (20%) having a prevalence >20%. Signs of trachomatous trichiasis were observed in 1.0% of adults examined. Active disease in 1999 was associated with a longer distance to the primary water source. CONCLUSIONS: Since 1983 there has been no mass antibiotic treatment programme in the district and little change in socioeconomic status. However, compared to the 1983 findings, active trachoma has been reduced by over 50% (p < 0.001) and trachomatous trichiasis by over 80%. In the 16-year interim (especially in the past 7 years) health, water and hygiene programmes were initiated and we hypothesize that the reduction in active disease is likely due to these changes. Our findings suggest that sustained reductions in active trachoma can be achieved without community-based antibiotic distribution.

Age Distribution↗

Inhibition of normal and experimental angiotumor endothelial cell proliferation and cell cycle progression by 2-methoxyestradiol.

With rapid growth and metabolism, aggressive cancers require an extensive vascular network, termed tumor angiogenesis. The body produces a variety of natural angiogenic inhibitors, among which is the mammalian estrogen metabolite, 2-methoxyestradiol (2-MeOE2). In this study, we compared the effects of 2-MeOE2 on a human umbilical vein cell line (HUVEC-C) and on an immortal, angiotumor-producing rat sinusoidal endothelial cell line (RSE-1). In vitro, the effects of varying concentrations of 2-MeOE2 from 0.01-100.0 microM were measured with cell counts and compared to control cells. HUVEC-C had an ED50 approximately 3.5 microM with approximately 27% inhibition of cell growth whereas RSE-1 had an ED50 approximately 2.2 microM with approximately 50% inhibition of cell growth compared with controls. The lowest concentration with maximal effect was 10.0 microM 2-MeOE2 for both cell lines. Using this concentration, flow cytometric analysis of cell cycles was performed with propidium iodide stained DNA of HUVEC-C and RSE-1 at 24 and 48 hr. Both demonstrated a significant (P < 0.0001) block at G2M of the cell cycle. At 48 hr, HUVEC-C had 32% of cells in G2M (control = 9% G2M), and RSE-1 had 36% of cells in G2M (control = 18% G2M). These findings demonstrate a strong in vitro antiproliferative effect of 2-MeOE2 on normal dividing endothelial as well as angiotumor cells mediated through a cell cycle-specific block at G2M. The antiendothelial, antiangiotumor effect of 2-MeOE2 supports its potential as a therapeutic agent against solid organ cancers, benign or malignant vascular growths, and other pathologic states dependent on angiogenesis.

2-Methoxyestradiol↗

Risk of nonshunt abdominal operation in the patient with cirrhosis.

BACKGROUND: The hazards of operative treatment for variceal hemorrhage and intractable ascites in patients with cirrhosis are well known. Much less information is available on the morbidity and mortality in these patients after abdominal operations not directly related to the sequelae of portal hypertension. STUDY DESIGN: We reviewed the records of 77 consecutive histologically proved cases of cirrhosis in patients undergoing 85 general surgical, abdominal procedures during a ten year period. Logistic regression analysis was done on 32 preoperative and intraoperative variables with relation to postoperative outcome. RESULTS: There were 47 men and 30 women, with a mean age of 61 years (range of 28 to 86 years). The 30-day mortality rate was 18 percent (15 of 77 patients). Emergent operation was associated with a mortality rate of 32 percent (11 of 35 patients) compared with 8 percent (four of 50 patients) after elective procedures (p < 0.05). Extensive complications occurred in 28 percent of patients (24 patients; 14 percent after elective operative treatment and 49 percent after emergent procedures). The mortality rate was greatest after gastric procedures (38 percent). Other factors of statistical significance (p < 0.05) associated with poor postoperative outcome included cachexia, preoperative transfusion of fresh frozen plasma, and intraoperative platelet transfusion. Surprisingly, operative blood loss, presence of ascites, and operative time were not associated with increased complications or death. CONCLUSIONS: We conclude that elective, nonshunt abdominal operations can be performed with acceptable morbidity and mortality rates in selected patients with cirrhosis.

Abdomen↗

Developmental disorders of the lymphatic system.

Approximately 67% of human conceptuses die prenatally. Of these, a significant number involve a disorder of the lymphatic system. A small number of live-born children also exhibit congenital lymphatic malformations, including an estimated 60% of patients with Turner syndrome. These observations have prompted a search for the genetic and dysmorphologic basis and the different patterns of congenital lymphedema and associated anomalies. In this article, we attempt to summarize available pertinent information on congenital disorders of the lymphatic system and to propose a conceptual overview of lymphatic development.

Adult↗

Chyle leakage after blunt trauma.

Three patients developed chylous leakage after major blunt trauma. In one patient with non-remitting right-sided chylothorax, lymphangioscintigraphy as well as conventional oil contrast lymphography demonstrated disruption of the thoracic duct at the aortic hiatus which eventually required transpleural mediastinal ductal ligation proximal to the fistula. The other two patients had chylous retroperitoneum and/or chylous peritoneum which was self-limited although one patient (a three-year-old boy) died of multiorgan failure from associated pulmonary contusions and cervical spine injuries. Chylous leak after non-penetrating trauma is usually attributed to hyperflexion-extension of the vertebral column with shearing of tethered lymphatics. Alternatively, sudden compression of lipemic and engorged mesenteric lymphatics, adjacent nodes and the lower thoracic duct aggravated by deformations associated with stretching and tearing motions may also directly disrupt chyle-containing lymphatics.

