In this review we present our own experimental findings as well as those from the literature related to the pathomechanisms for the inflammatory changes in psoriasis and its related diseases. A growing body of evidence has indicated that T cell-mediated immunity plays an important role in triggering and maintenance of psoriatic lesions. It has been revealed that lymphokines produced by activated T cells in psoriatic lesions have a strong influence on the proliferation of the epidermis. Characteristic neutrophil accumulation under the stratum corneum can be observed in the highly inflamed areas of psoriatic lesions. These neutrophils are chemotactically attracted and activated there by synergistic action of chemokines, IL-8 and Gro-α released by stimulated keratinocytes, and particularly by C5a/C5a des arg produced via the alternative complement pathway activation. We demonstrated that the infiltrating neutrophils adhere to iC3b-opsonized corneocytes to produce active oxygen and probably lysosomal enzymes. From a close relationship observed between neutrophil accumulation and high mitotic ratio of the lesional epidermis, we think that these stimulated neutrophils influence the growth and differentiation of epidermal keratinocytes. Aberrant expression of HLA-DR on neutrophils suggests their activation of infiltrating T cells in the presence of bacterial superantigen. These T cells in turn influence the transepidermal neutrophil migration through the effect of their cytokines on the keratinocyte production of proinflammatory mediators including IL-8 and C3. In this review we discuss the pivotal roles played by stratum corneum and neutrophils in several skin diseases, where neutrophils accumulate beneath the stratum corneum in a sterile condition.
Macular hole is a specific disease of the central retina that affects central visual acuity and central visual field. The purpose of this study is to investigate the alteration of visual processing in patients with macular hole who had small central scotoma. Six patients with macular hole participated in this study. We used positron emission tomography (PET) to measure task-related changes in regional cerebral blood flow to identify regions of the brain activated during visual stimulation. Three tasks were performed in each eye: control task, checkerboard task, shape-discrimination task. Checkerboard stimuli caused a greater blood flow activation response in normal eyes than in affected eyes at the occipital cortex. The area involved in the macular hole appeared to be 20 mm or more anteriorly from the occipital pole. The Shape-discrimination task in affected eyes activated angular gyrus, inferoparietal lobule, and middle frontal gyrus. Our findings demonstrated greater confidence in Horton's new retinotopic map than in Holmes' retinotopic map in cortical areas involved in macular function. The dorsal pathway of the visual system was activated more than the ventral pathway in patients with macular hole.
Effects of loading the long head of the biceps brachii (LHB) and arm rotation on the strain of the superior labrum (anterior and posterior) in 10 fresh frozen cadaveric shoulder joints were studied. Loads were applied to the rotator cuff muscles to stabilize the humeral head. The strain of the anterior and posterior portions of the labrum with the biceps loaded with 0.42 kg, 1.36 kg, and 2.31 kg were measured using linear transducers. The humerus was rotated externally (30, 45, 60, and 90°) and internally (30, 45, and 60°) with the arm elevated 60° at glenohumeral joint (simulated 90° elevation of arm to the trunk). The strain increased with an increase in the weight of the load to LHB and with increase in rotation angle both internally and externally. Since the strain in the posterior portion was larger than that of the anterior portion it seems likely that the labrum, especially the posterior portion, is subject to large strain during biceps loading and arm rotation.
Renal cell carcinoma (RCC) is highly metastatic. We previously showed that expression of globo-series ganglioside is associated with the metastatic potential of RCC. However, the mechanism of metastasis remains largely unknown, and there is no effective therapy for metastasis. It was recently shown that induction of differentiation of colon cancer cells by brefeldin A was accompanied by an increase of GM3 with a concomitant decrease of neolacto-series gangliosides. To get a clue to a new method of therapy for RCC, we investigated whether the similar changes occur in RCC cells expressing globo-series ganglioside. Growth suppression and an increase of GM3 simultaneous with a decrease of monosialosyl galactosyl globoside, a member of globo-series gangliosides, were observed in human RCC cell line ACHN following brefeldin A treatment. The resultant change of the ganglioside profile is inversely related to the ganglioside pattern associated with the malignant potential of RCC and almost coincided with that representative of RCC cases showing favorable prognoses. It is suggested that the inverse relationship of expression between GM3 and globo-series ganglioside is reflected on the degree of malignancy of RCC, and may be useful as one of the indicators for exploiting treatment methods of RCC.
The autosomal recessive disease 17α-hydroxylase/17, 20-lyase deficiency is characterized by mutation of the P450c17 enzyme, which catalyzes 17α-hydroxylation and 17, 20-lysis in the steroidogenic pathways. Although 17 mutations of this enzyme have been reported, only a few of them resulted in a completely unambiguous phenotype of female external genitalia in 46, XY individuals. We report here a Japanese patient with a 46, XY karyotype, who showed such a unambiguous female external genitalia. Nucleotide sequencing of the P450c17 gene revealed the patient to be a compound heterozygote carrying two different mutations (PHE53/54DEL in exon 1 and HIS373LEU in exon 6). As these mutations have been previously detected in unrelated Japanese patients, it is confirmed that these mutations accumulate regionally. Since these mutations could be screened by a multiple genotyping method, the method is applicable when 17α-hydroxylase/17, 20-lyase deficiency is suspected in Japanese patients.
A-16-year-old male adolescent with a 4-year history of protean clinical manifestations such as fever, abdominal pain, back pain, erythema nodosum and uveitis developed complete occulusion of left renal artery. Although he had been suspicious of having an autoimmune disease and treated with prednisolone, a definite diagnosis was not made. Finally, an angiography disclosed stenosis of abdominal aorta just beneath the origin of the renal arteries as well as complete occulusion of left renal artery. It has been reported that pediatric-onset Takayasu's arteritis sometimes shows protean clinical manifestations as in ours. Takayasu's arteritis should be considered as one of the underlaying disease, when a child develops protean manifestations suggesting an autoimmune disease.