Monitoring furosemide in racehorses participating in an EIPH program

We report a rare case of temporary and severe hypercalcemia: the patient, a 69-year-old woman, was admitted to Osaka City University Hospital on July 25, 1992, for severe hypercalcemia. The laboratory data on admission revealed severe hypercalcemia (14.9 mg/dl) and renal dysfunction with increased serum creatinine level (2.9 mg/dl). The urinary excretion of pyridinoline and deoxypyridinoline was increased, and serum levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D were decreased. The data suggested that increased bone resorption was a probable main factor in the development of the hypercalcemia. The development of hypercalcemia seemed to be of acute onset because of (1) her severe symptoms caused by hypercalcemia and (2) impaired renal function which was improved after normalization of serum calcium level. Combination therapy with saline infusion and furosemide was administered, and there was a gradual decrease and subsequent normalization of serum calcium level along with serum creatinine. Even 8 months after discontinuation of the therapy for hypercalcemia, the serum calcium level remained within the normal range. The measured values of serum factors which are suspected to have a hypercalcemic effect, such as PTH, parathyroid hormone-related peptide and the cytokines (interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha) were all within the normal range. In summary, the hypercalcemia in this patient was regarded to be a type of disequilibrium hypercalcemia due to a combination of increased bone resorption and decreased renal capacity to excrete calcium. Furthermore, since it was temporary and did not recur even in the absence of treatment, the hypercalcemia was concluded to have developed due to an imbalance in calcium regulation rather than as a result of organic disease.     

Reciprocal regulation of neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implications for human breast cancer

Neu (c-erbB2) is a proto-oncogene product that encodes an epidermal growth factor-like receptor tyrosine kinase. Amplification of wild-type c-Neu and mutational activation of Neu (Neu T) have been implicated in oncogenic transformation of cultured fibroblasts and mammary tumorigenesis in vivo. Here, we examine the relationship between Neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Recent studies have suggested that caveolins may function as negative regulators of signal transduction. Our current results show that mutational activation of c-Neu down-regulates caveolin-1 protein expression, but not caveolin-2, in cultured NIH 3T3 and Rat 1 cells. Conversely, recombinant overexpression of caveolin-1 blocks Neu-mediated signal transduction in vivo. These results suggest a reciprocal relationship between c-Neu tyrosine kinase activity and caveolin-1 protein expression. We next analyzed a variety of caveolin-1 deletion mutants to map this caveolin-1-dependent inhibitory activity to a given region of the caveolin-1 molecule. Results from this mutational analysis show that this functional in vivo inhibitory activity is contained within caveolin-1 residues 32-95. In accordance with these in vivo studies, a 20-amino acid peptide derived from this region (the caveolin-1 scaffolding domain) was sufficient to inhibit Neu autophosphorylation in an in vitro kinase assay. To further confirm or refute the relevance of our findings in vivo, we next examined the expression levels of caveolin-1 in mammary tumors derived from c-Neu transgenic mice. Our results indicate that dramatic reduction of caveolin-1 expression occurs in mammary tumors derived from c-Neu-expressing transgenic mice and other transgenic mice expressing downstream effectors of Neu-mediated signal transduction, such as Src and Ras. Taken together, our data suggest that a novel form of reciprocal negative regulation exists between c-Neu and caveolin-1.     

Functional dissociation between local and systemic immune response during anti-melanoma peptide vaccination

Peptide vaccination against tumor Ags can induce powerful systemic CTL responses. However, in the majority of patients, no tumor regression is noted. To study this discrepancy, we analyzed CTL reactivity in a melanoma patient (F001) vaccinated with g209-2M peptide, a single residue variant of gp100(209-217). G209/g209-2M-reactive CTL were identified in post- but not prevaccination PBL. Limiting dilution analysis identified one predominant CTL clone (C1-35), with TCR Vbeta6s2, recognizing g209/HLA-A*0201-expressing targets. Additionally, two autologous melanoma lines (F001TU-3 and -4) and 20 separate tumor-infiltrating lymphocyte cultures were generated from a fine needle aspirate of a metastatic lesion progressing after initial response to vaccination. Both F001TU did not express gp100 and were not recognized by C1-35. Loss of gp100 by F001TU correlated with a marked reduction of gp100 expression in the same metastatic lesion compared with prevaccination. Thus, ineffectiveness of C1-35 and tumor progression could be best explained by loss of target Ag expression. Interestingly, 12 of 20 tumor-infiltrating lymphocyte cultures recognized F001TU, but none demonstrated g209/g209-2M reactivity, suggesting a functional dissociation between systemic and local immune response. This study suggests that vaccination effects must be analyzed in the target tissue, rather than in the systemic circulation alone.     

