Wire-guided transoral esophagogastrostomy for carcinoma of the cervical esophagus.
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Anastomosis, Surgical↗
Biomedical subjects
M Oka
Publications and source records attributed to M Oka.
Anisotropy of osteoporotic cancellous bone.
To investigate the mechanism underlying femoral neck fracture, it is necessary to determine the various mechanical properties, including the bone strength, of the primary compressive group. We investigated the mechanical anisotrophy of the primary compressive group by comparing differences in its mechanical properties, depending on the loading direction. Twenty-three femoral heads of 20 female and 3 male patients with femoral neck fracture were studied. The mean age of these patients was 79.9 years (range, 63-98 years). A total of 82 cubic specimens (6.5 mm in length) were obtained (one to six specimens from each femoral head). The specimens obtained from each femoral head were randomly assigned into two groups: parallel and perpendicular. The parallel group included 43 specimens, and the perpendicular group included 39 specimens. A compressive load was applied either parallel or perpendicular to the primary compressive group of the specimens in each respective group. Three parameters were obtained: compressive stiffness, maximum stress, and maximum energy. We calculated the regression of three parameters against the square of the apparent dry density. These mechanical properties were compared between the two groups by testing the difference of the slopes in two regression lines by using analyses of covariance, in which two main effects of group (nominal value) and the square of the apparent dry density (continuous value) and an interaction between two factors were modeled. Three parameters were significantly correlated with the square of the apparent dry density in both groups. In all three measurements, the difference of the slopes between two regression lines was significantly different. This means that all three measurements decreased in the parallel group more than in the perpendicular one, as apparent dry density decreased. We consider that the bone strength of the proximal femur decreases more when stress is applied in the longitudinal direction (as in walking) and less when stress is applied in the transverse direction (as in a fall) when bone density decreases.
Aged↗
Tumour cells engineered to secrete interleukin-15 augment anti-tumour immune responses in vivo.
We examined the effect of interleukin-15 (IL-15) gene transfer into tumour cells on the host's anti-tumour response. In BALB/c mice IL-15 producing Meth-A cells (Meth-A/IL-15) underwent complete rejection, in a response characterized by massive infiltration of CD4+ T-cells and neutrophils. In contrast, Meth-A cells transfected with vector alone (Meth-A/Neo) grew rapidly. Moreover, rechallenged parental cells also were rejected in association with CD8* T-cell infiltration. However, in nude mice there was no drastic difference between Meth-A/IL-15 and Meth-A/Neo cells. These results demonstrate that IL-15-secreting tumour cells can stimulate local and systemic T-cell-dependent immunity and therefore may have a potential role in cancer therapy.
Animals↗
The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma.
Recently, nm23-H1, an anti-metastasis gene, has been reported to correlate with sensitivity to chemotherapeutic agents including cisplatin in human breast and ovarian carcinoma cells. The aim of this study was to evaluate a role for nm23-H1 in responsiveness to cisplatin-based chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC). The expression of nm23-H1 protein was examined immunohistochemically in 32 eligible patients with OSCC who underwent adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil after tumour resection. Fifteen (46.9%) of 32 patients were positive for nm23-H1 staining and 17 (53.1%) were negative. Both disease-free survival and overall survival rates of nm23-H1-negative patients were significantly shorter than in nm23-H1-positive patients (P < 0.01 for both). There was no significant difference in clinicopathologic characteristics between nm23-H1-positive and nm23-H1-negative groups. Multivariate analysis also showed that nm23-H1 expression was the most significant factor for overall survival of OSCC patients included in this study (P = 0.0007). To further study the role of nm23-H1, a human OSCC cell line (YES-2) was transfected with a plasmid containing a fragment of the nm23-H1 cDNA in an antisense orientation. Reduced expression of nm23-H1 protein in the antisense-transfected (AS) clones was found by Western blot analysis as compared to wild-type YES-2 and YES-2/Neo (clone transfected with the neomycin resistance gene alone). MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assay showed that reduced expression of the nm23-H1 protein in AS clones was consistent with the degree of increased resistance to cisplatin but not etoposide or 5-fluorouracil. These data support the conclusion that reduced expression of nm23-H1 may be associated with resistance to cisplatin, suggesting the value of nm23-H1 expression as a prognostic marker for OSCC patients who are to undergo cisplatin-based chemotherapy.
