Biomedical subjects

D Blumberg

Publications and source records attributed to D Blumberg.

At least 19 recordsLinked to original sources

PubMed2004

Raised serum prolactin in rheumatoid arthritis: genuine or laboratory artefact?

OBJECTIVES: Serum prolactin concentrations have been reported as higher, similar or lower in patients with rheumatoid arthritis (RA) compared with control subjects. We investigated whether low biological activity macroprolactin (a prolactin antibody complex), which is detected variably in different prolactin immunoassays, could account for the discrepant total prolactin results reported in RA. METHODS: We compared serum total prolactin and free prolactin in 60 women with RA and 31 female controls. RESULTS: No subject had hyperprolactinaemia or macroprolactinaemia. Serum concentrations of total and free (monomeric) prolactin were higher (P<0.05) in women with RA [mean (s.d.), 225.6 (104.6) and 201.6 (95.4) mU/l respectively] compared with controls [175.0 (68.5) and 154.0 (60.9) mU/l respectively]. CONCLUSIONS: We report higher serum free prolactin concentrations in women with RA compared with control subjects. This result indicates that the higher serum total prolactin levels in patients with RA are the consequence of increased free prolactin concentrations and are not due to macroprolactin.

Arthritis, Rheumatoid↗

PubMed2004

Backscattering of light from a dielectric layer on a reflecting substrate.

Scattering of light from rough dielectric films is studied experimentally. It is shown that the interference pattern of the scattered field depends critically on the power spectrum of the roughness, especially on its long-scale component. When the height of roughness is small compared with the wavelength, the backscattering peak (if it exists) is due to the interference of the singly scattered fields; hence the properties of the backscattered peak are rather unusual. In particular, the width of the peak is determined by the thickness of the film and is independent of the parameters of disorder. The intensity of the peak increases with an increase of the rms height of the surface roughness and becomes independent of the rms when the roughness is of the order of the wavelength.

Journal Article↗

PubMed2001

Restorative proctocolectomy: Ochsner Clinic experience.

BACKGROUND: Restorative proctocolectomy, a standard operation for ulcerative colitis and familial adenomatous polyposis has significant complications, even in experienced hands. METHODS: We studied surgical outcome by retrospectively reviewing cases of restorative proctocolectomy done at Ochsner Foundation Hospital from 1982 to 1995. Demographic and clinical data from two periods (1982 to 1989 and 1989 to 1995) were compared to determine factors associated with improved outcome. RESULTS: We performed 145 ileal pouch-anal procedures. In 56 patients, 104 complications occurred. The more recent group had a greater incidence of inflammatory bowel disease, steroid use, and staged operations; reduced operative times and hospital stays; more general but fewer pouch-related complications. Pouch failures were similar for both groups. CONCLUSIONS: Perioperative outcome appeared to be associated with technical experience, improved perioperative care, exclusion of patients with Crohn's disease,judicious surgical reoperation for pouch complications, and use of a 3-stage procedure in malnourished patients or those with acute or toxic colitis.

Adenomatous Polyposis Coli↗

PubMed2000

Significance of a normal surveillance colonoscopy in patients with a history of adenomatous polyps.

PURPOSE: The aim of this study was to determine the appropriate surveillance for patients with a history of adenomatous polyps whose last colonoscopic examination was normal. METHODS: This was a retrospective review of a database of 7,677 colonoscopies (1990 to 1996). In patients under colonoscopic surveillance, we reviewed cases of patients who had received three colonoscopies (an index (initial) colonoscopy positive for adenomas and 2 follow-up colonoscopies (interim and final)). The risk of adenomas and cancers at final follow-up colonoscopy was compared between patients having a normal interim colonoscopy and those with a positive interim colonoscopy. The risk at final colonoscopy was also stratified by time interval and the size and number of adenomas at the initial index colonoscopy. RESULTS: Two hundred four patients undergoing surveillance for adenomas met inclusion criteria. At index colonoscopy the median polyp size was 1 cm and median frequency was three polyps. At all follow-up colonoscopies, we detected 493 adenomas and one cancer (median follow-up, 55 months). At 36 months patients with a normal interim colonoscopy (n = 91) had significantly fewer polyps than patients with a positive interim colonoscopy (n = 113; 15 vs. 40 percent; P = 0.0001). By 40 months, adenomas were detected in more than 40 percent of patients in both groups. The risk after a normal interim colonoscopy was not affected by time interval or number or size of polyps. Adenomas found subsequent to a normal interim colonoscopy were dispersed throughout the colon in 28 patients and isolated to the rectosigmoid in 6 patients. CONCLUSIONS: In patients with a history of adenomas, a normal follow-up colonoscopy is associated with a statistically but not clinically significant reduction in the risk of subsequent colonic neoplasms. These patients require follow-up surveillance colonoscopy at a four-year to five-year interval.

