Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions.

Cell adhesion kinase beta (CAKbeta/PYK2) is the second protein-tyrosine kinase of the focal adhesion kinase subfamily. We identified a cDNA that encodes a CAKbeta-binding protein. This cDNA clone encodes the human homologue of Hic-5, the cDNA of which was cloned in 1994 as transforming growth factor beta1- and hydrogen peroxide-inducible mRNA. We found that Hic-5 exclusively localized at focal adhesions in a rat fibroblast line, WFB. This localization of Hic-5 was confirmed in WFB cells expressing Myc-tagged Hic-5. The amino acid sequence of Hic-5 is highly similar to that of paxillin in the four LD motifs as well as in the four contiguous LIM domains. The Hic-5 N-terminal domain directly associated in vitro with the extreme C-terminal region (residue 801 to the end) of CAKbeta. CAKbeta was coimmunoprecipitated with Hic-5 from the WFB cell lysate. The coimmunoprecipitation of CAKbeta with Hic-5 was markedly inhibited by the addition of the extreme C-terminal region of CAKbeta. Coimmunoprecipitation of Hic-5 with CAKbeta, which was shown in COS-7 cells doubly transfected with cDNA constructs of CAKbeta and Myc-tagged Hic-5, was lost when the CAKbeta amino acid residues 741-903 were deleted. Hic-5 was tyrosine-phosphorylated in Src-transformed 3Y1 cells and in cells treated with pervanadate. Hic-5 associated with CAKbeta was selectively tyrosine-phosphorylated in WFB cells exposed to hypertonic osmotic stress. These results indicate that Hic-5 is a paxillin-related component of focal adhesions and binds to CAKbeta, implying possible involvement of Hic-5 in the downstream signaling of CAKbeta.

Restricted expression of cell adhesion kinase-beta in rat tissues.

Cell adhesion kinase-beta (CAK-beta) is a protein tyrosine kinase of the focal adhesion kinase subfamily, which contains large amino- and carboxyl-terminal domains. We studied the tissue distribution of CAK-beta and its mRNA by immunohistochemical staining and in situ hybridization. In rat brain, CAK-beta was mainly found in the medulla whereas CAK-beta mRNA was expressed in most neurons, especially pyramidal cells and Purkinje cells. In the small intestine, CAK-beta protein and mRNA were detected in the absorptive epithelial cells, and the protein was concentrated in the brush border. Double immunostaining for CAK-beta and actin showed that they co-localized in the brush border of small intestine cells. Immunoelectron micrography revealed that the anti-CAK-beta antibody localized within microvilli. In the kidney, the protein was mainly expressed in proximal tubular cells, which have well developed microvilli, although CAK-beta mRNA was observed in most urinary tubular cells. In other tissues, the ciliated cells of the epididymis strongly expressed CAK-beta mRNA and CAK-beta localized in the cilia. In addition, alpha- and beta-tubulin were identified in the rat brain lysates immunoprecipitated with anti-CAK-beta antibody. The present results demonstrate that CAK-beta is present at relatively high levels in cilia, axons, and microvilli. This suggests that CAK-beta may play important roles in the functions of these structures or that the CAK-beta-related signaling pathway is closely associated with cytoskeletal components.

Preservation of central motor conduction in patients with spinal muscular atrophy type II.

We evaluated the central (motor cortex to C8 motoneuron) and peripheral (C8 motoneuron to the muscle) motor conduction in 14 limbs of 7 patients with the intermediate form of spinal muscular atrophy (SMA II). The central motor conduction time (CMCT) was calculated using motor evoked potentials (MEPs) by transcranial magnetic stimulation and the results of a conventional F wave study. Peripheral conduction abnormality was found in 6 median nerves (43%) and 10 ulnar nerves (71%). Even in these patients with peripheral conduction abnormalities, the CMCT was consistently normal whenever the MEP was recorded. These results indicate that the motor conduction of the corticospinal fibers remains normal in SMA II.

A correlation study between serum adenosine deaminase activities and peripheral lymphocyte subsets in Parkinson's disease.

Adenosine deaminase (ADA) and its isozyme activities in serum were measured together with peripheral lymphocyte subsets in 42 patients with idiopathic Parkinson's disease. The total and ADA 2 activities were significantly higher than normal controls (p < 0.01). As regards the peripheral lymphocyte subsets, the proportion of OKT 10+ cells (activated T lymphocytes) and the proportions of interleukin-2 receptor+ and HLA-DR+ cells (mainly activated T lymphocytes) were significantly higher than normal controls (p < 0.05, 0.01, 0.01, respectively). On the other hand, OKT 10+ cells demonstrated a significant correlation not only with total ADA but also with ADA 2 activity. These results suggest that high serum ADA activity may be involved in the pathogenesis of Parkinson's disease through peripheral T lymphocyte activation.

The first case of polymyositis associated with interferon therapy.

A 54-year-old man with renal cell carcinoma was treated with interferon (IFN)-gamma for 3 weeks soon after nephrectomy. Three months later he received IFN-alpha therapy for 8 weeks due to chronic active hepatitis C. He subsequently contracted polymyositis (PM): proximal muscle weakness, an elevation of muscle enzymes, myogenic patterns on the electromyograph and histologically specific findings in biopsied muscle specimens. After discontinuation of IFN his muscular weakness gradually recovered.

[A sporadic case of essential vitamin E deficiency manifested by sensory-dominant polyneuropathy and retinitis pigmentosa].

A 55-year-old woman with known retinitis pigmentosa for 25 years was progressively clumsy in gait and activities of daily living over the past 30 years. She was able to manage house work and social activities, but she developed swallowing disturbance associated with involuntary neck muscle spasm for 2 weeks, which brought her to our clinic on September 7, 1990. General physical examination was normal except for dry skin. Neurological examination was compatible with sensory-dominant polyneuropathy, showing distal dominant sensory impairment together with absent vibration sense and areflexia in lower limbs, but no gross muscular weakness. There were neck dystonia and bilateral poor visual acuity due to secondary optic atrophy of retinitis pigmentosa. The former responded to the combination of tiapride and trihexyphenidyl. She was admitted twice for further evaluation. Complete blood count and blood chemistry tests including lipids were all within normal limits, and so was cerebrospinal fluid. Pyruvate and lactate before and after exercise loading were also normal. Malignancy workup was negative. To our surprise, serum vitamin E level turned out very low (1.89 micrograms/ml), normal range being 4.7-20.3 micrograms/ml. Oral vitamin E administration test by 2g of alpha-tocopherol showed abnormal absorption curve followed fast clearance in serum. Stool was occasionally positive for fat corpuscles by Sudan III staining, but 99Tc-HSA leakage into the intestines was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric non-Hodgkin's lymphoma associated with Behçet's disease.

The first case of primary gastric lymphoma associated with Behçet's disease is reported. A 43-year-old woman, who had been treated for Behçet's disease for 15 years, was diagnosed as low-grade and small lymphocytic malignant lymphoma of the stomach. Although the patient had been treated for Behçet's disease, chemotherapy was performed and a complete remission of gastric lymphoma was achieved. The literature regarding the association of malignant diseases with Behçet's disease is briefly reviewed.