Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 289 records · Page 16Linked to original sources

PubMed1997

Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning.

1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.

Alopecia↗

PubMed1997

Induction of the 2B9 antigen/dipeptidyl peptidase IV/CD26 on human natural killer cells by IL-2, IL-12 or IL-15.

Activation of human natural killer (NK) cells involves sequential events including cytokine production and induction of cell surface molecules, resulting in the enhancement of cytolytic activity. To delineate the activation process of NK cells, we generated murine monoclonal antibodies (mAbs) against YT, a human large granular lymphocyte/natural killer (LGL/NK) cell line. Among the mAbs reactive with YT cells, one mAb, termed 2B9, was noted because of the lack of reactivity with most of the human T- and B-cell lines tested. In fresh peripheral blood mononuclear cells (PBMC), however, the majority of cells expressing this antigen (Ag) were T cells but not CD16+ nor CD56+ NK cells. Since YT cells showed an activated phenotype expressing interleukin-2 (IL-2) receptor alpha chain, we examined whether 2B9 Ag could be induced on normal human peripheral blood NK cells by cytokines known to activate NK cells. The 2B9 Ag was induced on NK cells by IL-2, IL-12 or IL-15 while no induction was observed by interferon-gamma (IFN-gamma). Biochemical analysis showed that anti-2B9 mAb recognized a 115 kDa molecule in YT cells. A cDNA clone encoding the 2B9 Ag was isolated from a cDNA expression library of YT cells and its sequence was identical to CD26 cDNA although it was not of full length. Transient expression of the 2B9 cDNA on COS-7 cells revealed that this cDNA encodes the antigenic epitope(s) recognized by anti-2B9 mAb as well as Ta1, an anti-CD26 mAb. These results showed that the 2B9 Ag is identical to CD26, and demonstrated that CD26 is an activation antigen on CD16+ CD56+ NK cells inducible by IL-2, IL-12 or IL-15.

Antibodies, Monoclonal↗

PubMed1997

Serum androgen levels in hyperthyroid women.

Thyroid hormone is known to affect androgen metabolism, however, there are few studies in which alterations of androgen metabolism are simultaneously examined in patients with clinical thyroid disorders. In this study, we investigated the alterations of thyroid hormone and androgens before and during treatment in patients with hyperthyroidism. Fifteen female patients with hyperthyroidism due to Graves' disease were studied. From these patients, blood samples were obtained before treatment and at 1 month (M), 2M, 3M, 4M and 6M after beginning of treatment. Concentrations of free T4(FT4), free T3(FT3), testosterone (T), androstenedione (delta 4A), dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha, 17 beta-diol(3 alpha-diol) and androsterone (AD) and sex hormone binding globulin (SHBG) were measured by radioimmunoassays (RIAs) or immunoradiometric assay (IRMA). As normal controls, ten healthy women were also studied. Before treatment concentrations of DHT (mean +/- SD: 3.35 +/- 0.78 nmol/L), 3 alpha-diol (0.78 +/- 0.11 nmol/L), AD (6.73 +/- 0.64 nmol/L) and SHBG (184.9 +/- 68.1 nmol/L) were significantly elevated compared with those of normal controls. T and delta 4A levels were not significantly different from normal values. DHT/T ratio indicating 5 alpha-reductase activity was 4.62 +/- 2.55 and significantly higher than that in normal controls. At 2 months after beginning of treatment with anti-thyroid drugs, thyroid function (FT4 and FT3) became normal and at 3 months after beginning of treatment, DHT, 3 alpha-diol, AD and DHT/T ratio decreased to normal range. SHBG level was gradually decreased, however still higher than that of the normal control group at 6 months after beginning of treatment. There was a time lag in recovery between serum androgen levels and SHBG level.

Adult↗

PubMed1997

The management of cervical incompetence with protruded membranes into the vagina by vaginal irrigation with granulocyte elastase inhibitor: ulinastatin and PVP-iodine solution.

