BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common proliferative disease affecting men. Numerous minimally invasive technologies are being developed or are currently in use to obviate the need for transurethral surgery. The goal of the present study was to develop a novel molecular based approach for the treatment of BPH using recombinant p53 adenoviral vector. The over-expression of wt-p53 can cause cell apoptosis or cell growth arrest, thus preventing the uncontrolled cell proliferation underlying BPH pathophysiology. METHODS: Ad-CMV-p53, a replication-deficient recombinant adenovirus containing cytomegalovirus promoter driving p53 gene, was used. Human prostate stromal (PS) cells were evaluated for apoptosis (TUNEL assay), mRNA levels of key cell cycle regulators influencing apoptosis (p-53, Bax and Bcl-2) using quantitative RT-PCR and cytotoxicity after Ad-CMV-p53. Ad-CMV-p53 was unilaterally injected into rat ventral prostates and growth inhibition was measured by prostate weight 3 weeks after injection. RESULTS: In vitro exposure to Ad-CMV-p53 significantly inhibited the proliferation of PS cells, induced mRNA over-expression of both wt-p53 and Bax, and increased the proportion of apoptotic cells. A 30% decrease in average prostate weight was demonstrated in rodents after Ad-CMV-p53 injection. CONCLUSIONS: The results suggest that further investigation of molecular gene therapy with recombinant wt-p53 adenovirus for the treatment of BPH is warranted.

Adenoviridae↗

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Apparent normobasemia as a negative prognostic sign immediately after hepatectomy.

The acid-base balance from the postoperative day (POD) 1 to POD 3 after cirrhotic liver resection was investigated in relation to operative outcome by conducting a retrospective study on the changes in arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, and arterial blood gas analysis. Patients were grouped according to their outcome: hospital death (HD) and or good outcome, the latter group acting as controls (CTR). Metabolic alkalosis developed in a significant number of the CTR patients (p < 0.01), who had high AKBR values. By contrast, metabolic alkalosis did not develop in the HD group, with significantly lower AKBR (p < 0.001), and there was almost normobasemia. There were no significant differences in the need for mechanical respiratory assistance, the amounts of fresh frozen plasma administered, and renal function test results between the two groups on each of 3 postoperative days. These data indicated that the absence of metabolic alkalosis during the early postoperative days reflects disruption of energy metabolism in the remnant liver, and that the apparent normobasemia is a significant indicator of poor prognosis after cirrhotic liver resection.

Acid-Base Equilibrium↗

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Interhemispheric EEG coherence during photic stimulation: sex differences in normal young adults.

The present study was conducted to examine sex differences in interhemispheric EEG coherence in 15 male and 15 female healthy young adults. EEG was recorded during rest and photic stimulation (PS) at 5, 10 and 15 Hz using a linked earlobe reference. Interhemispheric coherence of the resting EEG revealed no significant sex-related differences for any frequency band. In contrast, significant sex-related differences were found in EEG coherence during PS; the females had a significantly higher coherence than the males for F3-F4 and C3-C4 in the frequency band (4.5-5.5 Hz) corresponding to 5 Hz PS. In addition, the changes in interhemispheric coherence from rest to the stimulus condition (i.e. PS-related coherence reactivity) showed sex-related differences at the brain region primarily involved in visual functioning; the females had significantly greater coherence reactivity for O1-O2 in EEG during PS at 5 and 15 Hz. These findings indicate sex-related differences in interhemispheric EEG coherence during PS, and support the well-demonstrated evidence that sex differences exist in the degree of lateralization of cerebral function.

Adult↗

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Serial MRI findings of benign poliomyelitis.

A 14-year-old boy presented with incomplete transverse myelopathic symptoms associated with mild encephalitis. Magnetic resonance imaging (MRI) revealed involvement of the central portion of spinal cord extending from the C1 to T5 level on T2-weighted images with expansion of the cervical spinal cord. The boy made a full clinical recovery in a few weeks. Cultures of the pharyngeal exudate were positive for ECHO virus type 11. The lesion on MRI disappeared completely in a few months.

Adolescent↗

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Increased serum creatine kinase due to hypocalcemia in vitamin D deficiency.

