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Biomedical subjects

B Berg

Publications and source records attributed to B Berg.

At least 19 recordsLinked to original sources

SV40 T/t-antigen induces premature mammary gland involution by apoptosis and selects for p53 missense mutation in mammary tumors.

We recently established transgenic animals (WAP-SV-T/t) carrying the early coding region of Simian Virus 40 (SV40) under the transcriptional control of the whey acidic milk protein promoter (WAP), which restricts the expression of the transgene to mammary gland epithelial cells (ME-cells). SV40 T/t-antigen synthesis causes premature mammary gland involution during late pregnancy by inducing apoptosis and leads to development of mammary tumors after the first lactation period in both p53 positive (WAP-SV-T/t) and p53 negative double transgenic animals (WAP-SV-T/t.p53-/-). The high apoptotic rate persists in all of the T/t-antigen positive breast tumor cells, as well as in established ME-tissue culture cell lines. ME-cells which spontaneously switch off the expression of the WAP-SV-T/t transgene do not undergo apoptosis. However, these cells again exhibit an extensive DNA fragmentation when SV40 T/t-antigen synthesis is reintroduced, which indicates that it is the expression of T/t antigen which is the critical factor for induction of apoptosis. In addition, we isolated several ME-cell lines from different breast tumors which have spontaneously lost the T/t-antigen yet remain maximally transformed. Strikingly, these cells contain a missense mutation of the p53 gene at codon 242 (p53(242)), which substitutes alanine for glycine. This mutation increases p53 stability and it reduces the transactivating function of p53, albeit without affecting the ability of the protein to interact with the DNA. This indicates that p53 missense mutations are selected for in breast tumors initially expressing T/t-antigen. Therefore, the p53(242) mutation is sufficient to maintain the transformed state after the ME-cells have switched off the WAP-SV-T/t transgene. Interestingly, the p53 minus state per se is not sufficient to induce ME-cell transformation since homozygous null mice for the p53 gene (p53-/-) fail to develop breast cancer.

Animals

Non-evidence of estrogen receptors in the rectal mucosa.

The aim of the study was to investigate whether estrogen receptors are present in the rectal mucosa of premenopausal women compared to postmenopausal women and men. Thirty biopsies obtained from the rectal mucosa at colonoscopy, performed to investigate inflammatory bowel disease in 23 patients and neoplasia in 7, were examined by the avidin-biotin-peroxidase immunohistochemical technique for the presence of estrogen receptors. The study group (n = 10) were non-pregnant premenopausal women and the control group (n = 20) were postmenopausal women (n = 10) and men (n = 10). None of the subjects had fecal incontinence or was taking medication with hormones. In no case did the primary lesion involve the specimen used for laboratory analysis. All samples showed negative immunostaining for estrogen receptors. It was concluded that in continent women and men, a direct estrogenic effect on the rectal mucosa seems unlikely.

Adult

SV40 T1-mRNA trans-splicing and translation requires that the in vitro synthesized cRNA is capped before microinjection.

The purpose of this investigation was to study the effect on cap structure for trans-splicing in mammalian cells. The early SV40 Bst/Bam pre-mRNA (cRNA) was synthesized in vitro in both capped (cap-Bst/Bam-cRNA) and non-capped (Bst/Bam-cRNA) versions and microinjected into the nuclei of TC7 cells. Trans-splicing was monitored by immunofluorescence staining (T1-antigen) and by RT-PCR analysis. Cap-Bst/Bam-cRNA was trans-spliced with high efficiency, but not the Bst/Bam-cRNA molecules. Northern blot analysis revealed that both the capped and uncapped cRNA molecules had similar stability in the microinjected cells. The coinjected m7G(5')ppp(5')G cap analog did not inhibit the trans-splicing reaction in vivo and did not prevent nuclear export of the mRNA.

Animals

Hypertonic-hyperoncotic solution increases canine lymph flows.