In an attempt to prevent preterm premature rupture of the membranes (PPROM) and to prolong the duration of pregnancy in patients with a dilated cervix and with the membranes protruding into the vagina, the combination therapy of irrigation with a solution containing granulocyte elastase inhibitor (ulinastatin) and PVP-iodine onto the membranes, as well as the use of antibiotics and tocolytic agents, was tested. Ten patients with protruding membranes were treated by this combination therapy and five patients were instructed to have strict bedrest without any medication. In the non-treated group, all patients were delivered within 2 days of admission and all babies had a poor prognosis. In the treated group, the pregnancy was prolonged by between 3 and 108 days (mean values 33.6 days). Only two out of 10 patients had PPROM. In cases with protruding membranes, this combination therapy seemed to be useful in preventing rupture and so prolonging the pregnancy and increasing the survival rate of the infants.

Journal Article↗

PubMed1997

Dp260 disrupted mice revealed prolonged implicit time of the b-wave in ERG and loss of accumulation of beta-dystroglycan in the outer plexiform layer of the retina.

Dp260 is a C-terminal isoform of dystrophin and is expressed specifically in the retina. Abnormal electroretinograms (ERG) in some Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients are likely linked to a disruption of Dp260. To clarify the importance of Dp260 in the retina, we examined dystrophin exon 52 knock-out mice, whose expression of Dp260 is impaired. We also confirmed the localization of Dp260 in the outer plexiform layer (OPL) of the retina. Disruption of Dp260 causes a change in the localization of beta-dystroglycan, which is normally found in the OPL of the retina. This suggests a requirement for Dp260 for normal formation of the dystrophin-dystroglycan complex in the retina. Dp71, also expressed in the retina, was, however, not detected in the OPL. The difference in localization of Dp260 and Dp71 implies that the two isoforms have different functions. The dystrophin exon 52 knock-out mice had a prolonged implicit time of the b-wave in ERG, although no significant change was observed in amplitude. These ERG findings differed from those of DMD and BMD patients, especially with regard to amplitude of the b-wave, but make it clear that Dp260 is required for normal electrophysiology.

Animals↗

PubMed1997

Activation of plasma kinin system correlates with severe coagulation disorders in patients with ovarian hyperstimulation syndrome.

The aim of this study was to evaluate status of plasma kinin system in patients with ovarian hyperstimulation syndrome (OHSS), in order to investigate whether activation of the plasma kinin system correlates with increased blood coagulability. In the first part of the study, concentrations of plasma prekallikrein (PK) in OHSS cycles (n = 13) were monitored from the day of human chorionic gonadotrophin (HCG) administration to the mid-luteal phase, and were compared with those of control cycles (n = 17). The average value of PK in OHSS cycles began to decrease on day 8, and by day 10 was significantly lower than that of control cycles (86 +/- 6 versus 106 +/- 4%, P <0.01). The time course of changes in PK concentration correlated well with the clinical condition of OHSS patients. In the second part of the study, we obtained data from 26 patients who were hospitalized because of severe OHSS, to investigate the correlation between PK and other haemostatic markers. OHSS patients with severe PK reduction (<80% normal, n = 9) demonstrated significantly higher values of plasma thrombin-antithrombin III and plasmin-alpha2 antiplasmin, and more severe haemoconcentration, compared to those OHSS patients who had no reduction in PK (n = 17). In conclusion, our data suggest that activation of the plasma kinin system occurs specifically and occasionally in OHSS patients, and is associated with increased blood coagulability. Thus, when an OHSS patient demonstrates a low value of plasma PK, more careful management is required to prevent thromboembolic complications.

Adult↗

PubMed1997

The effect of nasal continuous positive airway pressure on plasma endothelin-1 concentrations in patients with severe cardiogenic pulmonary edema.

