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Biomedical subjects

J C Garcia

Publications and source records attributed to J C Garcia.

At least 19 recordsLinked to original sources
PubMed2002

Clinical evaluation of SyvekPatch in patients undergoing interventional, EPS and diagnostic cardiac catheterization procedures.

BACKGROUND: The SyvekPatch (Marine Polymer Technologies, Danvers, Massachusetts) has received Food and Drug Association market clearance for the rapid control of bleeding from vascular access sites and percutaneous catheters. A clinical evaluation was designed to determine the efficacy and safety of this vascular closure device in 1,000 consecutive patients after routine diagnostic and interventional procedures. METHODS: During a 3-month period, a total of 364 interventional patients (stenting, 55%; PTCA, 30%; EPS, 15%) and 636 diagnostic patients (left heart catheterization, 77%; right/left heart catheterization, 23%) were treated. Catheter sheaths ranged in size from 4 12 French (Fr). Antiplatelet therapy was employed in 35% of the interventional procedures. In approximately 20% of the cases, same-side repuncture occurred within 2 3 days. RESULTS: The use of the SyvekPatch on a total of 1,000 consecutive patients resulted in the rapid control of bleeding with only 1 major complication (0.1%; pseudoaneurysm) and few minor complications (1.3%). The pseudoaneurysm was most likely caused by the aberrant location of the sheath. All minor complications were either small hematomas (< 2.5 cm; rate, 0.75%) or slight oozing from the puncture site (rate, 0.6%). Outcomes measured included clinical effectiveness, ability to maintain the femoral access site for future interventions, major complication rates (access-site related hematoma that required blood transfusion or an extended hospital stay, pseudoaneurysm, arteriovenous fistula, arterial or venous thrombosis, and infection), patient comfort and operational efficiency. CONCLUSION: The strong safety and efficacy profile of the SyvekPatch has made a significant impact in our cardiac catheterization lab. Unlike existing vascular closure devices, the SyvekPatch was used following a diagnostic procedure even when a future interventional procedure was scheduled. The effectiveness of the SyvekPatch was not altered by anticoagulation or antiplatelet therapy. The patients and clinical staff were extremely satisfied with the use of the SyvekPatch .

Acetylglucosamine↗
PubMed2001

Antioxidant properties of alpha-crystallin.

alpha-Crystallin is a major chaperone lens protein to which has been ascribed antioxidant functions. In the present work we have evaluated the antioxidant and free radical scavenging properties of bovine alpha-crystallin in a series of in vitro models: zimosan-induced, luminol-enhanced chemiluminescence response of polymorphonuclear leukocytes, the autoxidation of brain homogenate, bleaching of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)-derived radical cations, trapping of peroxyl radicals, and reactivity toward hypochloric acid. In all these systems, the reactivity of alpha-crystallin is higher than or similar to that of bovine serum albumin. It is concluded that, given the high concentrations of ol-crystallin in the lenses, its capacity to interact with free radicals and to remove hypochlorous acid could contribute to the maintenance of the lens functionality.

Animals↗
PubMed1998

The diagnostic and predictive value of ascites nitric oxide levels in patients with spontaneous bacterial peritonitis.

Nitric oxide (NO) is a messenger molecule involved in pathogen suppression. Cirrhosis is characterized by an increased risk for infections, including spontaneous bacterial peritonitis (SBP). The role of NO in the infections that develop in cirrhosis has not been clearly established. The aim of this study was to investigate the utility of measuring ascites NO in the diagnosis of SBP and/or in determining the predisposition of cirrhotic patients to develop this infection. Nitric oxide metabolites (nitrites + nitrates [NOx]) were measured by chemiluminescence in 105 ascites samples obtained from 87 cirrhotic patients and in 87 simultaneously obtained serum samples. Ascites NO levels were not significantly different among ascites from patients with SBP (n = 39; median, 48 micromol/L), patients with sterile ascites (n = 54; median, 42 micromol/L), and samples obtained after patients with SBP had been treated (n = 12; median, 62 micromol/L). No differences in ascites NO levels were observed between culture-positive and culture-negative peritonitis. Among 50 patients with sterile ascites on initial paracentesis, 7 patients developed peritonitis during follow-up; no differences in baseline NO levels were observed between patients who developed peritonitis (median, 46 micromol/L) and those who did not (median, 41 micromol/L). Among patients with SBP, mortality was significantly higher in those with NO levels >60 micromol/L. A very significant direct correlation was found between ascites and serum NO levels (r2 = .86). In conclusion, ascites NO levels in cirrhotic patients are not useful either to diagnose or to determine predisposition to SBP. Rather, ascites NO levels reflect serum levels, are higher in cirrhotic patients with more severe liver disease, and may be a useful prognostic marker.

