Biomedical subjects

H Kohno

Publications and source records attributed to H Kohno.

At least 91 records · Page 5Linked to original sources

PubMed2000

Body mass index determines the success of lymph node dissection and predicts the outcome of gastric carcinoma patients.

We tried to determine the role of the body mass index (BMI) on the extent of lymph node dissection in gastric cancer surgery. Seven hundred and eighty-seven patients with gastric carcinoma were reviewed. Ninety-two (11%) patients exceeded the upper limit of the optimum BMI. Significantly fewer lymph nodes were removed following D2 (p = 0.002) and >/=D3 (p = 0.023) dissections, and the lymph node ratio was significantly (p = 0.0383) higher in overweight patients. The recurrence-free survival was significantly (p = 0.0297) shorter in T2/T3 cases with high BMI, and BMI (relative risk 1.85) became an independent prognostic factor in multivariate analysis. Higher BMI hampers regional lymph node dissection in gastric cancer patients and became an independent predictor of disease recurrences in T2/T3 gastric cancers.

Aged↗

PubMed2000

Involvement of transglutaminase in the receptor-mediated endocytosis of mouse peritoneal macrophages.

We investigated the effect of extracellular Ca2+ on the uptake of immunoglobulin G (IgG)-coated normal sheep red blood cells (SRBC) by the mouse peritoneal macrophages. The uptake of SRBC was dose dependently enhanced by Ca2+ concentration. We also investigated the effect of ryanodine on the uptake of SRBC. Ryanodine showed approximately 15% inhibition of the uptake. The activity of transglutaminase (TGase) in the cytosolic fraction of macrophages was enhanced as the Ca2+ concentration increased. The uptake of SRBC decreased by the addition of histamine, a TGase inhibitor. These results suggest that TGase is involved in the receptor-mediated endocytosis system of mouse peritoneal macrophages.

Animals↗

PubMed2000

Prevalence of GH-1 gene deletion in patients with isolated growth hormone deficiency in Japan. GH Gene Study Group.

A multicenter study was carried out to investigate the prevalence of growth hormone (GH-1) gene deletions among patients with isolated growth hormone deficiency (IGHD) and extremely short stature in Japan, using PCR method. Genomic DNA was extracted from the whole blood samples of 48 patients (34 males and 14 females) at 20 hospitals. All the patients fulfilled the inclusion criteria as follows: (1) IGHD patients whose every peak serum GH level in more than two tests <5 ng/ml and (2) pretreatment height < -- 3SD, regardless of family history and facial feature characteristic of GH-1 gene deletion. The subjects were screened for deletions in GH-1 gene, using a PCR method that could identify deletions of 6.7, 7.0 and 7.6 kbp. Three (6.25%) out of 48 subjects were found to have such deletion fragments. The first case was a boy homozygous for deletion of 6.7 kbp fragments. The second case was a girl heterozygous for 6.7 kbp deletion. A direct sequence analysis revealed a 2-bp deletion in exon 3 on the remaining allele that created a stop codon in exon 4. The third case was a boy also heterozygous for 6.7 kbp deletion. By direct sequencing analysis, three point mutations were detected in the promoter region on the opposite allele together with a four-base addition at base 250. One of the mutations was in the area of Pit-1 binding site (at base - 123). The latter two cases apparently represent new types of compound heterozygote of GH-1 gene deletion. Our results suggest that GH-1 gene mutation is not so rare in extremely short IGHD children in Japan.

Body Height↗

PubMed2000

Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats.