Adolescent↗

A yeast protein, homologous to the proteolipid of the chromaffin granule proton-ATPase, is important for cell growth.

We have characterized a gene, PPA1, adjacent to the yeast MAS2 gene. DNA sequence analysis of PPA1 predicts a hydrophobic protein of 23 kDa. This protein is homologous to the proteolipid of the bovine chromaffin granule proton ATPase and to the proteolipid of the yeast vacuolar proton ATPase. Gene disruption experiments indicate that the PPA1 protein is essential for viability in three unrelated yeast strains and important for optimal growth in a fourth strain.

Adenosine Triphosphatases↗

MAS1, a gene essential for yeast mitochondrial assembly, encodes a subunit of the mitochondrial processing protease.

We have previously described a yeast mutant (mas1) that accumulates mitochondrial precursor proteins at high temperature and is deficient in the activity of a matrix-localized protease which cleaves presequences from mitochondrial precursor proteins. We have now cloned and sequenced the wild-type MAS1 gene and found that it encodes a subunit of the mitochondrial processing protease, that it is essential for cell viability and that the protein product participates in its own cleavage during import into mitochondria. The MAS1 protein is thus the first genetically defined component of the mitochondrial protein import pathway.

Amino Acid Sequence↗

Whole body lymphangioscintigraphy in ferrets chronically infected with Brugia malayi.

Whole body lymphangioscintigraphy was performed after intradermal injection of 99mtechnetium human serum albumin or antimony colloid in the distal hindlimbs and forelimbs of ferrets chronically infected with Brugia malayi. The findings were compared with control ferrets and those with surgical interruption of the iliac lymphatics. While only one infected ferret manifested chronic hindlimb lymphedema, all exhibited delayed transport of radioisotope from the hindpaw with obstruction in the groin, poor or absent visualization of central lymphatic channels and regional lymph nodes, a picture similar to that following surgically induced lymphatic obstruction. In control ferrets, there was prompt visualization of peripheral lymphatic channels and regional lymph nodes with sharper and more extensive channel visualization after radiolabeled albumin and more intense sustained nodal visualization after radiolabeled antimony colloid. This noninvasive technique provides a readily repeatable investigative tool adaptable to small animals to study the evolution of lymphatic filariasis and other conditions associated with lymphatic obstruction.

Animals↗

Lymphatic endothelial cell line (CH3) from a recurrent retroperitoneal lymphangioma.

An endothelial cell line derived from a massive recurrent chyle-containing retroperitoneal lymphangioma was isolated in monolayer culture. Scanning and transmission electron microscopy and immunohistochemistry confirmed a close resemblance to blood vascular endothelium with typical cobblestone morphology, positive immunofluorescence staining for endothelial marker Factor VIII-associated antigen and fibronectin, and prominent Weibel-Palade bodies. The endothelial cells also exhibited other ultrastructural features characteristic of lymphatic endothelium, including sparse microvillous surface projections, overlapping intercellular junctions, and abundant intermediate filaments. This endothelial cell line represents a new source of proliferating lymphatic endothelium for future study, including structural and functional comparison to blood vascular endothelium.

Adult↗

The outer membrane of yeast mitochondria: isolation of outside-out sealed vesicles.

The yeast mitochondrial outer membrane was isolated and 10 of its major polypeptides were identified (mol. wts. 109, 70, 57, 45, 45, 42, 33, 29, 25 and 14 kd). The membrane has no major polypeptide in common with either mitochondrial inner membrane or rough microsomes. Protease treatment and immunochemical techniques showed that virtually all of the isolated outer membrane vesicles are sealed and display the same surface orientation as in the intact mitochondrion.

Journal Article↗

Yeast mitochondrial outer membrane specifically binds cytoplasmically-synthesized precursors of mitochondrial proteins.

The precursor of cytochrome b(2) (a cytoplasmically-synthesized mitochondrial protein) binds to isolated mitochondria or to isolated outer membrane vesicles. Binding does not require an energized inner membrane, is diminished by trypsin treatment of the membranes and is not observed with the partially processed (intermediate) form of the cytochrome b(2) precursor or with non-mitochondrial proteins. Upon energization of the mitochondria, the bound precursor is imported and cleaved to the mature form. Similar results were obtained with the precursor of citrate synthase. This receptor-like binding activity was present in isolated outer, but not inner membrane. It was solubilized from outer membrane with non-ionic detergent and reconstituted into liposomes.

Journal Article↗

[Experiences with duodenum-sparing pancreas head resection in chronic pancreatitis].

1. A duodenum-preserved resection of the pancreas head was performed in 12 patients with chronic pancreatitis and tumor of the pancreas head without malignancy. The defect of the pancreas was repaired by an interposition of an jejunal 100p. -- 2. The clinical lethality was 0%. Follow-up after an average of three years showed 75% of the patients were completely able to return to work. -- 3. This resection procedure saves the patient from partial gastrectomy, common duct resection, and duodenectomy as compared to duodenopancreatectomy.

Adult↗