Ascites↗
PubMed1998

Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced pancreatic carcinoma: a University of Chicago phase II consortium study.

BACKGROUND/OBJECTIVES: Uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) has broad anti-tumor activity for cancers arising from the gastrointestinal tract. However, there are no published data regarding the efficacy of leucovorin-modulated UFT in patients with pancreatic cancer. The objective of this trial was to determine the activity and evaluate the toxicity of UFT plus oral calcium leucovorin in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Fourteen patients with advanced measurable adenocarcinoma of the pancreas were enrolled onto the trial. Patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided doses every eight hours for 28 days repeated every 35 days. Objective tumor response was evaluated after two courses of therapy. RESULTS: Fourteen patients were evaluable for response and toxicity. No objective responses were seen. The median (range) time to progression and survival were 14 (1.6-37), and 15 (1.9-62) weeks, respectively. Toxicity was mild with severe (grade 3 or 4) hyperbilirubinemia, pain, diarrhea, transaminitis, venous thrombus, weakness, renal failure, confusion, and edema/ascites seen in three (21%), one (7%), two (14%), one (7%), one (7%), one (7%), one (7%), one (7%), and two (14%) patients, respectively. CONCLUSION: In the 14 patients evaluable, UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate anti-tumor activity against advanced pancreatic adenocarcinoma; however, this oral regimen was well tolerated and devoid of neutropenia, significant oral mucositis or diarrhea.

Adenocarcinoma↗
PubMed1998

Phase II and pharmacodynamic studies of pyrazine diazohydroxide (NSC 361456) in patients with advanced renal and colorectal cancer.

Pyrazine diazohydroxide (PZDH) is a novel antitumor agent that forms DNA adducts via the reactive pyrazine diazonium ion. In a recent Phase I study of PZDH, we identified a recommended Phase II dose of 100 mg/m2/day x 5, given as a 5-min i.v. bolus with the cycles repeated every 42 days (N. J. Vogelzang, et al, Cancer Res., 54: 114-119, 1994). There was a moderate negative correlation between serum chloride concentration and logarithm platelet nadir, suggesting the hypothesis that PZDH is activated in an acidic environment, leading to more toxicity in acidotic patients. Therefore, the University of Chicago Phase II cooperative network conducted two Phase II studies of PZDH in renal cancer (15 patients, 2 with liver metastases) and in 5-fluorouracil-refractory colorectal cancer (14 patients, 13 with liver metastases) to determine efficacy in each disease and to correlate safety and tolerance of the drug with PZDH pharmacokinetics/pharmacodynamics and with arterial blood gas measurements. There were no responses seen in either tumor type. The primary toxicity of PZDH was myelosuppression with neutropenia (absolute neutrophil count, < 1000/microl) and thrombocytopenia (<50,000 cells/microl), seen in 41 and 24% of all cycles, respectively. Other grade 3 and 4 toxicities were rare. Pharmacodynamic analysis revealed no significant correlation between plasma levels at 5, 60, and 120 min; WBCs; absolute neutrophil and platelet count nadirs; and initial serum chloride or blood pH levels. The colorectal patients experienced significantly more thrombocytopenia than did the renal cancer patients (median platelet nadir after cycle 1 was 151 x 10(3)/microl for renal patients versus 76 x 10(3)/microl for colon patients; P = 0.04), suggesting either that prior 5-fluorouracil and leucovorin reduced bone marrow reserve or that colorectal patients with liver metastases experienced more PZDH toxicity. Regression analyses revealed a possible relationship (P = 0.06) between serum pH and thrombocytopenia (i.e., for each increase of 0.03 in pH, there was a 34% increase in the platelet nadir), but there was no relationship between serum chloride and thrombocytopenia. Curiously, an increase in alkaline phosphatase was associated with an increase in the platelet nadir (P = 0.02). If PZDH continues to be developed as an antineoplastic agent, further studies of these relationships are suggested.

