Previous data suggest that natural anti-Galalpha1,3Gal (Gal) antibody (Ab) is produced by mature plasma cells. As thalidomide is effectively used in the treatment of patients with multiple myeloma, its effect on natural anti-Gal Ab production has been assessed in two baboons. During a 10-week course of thalidomide administration (until it reached toxic levels in one baboon), there was no major reduction in Ab levels or in their rate of return after a course of extracorporeal immunoadsorption. A significant reduction of CD3+ cells (75%), and particularly of CD4+ cells (65 to 95%), was measured in the blood by flow cytometry. This was associated with general hyporesponsiveness on mixed lymphocyte reactivity in one baboon, but not in the other. Thalidomide would appear to have little effect on the production of natural Ab, but these observations lend some support to previous work by others indicating that thalidomide may suppress the cellular response to an allograft or xenograft.

Animals↗

PubMed2003

Periocular injection of an adenoviral vector encoding pigment epithelium-derived factor inhibits choroidal neovascularization.

Gene transfer provides an exciting new approach for the treatment of retinal and choroidal diseases. Two areas of concern are the potential for vector-related toxicity and uncertainties associated with prolonged transgene expression. One way to address these concerns for transfer of genes encoding secreted proteins is to transduce cells on the outside of the eye, provided the gene product can gain access to the eye and have the desired effect. In this study, we investigated the feasibility of this approach. Periocular injection of an adenoviral vector encoding beta-galactosidase (AdLacZ.10) resulted in LacZ-stained cells throughout the orbit and around the eye. Compared to periocular injection of 5 x 10(9) particles of control vector, periocular injection of 5 x 10(9) or 1 x 10(9) particles of an adenoviral vector expressing pigment epithelium-derived factor (PEDF) regulated by a CMV promoter (AdPEDF.11) resulted in significantly elevated intraocular levels of PEDF and suppression of choroidal neovascularization. Periocularly injected recombinant PEDF was also found to diffuse through the sclera into the eye. Although similar experiments are needed in an animal with a human-sized eye, these data suggest that periocular gene transfer deserves consideration for the treatment of choroidal diseases.

Adenoviridae↗

PubMed2003

Clonal diversity and genetic differentiation in Ilex leucoclada M. patches in an old-growth beech forest.

We investigated clonal diversity within patches of Ilex leucoclada and genetic variation within and among patches using random amplified polymorphic DNA (RAPD) markers in a 1-ha plot within an old-growth beech forest. We found 38 patches that exhibited a clumped distribution in the middle of the plot. We identified a total of 166 RAPD phenotypes among the 215 stems sampled from 27 patches that were completely within the plot. The population showed high clonal diversity within patches (mean number of genets relative to number of stems = 0.79; mean Simpson's D = 0.89). Variation in RAPD phenotypes among patches was highly significant (PhiST in the molecular variance analysis = 0.316, P < 0.001), indicating genetic differentiation among patches. Pairwise genetic distances, PhiST, among patches did not correlate with geographical distances among patches. The cluster analysis based on the genetic distances showed few clear clusters of patches, indicating no spatial genetic structure among patches. High levels of clonal diversity both within patches and within the population may be explained by multiple founders, seedling recruitment during patch-formation, and somatic mutation. The significant genetic differentiation among patches may be caused by separate founding events and/or kin structuring within patches.

Cluster Analysis↗

PubMed2003

An atypical form of sporadic panencephalopathic Creutzfeldt-Jakob disease in Japan.

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Aged↗

PubMed2003

Aggressive surgical treatment for patients with T4 rectal cancer.

