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Biomedical subjects

J Lorenzo

Publications and source records attributed to J Lorenzo.

At least 19 recordsLinked to original sources
PubMed2006

Congenic mice provide in vivo evidence for a genetic locus that modulates serum insulin-like growth factor-I and bone acquisition.

We identified quantitative trait loci (QTL) that determined the genetic variance in serum IGF-I through genome-wide scanning of mice derived from C57BL/6J(B6) x C3H/HeJ(C3H) intercrosses. One QTL (Igf1s2), on mouse chromosome 10 (Chr10), produces a 15% increase in serum IGF-I in B6C3 F2 mice carrying c3 alleles at that position. We constructed a congenic mouse, B6.C3H-10 (10T), by backcrossing c3 alleles from this 57-Mb region into B6 for 10 generations. 10T mice have higher serum and skeletal IGF-I, greater trabecular bone volume fraction, more trabeculae, and a higher number of osteoclasts at 16 wk, compared with B6 (P < 0.05). Nested congenic sublines generated from further backcrossing of 10T allowed for recombination and produced four smaller sublines with significantly increased serum IGF-I at 16 wk (i.e. 10-4, 10-7, 10-10, and 10-13), compared with B6 (P < 0.0003), and three smaller sublines that showed no differences in IGF-I vs. age- and gender-matched B6 mice. Like 10T, the 10-4 nested sublines at 16 wk had higher femoral mineral (P < 0.0001) and greater trabecular connectivity density with significantly more trabeculae than B6 (P < 0.01). Thus, by comprehensive phenotyping, we were able to narrow the QTL to an 18.3-Mb region containing approximately 148 genes, including Igf1 and Elk-3(ETS domain protein). Allelic differences in the Igf1s2 QTL produce a phenotype characterized by increased serum IGF-I and greater peak bone density. Congenic mice establish proof of concept of shared genetic determinants for both circulating IGF-I and bone acquisition.

Animals↗
PubMed2005

Afferent pathways to the region of the vestibular nuclei that participates in cardiovascular and respiratory control.

Prior experiments have shown that a region of the medial and inferior vestibular nuclei contributes to cardiovascular and respiratory regulation. In addition to labyrinthine inputs, the majority of neurons in this region of the vestibular nuclei receive signals from the skin, muscle, and viscera, although the pathways conveying these nonlabyrinthine inputs to the vestibular nucleus neurons are unknown. To gain further insight into the afferent pathways to this functionally distinct subdivision of the vestibular complex, we combined monosynaptic mapping with viral transneuronal tracing in the ferret. First order afferent projections were defined by retrograde transport of the beta-subunit of cholera toxin (CTbeta), and the extended polysynaptic circuitry was defined in the same animals by injection of a recombinant of pseudorabies virus Bartha (PRV) into the contralateral vestibular nuclei. Neurons containing CTbeta or infected by retrograde transneuronal transport and replication of PRV were distributed throughout the spinal cord, but were 10 times more prevalent in the cervical cord than the lumbar cord. The labeled spinal neurons were most commonly observed in Rexed's laminae IV-VI and the dorsal portions of laminae VII-VIII. Both the CTbeta and PRV injections also resulted in labeling of neurons in all four vestibular nuclei, the prepositus hypoglossi, the reticular formation, the inferior olivary nucleus, the medullary raphe nuclei, the spinal and principal trigeminal nuclei, the facial nucleus, and the lateral reticular nucleus. Following survival times >/=3 days, PRV-infected neurons were additionally present in nucleus solitarius and the gracile and cuneate nuclei. These data show that an anatomical substrate is present for somatosensory and visceral inputs to influence the activity of cells in the autonomic region of the vestibular nuclei and suggest that these signals are primarily transmitted through brainstem relay neurons.

Afferent Pathways↗
PubMed2004

Jejunal leiomyosarcoma, a rare cause of obscure gastrointestinal bleeding diagnosed by wireless capsule endoscopy.

