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Biomedical subjects

D Gerber

Publications and source records attributed to D Gerber.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hysteroscopy in bitches.

The aim of this study was to determine whether the canine endometrium could be examined by hysteroscopy. Eight German shepherd bitches were used. Two bitches were in dioestrus, five were in anoestrus and one was about 8 weeks post partum. The uterus was exposed through a ventral celiotomy. A 3 mm straight laparoscope or a 4 mm laparoscope with a 30 degrees angle, and a catheter for inflation of the uterus were used. After hysteroscopy the bitches were spayed and the uterus of each bitch was examined macroscopically and histologically. Endometrium and uterotubal junctions were visible in all bitches. The cervix and caudal uterine body could not be visualized in three bitches as two bitches had uterine discharge and air escaped through the cervix in the other bitch. In the post-partum bitch, dark-brown sites of implantation were observed. Four bitches (aged 9, 22, 25 and 31 months) had endometrial cysts (0.5-2.0 mm in diameter). Hysteroscopy caused petechiae and ecchymosis in the endometrium of four bitches. Traumatization of the endometrium affected only the epithelium and the most superficial part of the lamina propria. In conclusion, hysteroscopy appears to be a very sensitive tool for evaluation of the canine endometrium. Further research is necessary to determine the effects of hysteroscopy on subsequent fertility.

Animals↗
PubMed2001

Visualization and molecular analysis of nuclear import of protein kinase CK2 subunits in living cells.

We have generated fusion proteins between the subunits of CK2 and GFP and characterized their behaviour in living cells. The expressed fusion proteins were functional and interacted with endogenous CK2. Imaging of NIH3T3 cells expressing low level of GFP-CK2alpha or GFP-CK2beta showed that both proteins were mostly nuclear in interphase. Both CK2 subunits contain nuclear localization domains that target them independently to the nucleus. Once in the nucleus, both subunits diffused rapidly in the nucleoplasm. In mitotic cells, CK2 subunits were dispersed throughout the cytoplasm and were not associated to chromatin. Our data are compatible with the idea that each subunit can translocate individually to the nucleus to interact with each other or with important cellular partners. Understanding the molecular mechanisms which regulate the dynamic localization of CK2 subunits will be of central importance.

3T3 Cells↗
PubMed2000

Insertion and organization within membranes of the delta-endotoxin pore-forming domain, helix 4-loop-helix 5, and inhibition of its activity by a mutant helix 4 peptide.

The pore-forming domain of Bacillus thuringiensis Cry1Ac insecticidal protein comprises of a seven alpha-helix bundle (alpha1-alpha7). According to the "umbrella model," alpha4 and alpha5 helices form a hairpin structure thought to be inserted into the membrane upon binding. Here, we have synthesized and characterized the hairpin domain, alpha4-loop-alpha5, its alpha4 and alpha5 helices, as well as mutant alpha4 peptides based on mutations that increased or decreased toxin toxicity. Membrane permeation studies revealed that the alpha4-loop-alpha5 hairpin is extremely active compared with the isolated helices or their mixtures, indicating the complementary role of the two helices and the need for the loop for efficient insertion into membranes. Together with spectrofluorometric studies, we provide direct evidence for the role of alpha4-loop-alpha5 as the membrane-inserted pore-forming hairpin in which alpha4 and alpha5 line the lumen of the channel and alpha5 also participates in the oligomerization of the toxin. Strikingly, the addition of the active alpha4 mutant peptide completely inhibits alpha4-loop-alpha5 pore formation, thus providing, to our knowledge, the first example that a mutated helix within a pore can function as an "immunity protein" by directly interacting with the segments that form the pore. This presents a potential means of interfering with the assembly and function of other membrane proteins as well.

Amino Acid Sequence↗
PubMed2000

Utility of postintubation chest radiographs in the intensive care unit.