BACKGROUND: Hypertonic-hyperoncotic solutions (HHS) have attracted a lot of interest in the treatment of various forms of hypovolaemic conditions during the last decade. It has been speculated that HHS might even be of therapeutic value in normo- and hypervolaemic conditions by mobilising extravascular fluid. METHODS: We studied thoracic and abdominal lymphatic flows and circulatory response following the administration of a single bolus injection of hypertonic-hyperoncotic solution, 10% dextran 60 in 7.2% saline (HHS), in a nonhypovolaemic canine model. A modified surgical procedure for collecting thoracic lymph is also presented. RESULTS: Both thoracic and abdominal lymph flow increased significantly by approximately 50% after administration of HHS. Cardiac output and calculated pulmonary capillary hydrostatic pressure increased. CONCLUSION: Hypertonic-hyperoncotic solution given intravenously as a single injection increased both thoracic and abdominal lymph flows in the initially normovolaemic animal.

Animals

Treatment of atypical leishmaniasis with interferon gamma resulting in progression of Kaposi's sarcoma in an AIDS patient.

Visceral leishmaniasis (kala-azar) affecting HIV-infected patient is being reported in increasing frequency. A 40-year-old German bisexual patient with full-blown AIDS is described who presented with Kaposi's sarcoma, epigastric pain, diarrhea, and weight loss but without fever. Leishmania amastigotes were initially found in biopsies from stomach, duodenum, and a cutaneous Kaposi's sarcoma lesion but were later also recovered from bone marrow and lymph node. The patient received three courses of a combination of pentavalent antimony and interferon-gamma. In addition to the common side effects such as fever, thrombocytopenia, and elevated amylase and lipase, a vivid progression of the Kaposi's sarcoma was noted. Tumor progression was temporally closely associated with treatment with interferon-gamma. Because this phenomenon has also been observed in other patients, we advise caution when using interferon-gamma in patients with Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome

The cost of nursing caries in a Native American Head Start population.

Nursing caries is a unique form of caries caused by prolonged exposure to pooled fermentable liquids and a lack of salivary flow during sleep. It is characterized by extensive destruction of the primary maxillary incisors generally beginning on the facial or lingual smooth surfaces. Nursing caries appears to have a particularly high prevalence in Native American populations and can be very costly to restore. The purpose of this study was (1) to determine the prevalence of nursing caries in a Mississippi Choctaw Indian Head Start program and (2) to determine the dollar costs of restoring nursing caries in a similar population. In part 1 of this study, 2 dentists independently examined 629 Native American Head Start children ranging in age from 3-5 years. It was found that 50.2% of these children had nursing caries. In part 2 of this study the cost of treating nursing caries in a Choctaw Indian population that ranged in age from 2-5 years was determined. It was found that the mean total cost of restoring a nursing caries patient requiring general anesthesia to provide treatment was $2,141.75. It was also determined that the mean cost of providing treatment for those children not requiring general anesthesia was $311.55. This study concluded that there was an extremely high prevalence of nursing caries in this Choctaw Indian Head Start population and that funds directed toward prevention would be a wise investment and that renewed and innovative efforts toward preventing nursing caries in these populations are indicated.

Bottle Feeding

Platelet concentrates in an additive solution prepared from pooled buffy coats. In vivo studies.

Leukocyte-depleted platelet concentrates were prepared from pools of 4 buffy coats on the day after blood collection (BC-PC). The storage medium was composed of citrate phosphate dextrose plasma and a platelet-additive solution. Autologous transfusions of 111In-labelled platelets in 9 healthy volunteers were performed on the day of preparation (day 1) and on day 5. The recovery was 54.6 +/- 8.7 (day 1) and 51.9 +/- 10.4% (day 5), T1/2 was 101 +/- 28 and 61 +/- 9 h, respectively. The survival was 8.3 +/- 1.7 and 5.7 +/- 1.0 days, respectively, using linear plot, and 7.8 +/- 2.0 and 5.8 +/- 0.5 days using the multiple hit method. In a prospective clinical study a comparison of the corrected posttransfusion increments was made between BC-PCs and apheresis-PC, and between fresh (1-2 days) and stored (3-5 days) preparations. No difference was found between BC-PCs and apheresis PCs. However, fresh BC-PCs gave higher increments than stored BC-PCs. A slight numerical difference between fresh and stored apheresis-PCs was not statistically significant. It is concluded that the BC-PC method results in platelets of equal quality to apheresis-PC.