Obscure gastrointestinal bleeding is a relatively frequent disorder and may account for as many as 5% of all cases of gastrointestinal bleeding. The etiology of these hemorrhages may be attributed to lesions in the small intestine, which may not show up in radiologic studies, located in areas inaccessible to conventional endoscopy. The case of a 50-year-old patient admitted to the hospital on two occasions for gastrointestinal bleeding requiring blood transfusions is reported. On the first occasion, the bleeding was thought to be caused by a duodenal ulcer because no other lesions prone to bleeding were found. At the next admission for recurrent bleeding, the ulcer was found to have healed and thus was ruled out as the cause. Wireless capsule endoscopy detected an ulcerated tumor invading the submucosa of the jejunum. The pathologic diagnosis was low-grade leiomyosarcoma. Wireless capsule endoscopy has proved to be far superior to other radiologic and endoscopic techniques for the diagnosis of obscure gastrointestinal bleeding and pathologies of the small intestine in general.

Blood Transfusion↗
PubMed2000

Human pancreatic ribonuclease 1: expression and distribution in pancreatic adenocarcinoma.

BACKGROUND: Human pancreatic ribonuclease (RNase 1) is a pancreatic enzyme that is present at high levels in the serum of most patients with pancreatic adenocarcinoma. For this reason, the authors studied its patterns of expression at the single-cell level in pancreatic adenocarcinoma tissues by immunohistochemical analysis and in situ hybridization (ISH). METHODS: Immunohistochemical analysis with polyclonal antibodies against RNase 1 and by ISH with digoxigenin-labeled RNase 1 probe were used to detect RNase 1 in the neoplastic cells of ductal type pancreatic adenocarcinomas. RESULTS: Fifteen of 18 carcinoma samples were positive for RNase 1, demonstrating that the expression of ribonuclease that the authors observed previously in human pancreatic adenocarcinoma cell lines was not an artifact of cell culture. The authors also found RNase 1 in some of the metaplastic ducts and atrophic islets in 4 of 6 chronic pancreatitis samples, and they observed RNase 1 immunostaining in hyperplastic ducts adjacent to one of the well-differentiated adenocarcinomas. CONCLUSIONS: The expression levels of RNase 1 by tumor cells from pancreatic adenocarcinomas are consistent with the high RNase 1 levels found in the serum of most patients with pancreatic adenocarcinoma. This expression of RNase 1, which is an acinar protein, demonstrates that the patterns of gene expression in pancreatic adenocarcinoma are distinct from those of normal pancreatic duct cells. Conversely, RNase 1 expression levels in altered ductal cells from some chronic pancreatitis tissues and hyperplastic ducts from carcinoma tissues suggest that abnormal expression levels may be an early event in pancreatic tumorigenesis.

Adenocarcinoma↗
PubMed1999

Cytochrome C is released from mitochondria into the cytosol after cerebral anoxia or ischemia.

Mitochondrial dysfunction may underlie both acute and delayed neuronal cell death resulting from cerebral ischemia. Specifically, postischemic release of mitochondrial constituents such as the pro-apoptotic respiratory chain component cytochrome c could contribute acutely to further mitochondrial dysfunction and to promote delayed neuronal death. Experiments reported here tested the hypothesis that ischemia or severe hypoxia results in release of cytochrome c from mitochondria. Cytochrome c was measured spectrophotometrically from either the cytosolic fraction of cortical brain homogenates after global ischemia plus reperfusion, or from brain slices subjected to severe hypoxia plus reoxygenation. Cytochrome c content in cytosol derived from cerebral cortex was increased after ischemia and reperfusion. In intact hippocampal slices, there was a loss of reducible cytochrome c after hypoxia/ reoxygenation, which is consistent with a decrease of this redox carrier in the mitochondrial pool. These results suggest that cytochrome c is lost to the cytosol after cerebral ischemia in a manner that may contribute to postischemic mitochondrial dysfunction and to delayed neuronal death.