Aged↗
Blockade by NS-7, a neuroprotective compound, of both L-type and P/Q-type Ca2+ channels involving depolarization-stimulated nitric oxide synthase activity in primary neuronal culture.
The effect of 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride (NS-7), a neuroprotective compound, on Ca2+ channels involving the activation of nitric oxide synthase (NOS) was investigated in primary neuronal culture. The NOS activity was estimated from the cyclic GMP formation. The KCl (25 mM)-stimulated cyclic GMP formation was totally abolished by a combined treatment with nifedipine and omega-agatoxin IVA (omega-Aga), whereas spontaneous cyclic GMP formation was partially but significantly reduced by nifedipine. In contrast to nifedipine, NS-7 blocked KCl-stimulated cyclic GMP formation without affecting spontaneous cyclic GMP formation. Subsequently, the effects of nifedipine and NS-7 on L-type Ca2+ channels were compared. Nifedipine blocked equally the cyclic GMP formation stimulated by various concentrations of (+/-)-Bay K 8644, whereas NS-7 inhibited the maximal response without affecting the responses induced by low concentrations of (+/-)-Bay K 8644. The effects of NS-7 on L-type and P/Q-type Ca2+ channels involving KCl-stimulated cyclic GMP formation were subsequently examined. NS-7 suppressed the KCl-stimulated cyclic GMP formation measured in the presence of omega-Aga to almost the same extent as that determined in the presence of nifedipine. In contrast, NS-7 had no influence on ionomycin-induced enhancement of cyclic GMP formation. Finally, NS-7 reversed KCl-induced elevation of the intracellular free Ca2+ concentration. These findings suggest that NS-7 inhibits NOS activation in primary neuronal culture by reducing Ca2+ entry through L-type and P/Q-type Ca2+ channels, in which the inhibition is largely dependent on Ca2+ channel activity.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
A high-fat diet aggravates tubulointerstitial but not glomerular lesions in obese Zucker rats.
BACKGROUND: Despite a large body of evidence that manipulation of dietary fat alters glomerular lesions, reports regarding the effects of dietary fat on tubulointerstitial lesions are limited. Obese Zucker rats (OZR) spontaneously develop glomerular and tubulointerstitial lesions in association with hyperlipidemia. We sought to elucidate the effects of dietary fat on glomerular and tubulointerstitial lesions in OZR versus lean Zucker rats (LZR) and to assess the involvement of macrophages in the development of these lesions. METHODS: We fed LZR and OZR either a low- (1%) or high-fat (20%) diet. After 30 weeks of the specified diet, the creatinine clearance (Ccr) and renal histology as well as plasma lipid concentrations were examined. For morphological evaluation, glomerular sclerosis (GSI) and tubulointerstitial indices (TII) were each determined by a point-counting method. Infiltrating macrophages were stained immunohistochemically using an avidin-biotin complex technique. RESULTS: The high-fat diet increased the plasma low-density lipoprotein concentration in OZR. Both low- and high-fat OZR groups had higher GSI and TII than LZR receiving either diet. The high-fat diet aggravated TII but not GSI or Ccr in OZR; conversely, high fat intake worsened GSI and Ccr but not TII in LZR. Tubulointerstitial macrophages were most prominent in the high-fat OZR group, followed by the low-fat OZR group. Glomerular macrophages were similar in number in all groups. CONCLUSIONS: The manipulation of dietary fat has diverse effects on the kidney. A high-fat diet aggravated macrophage-mediated tubulointerstitial lesions in OZR, whereas in LZR, the diet induced glomerulosclerosis.
Albuminuria↗
Protective effect of lactosucrose on intracolonic indomethacin-induced small-intestinal ulcers in rats.