Adenomatous Polyposis Coli↗

PubMed2000

The natural history of isolated rectosigmoid adenomatous polyps: is flexible sigmoidoscopy a safe alternative for surveillance?

PURPOSE: Colonoscopic surveillance is recommended for patients with adenomatous polyps. Significant cost savings would result from identification of subgroups of patients in whom less costly surveillance would suffice. This study was performed to determine the natural history of patients undergoing removal of isolated rectosigmoid adenomas and to establish whether flexible sigmoidoscopy might be adequate for follow-up. METHODS: A retrospective review of a database of 7,677 colonoscopies, from 1990 to 1996, identified patients who had a minimal follow-up of two years after removal of adenomatous polyps isolated to the rectosigmoid. Polyps detected on surveillance colonoscopy were categorized as distal (< or =60 cm from anal verge), proximal (>60 cm from anal verge), and diffuse (proximal plus distal). The risk of polyp formation was determined by actuarial analysis using the Kaplan-Meier method. RESULTS: Sixty-two patients undergoing surveillance for adenomas met inclusion criteria. At the index colonoscopy, 124 isolated rectosigmoid polyps were identified. The median polyp size was 1 cm and median frequency was one polyp. The median follow-up time for the entire cohort (N = 62) was 53 months. At follow-up surveillance colonoscopy, 105 additional adenomas were discovered and removed in 40 patients. No malignant polyps were detected. The pattern of polyps detected were proximal (n = 19), rectosigmoid (n = 16), and diffuse (n = 5). CONCLUSIONS: The majority (65 percent) of patients with isolated rectosigmoid polyps have additional polyps on long-term surveillance, and 60 percent of patients will have these polyps located proximal to the reach of a sigmoidoscope. Therefore, flexible sigmoidoscopy is not a safe alternative for surveillance of patients with isolated rectosigmoid polyps.

Adult↗

PubMed2000

Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity.

PURPOSE: Synovial sarcoma is a high-grade tumor that is associated with poor prognosis. Previous studies analyzing prognostic factors are limited because of inclusion of heterogeneous cohorts of patients with nonextremity and recurrent tumors. The objective of this study was to determine independent prognostic factors of primary synovial sarcoma localized to the extremity. PATIENTS AND METHODS: Between July 1, 1982, and June 30, 1996, 112 patients underwent surgical resection for cure at our institution and then were followed-up prospectively. Clinical and pathologic factors examined for prognostic value included age, sex, tumor site and location, depth, size, microscopic status of surgical margins, invasion of bone or neurovascular structures, and monophasic or biphasic histology. The end points analyzed were the time to first local recurrence that was not preceded by a distant recurrence, time to any distant recurrence, and time to disease-related mortality. These end points were modeled using the method of Kaplan and Meier and analyzed by the log-rank test and Cox regression. RESULTS: The median duration of follow-up among survivors in this cohort of 112 patients was 72 months. The 5-year local-recurrence, distant-recurrence, and mortality rates were 12%, 39%, and 25%, respectively. Tumor size > or = 5 cm (P =.001; relative risk [RR] = 2. 7; 95% confidence interval [CI], 1.5 to 5.2) and the presence of bone or neurovascular invasion (P =.04; RR = 2.3; 95% CI, 1.0 to 5. 3) were independent adverse predictors of distant recurrence. Tumor size > or= 5 cm (P =.003; RR = 2.3; 95% CI, 1.4 to 6.3) and the presence of bone or neurovascular invasion (P =.03; RR = 2.7; 95% CI, 1.0 to 6.5) were also independent adverse predictors of mortality. CONCLUSION: The natural history of primary synovial sarcoma of the extremity is related to tumor size and invasion of bone and neurovascular structures.