The modifying effects of dietary feeding of a polyisoprenylated benzophenone, garcinol, isolated from Garcinia indica fruit rind on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of garcinol on proliferating cell nuclear antigen (PCNA) index in ACF and activities of detoxifying enzymes of glutathione S-transferase (GST) and quinone reductase (QR) in liver. In addition, we examined the effects of garcinol on 12-O-tetradecanoylphorbol-13-acetate-induced O(2)(-) generation in differentiated human promyelocytic HL-60 cells and lipopolysaccharide (LPS)- and interferon (IFN)-gamma-induced nitric oxide (NO) generation in mouse macrophage RAW 264.7 cells. Western blotting analysis of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression was done in LPS- and IFN-gamma-treated mouse macrophage RAW 264.7 cells. Rats were given subcutaneous injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce ACF. They also received the experimental diet containing 0.01 or 0.05% garcinol for 5 weeks, starting 1 week before the first dosing of AOM. AOM exposure produced 97 +/- 15 ACF/rat at the end of the study (week 5). Dietary administration of garcinol caused significant reduction in the frequency of ACF: 72 +/- 15 (26% reduction, P < 0.01) at a dose of 0.01% and 58 +/- 8 (40% reduction, P < 0.001) at a dose of 0.05%. Garcinol administration significantly lowered PCNA index in ACF. Feeding of garcinol significantly elevated liver GST and QR activities. In addition, garcinol could suppress O(2)(-) and NO generation and expression of iNOS and COX-2 proteins. These findings might suggest possible chemopreventive ability of garcinol, through induction of liver GST and QR, inhibition of O(2)(-) and NO generation and/or suppression of iNOS and COX-2 expression, on colon tumorigenesis.

Animals↗

PubMed2000

Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients.

The role of cyclooxygenase-2 (COX-2) in tumor neovascularization of human colorectal carcinoma is yet to be delineated. One hundred colorectal carcinoma specimens were evaluated for COX-2 expression and CD34-stained microvessel density (MVD) by immunohistochemical methods. The relationships between COX-2 expression and clinicopathological feature of the patients, MVD, and survival time were analyzed. Increased COX-2 expression was significantly correlated with pathologically unfavorable findings such as tumor size (> 3.0 cm), tumor differentiation (poor, moderate > well differentiated), number of metastatic lymph nodes (24), and Dukes' stage (Dukes' B, C, and D). Larger number of microvessels congregated around the COX-2-expressing area, and the Spearman rank correlation test showed a strong correlation between COX-2 expression and tumor MVD (P < 0.0001). Patients with COX-2-positive tumors had a significantly (P = 0.037, by log-rank test) shorter survival time than those with negative tumors did. In the multivariate analysis, however, only Dukes' stage and number of metastatic lymph nodes remained as independent prognostic factors. Augmented tumor neovascularization may be one of the several effects of COX-2 responsible for poor prognosis in human colorectal carcinoma patients.

Aged↗

PubMed2000

Development of simple latex agglutination test for detection of astrovirus serotype 1.

Astroviruses are small RNA viruses associated with pediatric gastroenteritis. A latex agglutination (LA) test is more convenient and rapid than electron microscopy, enzyme immunoassay (EIA) and reverse transcription-polymerase chain reaction (RT-PCR) for detection of astroviruses in stool specimens was developed by using polyclonal antibody against cultured serotype 1 astrovirus, and tested on astrovirus positive- and negative- samples collected between 1985 and 1993 in Ehime, Japan. Cultured serotype 1 astrovirus was detected by the LA test, but serotype 2, 3, 4, 5, 6, and 7 viruses could not be detected, although they yielded high titer of the viruses. When tested on the 27 clinical samples, all 8 serotype 1 astroviruses determined previously by EIA were positive by the LA test, however, 9 other serotype astroviruses and 10 astrovirus negative-samples were all negative. PT-PCR was found to be the most sensitive followed by EIA and LA test. Further development of LA test with other serotypes is necessary.

Immunoenzyme Techniques↗

PubMed1999

Potent antitumor activity of MS-247, a novel DNA minor groove binder, evaluated by an in vitro and in vivo human cancer cell line panel.

We synthesized a novel anticancer agent MS-247 (2-[[N-[1-methyl-2-[5-[N-[4-[N,N-bis(2-chloroethyl) amino] phenyl]] carbamoyl]-1H-benzimidazol-2-yl] pyrrol-4-yl] carbamoyl] ethyldimethylsulfonium di-p-toluenesulfonate) that has a netropsin-like moiety and an alkylating residue in the structure. We evaluated antitumor activity of MS-247 using a human cancer cell line panel coupled with a drug sensitivity database and subsequently using human cancer xenografts. The average MS-247 concentration required for 50% growth inhibition against a panel of 39 cell lines was 0.71 microM. The COMPARE analysis revealed that the differential growth inhibition pattern of MS-247 significantly correlated with those of camptothecin analogues and anthracyclins, indicating that MS-247 and the two drug groups might have similar modes of action. MS-247 exhibited remarkable antitumor activity against various xenografts. A single i.v. injection of MS-247 significantly inhibited the growth of all 17 xenografts tested, which included lung, colon, stomach, breast, and ovarian cancers. In many cases, MS-247 was more efficacious than cisplatin, Adriamycin, 5-fluorouracil, cyclophosphamide, VP-16, and vincristine and was almost comparable with paclitaxel and CPT-11; these are the most clinically promising drugs at present. MS-247 was noticeably more effective than paclitaxel (in HCT-15) and CPT-11 (in A549, HBC-4, and SK-OV-3). The toxicity of MS-247, indicated by body weight loss, was reversible within 10 days after administration. The MS-247 mode of action showed DNA binding activity at the site where Hoechst 33342 bound, inhibited topoisomerases I and II (as expected by the COMPARE analysis) blocked the cell cycle at the G2-M phase, and induced apoptosis. These results indicate that MS-247 is a promising new anticancer drug candidate to be developed further toward clinical trials.