OBJECTIVE: To investigate the outcome of surgical treatment for patients with T4 rectal cancer and to evaluate prognostic factors influencing 5-year disease-free survival. PATIENTS: Of 1600 rectal cancers seen between 1985 and 1998, there were 197 patients with T4 of whom 128 were treated with curative intent. In this retrospective study organ invaded, the type of treatment and outcome were analysed. RESULTS: Of the 128 patients, 89% had visceral involvement and 11% had pelvic wall involvement. The most frequently involved organ was bladder, followed by prostate and vagina. Low anterior resection was performed in 52, abdomino-perineal resection in 35 and total pelvic exenteration in 41 patients. Of 81 with urinary tract invasion, 50% were treated with bladder-sparing surgery. Pathological examinations showed bladder involvement in only 44 of these and overall 5-year disease-free survival was 57%. Multivariate analysis revealed that body mass index, lymph node metastasis and inflammatory reaction were significant predictors of survival. CONCLUSION: Completeness of resection is the essential factor influencing oncological outcome.

Adult↗

PubMed2003

Morphological and functional analyses of adult onset vitelliform macular dystrophy.

AIM: To evaluate the morphology and visual function of the macula in eyes with adult onset vitelliform macular dystrophy (AVMD). METHODS: 12 eyes of six patients with AVMD were examined by ophthalmoscopy, scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and multifocal electroretinography (mfERGs). The macular lesions were bilateral in all patients and varied from the typical vitelliform (five eyes), faded vitelliform changes with retinal pigment epithelium (RPE) atrophy (five eyes), and a normal fovea associated with small flecks around the macula (two eyes). RESULTS: SLO demonstrated small abnormal bright spots in the deep retina throughout the posterior retina in all cases. OCT showed a highly reflective fusiform thickened layer at the level of the RPE and choriocapillaris in patients with a submacular yellow vitelliform lesion. A well circumscribed, optically clear space was observed beneath the retinal layer in the macular lesions with RPE atrophy. The mfERGs were significantly reduced not only in the macular area but also in the outermost ring (20-30 degrees ) of the mfERGs. CONCLUSIONS: The submacular materials that accumulate within the RPE or subepithelial layers reported in previous histopathological studies of vitelliform lesions can be detected by OCT. In the macular lesions with RPE atrophy, the material may have disappeared leaving a subretinal or subepithelial optical clear space. These SLO and mfERG observations suggest that the morphological and functional abnormalities may not be localised just in the macular area but may be present throughout the posterior pole in eyes with AVMD.

Adult↗

PubMed2003

Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture.

Accumulating evidence indicates that menaquinone-4 (MK-4), a vitamin K(2) with four isoprene units, inhibits osteoclastogenesis in murine bone marrow culture, but the reason for this inhibition is not yet clear, especially in human bone marrow culture. To clarify the inhibitory mechanism, we investigated the differentiation of colony-forming-unit fibroblasts (CFU-Fs) and osteoclasts in human bone marrow culture, to learn whether the enhancement of the differentiation of CFU-Fs from progenitor cells might relate to inhibition of osteoclast formation. Human bone marrow cells were grown in alpha-minimal essential medium with horse serum in the presence of MK-4 until adherent cells formed colonies (CFU-Fs). Colonies that stained positive for alkaline phosphatase activity (CFU-F/ALP(+)) were considered to have osteogenic potential. MK-4 stimulated the number of CFU-F/ALP(+) colonies in the presence or absence of dexamethasone. The stimulation was also seen in vitamin K(1) treatment. These cells had the ability to mineralize in the presence of alpha-glycerophosphate. In contrast, both MK-4 and vitamin K(1) inhibited 1,25 dihydroxyvitamin D(3)-induced osteoclast formation and increased stromal cell formation in human bone marrow culture. These stromal cells expressed ALP and Cbfa1. Moreover, both types of vitamin K treatment decreased the expression of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor (RANKL/ODF) and enhanced the expression of osteoprotegerin/osteoclast inhibitory factor (OPG/OCIF) in the stromal cells. The effective concentrations were 1.0 microM and 10 microM for the expression of RANKL/ODF and OPG/OCIF respectively. Vitamin K might stimulate osteoblastogenesis in bone marrow cells, regulating osteoclastogenesis through the expression of RANKL/ODF more than through that of OPG/OCIF.