Adolescent↗

PubMed1999

All patients with small intramural rectal cancers are at risk for lymph node metastasis.

PURPOSE: Although local excision can be curative in patients with early-stage rectal cancer, approximately 20 percent of patients will develop local recurrence, many as a result of unrecognized and unresected regional lymph node metastases. Our objective was to determine if standard pathologic factors can predict lymph node metastases in small intramural rectal cancers and provide a basis for patient selection for nonradical surgery. METHODS: Between June 1986 and September 1996, 318 patients with T1 or T2 rectal cancers underwent radical resection at our institution. Of these, 159 patients (48 T1 and 111 T2) were potentially eligible for curative local excision (< or =4 cm in size, < or =10 cm from the anal verge, no synchronous metastases), and the prevalence of lymph node metastases based on T stage and other pathologic factors was analyzed in this group. RESULTS: The overall frequency of lymph node metastasis was 15 percent (24/159 patients). T stage (T1, 10 percent; T2, 17 percent), differentiation (well-differentiated or moderately differentiated, 14 percent and poorly differentiated, 30 percent), and lymphatic vessel invasion (lymphatic vessel invasion-negative, 14 percent and lymphatic vessel invasion-positive, 33 percent) influenced the risk of lymph node metastasis. However, only blood vessel invasion (blood vessel invasion-negative, 13 percent and blood vessel invasion-positive, 33 percent) reached statistical significance as a single predictive factor (P=0.04). Tumors with no adverse pathologic features (low-risk group) had a lower overall frequency of lymph node metastasis (11 percent) compared with the remaining tumors (high-risk group, 31 percent; P=0.008). However, even in the most favorable group (T1 cancers with no adverse pathologic features) lymph node metastases were present in 7 percent of patients. CONCLUSION: In rectal cancer patients potentially eligible for local excision, the overall risk of undetected and untreated lymph node metastases is considerable (15 percent). The use of pathologic factors alone after local excision does not reliably assure the absence of lymph node metastases.

Adenocarcinoma↗

PubMed1998

Thymic carcinoma: current staging does not predict prognosis.

BACKGROUND: Thymic carcinomas are currently staged by Masaoka classification, a staging system for thymomas. We retrospectively evaluated surgical patients with thymic carcinoma to determine prognostic factors and to evaluate the usefulness of Masaoka staging in this disease. METHODS: Our computerized tumor registry yielded 118 patients with thymoma. Review of pathologic material revealed 43 cases of thymic carcinoma. Collection of data was by review of hospital and physician charts and telephone contact with patients. Analysis of prognostic factors was performed in patients undergoing complete resection by the method of Kaplan-Meier and Cox proportional hazards regression. RESULTS: Between 1949 and 1993, 43 patients underwent surgery for thymic carcinoma. Overall survival was 65% at 5 years and 35% at 10 years. Overall recurrence was 65% at 5 years and 75% at 10 years. On univariate analysis, survival was not dependent on age, sex, tumor size, or Masaoka stage but was dependent on innominate vessel invasion. By multivariate analysis, survival was dependent only on innominate vessel invasion. CONCLUSIONS: Patients with thymic carcinoma have a high rate of recurrence. Tumor invasion of the innominate vessels is associated with a particularly poor prognosis. Although Masaoka staging is useful in staging patients with thymoma, it does not appear to predict outcome for patients with thymic carcinoma.

Adult↗

PubMed1998

Stage I rectal cancer: identification of high-risk patients.