OBJECTIVE: To determine the clinical usefulness of immediate (stat) chest radiographs after endotracheal intubation when performed by experienced critical care personnel. PATIENTS AND METHODS: This was a prospective study. Endotracheal intubations in an 11-bed intensive care unit and a nine-bed intermediate intensive care unit were included. After intubations were performed by an experienced critical care operator, that individual recorded demographic and procedural data, and predicted radiographic findings on a data collection sheet. Experience at intubation was stratified into four levels of lifetime experience: fewer than 10 procedures, 10-20 procedures, 20-50 procedures, and more than 50 procedures. Radiographic findings evaluated included endotracheal tube position and procedure-related complications. The postintubation chest radiograph was then reviewed and the actual findings were also recorded. RESULTS: A total of 101 evaluable intubations were recorded, two of which were predicted to show tube malposition. Actual radiographic findings revealed 10 malpositions, three of which were too high and seven were too low (one at the level of the carina). A single witnessed aspiration that occurred during intubation was not radiographically apparent until 24 h later. Only the tube positioned at the carina was felt to be of acute clinical significance or to place the patient at any acute risk. CONCLUSIONS: The incidence of endotracheal tube malposition after intubation was underestimated. However, when performed by experienced critical care personnel, acutely significant malpositions were rare (one out of 101 intubations). We conclude that, in the absence of specific pulmonary complications, endotracheal intubations performed by experienced operators may be followed by routine, rather than 'stat' chest radiographs.

Clinical Competence↗
PubMed2000

Demographic and environmental correlates of pedestrian injury collisions: a spatial analysis.

Pedestrian injury collisions often occur when and where large numbers of pedestrians travel within complex roadway systems with high traffic flow. The pedestrian injury literature suggests a number of individual and environmental correlates of injury risks, however studies in this area have primarily focused upon demographic differences (e.g. related to age) and a few global characteristics of the roadway system (e.g. aspects of pedestrian traffic). Studies in which the geography of communities has been considered are primarily descriptive, identifying pedestrian injury 'hot spots'. The current study more extensively explores some geographic correlates of pedestrian injury collisions through a spatial analysis of data from the city of San Francisco, CA. A spatial autocorrelation corrected regression model was used to determine factors associated with pedestrian traffic injury in 1990. The study used a geographic information system to map locations of pedestrian injuries, and environmental and demographic characteristics of the city across census tract units. In addition to a number of demographic factors (gender, age, marital status, education, income and unemployment), it was proposed that several environmental features of the city would be related to injury rates (high traffic flow, complex roadway systems, greater population densities and alcohol availability). Results of the study showed that pedestrian injury rates were related to traffic flow, population density, age composition of the local population, unemployment, gender and education. Availability of alcohol through bars was directly related to pedestrian injury collisions in which the pedestrian had been drinking alcohol.

Accidents, Traffic↗
PubMed2000

Split-liver transplantation: a comparison of ex vivo and in situ techniques.

BACKGROUND/PURPOSE: The expanding applicability of liver transplantation as treatment for end-stage liver disease has fostered a disproportionate increase in liver transplant candidates in the face of an unchanging pool of donor organs. This has resulted in disparities in pretransplant waiting times and deaths. The splitting of a liver allograft allows for the transplantation of 2 recipients, usually an adult and a child, thus providing a means to expand the cadaveric donor pool. METHODS: The authors present their results on the performance of an ex vivo (back table) split and in situ (in a hemodynamically stable cadaveric donor) split to evaluate safety, applicability, and effectiveness. Between November 1989 through April 1998, 54 split-liver transplant recipient operations were performed (24 pediatric and 30 adult). Thirty donors were procured: the ex vivo splitting yielded 25 grafts from 13 donors (donor age, 24.6+/-11 years), and the in-situ technique yielded 29 grafts from 17 donors (mean donor age of 25.5+/-10.4 years). Five donors involved interinstitutional sharing for which the left side of the graft was kept at the host hospital and the right side grafts were utilized at our center. RESULTS: Overall 1-year patient survival was 85%, with a graft survival of 72%. Patient survival was similar with ex vivo (74%) as compared with the in situ splitting group (96%; P = .06), as was graft survival in ex vivo (61 %) versus in situ (81%) splitting (P = .15). The pediatric population benefited most from the in situ technique, with a 1-year patient survival rate of 100% with the in situ technique versus the ex vivo technique survival rate of 64% at 1 year (P = .02). The 1-year graft survival comparing these 2 techniques was 83% for the in situ group versus 45% for the ex vivo group. Analysis of the program evolution of split-liver transplantation suggested a time-dependent learning curve, which was applicable to surgical splitting technique, implantation, and recipient selection. CONCLUSIONS: The principle of splitting livers from cadaveric donors is fundamentally sound and technically feasible. The authors' outcomes analysis using 2 different procurement techniques suggests that the in situ technique is clinically efficacious, can be used alternatively with the ex vivo technique, and is comparable to whole-liver allograft transplantation.

Adult↗
PubMed2000

Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence.