Adult

Influence of positive end-expiratory pressure on extravascular lung water during the formation of experimental hydrostatic pulmonary oedema.

The influence of positive end-expiratory pressure (PEEP) on extravascular lung water measured with the double-indicator dilution technique (EVLWi) has been studied during formation of hydrostatic pulmonary oedema in a canine model. The oedema was created by elevating the mean pulmonary artery pressure (PAP) to 30 mmHg (4.0 kPa) by inflation of a left atrial balloon, and a simultaneous intravenous saline infusion of 15 ml.kg-1.h-1. All dogs were ventilated with zero end-expiratory pressure (ZEEP) until the initial EVLWi had increased by 50%. In one group (n = 5) a PEEP of 10 cmH2O (1.0 kPa) was applied and the dogs were studied for a further 4 h and in the other group (n = 5) ZEEP was maintained throughout the study. During the first 2 h after ZEEP/PEEP application EVLWi increased from 13.7 +/- 2.1 to 20.2 +/- 1.2 ml.kg-1 with ZEEP ventilation and from 13.6 +/- 1.2 to 18.6 +/- 1.9 ml.kg-1 with PEEP ventilation. EVLWi remained unchanged during the last 2 h in both groups. The gas exchange improved with PEEP, arterial oxygen tension increased from 30.4 +/- 8.9 kPa to 38.6 +/- 2.5 kPa (P less than 0.01), and the shunt fraction decreased from 6.0 +/- 3.8% to 1.2 +/- 0.8% (P less than 0.001). There were significant differences (P less than 0.01) in both PaO2 and shunt fraction between the ZEEP and PEEP groups throughout the study. In conclusion, positive end-expiratory pressure improves gas exchange but does not protect against increasing extravascular lung water during the creation of hydrostatic pulmonary oedema.

Animals

Influence of hypertonic-hyperoncotic solution and furosemide on canine hydrostatic pulmonary oedema resorption.

1. This study aimed at enhancing the clearance of experimental hydrostatic pulmonary oedema in dogs using hypertonic-hyperoncotic solution (HHS) and furosemide. 2. Anaesthetized dogs (n = 20) were mechanically ventilated with a positive end-expiratory pressure of 10 cmH2O (1.0 kPa). 3. Hydrostatic pulmonary oedema was induced by inflating a balloon inserted into the left atrium and simultaneously infusing isotonic saline rapidly. Oedema formation was terminated by deflating the balloon and reducing the infusion rate. 4. Four groups were studied: A, control; B, furosemide; C, HHS and D, HHS+furosemide. HHS, 6 ml kg-1, was given as a bolus injection and furosemide, 1 mg kg-1, intravenously as a bolus followed by an infusion of 0.5 mg kg-1 h-1. All dogs were studied for 4 h. 5. Serum osmolarity, plasma colloid oncotic pressure and diuresis in groups C and D (HHS groups) substantially increased; haemoglobin concentration decreased and pulmonary arterial wedge pressure remained constant. 6. Despite the combination of these factors favouring fluid flux from the extravascular to the intravascular compartment, extravascular lung water measured with the double indicator dilution technique decreased no faster in the HHS groups than in the two other groups (from over 26 to approximately 19 ml kg-1 in groups A, C and D and to 14.7 in group B (only furosemide)). 7. This was confirmed by postmortem gravimetric measurements of extravascular lung water; A, 11.0 +/- 5.7; B, 9.7 +/- 3.3; C, 10.5 +/- 3.1 and D, 10.6 +/- 1.8 g kg-1. 8. We speculate that mechanisms other than effective Starling gradients and enhanced diuresis might define a maximal rate of pulmonary oedema clearance.