Adult↗
PubMed1996

Aprotinin effects related to oxidative stress in cardiosurgery with mechanical cardiorespiratory support (CMCS).

There is evidence to support a relationship between oxidative stress and protease release in "ischemia-reperfusion damage." We have proposed that aprotinin may exert an antioxidant effect. A double blind clinical trial was performed with a control (G-1) and treated (G-2) groups, both submitted to CMCS. Blood samples were taken 5 times. Biochemical indicators were measured spectrophotometrically. Aprotinin was supplied by Bayer. Malonildialdehyde levels were greater in G-1 (7.2 +/- 3.6 nmoles/ml) than in G-2 (4 +/- 1.65) at the time of reperfusion. Phospholipase A2 exhibited a tendency of higher activity in G-1 than in G-2. Uric acid levels were higher in G-2 (431 +/- 274 mumoles/1) than in G-1 (224 +/- 188) at 5 minutes after aortic clamping, and catalase activity was greater in G-2 (294 +/- 55 KU/1) than in G-1 (118 +/- 47) at time of reperfusion. Low cardiac output was 10% in G-2 and 30% in G-1. Arrythmias appeared in 30% of G-2 and in 60% of G-1. These results suggest an antioxidant effect of aprotinin under ischemia-reperfusion conditions.

Aprotinin↗
PubMed1996

Use of cyanoacrylate tissue adhesive in small-incision cataract surgery.

BACKGROUND AND OBJECTIVE: A controlled clinical study was performed on three different groups of patients. PATIENTS AND METHODS: Each patient had a 6.5 mm-wide scleral tunnel with phacoemulsification. Sealing of the incision was done either without suture, with an anchor suture, or with tissue adhesive (cyanoacrylate). The authors observed whatever induced astigmatism was present during the 1st and 12th weeks of the postoperative period. RESULTS: In the immediate postoperative period, astigmatism was significantly less (P < .01) in the groups of patients with suture and tissue adhesive than in the unsutured group. The results after 12 weeks were similar for the three groups (P > .05), with no complications observed as a result of the use of cyanoacrylate. CONCLUSION: Cyanoacrylate seems to be a promising innovation in scleral tunnel surgery for cataracts. It is an effective, a quick, and a safe alternative to sutures.

Astigmatism↗
PubMed1995

Concomitant chemoradiotherapy, neutron boost, and adjuvant chemotherapy for anaplastic astrocytoma and glioblastoma multiforme.

The survival rate for patients with malignant gliomas is poor. We describe the results of a prospective study using concomitant chemoradiotherapy, neutron boost, and adjuvant chemotherapy for patients with malignant gliomas. Forty-two patients with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were treated with postoperative photon radiation 45 Gy/25 fraction (fxs) with concomitant continuous intravenous infusion of 5-fluorouracil at 300 mg/m2/day x 5 days and hydroxyurea 0.5 g orally every 12 hr for 6 days for 5 consecutive weeks, followed by a neutron boost of 450 N cGy/6 fxs delivered twice weekly. Adjuvant chemotherapy with procarbazine, CCNU, and vincristine (PCV) was given up to 1 year or until tumor progression. Thirty-four patients (81%) had GBM and 8 patients (19%) had AA. Sixteen patients (38%) were ineligible for the neutron boost because of large tumors or poor performance status and instead received a photon boost with concomitant chemotherapy for a total dose of 60-65 Gy to the tumor. The overall median survival is 68 weeks at a median follow-up of 203 weeks (range 166-302 weeks for the 11 patients remaining alive); 7/8 patients with AA are alive, 2 of these with progressive disease. For AA the median survival is not reached at a median follow-up of 203 weeks (range 166-302 weeks for the 7 patients alive with AA). Time to tumor progression for the 1 dead patient with AA was 35 weeks and the other 2 patients failed at 171 weeks and 179 weeks following treatment. The median survival for the 34 patients with GBM was 62 weeks; 4/34 patients with GBM are alive at 285, 238, 216, and 206 weeks. Multivariate survival analysis in the 34 patients with GBM revealed age and Karnofsky performance status as important prognostic factors. Extent of surgery and neutrons did not affect survival. Concomitant chemoradiotherapy was well tolerated by all patients. The only toxicities observed were mucositis < or = grade II in 3 patients (7%) and mild myelosuppression in 1 patient (2.4%). Adjuvant PCV was well tolerated. Continuous concomitant chemoradiotherapy was well tolerated by all patients with acceptable side effects. The survival rate for the patients with GBM suggests no significant impact on the prognosis for these patients. Patients with AA did well; however, the patient numbers are small.