Animals↗
PubMed1999

Characterization of immortalized osteoclast precursors developed from mice transgenic for both bcl-X(L) and simian virus 40 large T antigen.

We recently developed an immortalized osteoclast (OCL) precursor cell line that forms large numbers of OCLs. This cell line was derived from mice doubly transgenic for bcl-X(L) and large T antigen that was targeted to cells in the OCL lineage (bcl-X(L)/Tag cells). We have now characterized these cells in terms of their surface and enzymatic phenotype, responsiveness to osteotropic factors, and differentiation potential. The bcl-X(L)/Tag cells expressed interleukin-1 receptors 1 and 2, gelatinase B (MMP9), as well as Mac-1, CD16/CD32 (Fcgamma receptors), CD45.2 (common leukocyte marker), CD86 (costimulatory molecule expressed on B cells, follicular dendritic cells, and thymic epithelium), major histocompatibility complex I, and nonspecific esterase when cocultured with MC3T3E1 cells. However, they did not express the antigens for F4/80 (mature macrophage/dendritic cell marker) by immunostaining. Treatment of bcl-X(L)/Tag cells, cocultured with MC3T3E 1 cells, with the combination of 1,25-dihydroxyvitamin D3 and dexamethasone induced high levels of OCL formation. The bcl-X(L)/Tag cells formed large numbers of OCLs when cultured with RANK ligand and macrophage colony-stimulating factor in the absence of feeder cells. In the absence of RANK ligand and a feeder cell layer, 100% of the cells differentiated into F4/80-positive cells. However, neither PTH nor PTH-related protein enhanced OCL formation by bcl-X(L)/Tag cells even when they were cocultured with primary osteoblasts, suggesting that they differ from primary mouse bone marrow cells in their responsiveness to PTH/PTH-related protein. Thus, bcl-X(L)/Tag cells have many of the properties of primary mouse OCL precursors and should be very useful for studies of OCL differentiation and divergence of OCL precursors from the macrophage lineage.

Animals↗
PubMed1998

Comparative study of incomplete posterior vitreous detachment as a risk factor for proliferative vitreoretinopathy.

BACKGROUND: Abnormal vitreoretinal relationships have recently been implicated in many vitreoretinal disorders. Sites of abnormal vitreoretinal adherences are likely to exist in eyes predisposed to rhegmatogenous retinal detachment (RD), causing either retinal tears or incomplete posterior vitreous detachment (PVD). The present study was designed in two parts to identify the risk for preoperative and postoperative proliferative vitreoretinopathy (PVR) due to incomplete PVD. METHODS: We prospectively evaluated the vitreoretinal relationships using high-resolution kinetic echography in 102 consecutive eyes of 100 patients with rhegmatogenous RD. In the first part, a case-control study was conducted to compare the vitreous status in patients with preoperative PVR (cases) with that in patients with non-PVR-complicated RD (controls). During the second part, patients with noncomplicated RD (65 eyes) who were operated on by a simple retinal attachment procedure were followed up for a mean period of 6.6 months to compare the recurrence of RD due to postoperative PVR according to their vitreous status. RESULTS: Patients with PVR on study entry had a higher prevalence of partial PVD (28 of 32 eyes, 87%) than did controls (25 of 70 eyes, 35%). The statistical significance of this difference was independent of all other variables studied. After a mean follow-up period of 6.6 months, the incidence of recurrence of RD associated with postoperative PVR was 33% in the eyes with incomplete PVD, compared with 4.9% in the eyes without incomplete PVD. CONCLUSIONS: Our results support the notion that the occurrence of incomplete PVD in RD is a significant risk factor for preoperative and postoperative PVR.

Case-Control Studies↗
PubMed1998

Basic fibroblast growth factor induces osteoclast formation in murine bone marrow cultures.