BACKGROUND: Stage I rectal cancer (T1, T2 N0) is currently treated by surgical resection alone. Despite adequate surgical resection, approximately 10-15% of patients will develop recurrence. Identification of patients at high risk for recurrence could potentially lead to an improvement in outcome by selection of these patients for adjuvant therapy. METHODS: Between June 1986 and September 1996, 211 patients with primary rectal cancer (stage I) were treated by radical surgical resection alone. The medical data of all patients were entered into a database and prospectively followed. The following 10 prognostic factors were correlated with recurrence and tumor-related mortality: patient factors: age, gender, and preoperative carcinoembryonic antigen level; tumor factors: location from the anal verge (< 6 cm vs. > or = 6 cm), T stage (T1 vs. T2), intratumoral blood vessel invasion (BVI), intratumoral lymphatic vessel invasion, presence of tumor ulceration, and histologic differentiation; and treatment-related factors: extent of surgical resection--abdominal perineal resection versus low anterior resection. Univariate analysis of the effect of the prognostic factors on recurrence and tumor-related mortality were performed by the method of Kaplan-Meier and log rank test. Independent prognostic factors were determined by a multivariate analysis performed using the Cox proportional hazards model. RESULTS: The overall 5-year actuarial recurrence was 12% and tumor-related mortality was 10%. Independent predictors of recurrence were male gender and BVI. Independent predictors of tumor-related mortality were male gender, BVI, and poorly differentiated tumors. CONCLUSIONS: Despite radical resection, patients with stage I rectal cancer with male gender, BVI, and poorly differentiated tumors should be considered high-risk patients.

Abdomen↗

PubMed1998

Free circulating magnesium and renal magnesium handling during acute metabolic acidosis in humans.

Ion-selective electrodes have been designed for determining the ionized concentration of magnesium in blood, the biologically active form of this ion. The effect of acute acidosis induced by ammonium loading on circulating and urinary magnesium was investigated in 11 volunteers. No changes in plasma total and ionized magnesium were noted following administration of ammonium chloride. On the contrary, administration of ammonium chloride increased the plasma free magnesium fraction and the urinary magnesium excretion. The study demonstrates that the hypermagnesiuria induced by acute acidosis is not caused by ionized hypermagnesemia and supports the theory that acidosis decreases the circulating magnesium fraction that is bound to proteins.

Acidosis↗

PubMed1997

Evidence that perihypoglossal neurons involved in vestibular-auditory and gaze control functions respond to nerve growth factor.

Nerve growth factor (NGF), which has long been considered to be a trophic factor for peripheral sensory and sympathetic neurons, has been found recently to influence cholinergic neurons in the basal forebrain and neostriatum. In the present study, we provide evidence that brainstem neurons in the perihypoglossal area that relay information from the inner ear and vestibular apparatus to the cerebellum and tectum are responsive to NGF. These neurons, which are located in the nucleus prepositus hypoglossi (NPH), spinal vestibular nucleus, cochlear complex, and gigantocellular and paragigantocellular nuclei of the reticular formation, express functional receptors for NGF and up-regulate the expression of trkA receptors after injection of NGF into targets. In addition, the developmental up-regulation of NGF in the cerebellum coincides with the differentiation of the perihypoglossal nuclei. These results suggest that neurons representing the principal brain relays for auditory and vestibular pathways and perihypoglossal neurons involved in gaze coordination are a novel group of central neurons (besides cholinergic neurons in the basal forebrain and neostriatum) that respond to NGF.

Animals↗

PubMed1996

Effect of human growth hormone on human pancreatic carcinoma growth, protein, and cell cycle kinetics.