Animals

Evolution of white matter lesions in neurofibromatosis type 1: MR findings.

To characterize further the evolution of white matter lesions in neurofibromatosis type 1, we reviewed 68 MR images in 43 patients (age, 1-31 years), including 25 follow-up studies (mean interval, 27 months). Lesion number, location, morphology, signal characteristics, and contrast enhancement were assessed. Lesion characteristics and changes thereof were correlated with the patients' ages. Thirty-four patients (79%) had white matter lesions. These lesions were hyperintense on T2-weighted images, were isointense on T1-weighted images, and showed no mass effect or contrast enhancement in 31 patients; in three patients, T1-prolongation was observed (one with significant mass effect). None of the lesions evolved into a glioma. The most common locations were the cerebellum (49%), brainstem (22%), and internal capsule (19%). Nineteen patients had white matter lesions and follow-up studies. Lesions decreased in size or number in seven patients (average age, 13 years), showed no change in three (average age, 12 years), increased in size or number in four (average age, 5 years), and showed a mixed pattern (increased/decreased size/number) in four (average age, 7 years). White matter lesions in neurofibromatosis type 1 frequently increase in size or number early in childhood; this did not indicate neoplasia in our study. The lesions tend to resolve with increasing age. Lesion progression in a child more than 10 years old warrants close follow-up to rule out a neoplasm.

Adolescent

Thoracic lymph drainage in the dog: evaluation of a new model.

A new model for selective sampling of thoracic lymph flow (TLF) and abdominal lymph flow (TDA) in the dog was assessed to ascertain whether there were extrathoracic contributions of lymph to the TLF. Inflating a right atrial balloon in 4 dogs and a left atrial balloon in 2 dogs indicated good separation between TLF and TDA. Data on total lymph protein and albumin clearance before and after oleic acid induced pulmonary oedema in an additional 5 dogs indicated that TLF and TDA drained two differing regions. Our data demonstrate that this lymph preparation provides a sample of thoracic lymph flow with no major extrathoracic lymph contamination. We also propose an alternative method to test for extrathoracic contributions to thoracic lymph, by the application of positive end-expiratory pressure, thereby replacing right atrial balloon inflation.

Albumins

Furosemide, when used in combination with positive end-expiratory pressure, facilitates the resorption of extravascular lung water in experimental hydrostatic pulmonary oedema.

The study aimed to establish whether furosemide given intravenously improved resorption of hydrostatic pulmonary oedema in 14 dogs mechanically ventilated with positive end-expiratory pressure (PEEP). Hydrostatic pulmonary oedema was created by simultaneous inflation of a left atrial balloon and rapid intravenous infusion of isotonic saline. The hydrostatic process was terminated by deflating the balloon and reducing the infusion rate. A PEEP of 10 cmH2O (1.0 kPa) was applied in all animals; in seven, furosemide was administered (diuretic group), 1 mg/kg intravenously as a bolus followed by an infusion of 0.5 mg/kg per hour, while the remaining seven dogs served as a control group. All dogs were studied for a period of 4 h. The extravascular lung water measured with the double indicator dilution technique was 28.3 +/- 3.8 (diuretic group) and 28.2 +/- 6.8 ml/kg (control group) during maximum oedema. It was reduced to 16.4 +/- 2.2 (diuretic group) vs 19.8 +/- 3.7 ml/kg (control group) after 4 h of resorption, P less than 0.05. Postmortem gravimetric values of extravascular lung water were 9.1 +/- 3.4 (diuretic group) vs 12.6 +/- 5.0 g/kg (control group). In the diuretic group the urinary output increased threefold, and haemoglobin and serum protein concentrations were higher than in the control group. There was a significantly greater decrease in cardiac output and central blood volume in the diuretic group. In conclusion, furosemide given intravenously improved lung fluid resorption in hydrostatic pulmonary oedema, probably by increasing the plasma colloid osmotic pressure.

Animals