BACKGROUND: Little is known about the role of intestinal microflora in the development of indomethacin-induced enteropathy. The aim of this study was to evaluate the effects of lactosucrose, an indigestible oligosaccharide, on intestinal microflora and on indomethacin-induced enteropathy in rats. METHODS: Male Wistar rats were fed either sucrose (SC) or lactosucrose (LS) for 2 weeks. Indomethacin (24 mg/kg/ day) was administered into the colon twice, 24 h apart, and intestinal ulcers in SC and LS groups were compared macroscopically. In another experiment the bacterial composition in the mid-small-intestinal segment was determined in both groups before and after treatment with indomethacin. RESULTS: After indomethacin treatment small-intestinal ulcers were less severe in the LS than in the SC group (ulcer index: median, 0.13 (range, 0.05-0.19) versus 0.23 (0.13-0.34); P < 0.05). Total bacterial count did not differ significantly between the two groups. Indomethacin increased the number of Enterobacteriaceae in both groups, but the increase was less in the LS group. The number of streptococci was also significantly increased in the SC group but not in the LS group. CONCLUSION: These results suggest that LS has some protective effects on indomethacin-induced enteropathy and that this protective effect is in part due to the maintenance of intestinal microflora.
Animals↗
Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells.
In this paper, we provide direct evidence that glutathione S-transferase pi (GSTpi) detoxifies cisplatin (CDDP). We used human colonic cancer HCT8 cells sensitive and resistant to CDDP, the level of cisplatin-glutathione adduct (DDP-GSH) being higher in the resistant cells. There was an overexpression of GSTpi mRNA in these CDDP-resistant cells. Incubation of the cells with CDDP resulted in the formation of DDP-GSH dependent on the CDDP concentration and the incubation time. The formation of DDP-GSH was abolished when the cells were pre-treated with ethacrynic acid or ketoprofen, inhibitors of GSTpi. Purified GSTpi also catalyzed the formation of DDP-GSH in vitro, with an apparent Km of 0.23 mM for CDDP and an apparent Vmax of 4.9 nmol/min/mg protein. The increase in DDP-GSH produced by GSTpi was linear with incubation time up to 3 h and optimal of pH 7.4. A GSTpi transfectant cell line was constructed in HCT8 cells using a pcDNA3.1 (-)/Myc-His B with an expression vector containing cDNA for GSTpi. Transfection of GSTpi cDNA into HCT8 cells resulted in an increase in the expression of GSTpi by 1.4-fold in parallel with an augmentation of the formation of DDP-GSH. These results suggest that GSTpi plays a role in the formation of DDP-GSH and the acquisition of resistance to CDDP in cancer cells.
Cisplatin↗
Auxin polar transport and flower formation in Arabidopsis thaliana transformed with indoleacetamide hydrolase (iaaH) gene.
Involvement of auxin polar transport in flower formation of Arabidopsis thaliana was studied using a pinformed (pin) mutant (Rpin) transformed with the indoleacetamide hydrolase (iaaH) gene and the phenocopy of the pin mutant, which was induced by 9-hydroxyfluorene-9-carboxylic acid (HFCA). The application of indoleacetamide (IAM) did not change aberrant structure of the aerial part of Rpin (pin/pin), but extremely inhibited its root growth. Treatment with IAM increased the endogenous concentrations of free and conjugated IAA in Rpin normal (pin/+ or +/+) due to the expression of the iaaH gene, to 140% and 428% of those in non-treated plants, respectively, and those in Rpin to 378% and 120%, respectively. The activity of IAA polar transport in the inflorescence axis of Rpin remained low even in the presence of IAM, the activity being almost similar, to that in the pin mutant. The activity of IAA polar transport in the HFCA-induced phenocopy of the pin mutant was also extremely low, and it was not restored by the simultaneous application of IAA. Arabidopsis thaliana responded to HFCA applied from 7 to 11 d and from 25 to 29 d after germination in the wild-type plant (Enkheim ecotype) and the late flowering mutant (fb mutant), respectively. These results suggest that the construction of the system of auxin polar transport and its normal activities are essential for the differentiation and the formation of floral meristem in the early growth stage of Arabidopsis thaliana.