We determined the effect of basic fibroblast growth factor (bFGF) on osteoclast-like cell (OCL) formation in bone marrow cultures using C57BL/6 mice. Cells were cultured for 7 days with or without bFGF at various concentrations or 10(-8) mol/L 1,25(OH)2 vitamin D3 [1,25(OH)2D3]. bFGF dose-dependently increased OCL formation per well (10(-10) mol/ L = 40 +/- 2; 10(-9) mol/L = 146 +/- 13; 10(-8) mol/L = 156 +/- 12) compared with control (< 7 per well). The effects of bFGF at 10(-9) and 10(-8) mol/L were similar to that of 10(-8) mol/L 1,25(OH)2D3 (154 +/- 11 per well). OCLs formed by bFGF were multinuclear, tartrate-resistant acid phosphatase (TRAP)-positive, expressed calcitonin receptors, and formed characteristic resorption pits. We also determined whether bFGF enhanced OCL formation during the early proliferative or late differentiating phases of the cultures. When bFGF (10(-8) mol/L) was added only on days 1-2 or days 3-4 of 6 day cultures, there was a significant increase in OCL formation. In contrast, when bFGF was added only on days 5-6 few OCLs formed. Addition of bFGF at days 1-6 or days 1-2 and days 5-6 caused similar increases in OCL formation, which were greater than OCL formation induced by treatment for days 1-2 or days 1-4. We examined the production of prostaglandin E2 (PGE2) in the cultures because bFGF is a potent stimulator of PGE2 synthesis in bone, and PGE2 stimulates OCL formation. bFGF treatment significantly increased PGE2 levels in 7 day cultures (controls = 1.4 +/- 0.1 nmol/L, 10(-8) mol/L bFGF = 132.5 +/- 0.7 nmol/L). In addition, treatment of marrow cultures with the prostaglandin synthesis inhibitors, indomethacin or NS-398 (both at 10(-6) mol/L), completely blocked bFGF-induced OCL formation. We conclude that bFGF stimulates OCL formation in C57BL/6 bone marrow cultures by mechanisms that require prostaglandin synthesis. This pathway is likely to be one mechanism by which bFGF stimulates resorption.

Actins↗
PubMed1998

[1,25(OH)2 vitamin D3 induces IL-1 alpha mRNA expression from osteoblastic-like and bone marrow co-culture cells].

OBJECTIVE: The purpose of this research is to investigate the relationship between 1,25(OH)2 Vitamin D3[1,25(OH)2D3] and Interleukin-1 (IL-1) in regulating osteoclast formation. The result may enrich our knowledge about biological mechanisms of periodontal tissue remodeling during orthodontic tooth movement. METHODS: We found IL-1 alpha mRNA expression in bone marrow and osteoblastic cell co-cultures by semi-quantitative RT-PCR. RESULTS: 1,25(OH)2D3 increased IL-1 alpha mRNA expression from this co-culture cells in a dose dependent manner, and the expression reached its peak in day 2 and decreased thereafter. CONCLUSION: These results demonstrate that IL-1 alpha involves in osteoclast formation induced by 1,25(OH)2D3. And we propose IL-1 alpha may stimulate the proliferation of osteoclast progenitor during the first 4 days of total 6 days culture period.

Animals↗
PubMed1996

Regulation of NFIL-6 and IL-6 expression by basic fibroblast growth factor in osteoblasts.

We determined whether basic fibroblast growth factor (bFGF) regulated the expression of IL-6 and NFIL-6 in osteoblasts. In mouse osteoblastic MC3T3-E1 cells, bFGF (10(-8) M) increased NFIL-6 mRNA 2-fold at 30 minutes and 3-fold at 2 h. IL-6 mRNA was increased by bFGF 10(-8) M after 1 h. IL-6 protein was detectable in control cultures but was significantly increased by bFGF (10(-8) M) at 4 h. Immunofluorescence analysis of MC3T3-E1 cells showed primarily cytoplasmic and perinuclear NFIL-6 staining in control cultures while bFGF-treated cells showed increased NFIL-6 staining at 2 and 4 h. Western blotting revealed that bFGF increased NFIL-6 protein at 2 h. In calvarial mouse osteoblasts, bFGF 10(-8) M induced IL-6 mRNA as early as 1 h and significantly increased IL-6 protein levels as early as 2 h. In conclusion, bFGF stimulates IL-6 and NFIL-6 mRNA in osteoblasts. The increase in NFIL-6 mRNA was associated with increased NFIL-6 protein. The increase in IL-6 mRNA was also associated with increased IL-6 protein. We propose that activations of NFIL-6 and IL-6 may be important mediators of the effects of bFGF on bone cells.