Acute liver failure

PURPOSE: This article reviews the literature on radiographic imaging techniques and image interpretation for dental implant treatment. MATERIALS AND METHODS: MEDLINE was used to identify published peer-reviewed literature for this report. RESULTS: Radiographic images are indispensable in the evaluation of osseous structures when planning treatment for dental implants. Potential bone sites for implant placement can be assessed clinically by means of palpation or probing through the mucosa; however, diagnostic imaging provides the best means for indirectly measuring bone dimensions. After healing of the implant site, the application of radiology is useful to verify the amount of bone adjacent to the implant and that the transmucosal abutments fit the implant. Upon completion of the implant prosthesis, radiology may be used to monitor initial and long-term success of implant treatment. CONCLUSION: Recommendations for the application of radiology over the course of treatment are made for various implant cases ranging from the overdenture to the single-tooth implant.     

Macrophage migration inhibitory factor production by Leydig cells: evidence for a role in the regulation of testicular function

Macrophage migration inhibitory factor (MIF), described originally as a product of activated T lymphocytes, recently has been found to be released by monocytes/macrophages and the anterior pituitary gland. Immunohistochemical studies of the adult rat testis using an affinity-purified polyclonal antimurine MIF antibody demonstrated strong staining for MIF in Leydig cells and their putative precursors. Peritubular myoid cells and the seminiferous epithelium were negative for MIF staining; however, a weak reaction around the heads of elongated spermatids also was observed. The expression of MIF messenger RNA and protein in whole rat testis was demonstrated by Northern blot and Western blot analyses, respectively. Both MIF messenger RNA and protein immunoreactivity in Leydig cells was observed in testes obtained from long term hypophysectomized rats. Significant concentrations of intracellular MIF were detected in lysates of the TM3 Leydig cell line (7.23 +/- 2.6 pg/microgram protein), and testicular interstitial fluid contained 14.7 +/- 1.6 ng/ml MIF protein, as measured by MIF-specific enzyme-linked immunosorbent assay. To gain insight into the possible biological role of MIF in the testis, cultures of adult rat seminiferous tubules and purified Leydig cells were incubated together with recombinant murine MIF (rMIF). Neither rMIF (50 ng/ml) nor a neutralizing anti-MIF antiserum was found to affect basal or LH-stimulated Leydig cell steroidogenesis in vitro. However, a dose-dependent decrease in the secretion of inhibin by the seminiferous tubules was observed at rMIF concentrations ranging from 10-100 ng/ml. Taken together, these data indicate that Leydig cells produce MIF in vivo and suggest an important regulatory role for this newly discovered mediator of testicular function.     

Clinical presentation of HIV infection in patients aged 50 years or older

A case of metachronous malignancy in an elderly postmenopausal lady is presented. She had previously been successfully treated for squamous cell carcinoma of the cervix and now four years later, presented with a right lower lobe lung abscess. On evaluation she was found to have a small cell carcinoma of the lung involving the right intermediate and right lower lobe bronchus. She improved clinically and radiologically with parenteral antibiotics, combination chemotherapy and local external radiotherapy.     

Dietary intake of essential and long-chain polyunsaturated fatty acids in pregnancy

The dietary intake of EFA and long-chain PUFA (LCPUFA) by women with (n=14) and without (n=31) gestational diabetes mellitus (GDM) was determined by repeated 24-h recalls. Women with GDM consumed significantly more energy as fat compared with women who had uncomplicated pregnancies; absolute dietary fat did not differ. Dietary n−3 LCPUFA was substantially lower than the current recommendation for pregnancy, whereas intake of saturated FA (SFA) exceeded it. We conclude that replacing dietary sources of SFA with those of EFA and LCPUFA, especially n−3 LCPUFA, would benefit the dietary fat profiles of all pregnant women.