Amidohydrolases↗
Tc-99m colloid and Ga-67 imaging of splenic inflammatory pseudotumor correlation with ultrasound, CT, and MRI.
Splenic inflammatory pseudotumor is extremely rare and may mimic splenic neoplasms, such as lymphomas or hamartomas, clinically and radiologically. A case of a surgically proved splenic inflammatory pseudotumor is presented in which Tc-99m colloid SPECT and Ga-67 scintigraphy characterized the changes in the spleen, but the findings of ultrasound and unenhanced CT and MRI were nonspecific. This report indicates the utility of radionuclide imaging for diagnosing splenic inflammatory pseudotumor.
Gallium Radioisotopes↗
E4021, a selective phosphodiesterase 5 inhibitor, potentiates the vasodilator effect of inhaled nitric oxide in isolated perfused rat lungs.
To test whether E4021, a potent selective cyclic guanosine 3'-5'-monophosphate (cGMP) phosphodiesterase inhibitor, causes pulmonary vasodilation and whether it enhances the vasodilator action of inhaled nitric oxide (NO), we studied its effects on pulmonary vascular tone and inhaled NO-induced pulmonary vasodilation in isolated perfused rat lungs. Lungs were perfused at a constant flow rate with salt-Ficoll solution and ventilated with air plus 5% CO2. After equilibration, vasodilator responses to either E4021, inhaled NO, or both were evaluated under conditions of increased perfusion pressure induced by infusion of U46619. E4021 had no effect on the baseline perfusion pressure, whereas it caused dose-dependent pulmonary vasodilation when the vasomotor tone was increased by U46619. Inhaled 1, 5, and 20 ppm NO reduced the increased perfusion pressure by 60+/-5%, 83+/-3%, and 92+/-2%, respectively. Pretreatment with E4021 significantly potentiated the vasodilator effect of 1 ppm NO (from 53+/-6% to 71+/-2%; p < 0.05) but did not alter that of 5 ppm NO (from 77+/-3% to 78+/-4%; p > 0.05). In addition, pretreatment with E4021 significantly augmented the vasodilator response to sodium nitroprusside but not to isoproterenol. These results indicate that E4021 causes pulmonary vasodilation and potentiates the vasodilator effect of low concentrations of inhaled NO, probably through a cGMP-dependent mechanism in salt-solution perfused rat lungs. We conclude that E4021 may possibly be useful for the treatment of pulmonary hypertension, either alone or in combination with inhaled NO.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988-991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 microg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 +/- 132 versus 995 +/- 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% +/- 22.1%) and high at neutrophilia with rhG-CSF therapy (73. 0% +/- 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r2 = 0.91; P < 0.0001) and neutrophil count (r2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.
Adjuvants, Immunologic↗
Chronic hypoxia augments endothelin-B receptor-mediated vasodilation in isolated perfused rat lungs.
To investigate whether chronic hypoxia affects endothelin-B (ETB) receptor-mediated pulmonary vasodilation, we compared the vasodilator responses to IRL-1620, a selective ETB-receptor agonist, in isolated perfused lungs from normoxic and chronically hypoxic adult male rats. IRL-1620 caused a dose-dependent vasodilation that was greater in the hypertensive lungs than in the normotensive lungs. In normotensive lungs, a nitric oxide (NO) synthase inhibitor, Nomega-nitro-L-arginine (L-NNA; 300 microM), and an ATP-sensitive potassium (KATP)-channel inhibitor, glibenclamide (Glib; 10 microM), each reduced the vasodilator response to IRL-1620 (1 nM), but the combination of L-NNA and Glib inhibited it more effectively than either drug alone. In contrast, L-NNA alone, but not Glib alone, completely blocked IRL-1620-induced vasodilation in hypertensive lungs. The vasodilator response to a KATP-channel opener, NIP-121 (1 microM), but not the response to sodium nitroprusside (1 microM), was enhanced in hypertensive lungs. We also found increased expression of mRNA for the ETB receptor in lung tissue after hypoxic exposure. In addition, semiquantitative immunohistochemistry demonstrated higher expression levels of ETB receptors in the endothelium of distal segments of the pulmonary artery in hypoxic than in normoxic rats. These results suggest that ETB receptor-mediated pulmonary vasodilation is augmented after chronic hypoxic exposure and that release of NO may be the sole mechanism of this vasodilation in hypertensive lungs, whereas both release of NO and activation of KATP channels are involved in normotensive lungs. We speculate that the underlying mechanism responsible for this augmentation may partly be related to upregulation of ETB receptors in the endothelium of pulmonary resistance arteries in hypertensive lungs.