Adolescent↗
PubMed1994

The benefit of lateral radiographs in an intensive care unit.

The portable anteroposterior (AP) radiograph (CXR) is an essential component of clinical management in the intensive care unit (ICU). In view of the immobility of patients, and overlying tubes, wires, and catheters, lateral (LAT) CXRs are infrequently ordered. We constructed a portable acrylic (Plexiglas) CXR cassette holder and were able to obtain reproducible quality LAT CXRs in the ICU. Of the 72 simultaneously obtained AP and LAT CXRs, 60 were technically acceptable for interpretation. We found an 11 percent incidence of either unexpected conditions or we were able to improve on the AP CXR interpretation. Lateral CXRs should be obtained routinely in the ICU in select patients.

Adolescent↗
PubMed1992

Subclinical ductal carcinoma in situ of the breast. Treatment by local excision and surveillance alone.

BACKGROUND: Mammography has led to earlier detection of subclinical ductal carcinoma in situ (DCIS) of the breast either as nonpalpable calcifications or as an incidental finding in a biopsy performed for another reason. Many women in whom DCIS was detected early may not be destined to have an invasive carcinoma. How should subclinical DCIS be treated if that is the case? What is the role of excision and surveillance only as an alternative to mastectomy or irradiation? METHODS: All patients with DCIS detected as nonpalpable calcifications or as an incidental finding were eligible for this study. Diagnosis was confirmed, and the histologic subtype was determined. Results of postbiopsy mammography confirmed excision of calcifications; wide local reexcision and assessment of margins was also performed in most patients. The maximum diameter of calcifications considered suitable for this treatment was 25 mm. RESULTS: Between 1978 and 1990, 70 women (72 breasts) were entered into this study (mean follow-up time, 49 months; median follow-up time, 47 months). Of this group, 66% were detected as calcifications and 33% were detected as incidental findings. The recurrence rate was 15.3%. All but one of the patients who experienced a recurrence had the comedo type of DCIS as the initial lesion. Each of the recurrences was of the comedo type. All but one recurrence was at the same site as the primary lesion. None of the patients with DCIS as an incidental finding experienced a recurrence. CONCLUSIONS: Excision and surveillance is a reasonable alternative to mastectomy or irradiation for selected women with DCIS that presents as nonpalpable calcifications or as an incidental finding.

Adult↗
PubMed1992

Amino acid substitutions at tryptophan 388 and tryptophan 412 of the HepG2 (Glut1) glucose transporter inhibit transport activity and targeting to the plasma membrane in Xenopus oocytes.

All 6 tryptophan residues in the human HepG2-type glucose transporter (Glut1) were individually altered by site-directed mutagenesis to investigate the role of these residues in transport function. Tryptophan residues in positions 48, 65, 186, 363, 388, and 412 of Glut1 were changed to either a glycine or leucine residue. Mutant mRNAs were synthesized and injected into Xenopus laevis oocytes. Transporter function as assessed by uptake of 2-deoxy-D-[3H]glucose or transport of 3-O-[3H]methylglucose was decreased in the 388 and 412 mutants but was unaltered in all other mutants. The amount of the mutant transporters expressed in total membrane and plasma membrane fractions was measured using Glut1-specific antibodies. Calculation of the intrinsic transport activity of each of the mutants using these data demonstrated that the reduced transport activity of the 412 mutants was caused entirely by a dramatic decrease in the intrinsic activity of the mutant proteins whereas the reduced activity of the 388 mutants was a result of a decreased level of the protein in oocytes, decreased targeting to the plasma membrane, and a modest decrease in the intrinsic activity. Protease/glycosidase mapping of in vitro translation products indicated that the effects of the 388 and 412 point mutations could not be attributed to a disruption in the ability of the mutant proteins to insert properly into the membrane. The ID50 for cytochalasin B inhibition of 2-deoxyglucose uptake was increased from 5 x 10(-7) M for the wild-type Glut1 to 4 x 10(-6) M in the 388 mutants but was unaltered in the 412 mutants. These observations suggest that 1) Trp-412 may comprise part of a hexose binding site or is involved in maintaining a local tertiary structure critical for transport function; 2) Trp-388 is involved in stabilizing the equilibrium binding of cytochalasin B to the transporter. Trp-388 may therefore lie near a substrate binding site and also appears to participate in stabilization of local tertiary structure important for full catalytic activity and efficient targeting to the Xenopus plasma membrane.