We investigated the effects of nasal continuous positive airway pressure (CPAP) on plasma endothelin-1 (ET-1) concentrations in patients with cardiogenic pulmonary edema. Thirty patients were randomly assigned to two groups: 15 patients who received oxygen plus nasal CPAP (CPAP group), and 15 patients who received only oxygen by face mask (oxygen group). The heart rate and the mean pulmonary artery pressure decreased significantly in the CPAP group. The PaO2/ fraction of inspired oxygen (FIO2) ratio increased in the CPAP group (163 +/- 70 to 332 +/- 104, P < 0.01) after 6 h and was significantly higher than that in the oxygen group. Arterial plasma ET-1 concentrations decreased from 6.2 +/- 2.0 pg/mL to 4.8 +/- 1.7 pg/mL (P < 0.05) after 6 h and to 3.3 +/- 0.7 pg/mL (P < 0.01) after 24 h in the CPAP group. Arterial plasma ET-1 concentrations in the CPAP group compared with the oxygen group were significantly lower at 24 h. There was a correlation between the arterial plasma ET-1 concentrations and mean pulmonary artery pressure (r = 0.62, P < 0.001), and PaO2/FIO2 (r = -0.46, P < 0.01). Nasal CPAP led to an early decrease in plasma ET-1 concentrations, and improvement in oxygenation and hemodynamics.

Aged↗

PubMed1997

Detection of mutant K-ras in dissected paraaortic lymph nodes of patients with pancreatic adenocarcinoma.

In this study, we attempted to detect K-ras point mutations by means of two-stage polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) to diagnose micrometastases in paraaortic lymph nodes of patients with pancreatic adenocarcinoma. Main carcinoma tissues and corresponding lymph nodes in the paraaortic region were obtained from 15 patients who underwent extended radical surgery including the wide dissection of lymph nodes and who were diagnosed as lymph node negative by routine histological examination. DNA was extracted from the tissue specimens, and PCR/RFLP analysis was used to detect K-ras oncogene mutations at codon 12. Thirteen of the primary tumors were found to have K-ras mutations. In eight of the 13 cases, 42 of the 101 lymph nodes showed K-ras point mutations in the paraaortic lymph nodes. These results suggested that PCR/RFLP analysis is potentially highly sensitive for the detection of micrometastases in lymph nodes and that it may be useful in reaching an accurate assessment of the lymphatic dissemination of pancreatic adenocarcinoma at the molecular level.

Adenocarcinoma↗

PubMed1997

Delayed elevation of plasma endothelin-1 during unilateral alveolar hypoxia without systemic hypoxemia in humans.

BACKGROUND: The mechanisms by which acute alveolar hypoxia induces pulmonary vasoconstriction remain unclear. We investigated whether endothelin-1 (ET-1) could be detected in plasma during pulmonary alveolar hypoxia without systemic hypoxemia (one-lung hypoxia) and whether the levels could be related to hemodynamic status in humans. METHODS: Thirteen adult patients with primary lung carcinoma were studied prior to surgery. Anesthesia was induced with fentanyl, diazepam, and pancuronium iv. Differential lung ventilation was performed for 40 min. The right lung was ventilated with a mixture of 6% O2, 5% CO2, and 89% N2 and the left lung ventilated with 100% O2. Blood gas values, hemodynamic parameters, and plasma ET-1 levels were measured. RESULTS: Mean pulmonary artery pressure increased from 13.0 +/- 3.5 to 17.2 +/- 3.2 mm Hg (P < 0.01) after 20 min of one-lung hypoxia. The plasma ET-1 levels in arterial blood and wedged right pulmonary arterial blood increased from 1.69 +/- 0.61 to 2.13 +/- 0.48 pg/ml (P < 0.01) and from 1.75 +/- 0.47 to 2.26 +/- 0.40 pg/ml (P < 0.001), respectively, after 40 min of one-lung hypoxia. At baseline and after 40 min of one-lung hypoxia, there was a significant correlation between the mean pulmonary artery pressure and arterial plasma ET-1 levels (r = 0.650, P < 0.01) in the wedged pulmonary arterial plasma levels (r = 0.484, P < 0.05). The increase in plasma ET-1 levels in arterial blood and in the wedged pulmonary arterial blood of the hypoxic lung occurred slowly. CONCLUSION: We concluded that ET-1 may a supporting, but not a primary, role in human hypoxic pulmonary vasoconstriction.