The role of human growth hormone (hGH) as a nutritional adjunct for cancer patients is controversial because of its potential mitogenic effects on tumor growth. No studies to date have examined the effect of hGH on human tumor response in vivo. In Vitro: Athymic mice were injected (s.c.) daily with hGH (GH, n=14) or saline (CTL, n=14). On Day 10, serum was collected and added to human pancreatic carcinoma cells in culture. In Vivo: Athymic mice were inoculated (s.c.) with human pancreatic carcinoma cells. On Day 14, mice were randomized to receive daily either hGH (GH, n=14) or saline (CTL, n=12). On Day 29, animals received [3H]phenylalanine for tissue protein fractional synthetic rate (FSR) measurement. Tumors were excised and cell cycle kinetics analyzed. Data are expressed as mean +/- SEM. Statistical analysis was performed by unpaired t test and/or ANOVA where appropriate. In Vitro: Serum from GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Serum for GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Growth hormone had no significant effect on tumor growth rate (mm3/day) (1.45 +/- 0.47 CTL vs 1.57 +/- 0.66 GH), final tumor weight (mg) (0.19 +/- 0.15 CTL vs 0.17+/- 0.06 GH), DNA Index (1.5 +/- 0.1 CTL vs 1.5 +/- 0.1 GH), percent S phase (20.3 +/- 3.3 CTL vs 22.1 +/- 3.0 GH), or tumor FSR (%/day) (51.1 +/- 17.8 CTL vs 70.2 +/- 61.1 GH). Growth hormone significantly elevated serum IGF-1 levels (ng/ml) (176 +/- 48 CTL vs 222 +/- 53 GH, P<0.005) and liver FSR (%/day) (62.8 +/- 17.8 CTL vs 79.7 +/- 12.7 GH, P<0.005). Serum of GH-treated mice increased human pancreatic cell growth in vitro. In vivo, GH administration raised serum IGF-1 levels and increased liver protein FSR, without tumor growth, cell cycle kinetics, or protein FSR.

Animals↗

PubMed1996

Depletion of high energy phosphate compouds in the tumor-bearing state and reversal after tumor resection.

BACKGROUND: Cancer cachexia is a syndrome manifested by a variety of metabolic abnormalities that include depletion of host energy stores. We studied liver and skeletal muscle high energy phosphate compounds, inorganic phosphorus (Pi), and the energy charge in tumor-bearing (TB), pair fed non-tumor-bearing (NTB), and tumor-bearing resected (RES) rats. METHODS: F344 rats were randomized into TB (n = 13), NTB (n = 13), and RES (n = 5) groups. On day 0, the flanks of the TB and RES animals were injected with 1 x 10(7)n methylcholanthrene (MCA)-induced sarcoma cells. On day 19, TB and NTB rat liver and skeletal muscle were analyzed for adenine nucleotides, phosphocreatine, and Pi, and RES animals underwent tumor resection followed by tissue analysis 10 days later. RESULTS: Although the liver adenylate energy charge was maintained, the level of liver adenosine monophosphate was significantly increased and the liver adenosine diphosphate level was decreased in the TB animals (3.55 +/- 0.6, 3.70 +/- 0.3 mumoles/gm dry weight, p < 0.05, p = 0.05, respectively) when compared with the NTB animals (3.06 +/- 0.4, 4.00 +/- 0.5 mumoles/gm dry weight, respectively). Muscle adenosine diphosphate levels were significantly decreased in the TB animals (1.57 +/- 0.7 mumoles/gm dry weight) as compared with NTB animals (2.23 +/- 0.7 mumoles/gm dry weight, p < 0.05). In addition, muscle adenosine triphosphate, phosphocreatine, and phosphocreatine/adenosine triphosphate ratios were significantly decreased in TB animals (19.94 +/- 4.5, 81.51 +/- 12.8, and 4.20 +/- 0.8 mumoles/gm dry weight, respectively) as compared with NTB animals (24.44 +/- 1.9, 116.72 +/- 7.5, and 4.81 +/- 0.4 mumoles/gm dry weight, respectively, p < 0.05) and RES animals (24.08 +/- 3.3, 124.10 +/- 12.2, and 5.19 +/- 0.5 mumoles/gm dry weight, respectively, p < 0.05). CONCLUSIONS: These alterations in high energy phosphate compounds in liver and skeletal muscle indicate that although the energy charge is maintained, energy depletion occurs early in the tumor-bearing state. These changes are tumor specific, not related to anorexia, and revert to non-tumor-bearing levels after tumor resection.

Adenosine Triphosphate↗

PubMed1996

GTPase-deficient G alpha 16 and G alpha q induce PC12 cell differentiation and persistent activation of cJun NH2-terminal kinases.