An 8-year-old boy with vitamin D-deficiency rickets, increased serum creatine kinase (CK), and hypocalcemia is described. At 5 years of age, he was evaluated because of recurrent tonic seizures. He had growth retardation, microcephaly, quadriplegia, mental retardation, and epilepsy. Muscle strength was difficult to assess because of multiple joint contractures. Deep tendon reflexes were hyperactive. Laboratory data indicated rachitic changes on x-ray, hypocalcemia, low serum 25-hydroxyvitamin D3 (25-OH-D) and 1-alpha-25-dihydroxyvitamin D3 (1-alpha-25-[OH]2-D) levels, a normal response to the Ellsworth-Howard test, and markedly increased CK. Electromyography and nerve conduction velocities were normal. The patient responded to 1-alpha-OH-D treatment with increased serum calcium and normal CK activity; a significant correlation (p less than 0.01) was observed between calcium and log CK. The clinical course and laboratory findings supported the hypothesis that the increased CK was due to hypocalcemia, which in turn was due to the vitamin D deficiency in the severely handicapped child with malnutrition.

Alkaline Phosphatase↗

PubMedDate not supplied

Molecular genetic analysis of ABCR gene in Japanese dry form age-related macular degeneration.

PURPOSE: To explore whether the mutation in the retina-specific ATP-binding cassette transporter (ABCR) gene, the Stargardt's disease gene, contributes to the prevalence of the dry form of age-related macular degeneration (dry AMD) in Japanese unrelated patients. METHODS: Twenty-five Japanese unrelated patients with dry AMD who were diagnosed by fluorescein angiography and indocyanine green angiography were chosen as the dry AMD group. None of these cases had apparent choroidal neovascularization. To detect the mutations in the ABCR gene, genomic DNA was extracted from leukocytes of peripheral blood, and 26 exons of the ABCR gene were amplified by polymerase chain reaction (PCR). All the PCR products were then directly sequenced. When a mutation was detected, the occurrence of a mutation was compared between these AMD patients and the control group. RESULTS: After direct sequencing, a point mutation in exon 29 was found in one of the 25 dry AMD patients. In addition, a polymorphism in exon 45 was found in two other patients, and three sequence variations in exon 23 were detected in all patients. The incidence in AMD patients in whom a mutation in exon 29 (4%) was detected was less than that in controls (5%). Screening of the intron-exon boundaries also led to the identification of intronic mutation in intron 33. CONCLUSION: In this study we found no relationship between allelic variation in the ABCR gene and the prevalence of dry AMD in Japanese unrelated patients.

ATP-Binding Cassette Transporters↗

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Collagenolytic activity of keratocytes cultured in a collagen matrix.

To study the mechanism of collagen degradation by keratocytes, we developed the new in vitro model in which keratocytes were cultured three-dimensionally in a collagen matrix. Subcultured rabbit keratocytes were embedded in a type I collagen matrix and cultured in serum-free medium. Collagenolytic activity of the cells was determined by measuring the amount of hydroxyproline released into the medium from degraded collagen. Activities of collagenase in the medium were also measured, using collagen labeled with fluorescein isothiocyanate as a substrate. The presence of plasminogen was required for collagen degradation by keratocytes. In the presence of plasminogen, the amount of collagen degradation depended on both the cultivation period and the number of cells. The addition of interleukin-1 (IL-1) stimulated the collagen degradation in a dose-dependent manner. This stimulatory effect of IL-1 was completely inhibited by the addition of IL-1 receptor antagonist (IL-1ra). Collagenase activity in the medium was stimulated by the addition of IL-1, and IL-1ra antagonized this stimulatory effect. These findings indicate that our present model may be useful for investigating the mechanism of collagen degradation by keratocytes.

Animals↗

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The effect of corneal epithelial cells on the collagen gel contraction by keratocytes.

To understand the mechanism of the contraction of cicatricial tissues after corneal stromal wounding, we investigated the effect of corneal epithelial cells on the collagen gel contraction by keratocytes. Subcultured rabbit keratocytes were embedded in type I collagen gel and cultured. Rabbit corneal epithelial cells were cultured separately and the culture medium was collected and used as an epithelial cell-conditioned medium (ECCM). The collagen gel contraction by keratocytes was determined by measuring the diameters of the collagen disks once a day for 5 days. In the presence of fetal calf serum, the diameter of the collagen gel decreased in linear proportion to the number of keratocytes, but in inverse proportion to the concentration of collagen. The addition of the ECCM enhanced the collagen gel contraction by keratocytes in a dose-dependent manner. This stimulatory activity was found in the ECCM obtained from 3- to 7-day cultures of epithelial cells. These findings suggest that corneal epithelial cells secrete factor(s) that stimulate the collagen gel contraction by keratocytes.

Animals↗