Aged↗

PubMed1997

Amrinone improves lung compliance in patients receiving mechanical ventilation for cardiogenic pulmonary edema.

BACKGROUND: Decrease in lung compliance is one of the major causes of respiratory failure. We investigated whether amrinone could improve lung compliance. METHODS: We selected 20 consecutive patients with respiratory failure due to severe cardiogenic pulmonary edema to receive mechanical ventilation. Patients were administered a bolus injection (1 mg.kg-1) over 10 min followed by continuous intravenous infusion (10 micrograms.kg-1.min-1) of amrinone. Lung compliance, blood gas values, hemodynamic parameters, and sample plasma amrinone levels were assessed over a 120-min period after the onset of the continuous infusion of amrinone. RESULTS: Ten min following amrinone infusion, dynamic compliance (Cdyn) and static compliance (Cst) increased from 30 +/- 11 to 36 +/- 12 ml/cm H2O and from 37 +/- 12 to 42 +/- 13 ml/cm H2O, respectively (P < 0.01). Plasma amrinone levels reached a therapeutic level as vasodilator and positive inotropic effects at 10 min after amrinone infusion. The significant change in mean pulmonary artery pressure and pulmonary artery wedge pressure occurred later than the change in compliance of respiratory system. However, there were significant correlations between the mean pulmonary artery pressure and Cdyn (r = 0.36, P < 0.01) and Cst (r = 0.44, P < 0.01), as well as between plasma amrinone levels and Cdyn (r = 0.30, P < 0.05) and Cst (r = 0.41, P < 0.01). CONCLUSIONS: Amrinone-induced improvement in lung compliance was considered mainly to be due to an increase in the number of functioning lung units by improvement of the hemodynamics and a direct positive effect of amrinone on respiratory muscle contraction.

Aged↗

PubMed1997

The combination of external high-frequency oscillation and pressure support ventilation in acute respiratory failure.

BACKGROUND: Effective gas exchange can be maintained in animals by using external high-frequency oscillation (EHFO). The present study evaluates the effect of relatively long-term duration EHFO combined with pressure support ventilation (PSV) in patients with acute respiratory failure. METHODS: Twelve patients were ventilated with EHFO combined with PSV for 8 h at 60 oscillations.min-1, with a cuirass pressure of 36 cm H2O: -26 to +10 cm H2O (27 mm Hg: -19.5 to +7.5 mm Hg) and an inspiratory-to-expiratory ratio of 1:1. Blood gas values and hemodynamic parameters were measured. RESULTS: Significant increases were noted in cardiac index (3.0 +/- 0.7 to 3.2 +/- 0.7 1.min-1.m-2, P < 0.05) and stroke volume index (32 +/- 14 to 35 +/- 13 ml.m-2, P < 0.05) without changes in pulmonary artery wedge pressure at 1 h after EHFO. PaO2 (kPa)/FiO2 and PaCO2 improved from 21.9 +/- 7.5 to 26.8 +/- 8.0 (P < 0.05) at 2 h and from 6.9 +/- 1.7 to 6.1 +/- 0.9 (P < 0.01) at 30 min after EHFO, respectively. Breath sounds could be heard well throughout the lung fields after institution of EHFO. The mucous rales also decreased. CONCLUSIONS: As a method of ventilation for patients with acute respiratory failure, EHFO combined with PSV may have potential advantages over conventional mechanical ventilation when drainage of secretions if facilitated. Beneficial effects of EHFO may appear after several hours.

Aged↗

PubMed1997

Ovarian pregnancy diagnosed in the third trimester: a case report.

We observed a patient with a primary ovarian pregnancy complicated by severe preeclampsia and a presumed fetal anomaly. Diagnosis was made at cesarean section at 30 weeks of gestation. Etoposide, given intravenously at a dose of 100 mg daily for 5 days, prevented massive bleeding during the procedure that was subsequently performed to separate the placenta.