Alkaline Phosphatase↗

PubMed2003

Expression of 11beta-hydroxysteroid dehydrogenases in bovine follicle and corpus luteum.

In glucocorticoid target organs, local concentrations of active glucocorticoid are determined by the relative expression of two 11beta-hydroxysteroid dehydrogenases (HSDs): bi-directional 11beta-HSD type1 (11HSD1) that mainly activates cortisone to cortisol, and dehydrogenase 11beta-HSD type2 (11HSD2) that inactivates cortisol to cortisone. In this study, we examined the expression of mRNA encoding these two 11beta-HSDs in bovine granulosa cells harvested from preovulatory follicles and corpora lutea (CL). Ovaries were obtained from Holstein cows at a local slaughterhouse. Follicles larger than 10 mm in diameter and CL were dissected and follicular fluid and granulosa cells were taken. Corpora lutea were weighed and their stages were morphologically assessed (stage I, days 1-4; stage II, days 5-10; stage III, days 11-17; stage IV, days 8-20). Follicles were classified into four groups according to their hormonal status (oestradiol (E(2)): progesterone (P(4))>1: oestrogen active; E(2):P(4)<1: oestrogen inactive) and stage of the oestrous cycle (luteal or follicular phase). Total RNA was extracted with phenol-chloroform and subjected to a semi-quantitative RT-PCR for 11HSD1, 11HSD2 and beta-actin. Concentrations of steroids in follicular fluid were determined by an enzyme immunoassay. In granulosa cells, only 11HSD1 mRNA was detected. There was a negative correlation between the expression of 11HSD1 and the concentration of cortisol in follicular fluid (P<0.05), indicating 11HSD1 may act as a dehydrogenase in the bovine follicle. Both types of 11beta-HSDs were expressed in CL. The levels of mRNA for both isozymes were high in stage I and II, and were decreased in stage III CL. In stage IV CL, the expression of 11HSD2 but not 11HSD1 mRNA increased. These results indicate that the bovine granulosa cells and CL express 11HSD1 and 11HSD2, and they may play an important physiological role in the bovine ovary through modulating the local glucocorticoid environment.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2003

Rotational acetabular osteotomy in patients forty-six years of age or older: comparison with younger patients.

BACKGROUND: Satisfactory intermediate and long-term results of periacetabular rotational osteotomy for early osteoarthritis secondary to dysplasia of the hip have been reported for patients in the third and fourth decades of life. The purpose of the present study was to examine the usefulness of rotational acetabular osteotomy in patients older than forty-six years of age. METHODS: A retrospective review of two groups of patients who had been treated with a rotational acetabular osteotomy was conducted. The older group consisted of twenty-four patients (twenty-six hips) with early-stage osteoarthritis who had a mean age at the time of surgery of 50.9 years (range, forty-six to fifty-eight years) and a mean duration of follow-up of 8.2 years (range, five to thirteen years), and the younger group consisted of sixty patients (sixty-three hips) who had a mean age at the time of surgery of 34.4 years (range, thirteen to forty-five years) and a mean duration of follow-up of 8.3 years (range, five to fourteen years). Clinical follow-up was based on the system of Merle d'Aubigne and Postel. The center-edge angle, acetabular roof angle, and head lateralization index were measured on radiographs made preoperatively, postoperatively, and at the time of follow-up. Preoperative and postoperative joint congruencies were classified into four grades. RESULTS: Preoperatively, the mean Merle d'Aubigne clinical score was 13.9 points in the older group and 14.1 points in the younger group. In both groups, this score improved significantly to a mean postoperative follow-up score of 16.6 points (p < 0.0001), with no significant difference between the two groups. The mean center-edge angle improved from 3.2 degrees preoperatively to 34 degrees postoperatively (p < 0.0001) in the older group and from -2.1 degrees preoperatively to 34 degrees postoperatively (p < 0.0001) in the younger group. The mean acetabular roof angle improved from 29 degrees to 5.9 degrees (p < 0.0001) in the older group and from 31 degrees to 2.9 degrees (p < 0.0001) in the younger group. The mean head lateralization index improved from 0.67 to 0.64 (p < 0.01) in the older group and from 0.66 to 0.61 (p < 0.0001) in the younger group. Progression of osteoarthritis was observed radiographically at the time of follow-up in five hips in the older group and in four hips in the younger group. Kaplan-Meier survivorship analysis, with radiographic progression of osteoarthritis as the end point, predicted a ten-year survival rate of 70.0% in the older group and 93.7% in the younger group; this difference was not significant, with the numbers available (p = 0.062, log-rank test). CONCLUSIONS: Our results indicate that rotational acetabular osteotomy for elderly patients can prevent progression of osteoarthritis (as indicated by a survival rate of 70% at ten years) and that in selected cases it is worthwhile at least as a temporizing operation.