OBJECTIVE: To describe our experience with total hepatectomy and liver transplantation as treatment for primary hepatoblastoma (HBL) and hepatocellular carcinoma (HCC) in children. STUDY DESIGN: A retrospective analysis of the perioperative course of 31 children with unresectable primary HBL (n = 12) and HCC (n = 19) who underwent transplantation between May 1989 and December 1998. Systemic (n = 18) and intraarterial (n = 7) neoadjuvant chemotherapy were administered; follow-up ranged from 1 to 185 months. RESULTS: For HBL, 1-year, 3-year, and 5-year posttransplantation survival rates were 92%, 92%, and 83%, respectively. Intravenous invasion, positive hilar lymph nodes, and contiguous spread did not have a significant adverse effect on outcome; distant metastasis was responsible for 2 deaths. Intraarterial chemotherapy was effective in all patients treated. For HCC, the overall 1-year, 3-year, and 5-year disease-free survival rates were 79%, 68%, and 63%, respectively. Vascular invasion, distant metastases, lymph node involvement, tumor size, and gender were significant risk factors for recurrence. Intraarterial chemotherapy was effective in 1 of 3 patients. Six patients died of recurrent HCC, and 3 deaths were unrelated to recurrent tumor. CONCLUSION: Liver transplantation for unresectable HBL and HCC can be curative. Risk factors for recurrence were significant only for HCC, with more advanced stages amenable to cure in the HBL group.

Adolescent↗
PubMed1999

An analysis of pretransplantation variables associated with long-term allograft outcome in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy.

BACKGROUND: The present study analyzes pretransplantation variables associated with long-term liver allograft survival in 278 children who underwent transplantation under primary tacrolimus (FK506) therapy at a single center between October 1989 and October 1996. METHODS: The influence of 17 pretransplantation variables on long-term liver allograft outcome was analyzed. Donor variables included age, weight, gender, and cold ischemia time. Recipient variables included age, weight, gender, original liver disease, pretransplantation waiting time, previous abdominal surgery, United Network of Organ Sharing (UNOS) status, ABO blood group, bilirubin level, prothrombin time, ammonia level, creatinine level, and reduced-size/split liver grafts. RESULTS: Overall actuarial graft survival was 79.9% at 1 year, 79.1% at 2 years, and 78.3% at 3, 4, and 5 years. Retransplantation rate was 10.8%. Pretransplantation variables with a significant adverse effect on graft survival by univariate analysis were donor age < or = 1 year (P<0.004), donor weight < or = 10 kg (P<0.003), UNOS status I and II (P<0.007), ABO type O, B, and AB (P<0.03), and reduced-size/split liver grafts (P<0.02). Pretransplantation variables significant by multivariate analysis and therefore independent predictors of inferior graft outcome were donor weight '10 kg (relative risk [RR] 2.91, confidence interval [CI] 1.53-5.51); reduced-size/split liver grafts (RR 2.53, CI 1.30-5.64); and UNOS status I (RR 2.22, CI 1.11-4.43). CONCLUSIONS: Pediatric liver transplant recipients receiving primary tacrolimus therapy have long-term graft survival rates approaching 80%. UNOS status, donor weight, and the use of reduced-size/split liver grafts are the most important factors affecting survival.

Adolescent↗
PubMed1999

Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes.

Calnexin was initially identified as an endoplasmic reticulum (ER) type I integral membrane protein, phosphorylated on its cytosolic domain by ER-associated protein kinases. Although the role of the ER luminal domain of calnexin has been established as a constituent of the molecular chaperone machinery of the ER, less is known about the role of the cytosolic phosphorylation of calnexin. Analysis by two-dimensional phosphopeptide maps revealed that calnexin was in vitro phosphorylated in isolated microsomes by casein kinase 2 (CK2) and extracellular-signal regulated kinase-1 (ERK-1) at sites corresponding to those for in vivo phosphorylation. In canine pancreatic microsomes, synergistic phosphorylation by CK2 and ERK-1 led to increased association of calnexin with membrane-bound ribosomes. In vivo, calnexin-associated ERK-1 activity was identified by co-immunoprecipitation. This activity was abolished in cells expressing a dominant-negative MEK-1. Activation of ERK-1 in cells by addition of serum led to a 4-fold increase in ribosome-associated calnexin over unstimulated cells. Taken together with studies revealing calnexin association with CK2 and ERK-1, a model is proposed whereby phosphorylation of calnexin leads to a potential increase in glycoprotein folding close to the translocon.

Animals↗
PubMed1999

Novel bioartificial liver support system: preclinical evaluation.