Adult↗

PubMed1997

In-vivo assessment of extrahepatic metabolism of paeoniflorin in rats: relevance to intestinal floral metabolism.

The extraction ratios of paeoniflorin in gut wall (EG), liver (EH) and lung (EL) were assessed by comparing AUCs after various routes of its administration to estimate the first-pass effects and the metabolism by intestinal flora. Pulmonary extraction ratio of paeniflorin was assessed by comparing AUCs calculated from venous and arterial plasma concentrations after its intravenous administration (0.5 mg kg-1). The mean pulmonary extraction ratio was estimated to be 0.06. The hepatic extraction ratio (EH was assessed by comparing AUCs after intraportal and intravenous administrations (0.5 and 5 mg kg-1). The plasma concentration profiles of paeoniflorin after intraportal administration were very close to those after intravenous administration, suggesting a negligible hepatic extraction ratio of paeoniflorin. The AUC value after intraperitoneal administration (0.5 mg kg-1) was greater than that after intraportal or intravenous administration. This finding suggests that paeoniflorin is not metabolized in the gut wall. The transference of paeoniflorin from the serosal side to the mucosal side was evaluated by the in-vitro everted sac method. The low intestinal permeability (19.4% at 60 min) was demonstrated by the comparison with phenobarbital (63.1% at 60 min). We conclude that paeoniflorin is not metabolize by gut wall, liver and lung, its poor absorption from the intestine results in extremely low bioavailability and the unabsorbed fraction of paeoniflorin is degraded by the intestinal flora.

Animals↗

PubMed1997

[Relation between candidiasis and nutrition of patients and MRSA infection].

We evaluated the relation with nutritional state and methicillin-resistant Staphylococcus aureus (MRSA) infection of 20 patients who isolated Candida of 31 patients who were suspected as candidiasis. All of the patients who were hospitalized in internal medicine wards in our hospital between February 1993 and January 1994. All patients with hematological disease were excluded. MRSA is now gotten much attention as pathogen of hospital infection, but each MRSA is detected not only alone but also concomitant with other bacterium. In our hospital MRSA was detected alone 36.8% (39/106). Candida 9.4% (10/106) was frequent as mixed infectious pathogen concomitant with MRSA following Pseudomonas aeruginosa 19.8% (21/106) and Enterococcus faecalis 12.3% (13/106). Intension of host-immunity is a important factor as prevention of both infection. We evaluated the nutritional state of patients with 7 cases of infection group and 13 cases of colonization group. There was no significance between two groups as for serum total protein (mean) were 5.97 g/dl in infection group and 5.96% g/dl in colonization group. Furthermore there were significance (p < 0.01) for mean serum albumin (mean) were 3.11 g/dl v.s. 3.27 g/dl. But both serum total protein and serum albumin of these evaluated patients who isolated Candida were less than normal limit. Therefore we considered nutritional disturbance was important addition to over-use of antibiotics and severe underlying diseases as risk factor of candidiasis, and revealed the importance of improvement of nutritional state at the prevention and therapy.

Adult↗

PubMed1997

In vivo assessment of changes in air and tissue volumes after pneumonectomy.

We examined the progression and topographical distribution of postpneumonectomy volume changes in immature foxhounds undergoing right pneumonectomy (R-Pnx, n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequently raised to maturity. Volumes of lung air (Vair) and tissue (Vti) were estimated by computerized tomography (CT) scan at 7, 22, and 52 wk after surgery at a transpulmonary pressure of 20 cmH2O. Estimates of Vti by CT scan included both septal tissue as well as nonseptal tissue (small- and medium-sized airways and blood vessels); these were compared with estimates of septal Vti by an acetylene rebreathing (Rb) method. We found significant correlations between these techniques (Vair(CT) = 0.83 Vair(Rb) + 275, R = 0.97; Vti(CT) = 1.62 Vti(Rb) - 30, R = 0.81). Extravascular septal Vti returned to normal 7 wk after R-Pnx and remained normal up to maturity. Nonseptal Vti remained significantly below normal. The greatest increase in Vti occurred in the midlung region just cephalad and caudal to the heart. After an early period of accelerated tissue growth after R-Pnx, the rate of septal tissue growth matched that of somatic growth, whereas nonseptal tissue growth lagged behind. Compensatory growth of the remaining left lung was not associated with selective alterations in thoracic development.