Adenosine Triphosphate↗
E-4010, a selective phosphodiesterase 5 inhibitor, attenuates hypoxic pulmonary hypertension in rats.
The purpose of this study was to determine whether E-4010, a newly synthesized potent and selective orally active phosphodiesterase (PDE) 5 inhibitor, would prevent the development of chronic hypoxia-induced pulmonary hypertension in rats. In conscious, pulmonary hypertensive rats, a single oral administration of E-4010 (1.0 mg/kg) caused an acute, long-lasting reduction in mean pulmonary arterial pressure (PAP), with no significant effects on systemic arterial pressure, cardiac output, and heart rate. In rats that received food containing 0.01 or 0.1% E-4010 during the 3-wk exposure to hypoxia, mean PAP was significantly decreased (mean PAP 24.0 +/- 0.9, 16.2 +/- 0.8, and 12.8 +/- 0.5 mmHg in rats treated with 0, 0.01, and 0.1% E-4010-containing food, respectively), whereas mean systemic arterial pressure was unchanged and cardiac output was slightly increased compared with chronically hypoxic control rats. Right ventricular hypertrophy, medial wall thickness in pulmonary arteries corresponding to the respiratory and terminal bronchioles, and the degree of muscularization of more distal arteries were less severe in E-4010-treated rats. Long-term treatment with E-4010 caused an increase in cGMP levels in lung tissue and plasma but not in aortic tissue and no significant change in cAMP levels in either lung, aorta, or plasma. These results suggest that long-term oral treatment with E-4010 reduced the increase in PAP, right ventricular hypertrophy, and pulmonary arterial remodeling induced by exposure to chronic hypoxia, probably through increasing cGMP levels in the pulmonary vascular smooth muscle.
Animals↗
Effect of cautery with irrigation forceps on the remnant liver after hepatectomy in rats.
Monopolar cautery with irrigation forceps (CIF) was devised for use in liver resection that does not require occlusion of inflow to the remnant liver. However, a high power output is required to divide the hepatic parenchyma which boils the irrigation water. This study was performed to investigate the effects of using CIF on the hepatic parenchyma. Histologic and biochemical examination was performed in rats which had undergone hepatectomy using the CIF, irrigating bipolar (IB), Pringle's maneuver with blunt dissection (group P), or a sham operation. A greater cautery distance was obtained with the CIF than the IB. There was no significant difference in the remnant liver function after the 1st postoperative day in any of the groups. CIF is an effective instrument for anatomic or nonanatomic hepatic resection.
Animals↗
Localization and distribution of endothelin receptor subtypes in pulmonary vasculature of normal and hypoxia-exposed rats.
