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Biomedical subjects

L Berger

Publications and source records attributed to L Berger.

At least 55 records · Page 3Linked to original sources

Pathology of mucormycosis of cane toads in Australia.

The gross and microscopic pathology of a fungal septicaemia caused by the zygomycete. Mucor amphibiorum in 27 free-ranging cane toads, Bufo marinus, in Australia is described. Seven of the 27 toads had clinical signs of illness when discovered and five of these seven were moribund. Multiple granulomas were found in many organs, and in massive infections granulomas tended to coalesce. Liver, spleen, kidneys, urinary bladder, heart and lung were most commonly involved, but granulomas also occurred in subcutaneous lymph spaces, skin, gastro-intestinal tract, voluntary muscle, bone, cranial cavity and the oral cavity. Single lesions appeared grossly as a lemon coloured nodule < or = 5 mm in diameter. Histologically, the primary lesion was a granuloma composed of multinucleate giant cells, macrophages, occasional lymphocytes and eosinophils surrounding the distinctive sphaerules of M. amphibiorum. Fibroblasts occurred in greater numbers at the periphery and collagen formed a dense fibrous capsule around some nodules. A less common lesion resembled a microabscess and consisted of mononuclear cells, neutrophils and eosinophils surrounded by macrophages. Many of the centrally placed mixed inflammatory cells appeared necrotic. This reaction appeared to be more acute. Both types of lesions sometimes occurred concurrently, but the latter was less common. The pattern of lesions and natural history of M. amphibiorum suggested that ingestion of contaminated soil may have been the route of infection.

Animals↗

Mucormycosis in a free-ranging green tree frog from Australia.

Mucor amphibiorum is reported for the first time from a free-ranging native amphibian, a green tree frog (Litoria caerulea) from Queensland, Australia. The nasal cavity was largely replaced by granulomatous inflammatory tissue, and most internal organs had nodular granulomas. Typical mother and daughter sphaerules of M. amphibiorum occurred in these nodules which were due to granulomatous inflammation as well as areas of more active mixed inflammation with necrosis. Tissue homogenate from the spleen was inoculated into two cane toads (Bufo marinus), and one toad became infected with M. amphibiorum.

Animals↗

Activation of the erythropoietin gene in the majority of F-MuLV-induced erythroleukemias results in growth factor independence and enhanced tumorigenicity.

Retroviral insertional activation of Fli-1 is the first detectable genetic alteration associated with F-MuLV-induced primary erythroleukemias, while mutations within p53 are only observed in Epo-dependent (ED) cell lines derived from syngeneic mice serially transplanted with F-MuLV-induced primary erythroleukemias. In this study we have determined the mechanism of growth factor independence in several Epo-independent (EI) cell lines established from adult mice previously injected with ED-erythroleukemia cell lines or serially transplanted primary tumor cells. Here we have shown constitutive expression of the Epo gene in 12 of 15 (80%) EI-erythroleukemia cell lines. Among these 12 cell lines, eight were shown to possess clonal rearrangement of the Epo gene which could be detected in the tumors used to establish the majority of these EI-cell lines. Analysis of the pattern of proviral integration revealed that the activation of the Epo gene in these cell lines is independent of retroviral insertional mutagenesis, but apparently the result of genomic rearrangements. Furthermore, the acquisition of growth factor independence by these leukemic cells confers a selective growth advantage in vivo and is associated with enhanced tumorigenicity. Together these observations suggest that the activation of the Epo gene in the large majority of these F-MuLV-induced erythroleukemic cell lines establishes an autocrine loop resulting in the constitutive activation of the Epo receptor signal transduction pathway, thereby conferring a growth and survival advantage in vito and in vitro.

Animals↗

Liver regeneration in children after major hepatectomy for malignancy--evaluation using a computer-aided technique of volume measurement.