Persistent stimulation of specific protein kinase pathways has been proposed as a key feature of receptor tyrosine kinases and intracellular oncoproteins that signal neuronal differentiation of rat pheochromocytoma (PC12) cells. Among the protein serine/threonine kinases identified to date, the p42/44 mitogen-activated protein (MAP) kinases have been highlighted for their potential role in signalling PC12 cell differentiation. We report here that retrovirus-mediated expression of GTPase-deficient, constitutively active forms of the heterotrimeric Gq family members, G alpha qQ209L and G alpha 16Q212L, in PC12 cells induces neuronal differentiation as indicated by neurite outgrowth and the increased expression of voltage-dependent sodium channels. Differentiation was not observed after cellular expression of GTPase-deficient forms of alpha i2 or alpha 0, indicating selectivity for the Gq family of G proteins. As predicted, overexpression of alpha qQ209L and alpha 16Q212L constitutively elevated basal phospholipase C activity approximately 10-fold in PC12 cells. Significantly, little or no p42/44 MAP kinase activity was detected in PC12 cells differentiated with alpha 16Q212L or alpha qQ209L, although these proteins were strongly activated following expression of constitutively active cRaf-1. Rather, a persistent threefold activation of the cJun NH2-terminal kinases (JNKs) was observed in PC12 cells expressing alpha qQ209L and alpha 16Q212L. This level of JNK activation was similar to that achieved with nerve growth factor, a strong inducer of PC12 cell differentiation. Supportive of a role for JNK activation in PC12 cell differentiation, retrovirus-mediated overexpression of cJun, a JNK target, in PC12 cells induced neurite outgrowth. The results define a p42/44 MAP kinase-independent mechanism for differentiation of PC12 cells and suggest that persistent activation of the JNK members of the proline-directed protein kinase family by GTPase-deficient G alpha q and G alpha 16 subunits is sufficient to induce differentiation of PC12 cells.

Animals↗

PubMed1996

Neurotrophin and neurotrophin receptor proteins in medulloblastomas and other primitive neuroectodermal tumors of the pediatric central nervous system.

Primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) are poorly understood childhood neoplasms, and medulloblastomas are the most common pediatric PNETs. Neoplastic cells in medulloblastomas and other PNETs resemble progenitor cells of the developing central nervous system, but they also may exhibit the molecular phenotype of immature neurons or glia. As neurotrophins play a role in regulating differentiation, proliferation, and cell death in the normal developing central nervous system, and recent evidence suggests that neurotrophins may influence the behavior of medulloblastomas, we studied 29 PNET biopsy samples (27 of which were posterior fossa medulloblastomas) by immunobistochemistry using antibodies specific for each of the major high affinity neurotrophin receptor proteins, ie, TrkA, TrkB, and TrkC. A subset of these tumors also was examined by Western blot. Immunoreactive TrkA, TrkB, and TrkC were observed in neoplastic cells in 8 (27%), 18 (62%), and 14 (48%) of these PNETs, respectively. Additional immunohistochemical studies of a subset of these PNETs using antibodies to neurotrophins that primarily activate TrkB and TrkC, ie, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5, showed that immunoreactive brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 were detected in 22, 9, and 19% of these PNET biopsies, respectively. Finally, 19 pediatric brain tumors other than these PNETs also were studied here, and they expressed these neurotrophins and their receptors to a variable extent. The demonstration here that neurotrophins and their cognate receptor proteins are expressed in PNETs as well as in other pediatric brain tumors may imply that signal transduction pathways mediated by neurotrophins and/or their receptors influence the induction or progression of these common childhood neoplasms.

Adolescent↗

PubMed1995

Specificity of nerve growth factor signaling: differential patterns of early tyrosine phosphorylation events induced by NGF, EGF, and bFGF.