Animals↗

PubMed1999

Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease.

Microtubule-associated protein tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer's disease (AD), but there is overlap between AD patients and non-AD controls. To improve the diagnostic accuracy, we measured phosphorylated tau in CSF, because phosphorylated tau accumulates as pathological paired helical filaments in neurons of the AD brain. Immunoblot showed that CSF contained a 32 kDa N-terminal fragment of tau that was partially phosphorylated on Ser199, Thr231 and Ser235. A sandwich enzyme immunoassay revealed that phosphorylated CSF-tau levels were significantly higher in AD patients than those in non-AD controls. Discrimination between the two groups was clearer in phosphorylated CSF-tau than in total CSF-tau. The data indicate that elevated phosphorylated CSF-tau level is a more specific diagnostic marker for AD.

Alzheimer Disease↗

PubMed1999

MAP kinase-independent induction of proto-oncogene c-fos mRNA by hemin in human cells.

Treatment of HeLa cells or human skin fibroblast cells with hemin led to a time- and dose-dependent rapid induction of c-fos mRNA. This induction was absent in the cells treated with actinomycin D, indicating that the c-fos induction by hemin occurs at the level of transcription. Metalloporphyrins, including zinc-, cobalt-, and tin-protoporphyrin, ferric ion, and protoporphyrin also induced c-fos mRNA. Transient reporter assay with the reporter constructs of the human c-fos gene promoter up to -404 bp connected to the luciferase gene showed high activity but no induction by hemin, suggesting that cis-acting elements, including the serum response element located about -310 bp upstream of the human c-fos gene promoter, may not contribute to the heme-dependent induction. With in-gel assay of protein kinases, the activity of the mitogen-activated protein (MAP) kinases such as extracellular signal-regulated kinase 12 or p38 MAP kinase in hemin-treated HeLa cells was not stimulated. Stimulation of c-Jun N-terminal kinase by hemin was nil. Furthermore, PD58059 and SB203580, inhibitors for MAP kinases, did not affect the hemin-dependent c-fos induction. Of the inhibitors for protein kinases so far tested, KN-62, a specific inhibitor for calmodulin-dependent protein kinase II (CaMK II), inhibited the induction of c-fos mRNA by hemin. Phosphorylation of CaMK II in hemin-treated cells increased. With gel mobility assay, the DNA AP-1 binding activity transiently increased when treating HeLa cells with hemin. Therefore, induction of c-fos led to an activation of AP-1 in the presence of hemin. We suggest that calmodulin-dependent protein kinase II rather than the MAP kinase family regulates the induction of the human c-fos gene expression by hemin.

Arsenites↗

PubMed1999

Structure and transcriptional regulation of the mouse ferrochelatase gene.

Ferrochelatase (EC.4.99.1.1), the final step in the biosynthesis of heme, is widely expressed in various tissues and is induced in erythroid cells. We determined the structure of the mouse ferrochelatase gene after isolation and characterization of lambda phage clones mapping discrete regions of the cDNA. The gene spans about 25 kb and consists of 11 exons. The exon/intron boundary sequences conform to consensus acceptor (GTn)/donor (nAG) sequences, and exons in the gene encode functional protein domains. The promoter region contains multiple Sp1 sites, a CACCC box and GATA-1 binding sites. Function analysis of the promoter by transient transfection assay demonstrated that one Sp1 binding site located at -37/-32 is essential for basic expression of the ferrochelatase gene in both mouse erythroleukemia (MEL) and non-erythroid EL4 cells. In addition, the region (-66/-51) containing a CACCC box and the neighboring GC box partly contributes to the inducible activity of the reporter in MEL cells upon induction with dimethylsulfoxide. It appears that at least two promoter regions of the mouse ferrochelatase gene function in basic and inducible expression.