To clarify the roles of two different endothelin (ET) receptors in the pulmonary vasculature, the localization and distribution of endothelin-A (ETA) and ETB receptors were investigated in rat lung under normal and hypoxic conditions by an immunohistochemical method. We also carried out in situ hybridization for ETB receptor. In normal rats, ETA receptor is localized in the media of the pulmonary artery and vein with predominant distribution in such proximal segments as elastic arteries and large muscular arteries. ETB receptor is expressed in the intima and media of pulmonary vessels. The distribution of ETB receptor in the media predominates in the distal segments of the pulmonary artery, whereas its distribution in the intima is greater in the proximal segments. Immunoreactivity for ETA receptor increases in the media of the distal segments of the pulmonary artery after exposure to hypobaric hypoxia. Semiquantitative evaluation showed immunoreactivity for ETA receptor in the pulmonary arteries accompanying the terminal bronchioles, respiratory bronchioles, and alveolar ducts to be increased by 2.5-, 5-, and 20-fold after 14 d exposure to hypoxia, respectively. The messenger RNA and immunoreactivity for ETB receptor increased significantly in the intima of the distal segments of pulmonary artery after 7 and 14 d exposure to hypoxia. These results suggest that the vasoconstrictive effects of ET-1 are exerted mainly through ETA receptor in the proximal segments of the pulmonary artery and vein, whereas its effects in the distal segments are mediated by ETA and ETB receptors in normal rats. ETA receptors that increase in resistance arteries after exposure to hypoxia appear to play an important role in the vascular remodeling associated with hypoxic pulmonary hypertension. Because ETB receptors in the endothelium mediate ET-1-induced vasodilatory effects, the increase in endothelial ETB receptors may counteract the development of hypoxic pulmonary hypertension.
Animals↗
Dietary behaviors and sources of support in hemodialysis patients.
Individuals with chronic renal failure generally have strict dietary guidelines. This descriptive study was designed to identify the relationship between sources of social support and dietary management by Japanese hemodialysis patients. A self-administered questionnaire was completed by a convenience sample of 325 adults receiving dialysis. Subjects 65 years and older received more support from family members, doctors, nurses, and technicians than younger subjects. Subjects who had been on dialysis for less than 3 years received more support from nurses and doctors than those who had been on dialysis for longer periods of time. Multiple regression analysis identified that support from family members and nurses were significantly related to dietary behaviors. Nurses working with dialysis patients should remember to use their influence to positively support their patients and to bear in mind that long-term dialysis patients, especially those who are young and unmarried, may benefit from ongoing nursing support and encouragement.
Adult↗
Serum free insulin-like growth factor I (IGF-I), total IGF-I, and IGF-binding protein-3 concentrations in normal children and children with growth hormone deficiency.
To evaluate the role of serum free or unbound insulin-like growth factor I (IGF-I) on bone growth, we measured serum free IGF-I levels in 354 healthy children and adults (193 males and 161 females, aged 0-40 yr) and in 21 prepubertal GH-deficient (GHD) children (complete GHD, n = 5; partial GHD, n = 16) using a recently developed immunoradiometric assay. We obtained the following results. 1) In the normal children, the serum free IGF-I levels were low in infancy (<1 yr of age; males, 0.71 +/- 0.26 microg/L, mean +/- SD; females, 1.05 +/- 0.49 microg/L), increased during puberty (males, 5.84 +/- 2.18 microg/L; females, 5.80 +/- 1.49 microg/L), and declined thereafter. 2) Free IGF-I in the serum occupied about 0.95-2.02% of the total IGF-I values, with the highest ratio occurring in infancy (males, 1.77 +/- 0.60%; females, 2.02 +/- 0.87%). 3) The SD scores of serum free IGF-I in the 21 GHD children ranged from -3.30 to 0.30, and the 5 complete GHD children had free IGF-I values more than -2 SD below those of age-matched normal subjects. 4) There was a significant correlation between the SD scores of free IGF-I and those of total IGF-I (r = 0.715; P < 0.0005) in the GHD children. 5) In the 16 partial GHD children receiving GH treatment, the serum free IGF-I levels were elevated to 209% of pretreatment levels after 1 month of GH treatment and remained high during GH therapy. The GH-induced increase in the serum free IGF-I levels was significantly higher than those of the total IGF-I and IGF binding protein-3 levels. 6) The percent increase in the serum free IGF-I level after 1 month of GH treatment showed a significant positive correlation with that of the GH-induced improvement in the percent increase in the height velocity during 1 yr of GH therapy (r = 0.526; P < 0.05). These results show that free IGF-I in the serum has an essential role in bone formation because the higher free IGF-I levels were observed when the growth rate accelerated. The measurement of serum free IGF-I may become a useful tool for both diagnosing GH deficiency and predicting growth responses to long term GH therapy.
Adolescent↗