PURPOSE: The time course of hepatic volume regeneration and return of excretory and synthetic function was studied in eight children undergoing lobar or extended lobar liver resections for hepatoblastoma (n = 5), hepatoma (n = 1), and recurrent nephroblastoma (n = 2). Five patients received preoperative and all were administered postoperative chemotherapy. Whole-liver irradiation was administered to one patient. One additional patient who underwent an extended hepatic resection for benign disease and did not receive chemotherapy was included for comparison. METHODS: A previously validated technique of computer-aided volume measurement was used to measure liver volumes from serial CT scans obtained after hepatic surgery. Normal liver volume as a function of age was determined from the literature and the time course of regeneration was compared to normal liver growth. Postoperative serum albumin, total bilirubin, serum glutamic oxaloacetic transaminase, and alkaline phosphatase levels were recorded and correlated with volume regeneration. RESULTS: In six patients hepatic regeneration had progressed to normal volume by 90 days after resection (normal volume for age was achieved by 50 days in three patients). There was an initial rapid rate of regeneration (> 10 cc/day) which declined to a normal rate of less than 0.5 cc/day at 90 days after surgery. Two children with failure to thrive displayed the same pattern of rapid regeneration, attaining a volume appropriate for weight but less than that expected for age. The shape of the liver volume regeneration curve was similar in one additional patient undergoing an extended left lobectomy for benign disease. A brief rise in bilirubin occurred during the first week and a transient fall in serum albumin was followed by resumption of normal synthetic capacity within 6 weeks in all but two patients. CONCLUSIONS: Liver regeneration in children is a rapid process occurring despite the administration of cytotoxic agents and hepatic irradiation.

Child↗

Randomized controlled trial of a drug regimen that includes ciprofloxacin for the treatment of pulmonary tuberculosis.

The fluoroquinolones are promising new antituberculous agents. A randomized controlled trial of 200 adult patients with sputum smear-positive pulmonary tuberculosis was conducted in Tanzania. Patients received either a trial regimen (HRC) consisting of isoniazid (300 mg), rifampin (600 mg), and ciprofloxacin (750 mg) or a control regimen (HRZE) consisting of isoniazid (300 mg), rifampin (600 mg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg). The 168 evaluable patients all had negative smears and cultures by month 6, but the time to conversion to negativity was longer for the HRC group than for the HRZE group because of the poor response of patients infected with human immunodeficiency virus (HIV) to the HRC regimen. Relapse was more frequent in the HRC group. The sterilizing activity of ciprofloxacin does not appear to be equal to that of the combination of pyrazinamide and ethambutol, but the difference in outcome was significant only among HIV-infected patients.

AIDS-Related Opportunistic Infections↗

The ultrasound diagnosis and clinical significance of varicocele.

A study was carried out to determine the relationship between clinically diagnosed and ultrasound-diagnosed varicoceles in 151 men with normal and abnormal semen analysis. In only 60 cases (40%) was the clinical diagnosis confirmed by ultrasound. Of the men with ultrasound-diagnosed varicocele, 14% were found to have a normal semen analysis compared to 31% of men without a varicocele, and this difference was statistically significant (p < 0.05). Bilateral varicoceles were associated with an even greater chance of having an abnormal semen analysis (p < 0.01), and with a significantly (p 0.05) decreased chance of spontaneous pregnancy. These men and also men with unilateral varicocele, whose partners have a relative cause of female subfertility, may benefit from earlier intervention for the treatment of their subfertility.

Adult↗

Implication of mRNA binding proteins in the regulation of cyclo-oxygenase in human amnion at term.

The onset of labour is associated with an increase in prostaglandin synthesis in amnion which appears to be mediated at least in part by an increase in cyclo-oxygenase (COX) expression. We have tested the hypothesis that COX expression is controlled in amnion by the binding of a protein to the COX mRNA which may inhibits its translation, as has been seen in vascular smooth muscle cells. Using differential RNA extraction protocols which extract either total mRNA or only mRNA which is not protein bound, we have found that, in amnion, the increase in COX-2 expression seen after the onset of labour is entirely in the protein bound fraction. Unlike in vascular smooth muscle, increased expression of COX-2 in amnion cells is therefore associated with increased rather than decreased protein binding to the mRNA. This protein may be involved in translation initiation or elongation or in mRNA stability. There does not appear to be a protein bound COX-1 mRNA fraction.

Amnion↗

The relative abundance of type 1 to type 2 cyclo-oxygenase mRNA in human amnion at term.