Animals↗

PubMed1999

Latent infection and reactivation of human herpesvirus 6 in two novel myeloid cell lines.

It has been reported that reactivation of human herpesvirus-6 (HHV-6) causes a failure of hematopoiesis. To clarify the mechanisms of bone marrow suppression induced by HHV-6 infection, it is necessary to establish an in vitro model of HHV-6 infection in hematopoietic progenitor cells. We have established two novel Philadelphia chromosome-positive myeloid cell lines, SAS413 and SAS527, which possess different hematologic characteristics and show distinct susceptibility to infection by HHV-6, from a patient with blast crisis of chronic myelogenous leukemia (CML). HHV-6 subgroup A (HHV-6A) showed marked replication in SAS413, forming syncytia and inducing cell lysis in short-term culture. On the other hand, HHV-6A-inoculated SAS527 continued to proliferate without cell lysis and only a few cells showed HHV-6 antigen expression. In contrast to HHV-6A infection, inoculation with HHV-6 subgroup B (HHV-6B) did not induce any cytopathic effect (CPE) or viral antigen expression in either of the cell lines. Although HHV-6B replication was undetectable, the presence of the HHV-6 genome in both cell lines was shown by polymerase chain reaction (PCR) during culture for more than 10 months, suggesting that HHV-6B latently infected SAS413 and SAS527. Phorbol ester treatment of SAS527 latently infected with HHV-6B resulted in reactivation of HHV-6, as shown by the appearance of a CPE, positive reactivity for the HHV-6 antigen, and isolation of infectious HHV-6. These novel cell lines should be useful for studying the mechanisms of HHV-6-induced hematopoietic failure and HHV-6 latency and reactivation, as well as differentiation, of the myeloid cell lineage.

Adult↗

PubMed1999

p53 mutation and allelic loss of chromosome 3p, 9p of preneoplastic lesions in patients with nonsmall cell lung carcinoma.

BACKGROUND: An accumulation of mutations can result in carcinogenesis. Comparing genetic alterations in preneoplastic lesions with those seen in cancer in the same patient may be helpful in the early diagnosis of lung carcinoma or preneoplastic lesions. METHODS: To identify genetic alterations that may play a role in the development of nonsmall cell lung carcinoma (NSCLC), the authors examined the p53 gene and microsatellite markers on chromosome 3p (D3S643, D3S1317), 9p (D9S171, IFNA) in 35 bronchial metaplastic lesions and 28 alveolar hyperplastic lesions from 61 patients. RESULTS: A total of 8 metaplastic lesions (1 squamous metaplasia and 7 dysplasias) and 3 alveolar hyperplastic lesions (with atypia) showed genetic alterations, including loss of heterozygosity (LOH) of 3p, 9p and mutations of the p53 gene. In an analysis of microsatellite markers, 5 of 35 cases of squamous cell carcinoma (SCC) and 3 of 26 cases of adenocarcinoma (Ad) showed LOH in both preneoplastic lesions and synchronous cancers. Nine patients (25.7%) with SCC and 6 patients (23.1%) with Ad were shown to have mutations of the p53 gene by single-strand conformation polymorphism. In 2 of these 9 patients with SCC, the same mutation was observed in both dysplasia and SCC. CONCLUSIONS: These findings suggest that several genetic alterations may occur in preneoplastic lesions or the early stage of SCC of the lung, whereas the genetic alterations examined appeared to occur relatively late in the pathogenesis of pulmonary adenocarcinoma.

Adult↗

PubMed1999

Prognostic factors after extended esophagectomy for squamous cell carcinoma of the thoracic esophagus.