The specificity of nerve growth factor (NGF) action was examined by comparing early tyrosine phosphorylation events induced by NGF, epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF). In PC12 cells, administration of either the differentiation factor NGF or the mitogenic factor EGF led to tyrosine phosphorylation of multiple polypeptides in the 100-110 kDa size range associated with PI-3 kinase. However, NGF induced a more prolonged phosphorylation, relative to a transient EGF effect. In contrast, the differentiation factor bFGF failed to induce measurable tyrosine phosphorylation of PI-3 kinase-associated proteins. Similarly, NGF but not bFGF induced marked tyrosine phosphorylation of PLC gamma, another early signaling molecule, suggesting that multiple pathways exist for promoting differentiation, and/or that these signaling molecules are not essential for differentiation. TrkA signaling was also compared between PC12 cells and NIH-3T3 cells heterologously expressing trkA, where receptor activation promotes mitogenesis. In this comparison, significant differences were observed in the tyrosine phosphorylation pattern of PI-3 kinase-associated polypeptides, suggesting the existence of cell type-specific molecular interactions influencing trkA signaling. Mechanistically, NGF stimulation of PC12 cells resulted in a weak or possibly indirect association between trkA and PI-3 kinase. Furthermore, NGF did not appear to activate or substantially alter the overall level of PI-3 kinase activity, raising the possibility that ligand-induced phosphorylation may serve instead to relocalize constitutively active PI-3 kinase molecules within the cell. Taken together, data presented suggest that the temporal pattern of induced phosphorylation, the nature of induced associations with other phosphoproteins, and cell type-specific components may all contribute to the generation of NGF signaling specificity.

3T3 Cells↗

PubMed1995

Tumor necrosis factor alpha stimulates gluconeogenesis from alanine in vivo.

An increase in gluconeogenesis contributes to the cachexia seen in severe injury, sepsis, and malignancy by converting amino acids from skeletal muscle to glucose. Since tumor necrosis factor alpha (TNF alpha) may mediate this cachexia, we examined the effect of this cytokine on gluconeogenesis. Twenty-eight male Fischer rats were injected intraperitoneally with TNF alpha (250 micrograms/kg) or saline, and after 4 hours, isolated hepatocytes were obtained by in situ collagenase liver perfusion. Hepatocytes were incubated with alanine (10 mM), and rates of gluconeogenesis were determined. Plasma lactate, glucose, insulin, glucagon, cortisol, and amino acids were measured. TNF alpha administration resulted in a 50% increase in gluconeogenesis from alanine (P < 0.05) and a three-fold increase in plasma glucagon (P = 0.01). Total and glucogenic plasma amino acids decreased with TNF alpha injection (P < 0.05). In vivo TNF alpha causes an increase in hepatic gluconeogenesis associated with increased plasma glucagon.

Alanine↗

PubMed1995

Perioperative growth hormone improves wound healing and immunologic function in rats receiving adriamycin.

Administration of perioperative growth hormone may reverse alterations in wound healing and immunologic function in animals receiving chemotherapy. F344 rats were randomized into three groups: Control (n = 12), Chemo (n = 13), and Chemo + GH (n = 12). Human growth hormone (GH) (3 mg/kg sc bid) was begun on Day 0 and continued for 2 weeks. On Day 7, all animals underwent a standardized midline laparotomy, gastrotomy, and placement of a subcutaneous wound sponge. In addition, a single dose of adriamycin (5 mg/kg i.v.) was administered to those animals receiving chemotherapy. On Day 12, right hindlimb footpads were challenged with 50 micrograms of dinitrochlorobenzene. On Day 14, bursting strengths of the laparotomy and gastrotomy were measured. The wound sponge and gastric anastomosis were analyzed for hydroxyproline (OH-Pro) content. Animal spleens were weighed and splenocytes harvested for NK cell activity. Delayed type hypersensitivity (DTH) is reported as percentage of hind-limb foot pad swelling (%FPS). Data are expressed as means +/- SD and comparisons by ANOVA. The laparotomy bursting strength (mm Hg) in the Chemo + GH group (81 +/- 14) was significantly higher than that in the Chemo group (66 +/- 15, P < 0.05). The anastomotic tissue OH-Pro levels (mumole/g dry tissue) in the Chemo + GH group (107.9 +/- 15.2) were significantly higher than those in the Chemo group (62.9 +/- 8.5, P < 0.001). GH increased splenic weights (mg) over those of Chemo (0.50 +/- 0.13 vs 0.37 +/- 0.05, P < 0.05). NK cell activity (% killing) was significantly elevated in the Chemo+GH group compared to that in Chemo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