Animals↗
PubMed1996

Oncostatin-M: a new bone active cytokine that activates osteoblasts and inhibits bone resorption.

Osteoblasts and their precursors respond to specific cytokines, growth factors, and hormones. One facet of this response includes the secretion of additional cytokines, some of which are part of the circuitry involved in the regulation of osteoblast and osteoclast function. Therefore, understanding which cytokines are able to activate osteoblastic cells and the consequences of that activation are central to understanding normal and pathologic bone remodeling. Oncostatin M (OSM) is a glycoprotein belonging to a new subfamily of cytokines related by sequence and structural homology and the use of the signal transducing receptor component gp130. Osteoblastic cells secrete and respond to leukemia-inhibiting factor (LIF) both in vitro and in vivo, suggesting that LIF is an autocrine regulatory factor. OSM is closely related to LIF, and therefore we hypothesized that OSM should regulate the function of cells in the osteoblastic lineage. Primary neonatal murine or fetal rat calvarial osteoblastic cultures were treated with OSM or LIF and a series of biochemical and biological parameters were determined. In these cultures, OSM induced proliferation, collagen synthesis, and interleukin-6 secretion, whereas it inhibited alkaline phosphatase activity. Bone resorption was also inhibited by OSM. These data represent the first report of OSM's effects on bone cell function and indicate that, like some other members of the LIF/interleukin-6 subfamily, OSM has potent bone regulatory activity.

Alkaline Phosphatase↗
PubMed1994

Expression and regulation of basic fibroblast growth factor mRNA levels in mouse osteoblastic MC3T3-E1 cells.

Basic fibroblast growth factor (bFGF) is a potent mitogen for bone cells and is a constituent of the bone matrix. We have found that osteoblastic MC3T3-E1 cells expressed bFGF mRNA transcript of 4.5 kilobases (kb). We examined factors that regulate the expression of bFGF mRNA and protein in MC3T3-E1 cells. Treatment of MC3T3-E1 cells with bFGF (10 nM) for 4-48 h induced another 7-kb bFGF transcript at 4 h. Treatment of MC3T3-E1 cells with TGF beta (10 ng/ml) also induced the 7-kb transcript of bFGF mRNA. In contrast, heparin, parathyroid hormone, and interleukin-1 had no effect on bFGF mRNA. Western blot analyses revealed that MC3T3-E1 cells produced a 24-kDa bFGF protein, which was increased by TGF beta. Immunofluorescence showed that bFGF protein was localized to the cytoplasm in serum-deprived MC3T3-E1 cells. Treatment of these cultures with medium containing fetal calf serum or TGF beta caused increased cytoplasmic staining for bFGF and marked shape change. Furthermore, in the cells treated with TGF beta there was both nuclear and cytoplasmic staining for the protein. These data demonstrate that bFGF mRNA and protein are expressed in osteoblastic cells and are regulated by treatment with TGF beta and bFGF. Production of bFGF may be important as an autocrine and paracrine mediator of bone cell replication, differentiation, and function.

Animals↗
PubMed1994

Ocular blood flow velocity reduction after buckling surgery.