BACKGROUNDS AND OBJECTIVES: In Japan, extended esophagectomy with extensive lymphadenectomy has become the standard surgical procedure for carcinoma of the thoracic esophagus. Although mortality and morbidity rates after such extensive esophagectomy have been acceptable, the long-term outcomes are not necessarily satisfactory. METHODS: Among 235 patients with primary squamous cell carcinoma of the thoracic esophagus between June 1981 and March 1998, 143 patients (60.9%) underwent extended esophagectomy with extensive lymphadenectomy. To exclude the effects of surgery-related postoperative complications, 14 patients who died within 90 days after operation were excluded. Thus, clinicopathological characteristics and prognostic factors of 129 patients were retrospectively investigated. RESULTS: Sixty-three patients were alive and free of cancer. Sixty-six patients died: 37 of recurrence of the esophageal cancer and 29 of other causes. The 1-, 3-, 5-, and 10-year overall survival rates in the 129 patients were 78.8%, 53.5%, 45.8%, and 30.9%, respectively, and the disease-specific survival rates were 85.7%, 69.1%, 67.9%, and 56.2%, respectively. The factors influencing the disease-specific survival rate were tumor location (upper third vs. non-upper third), Borrmann classification (0, 1 vs. 2, 3), size of tumor (</=3.0 vs. >3.0 cm), depth of invasion (T1, 2 vs. T3, 4), number of lymph node metastases (0 or 1 vs. >/=2), time of operation (</=420 vs. >420 min), amount of blood transfused (</=2 vs. >/=3 U), lymph vessel invasion (marked vs. not marked), and blood vessel invasion (marked vs. not marked). Among those significant variables, independent prognostic factors for survival determined by multivariate analysis were number of lymph node metastases (P < 0.001), amount of blood transfusions (P = 0.0016), and tumor location (P = 0.0382). CONCLUSIONS: Patients with a single metastatic node after extended esophagectomy should be considered to have excellent prognosis, like patients with pN0 tumors. Patients with multiple involved nodes should receive aggressive postoperative adjuvant treatments. Reduced blood loss during extended esophagectomy and minimal blood transfusions might improve the outcome of curative esophageal resections.

Aged↗

PubMed1999

Pulmonary blastoma: report of a case.

A 30-year-old woman was admitted to our hospital for investigation of an abnormal shadow in the right pulmonary hilus on a chest X-ray film. A percutaneous needle biopsy was performed, which revealed pulmonary blastoma. A right upper lobectomy was performed and the pathological stage was confirmed to be IIIa (T3N0M0). An analysis of preoperative cytological specimens showed that epithelial tumor cells with thin cytoplasm were either tubular or papillary, while some mesenchymal tumor cells with elliptic and spindle-shaped nuclei were also found in the necrotic background. Thus, pulmonary blastoma should be considered when a two-cell pattern consisting of both epithelial and mesenchymal components is observed. DNA analysis was performed on previously identified areas of the epithelial or sarcomatous components, using a microdissection method. An analysis of the p53 gene by the single-strand conformation polymorphysm method showed an abnormal band with shifted mobility of exon 8 in only the sarcomatous component.

Adult↗

PubMed1999

Indications and operative techniques for combined aortoesophageal resection.

Combined aortoesophageal resection was performed in 8 patients, including 7 with esophageal carcinoma and 1 with aortoesophageal fistula. Aortic resection procedures included segmental resection with permanent aorto-aortic bypass (1 case), segmental resection with graft interposition (1 case), semicircumferential resection with patch aortoplasty (3 cases), wedge resection with lateral aortorrhaphy (1 case), and resection of adventitia (2 cases). Protective methods during aortic cross-clamping included one aorto-aortic permanent bypass, one subclavian-aortic bypass, and three axillo-femoral bypass. Postoperative complications include mediastinal abscess, paresis, arrythmia, and pneumonia. Five patients with esophageal carcinoma died within 6 postoperative months. In 4 of these 5 nonsurvivors, metastasis to distant organs including the liver, bone and peritoneal cavity were found at the time of death or autopsy. Those early recurrence cases were characterized by skip lesions and extensive lymph node metastasis with extranodal invasion. The clinical benefit of aortoesophageal resection will be attained by careful preoperative evaluation for case selection and a sufficient protective method for aortic cross-clamping.

Aged↗

PubMed1999

Maximal period of cryopreservation with the Bicell biofreezing vessel for rat tracheal isografts.