Preclinical safety and efficacy evaluation of a novel bioartificial liver support system (BLSS) was conducted using a D-galactosamine canine liver failure model. The BLSS houses a suspension of porcine hepatocytes in a hollow fiber cartridge with the hepatocytes on one side of the membrane and whole blood flowing on the other. Porcine hepatocytes harvested by a collagenase digestion technique were infused into the hollow fiber cartridge and incubated for 16 to 24 hours prior to use. Fifteen purpose-bred male hounds, 1-3 years old, 25-30 kg, were administered a lethal dose, 1.5 g/kg, of D-galactosamine. The animals were divided into three treatment groups: (1b) no BLSS treatment (n = 6); (2b) BLSS treatment starting at 24-26 h post D-galactosamine (n = 5); and (2c) BLSS treatment starting at 16-18 h post D-galactosamine (n = 4). While maintained under isoflurane anesthesia, canine supportive care was guided by electrolyte and invasive physiologic monitoring consisting of arterial pressure, central venous pressure, extradural intracranial pressure (ICP), pulmonary artery pressure, urinary catheter, and end-tidal CO2. All animals were treated until death or death-equivalent (inability to sustain systolic blood pressure > 80 mmHg for 20 minutes despite massive fluid resuscitation and/or dopamine administration), or euthanized at 60 hours. All animals developed evidence of liver failure at 12-24 hours as evidenced by blood pressure lability, elevated ICP, marked hepatocellular enzyme elevation with microscopic massive hepatocyte necrosis and cerebral edema, elevated prothrombin time, and metabolic acidosis. Groups 2b and 2c marginally prolong survival compared with Group 1b (pairwise log rank censored survival time analysis, p = 0.096 and p = 0.064, respectively). Since survival times for Groups 2b and 2c are not significantly different (p = 0.694), the groups were combined for further statistical analysis. Survival times for the combined active treatment Groups 2b and 2c are significantly prolonged versus Group 1b (p = 0.047). These results suggest the novel BLSS reported here can have a significant impact on the course of liver failure in the D-galactosamine canine liver failure model. The BLSS is ready for Phase I safety evaluation in a clinical setting.

Animals↗
PubMed1999

Characterisation of a potentially abortigenic strain of feline calicivirus isolated from a domestic cat.

Feline calicivirus (FCV) was isolated from one of four dead fetuses delivered by ovariohysterectomy from a queen with an acute FCV infection. The most prominent lesions in the fetuses were petechial haemorrhages in the skin. The virus isolated was characterised as FCV by antigenic analysis and cDNA sequence analysis. This is the second report of abortion associated with acute FCV infection.

Abortion, Veterinary↗
PubMed1999

Management of portal hypertension-related bleeding.

Although endoscopic sclerotherapy and TIPS remain the primary therapeutic tools in management of acute variceal bleeding, surgical shunts must be considered for low-risk patients with bleeding. OLTx is the only definitive treatment for patients with end-stage liver disease and vascular decompensation. Furthermore, the current prospective multicenter randomized study, funded by the National Institutes of Health and Human Services, will help determine the role of DSRS versus TIPS in cirrhotic patients with good hepatic reserve. This is a necessity in a time in which organ shortages are ever-increasing because of a growing disparity between the number of patients listed for transplantation each year versus the number of suitable organ donors. The various surgical techniques should be applied in different situations based on patients' clinical status at the time of the bleed and whether they are considered candidates for liver transplantation.

Acute Disease↗
PubMed1999

The sedative and analgesic effects of detomidine-butorphanol and detomidine alone in donkeys.

Butorphanol and detomidine constitute an effective combination for sedation and analgesia in horses. This trial was undertaken to assess the effectiveness of this combination in donkeys. The detomidine and butorphanol were given intravenously one after the other. A dose of 10 microg/kg of detomidine and 25 microg/kg of butorphanol was used. Sedation is easily extended by additional doses of butorphanol. The average dose of detomidine was 11.24 microg/kg and that of butorphanol was 28.0 microg/kg. Four donkeys in the detomidine group required additional sedation and analgesia. Detomidine alone did not totally eliminate coronary band pain. Heart rates dropped significantly in the first minute after the injection of the combination. One donkey developed an atrioventricular block, while another developed a sino-atrial block. Four donkeys developed a Cheyne-Stokes respiratory pattern. The combination of detomidine and butorphanol is an effective combination for sedation and analgesia of donkeys for standing procedures.