Acetylene↗

PubMed1997

Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is highly homologous to genes encoding Xenopus importin, yeast SRP1 and human RCH1.

From a human fetal-brain cDNA library, we isolated and characterized a novel gene (KPNA3) encoding a protein highly homologous to certain nuclear transport proteins of Xenopus and human. The complete cDNA clone, designated karyopherin alpha 3, contained an open reading frame of 1,563 nucleotides encoding 521 amino acids. The predicted amino acid sequence showed 48%, 45% and 48% identity with Xenopus importin, yeast SRP1 and human RCH1, respectively. The similarities among these proteins suggest that karyopherin alpha 3 may be involved in the nuclear transport system. Eight repeats of the arm motif were well conserved among these proteins. The N-terminal region of the predicted karyopherin alpha 3 product was highly basic and the C-terminal region was strongly acidic. A 4.3-kb transcript was expressed in all adult human tissues examined by Northern blotting. The cDNA clone was assigned to chromosome band 13q14.3 by fluorescence in situ hybridization.

Amino Acid Sequence↗

PubMed1997

Cloning, expression and mapping of a novel human zinc-finger gene TCF17 homologous to rodent Kid1.

We isolated a novel human zinc-finger gene TCF17 homologous to rat Kid1, a zinc-finger gene of the Krüppel type expressed predominantly in kidney. In the rat this gene seems to be a transcription factor expressed in response to renal injury and ischemia. The 2435-bp human cDNA contained an open reading frame encoding 605 amino acids. The deduced amino acid sequence showed 86.0% and 87.2% identity (91.6% and 92.8% similarity) with the rat Kid1 and mouse Tcf17 respectively. In contrast with rat Kid1, human TCF17 was expressed in all human tissues examined, including kidney. This gene was mapped by FISH to chromosome 5q35.3, where cytogenetic and molecular abnormalities have been reported often in renal cell carcinomas.

Animals↗

PubMed1997

Localization of low-KM cAMP phosphodiesterase in rat nephron segments.

To evaluate the roles of cAMP degradation on hormonal actions in the kidney, we examined the segmental distribution and activities of cAMP-phosphodiesterase (PDE), a key enzyme for cAMP hydrolysis, in dissected segments of the rat nephron and characterized the isozyme compositions with subtype-specific inhibitors. Summary of the nephron distribution of PDE activities showed that cAMP-PDE activities were detected in all nephron segments and the distal convoluted tubules (DCTs) had the highest activity. Both in proximal convoluted tubules (PCTs) and medullary collecting ducts (MCDs), more than 80% of the total cAMP-PDE activities were inhibited by a nonspecific PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX). In PCTs, rolipram (type-IV PDE inhibitor) was an equally potent inhibitor of IBMX, while 8-methoxymethyl-IBMX (MM-IBMX, type-I PDE inhibitor) and cilostamide (type-III PDE inhibitor) inhibited cAMP-PDE by 35 and 57%, respectively. In MCDs, inhibition by rolipram (40%) was less than that by MM-IBMX (70%) or cilostamide (66%). Rolipram potentiated the parathyroid hormone (PTH)-induced cAMP content in PCTs most effectively. Rolipram and MM-IBMX increased the vasopressin (AVP)-stimulated cAMP content equally in MCDs. Cilostamide had no effect on the cAMP content stimulated by PTH or AVP in PCTs and MCDs. These results indicate that PDE activities were unevenly distributed along the rat nephron and cAMP-PDE was composed of at least three isoforms, namely type I, III and IV in PCTs and MCDs. Among these, type-IV PDE was responsible for hydrolysis of cAMP in PCTs, and type-I and IV PDE were responsible for that in MCDs.

3',5'-Cyclic-AMP Phosphodiesterases↗