The onset of labor in humans is associated with an increase in prostaglandin production. One of the key steps is the conversion of arachidonic acid to prostaglandin E2 by cyclo-oxygenase (Cox). Cox has been found to exist as two distinct genes, Cox-1 and Cox-2. We have used RT-PCR to study the relative abundance of mRNA from each Cox gene in amnion at term. Quantitation of PCR efficiency indicated an approximate 100 fold excess of Cox-2 messenger RNA over that for Cox-1. These data point to the importance of Cox-2 in the increased prostaglandin synthesis associated with labor. Further studies should therefore focus on the control mechanisms for Cox-2.

Amnion↗

Physicians and smoking cessation. A survey of office procedures and practices in the Community Intervention Trial for Smoking Cessation.

OBJECTIVE: To obtain a baseline measure of tobacco control activities carried out by physicians and of tobacco control policies and practices in physician offices. DESIGN: All primary care physicians in 11 communities were asked through a mail survey about their tobacco control practices. Thirty offices in each community were randomly selected and interviewed by telephone to determine office policies and practices. SETTING: Both surveys assessed primary care settings in the 11 intervention communities. RESULTS: The physicians' survey (response rate, 48%) indicated that physicians report intervention with smokers more than 70% of the time, but the interventions rarely include key behavioral elements necessary for smoking modification. Physicians who received formal training in smoking cessation reported that they believed themselves to be more prepared and that they spent more time counseling patients than physicians who were not trained. The office survey (response rate, 83.2%) indicated that smoke-free policies are in place in most clinics and offices and that many offices provide printed materials on smoking cessation. However, few offices had staff to coordinate smoking cessation activities. These surveys will be repeated following the intervention phase of the Community Intervention Trial for Smoking Cessation to assess changes in counseling practices and office policies. CONCLUSION: There is a positive relationship between attending training and intervening with more cessation activities. Physicians perceive themselves as prepared to help smokers, but few are providing more than advice to stop smoking.

Counseling↗

The expression of phospholipase A2 and lipocortins (annexins) I, II and V in human fetal membranes and placenta in association with labour.

We have studied the expression of the cellular, type two phospholipase A2 and lipocortins (annexins) I, II and V in human amnion, chorion-decidua and placenta using northern analysis. We found no difference in the expression of phospholipase A2 or lipocortin V in tissues obtained before or after labour. Lipocortin I expression was found to decrease in amnion and placenta but increase in chorion decidua with the onset of labour, while expression of lipocortin II increased only in amnion. These results support the hypothesis that the increased phospholipase A2 activity in the fetal membranes and placenta which is associated with labour is not due to increased phospholipase A2 gene expression, but that post translational control of phospholipase A2 activity may be mediated through changes in lipocortin I expression.

Annexin A1↗

cdc2 phosphorylation of threonine 124 activates the origin-unwinding functions of simian virus 40 T antigen.

Phosphorylation of simian virus 40 (SV40) T antigen on threonine 124 activates viral DNA replication in vivo and in vitro. We have manipulated the modification of T-antigen residue 124 both genetically and biochemically and have investigated individual replication functions of T antigen under conditions suitable for in vitro DNA replication. We find that the hexamer assembly, helicase, DNA polymerase alpha-binding, and transcriptional-autoregulation functions are independent of phosphorylation of threonine 124. In contrast, neither T antigen with an alanine mutation of threonine 124 made in human cells nor unphosphorylated T antigen made in Escherichia coli binds the SV40 replication origin as stably as phosphorylated wild-type T antigen does. Furthermore, modification of threonine 124 is essential for complete unwinding of the SV40 replication origin. We conclude that phosphorylation of threonine 124 enhances specific interactions of T antigen with SV40 origin DNA. Our findings do not exclude the possibility that phosphorylation of threonine 124 may affect additional undefined steps in DNA replication. We also show that DNase footprinting and KMnO4 modification assays are not as stringent as immunoprecipitation and origin-dependent strand displacement assays for detecting defects in the origin-binding and -unwinding functions of T antigen. Differences in the assays may explain discrepancies in previous reports on the role of T-antigen phosphorylation in DNA binding.

Amino Acid Sequence↗