Analgesics↗
PubMed1998

Impact energy measurement in time-of-flight mass spectrometry with cryogenic microcalorimeters.

Time-of-flight mass spectrometry-most notably matrix-assisted laser-desorption-ionization time-of-flight (MALDI-TOF) spectrometry-is an important class of techniques for the study of proteins and other biomolecules. Although these techniques provide excellent performance for masses up to about 20,000 daltons, there has been limited success in achieving good mass resolution at higher masses. This is because the sensitivity of the microchannel plate (MCP) detectors used in most systems decreases rapidly with increasing particle mass, limiting the utility of MCP detectors for very large masses. It has recently been proposed that cryogenic particle detectors may provide a solution to these difficulties. Cryogenic detectors measure the thermal energy deposited by the particle impact, and thus have a sensitivity that is largely independent of particle mass. Recent experiments have demonstrated the sensitivity of cryogenic particle detectors to single biomolecules, a quantum efficiency several orders of magnitude larger than the MCP detectors, and sensitivity to masses as large as 750,000 daltons. Here we present results demonstrating an order of magnitude better energy resolution than previous measurements, allowing direct determination of particle charge state during acceleration. Although application of these detectors to practical mass spectrometry will require further development of the detectors and cryogenics, these detectors can be used to elucidate the performance-limiting processes that occur in such systems.

Animals↗
PubMed1998

Persistent interactions of core histone tails with nucleosomal DNA following acetylation and transcription factor binding.

In this study, we examined the effect of acetylation of the NH2 tails of core histones on their binding to nucleosomal DNA in the absence or presence of bound transcription factors. To do this, we used a novel UV laser-induced protein-DNA cross-linking technique, combined with immunochemical and molecular biology approaches. Nucleosomes containing one or five GAL4 binding sites were reconstituted with hypoacetylated or hyperacetylated core histones. Within these reconstituted particles, UV laser-induced histone-DNA cross-linking was found to occur only via the nonstructured histone tails and thus presented a unique tool for studying histone tail interactions with nucleosomal DNA. Importantly, these studies demonstrated that the NH2 tails were not released from nucleosomal DNA upon histone acetylation, although some weakening of their interactions was observed at elevated ionic strengths. Moreover, the binding of up to five GAL4-AH dimers to nucleosomes occupying the central 90 bp occurred without displacement of the histone NH2 tails from DNA. GAL4-AH binding perturbed the interaction of each histone tail with nucleosomal DNA to different degrees. However, in all cases, greater than 50% of the interactions between the histone tails and DNA was retained upon GAL4-AH binding, even if the tails were highly acetylated. These data illustrate an interaction of acetylated or nonacetylated histone tails with DNA that persists in the presence of simultaneously bound transcription factors.

Acetylation↗
PubMed1997

The T cell receptor repertoire of intestinal intraepithelial gammadelta T lymphocytes is influenced by genes linked to the major histocompatibility complex and to the T cell receptor loci.

Most of the gammadelta T cells in the intestinal epithelium of normal mice use the Vgamma1 or the Vgamma7 gene segments. However, the relative proportions of gammadelta intraepithelial lymphocytes expressing either the Vgamma1 or the Vgamma7 chain vary among different strains of mice whereas they are quite constant between different individuals of the same strain, suggesting that genetic factors, rather than environmental factors, are responsible for the observed differences. To analyze the genetic factors influencing the representation of different gammadelta T cell subsets in the intestinal epithelium, we used available anti-T cell antigen receptor (TCR) V region-specific mAbs against Vgamma1, Vgamma4, Vgamma7, and Vdelta4 to examine the TCR repertoire of intraepithelial gammadelta lymphocytes in a set of (C57BL/6 x DBA/2) recombinant inbred strains. Our results show that the representation of different Vgamma and Vdelta gene products among gammadelta intestinal intraepithelial lymphocytes is under a complex genetic control with a marked influence by genes closely linked to the TCRgamma, TCRdelta, and major histocompatibility complex loci.

Animals↗
PubMed1996

Subregion- and cell type-restricted gene knockout in mouse brain.

Using the phage P1-derived Cre/loxP recombination system, we have developed a method to create mice in which the deletion (knockout) of virtually any gene of interest is restricted to a subregion or a specific cell type in the brain such as the pyramidal cells of the hippocampal CA1 region. The Cre/loxP recombination-based gene deletion appears to require a certain level of Cre protein expression. The brain subregional restricted gene knockout should allow a more precise analysis of the impact of a gene mutation on animal behaviors.

Animals↗