Acetabulum↗

PubMed2003

Successful perioperative blood purification therapy in patients with maintenance hemodialysis therapy who underwent living donor liver transplantation.

Living donor liver transplantation (LDLT) is a treatment for end-stage liver failure, and was developed to overcome the distinct insufficiency of cadaveric donors. Case 1 is a 56-year-old man who had undergone maintenance hemodialysis therapy for 4 years. An LDLT was performed for the treatment of advanced liver cirrhosis and hepatocellular carcinoma. Continuous hemodiafiltration (CHDF) was performed from the 2nd to 5th days after the operation. Case 2 is a 55-year-old man with primary amyloidosis and chronic renal failure. An LDLT was performed for the treatment of severe abdominal distention caused by a large liver volume. Although CHDF was started at the 3rd day after the operation, it was discontinued within 24 hours because of an increased urinary volume. CHDF was required again from the 6th-8th days, after which the blood purification mode was switched to regular intermittent hemodialysis. Meanwhile, no major problems occurred in either case. In conclusion, CHDF was required for about 5 days from the 2nd day after the operation. The application of careful and aggressive blood purification therapy during the perioperative period is a key to successful LDLT in dialysis patients.

Hemodiafiltration↗

PubMed2003

[Surgical treatment for esophageal cancer in elderly patients over 75 years of age].

UNLABELLED: We performed 127 esophageal resections for the esophageal cancer patient from December 1995 to September 2001. It was separated to under 70 years old patients group (group I), 71-74 years old patients group (group II), and over 75 years old patients group (group III). RESULTS: Postoperative complication was occurred in 53 cases (41.7%) within all of 127 esophageal resected cases. It was 33.7% in group I, 53.6% in group II, 62.5% in group III. Four years survival rate of each group is 38.3% in group I, 44.6% in group II, 31.3% in group III. It is significantly better in group II rather than in group III. Operative death rate is 12.5% (2 cases) in group III, 7.1% (2 cases) in group II, 3.6% (3 cases) in group I, and it is gradually higher and higher by patient's age. CONCLUSIONS: (1) In the esophageal cancer patient over 75 years old, postoperative complication rate is higher than under 74 years old patients, and prognosis is significantly poor rather than in 70-74 years old patients group. (2) In the esophageal cancer patient over 75 years old, we considered it is good indication of esophagectomy for stage I and stage II patient without preoperative complication, however, there are no operative indication for stage III and stage IV patient.

Age Factors↗

PubMed2003

[Needle tract implantation of thymoma after transthoracic needle biopsy].

A 53-year-old man was admitted to hospital because of an anterior mediastinal mass. For definite diagnosis, needle biopsy was performed under ultrasonic examination. The histopathological diagnosis was thymoma and thymo-thymectomy was performed. The tumor recurred in the right anterior chest wall 10 years later. It is suggested that the thymoma tissue had been implanted in the needle tract. To our knowledge, this is the 2nd reported case of thymoma which has been implanted in the needle tract.

Biopsy, Needle↗