BACKGROUND: It has been reported that scleral buckling reduces the blood flow velocity in retinal vessels. Blood flow changes may also appear in other ocular and extraocular vessels. This study describes the blood flow velocity changes in the ophthalmic artery (OA) after performing this procedure. METHODS: The study was carried out in 12 patients (12 eyes) with rhegmatogenous retinal detachment. Color Doppler imaging was used to measure the peak and average blood flow velocity in the OA. Measurements were taken 1 day before and 2 days after scleral buckling surgery was performed. Intraocular pressure (IOP) was measured prior to each ultrasound study. RESULTS: We found that statistically significant reductions in the peak flow velocity (33%) and average flow velocity (31%) occur in the OA after scleral buckling. All patients showed an increase in IOP after surgery. CONCLUSION: Buckling surgery reduces the blood flow velocity in the OA. Since the OA is the origin of the arterial branches that supply blood to the eye, our results suggest that scleral buckling may decrease not only retinal but also choroidal blood perfusion. Some extraocular structures might also be affected.

Adult↗
PubMed1991

Choledochoduodenal fistulas.

In 2,012 ERCP studies reviewed in the period between 1976 and 1989, we observed 14 choledochoduodenal fistulas found in the upper portion of the papilla of Vater. Two fistulas occurred spontaneously due to necrosis of the duodenal wall caused by stones located in the distal common bile duct above the sphincter of the papilla. In these two cases the stones were removed endoscopically. The twelve remaining cases were iatrogenic, caused during surgical papillotomy which resulted in a false tract. All patients showed raised AP and gamma GT. Eight had acute cholangitis, 7 were jaundiced, there was one case each of acute pancreatitis and chronic recurrent pancreatitis. Nine patients had stones located in the distal common bile duct. In eight cases it was possible to cannulate the papillary opening and do a papillotomy thereby connecting the fistulous orifice with the opening of the papilla. The other patient was treated surgically. Two patients had papillary stenosis. One was successfully treated with papillotomy through the papillary opening. In the other, the fistulous orifice was joined with the papillary opening using a diathermy scalpel. This patient suffered a posterior duodenal wall perforation. One patient with acute pancreatitis and common bile duct stones distal to the fistula improved with papillotomy and stone removal. The patient with chronic recurrent pancreatitis without lithiasis refused any form of treatment.

Ampulla of Vater↗
PubMed1988

Osteofibrous dysplasia. A report of two cases.

Two cases of osteofibrous dysplasia of long bones are reported, one in a neonate with ipsilateral tibial and fibular involvement and the other in a 6-year-old patient with bilateral tibial lesions. The radiological features of the younger patient were remarkably different from those of the older one. These two different and age-related radiological patterns have also been found in most cases previously reported. All the lesions tended to regress spontaneously.

Child↗
PubMed1987

Maternal factors modulating nutrient transfer to fetus.

Current knowledge of the modulation of maternal-fetal transfer of metabolites is reviewed and new data on the actual placental transport of D-glucose, L-alanine and glycerol in the rat are presented. Twenty-one day pregnant rats were infused with the 14C-labelled substrates throughout the left uterine artery. Radioactivity appearing in fetuses was corrected by the specific dilution of the tracer at maternal arterial plasma and the uterine artery blood flow to estimate placental transfer. This parameter appeared to be 127 mumol X kg-1 fetal b.w. X min-1 for D-glucose, 23 for L-alanine, and 1 for glycerol--values which are much higher than those described for larger species. There is a parallelism between the magnitude of transfer to fetus and arterial concentration in mother for each studied metabolite and actually variations in their plasmatic levels affect this transport process. This is clearly seen in the case of glucose where placental transfer is reduced during fasting hypoglycemia and greatly increased in diabetes. Placental transfer of L-alanine and blood flow to the placenta were reduced in both 48-hour starved and streptozotocin-induced diabetic late pregnant rats. Results show the main role of maternal nutrient concentration as a modulator of their transfer to fetus, the deleterious effect of reductions of uterine blood flow on placental transport of amino acids as well as the small placental transfer of glycerol as compared to either glucose or alanine.

Alanine↗