OBJECTIVE: The maximal period of cryopreservation for the trachea is still unsolved. We assessed the maximal period of cryopreservation using the Bicell biofreezing vessel as an easy and cheap slow-freezing instrument for viable tracheal grafts in 95 rats. METHODS: Each isograft was harvested from 17 donor rats, immersed in the preservative solution, and stored in a Bicell device in a deep freezer at -80 degrees C. The tracheal isografts were then randomly assigned to 9 groups according to cryopreservation periods ranging from 0 to 12 months. Included in the 9 groups were 2 subgroups (n = 6 per subgroup) that were observed immediately after being thawed and 1 month after heterotopic transplantation into the omentum after being thawed. Four subgroups (n = 6 per subgroup) were added according to the cryopreservation period for 1, 3, 6, and 12 months to evaluate the graft morphology 3 months after being thawed and transplanted heterotopically. RESULTS: A prolonged period of cryopreservation had a degenerative effect on both the epithelium and cartilage. One month after transplantation, degeneration was more pronounced in the cartilage than in the epithelium, as characterized by the viable chondrocyte ratio and the epithelial score of isografts undergoing cryopreservation for more than 9 months. Three months after transplantation, the morphology of the epithelium and cartilage in isografts undergoing cryopreservation for less than 3 months was better preserved, whereas the morphology of both deteriorated in isografts undergoing cryopreservation for more than 6 months. CONCLUSIONS: We conclude that the permissible period of cryopreservation to maintain tracheal isograft viability in this simple system using a Bicell biofreezing vessel is 3 months.

Animals↗

PubMed1999

Mode of action of novel 2-(benzylamino)-4-methyl-6-(trifluoro- methyl)-1,3,5-triazine herbicides: inhibition of photosynthetic electron transport and binding studies.

Novel 2-(benzylamino)-4-methyl-6-(trifluoromethyl)-1,3,5-triazines have the same 1,3,5-triazine skeleton as atrazine, although some of them, for example, 2-(3-chlorobenzylamino)-4-methyl-6-(trifluoromethyl)-1,3,5-tria zin e [pI(50)(spinach) = 7.21], show a >3 times stronger photosynthetic electron transport inhibitory activity than atrazine [pI(50)(spinach) = 6.72]. The new triazines have only one amino group at the triazine ring, and their molecular shapes are different from atrazine. The replacement of the bound [(14)C]atrazine by 1,3,5-triazines was tested to determine whether the novel 1,3,5-triazine analogues exhibit the same binding pattern at the D1-protein as atrazine. It was found that [(14)C]atrazine bound to the D1-protein was replaced by the triazine tested by a clearly competitive interaction. Obviously, the novel 1,3,5-triazines are attached to the same binding niche as atrazine.

Electron Transport↗

PubMed1999

Unfavourable impact of growth hormone (GH) discontinuation on body composition and cholesterol profiles after the completion of height growth in GH-deficient young adults.

AIM: Growth hormone (GH) plays an important role in the regulation of body composition and metabolism. GH deficiency is associated with obesity and hypercholesterolemia, which respond to GH treatment. In this study we evaluated changes in body composition and cholesterol profiles after discontinuation of GH therapy to assess atherogenic risk factors in GH-deficient patients. METHODS: We studied 18 male patients with GH deficiency 17-20 years of age at the time of discontinuing GH therapy. Body composition and cholesterol were measured 6 months before discontinuation of GH therapy with a weekly dose of 0.5 IU/kg (approximately 0.19 mg/kg), and immediately, 2 months, and 6 months after the end of GH therapy. RESULTS: Two months after termination of GH therapy the percentage of body fat and fat mass increased from 7.4% to 9.4% and from 3.8 kg to 5.0 kg, respectively, and remained high thereafter. Lean body mass decreased gradually, but the change was not significant. Lean body mass: fat mass ratio decreased from 14.7 at termination of GH therapy to 10.9 at the end of study. Total cholesterol (TC) showed a significant linear increase from 156 mg/dl immediately after discontinuation to 169 mg/dl 6 months after discontinuation of GH, whereas high-density lipoprotein cholesterol (HDLC) showed no change during the study. The TC to HDLC ratio showed a slight but insignificant trend toward an increase. There were no significant changes in any variables during the last 6 months of GH therapy. CONCLUSION: GH therapy in patients with GH deficiency can reduce risk factors for obesity-related diseases and atherosclerosis. These beneficial effects are reversed after discontinuation of GH therapy. Further long-term studies of the effects of the GH withdrawal on lipid profiles, adiposity and life expectancy must be performed.

Adolescent↗