Animals↗
PubMed1990

Inhibitors of protein kinase-C modulate desensitization of the parathyroid hormone receptor-adenylate cyclase system in opossum kidney cells.

The mechanisms involved in mediating desensitization and down-regulation of renal PTH receptors have not been defined. Recent studies indicate that PTH binding promotes not only stimulation of adenylate cyclase and activation of protein kinase-A (PK-A), but also, stimulation of phospholipase-C, leading to activation of PK-C. PK-C has been shown to alter both receptor and adenylate cyclase function in other systems. Therefore, the present studies were conducted to test whether PK-C might play a role in the regulation of the PTH receptor-cyclase system after exposure to PTH. Exposure of confluent cultures of opossum kidney (OK) cells to rat PTH-(1-34) (100 nM) for 6 h resulted in a 48 +/- 8% (n = 5) decrease in stimulation of cAMP accumulation in response to further exposure to PTH. PTH receptor binding, assessed with 125I-[Nle8,Nle21,Tyr34]rat PTH-(1-34)NH2 as radioligand, was decreased to a similar extent. Phorbol ester (4 beta-12,13-didecanoate; 1 microM) treatment of the cells in the absence of PTH caused a 58 +/- 3% decrease in PTH-stimulated cAMP production, but equilibrium PTH receptor binding was not different from the control value. Both 50 microM H-7 and 0.5 microM Staurosporine (inhibitors of PK-C) completely blocked the effects of phorbol ester. Pretreatment with PTH, however, in the presence of H-7 or Staurosporine resulted in a completely normal cAMP response to restimulation with PTH. Thus, two inhibitors of PK-C completely prevented desensitization to PTH. The decrease in equilibrium PTH binding, seen after incubation with PTH alone, was also blunted by the inhibitors of PK-C. These data indicate that activation of PK-C by stimulation with PTH may play a role in the regulation of the PTH receptor-cyclase system in OK cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Comparison of the frequency response characteristics of catheter-mounted piezoelectric and micromanometric phonotransducers.

This study compares the frequency response characteristics of catheter-mounted piezoelectric sound transducers with micromanometric transducers. The tip of a 8F catheter with two piezoelectric transducers and two micromanometers was inserted into a water-filled chamber that had a speaker fixed at one end. The speaker was driven by a power amplifier and sine wave generator. The outputs of the transducers were connected to a low-level amplifier. The piezoelectric transducer behaved as a tunable high-pass filter that could be modified by altering the input impedance of the low level amplifier; the frequency response characteristics were examined at five input impedances ranging from 0.96 to 11.8 megohms. The peak-to-peak outputs of the piezoelectric and pressure transducers were recorded at frequency ranges from DC to 1 kHz with a wide-band oscilloscope. The ratio of the outputs from the piezotransducer and micromanometer (Vph/Vpr) was plotted vs. frequency for each input impedance and analyzed to determine the piezotransducer's output resistance and equivalent capacitance; roll-off frequencies were then calculated. The equivalent capacitance of the piezo-element was determined to be 500-700 picofarads. Series capacitance acted with network resistance to produce a predictable frequency-dependent change in signal amplitude and phase angle. The inherent noise of the pressure transducer was found to be approximately 0.2 mm Hg, while the noise of the piezoelectric transducer was immeasurably low. The piezoelectric phonotransducers were superior to micromanometer transducers in their higher gain and lower noise, suggesting that these transducers may prove useful to physiologic and clinical studies for measuring intravascular sound.

Cardiac Catheterization↗
PubMed1989

Separate binding sites for intact PTH 1-84 and synthetic PTH 1-34 in canine kidney.

The present studies examine the characteristics of parathyroid hormone (PTH) receptor binding in canine basolateral renal cortical membranes using iodinated preparations of intact bovine PTH 1-84 and [Nle8,Nle18,Tyr34] bPTH 1-34 amide. A solid phase lactoperoxidase technique was used to iodinate the bPTH 1-84. The PTH 1-34 analog was iodinated using chloramine T. Both radioligands were purified by reverse phase high pressure liquid chromatography (HPLC). Specific binding of 125I PTH 1-84 reached equilibrium at 3 hours whereas binding of the 125I PTH 1-84 analog reached equilibrium at 45 minutes. Excess bPTH 1-84 resulted in complete inhibition of binding of 125I bPTH 1-84, whereas 22 +/- 1.6% of the bound radioligand remained bound in the presence of excess synthetic bPTH 1-34. These data suggested the possibility of a binding site for the carboxy-terminal region of intact PTH, or binding sites selective for intact hormone. Therefore, additional studies were performed with PTH fragments, PTH 28-53, PTH 35-84, and PTH 53-84. In contrast to previous studies in other systems, these fragments did not result in significant displacement of 125I PTH 1-84. Analysis of binding of 125I PTH 1-84 and 125I [Nle8,Nle18,Tyr34] PTH 1-34 amide, using LIGAND, both indicated a single site model with similar affinities. Thus, the data are consistent either with multiple receptors with similar affinities or a second binding site for bPTH 1-84 on the same receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1989

Diagnosis of autoerythrocyte sensitization syndrome in the emergency department.

Autoerythrocyte sensitization syndrome is characterized by sudden and spontaneous painful bruising and swelling occurring in young female patients with psychiatric disorders. This syndrome may present with such severe swelling of involved areas that aspiration or excision may be needed to relieve pressure. The presentation of this condition in the emergency department must be differentiated from more common coagulopathies. Differentiation from the self-mutilation disorder, which often presents to the ED, can be difficult. Although the pathogenesis is uncertain, purpuric lesions are reproduced by injections of washed red cell erythrocyte stroma, suggesting an autoimmune etiology. We describe a patient with recurrent bruising diagnosed in the ED who responded with classic inflammation to autologous injection of red blood cells.

Adult↗
PubMed1989

Protein kinase-A and the effects of parathyroid hormone on phosphate uptake in opossum kidney cells.

Current evidence indicates that signal transduction after receptor binding of PTH involves the stimulation of adenylate cyclase as well as stimulation of phosphoinositide metabolism. Recent studies, showing that PTH alters phosphate transport in opossum kidney cells at concentrations which do not increase cAMP production and that activators of protein kinase-C also alter phosphate transport, have led to the suggestion that there is a dual mechanism for the regulation of phosphate transport by PTH, namely, protein kinase-C at physiological levels of PTH and cAMP at higher levels of PTH. The present studies were designed to evaluate the relationship between cAMP-dependent protein kinase (PK-A), a more sensitive indicator of alterations in cAMP metabolism than measurements of total cellular cAMP, and phosphate transport in opossum kidney cells, in response to bovine (b)PTH 1-34 and [Nle8,Nle18,Tyr34]bPTH 3-34 amide. While bPTH 1-34 markedly stimulated cAMP accumulation (half-maximal stimulation between 1 and 10 nM), PTH 3-34 analog did not. Phosphate transport was inhibited in a dose-dependent manner by bPTH 1-34, with half-maximal effect occurring between 0.1 and 1 nM. [Nle8,Nle18,Tyr34]bPTH 3-34 amide also altered phosphate transport, although this peptide was 3 orders of magnitude less potent than bPTH 1-34. PK-A activity increased in response to bPTH 1-34 and correlated closely with the effects of PTH on phosphate transport. [Nle8,Nle18,Tyr34]bPTH 3-34 amide, which did not appear to increase cAMP, also resulted in a significant increase in the activity of PK-A. Studies of inhibition of cAMP accumulation using 2',5'-dideoxyadenosine demonstrated that while this agent markedly inhibited the accumulation of cAMP in response to PTH, the effects of PTH on phosphate transport were not altered. However, in spite of the reduction in cAMP the activation of PK-A was similar to control. These data indicate that the effects of PTH peptides on phosphate transport are more closely related to changes in the activity of PK-A than to levels of total cAMP. Activation of PK-A in response to PTH is demonstrable at the lowest doses of PTH that alter phosphate transport.

Animals↗