Locomotor improvement of spinal cord-injured rats through treadmill training by forced plantar placement of hind paws.

STUDY DESIGN: Experimental training model of rats with spinal cord injury (SCI). SETTING: Osaka, JapanObjective:To investigate the effect of forced treadmill training by plantar placement (PP), as compared with dorsal placement (DP), of the dorsal paws on the locomotor behaviors of spinal cord-injured rats. METHODS: The spinal cord was contusion-injured at the thoracic level. Rats were divided into three groups: forced training involving stepping by PP and DP and non-forced training/assistance (nT). Training began 1 week after injury and was conducted for 4 weeks. Locomotor behaviors were estimated using Basso-Beattie-Bresnahan (BBB) scores, dorsiflexion of the hind paws and footprints of the hind paws. Histological and immunohistochemical examinations of the spinal cord lesions were conducted after 4 weeks of training. RESULTS: The values, respectively, of PP, DP and nT groups at 4 weeks of training were as follows: BBB scores were 15.6±0.8, 7.7±1.3 and 10.3±0.4. The paw dorsiflexion angles were 34.1±5.2, 16.4±2.4 and 23.6±3.0 degrees, respectively. The stride angles were 5.1±0.9, 13.7±4.9 and 17.8±4.0 degrees for the left paws. Cavity volumes were 10.3±2.1, 31.0±2.0 and 28.2±4.9%. In addition to cavities, there were astrocyte-devoid areas containing some loose tissues, through which many axons extended longitudinally. CONCLUSIONS: The BBB score, dorsiflexion angle and stride angle were consistently improved in the PP group. Cavity formation was more reduced, and many axons extended through coarse tissues formed in astrocyte-devoid areas at the lesion in the PP group. Forced training by PP of the hind paws promoted the behavioral and histological improvement of rats with SCI.

Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement.

Using the clone-specific rearrangement of the T cell receptor gene as the genetic marker of the clonotype, we analyzed the clonal origin of the interleukin 2 (IL-2)-dependent human T-lymphotrophic virus I (HTLV-I)-positive T cell lines established from various adult T cell leukemia (ATL) patients. From a patient with chronic ATL, whose leukemic cells proliferated in vitro in response to IL-2, we repeatedly established leukemic T cell clones having the same rearrangement profile of the T beta chain gene as the leukemic cells. By contrast, established cell lines from acute ATL patients had different beta chain gene rearrangements from those of the leukemic cells. These HTLV-I+ T cell lines might not be the direct progeny of the leukemic cells, but that of T cells infected either in vivo or in vitro. These IL-2-reactive nonleukemic T cells might have been selected in vitro, because their leukemic cells failed to respond to IL-2, despite the expression of IL-2 receptor. The analysis of the T cell receptor gene rearrangement may give a new approach for the elucidation of the mechanism of leukemogenesis and the origin of the HTLV-I+ T cell lines in ATL.

Inhibition of the proliferation of transformed epidermal cells in culture by various prostaglandins.

Cytotoxic action of various prostaglandins (PGs) was examined on the PAM 212 transformed mouse epidermal cell line, and delta 7-PGA1 was found most active. delta 7-PGA1 exerted a dose-dependent inhibition of PAM 212 cell growth over 0.1 microgram/ml (0.3 microM). At 1.6 microgram/ml (4.6 microM) growth was completely inhibited, and the number of viable cells decreased remarkably during culture. The concentration needed for 50% growth inhibition (IC50) value of delta 7-PGA1 on PAM 212 cell growth was calculated as 0.4 microgram/ml (1.1 microM). At this concentration, the DNA synthesis in 24- and 48-h cultured cells was decreased to a half of the level in the control cells, and microscopically, remaining cells showed degenerative changes with many vacuoles in their cytoplasm. Prostaglandin D2, a major PG in mast cells, also showed potent cytotoxic activity. However, this action was expressed as 9-deoxy-delta 9,12-13,14-dihydro-PGD2 (delta 12-PGJ2), which was converted from PGD2 in plasma, and had a 3-fold stronger growth inhibitory activity than PGD2; the IC50 values of PGD2 and delta 12-PGJ2 were 2 micrograms/ml (5.7 microM) and 0.75 microgram/ml (2.1 microM), respectively. Among other PGs tested, PGA2 showed a comparable growth inhibitory activity, and PGB2, PGE1, and PGE2 less but significant activity. Prostaglandin F2 alpha and PGI2 however, had no such effect on cell proliferation at 5 micrograms/ml (14.3 microM) concentration, suggesting that cyclopentenone structure is an essential moiety of PG derivatives for cell growth inhibition. This cytotoxic action of delta 7-PGA1 and delta 12-PGJ2 appears to be independent of cyclic-AMP, since these PGs were virtually inactive in raising intracellular cyclic-AMP levels in PAM 212 cells.

A monoclonal antibody specifically reactive to human Langerhans cells.

We prepared a mouse monoclonal antibody that reacts specifically to human Langerhans cells (LC). The protein recognized by this antibody was mainly in the membranes of Birbeck granules and related structures. Using this antibody, we could identify LC in various tissues; these cells were in the skin, stratified squamous mucosal epithelia, lymph nodes, and the thymus. The antibody did not react with monocytes, tissue macrophages, lymphoid dendritic cells, follicular dendritic cells, or interdigitating cells. The antigen purified with this antibody was a heterogeneously glycosylated protein of Mr approximately 40,000 without interchain disulfide bonds. This antibody may be useful for identifying LC in various human tissues with or without abnormalities, and for studying the origin and fate of Birbeck granules of LC.

Changes in the localization of NAP-22, a calmodulin binding membrane protein, during the development of neuronal polarity.

NAP-22, a neuronal tissue-enriched acidic membrane protein, is a Ca(2+)-dependent calmodulin binding protein and has similar biochemical characteristics to GAP-43 (neuromodulin). Recent biochemical studies have demonstrated that NAP-22 localizes in the membrane raft domain with a cholesterol-dependent manner. Since the raft domain is assumed to be important to establish and/or to maintain the cell polarity, we have investigated the changes in the localization of NAP-22 during the development of the neuronal polarity in vitro and in vivo, using cultured hippocampal neurons and developing cerebellum neurons, respectively. Cultured hippocampal neurons initially extended several short processes, and at this stage NAP-22 was distributed more or less evenly among them. During the maturation of neuronal cells, NAP-22 was sorted preferentially into the axon. Throughout the developmental stages of hippocampal neurons, the localization change of NAP-22 was quite similar to that of tau, an axonal marker protein, but not to that of microtubule-associated protein-2 (MAP-2), a dendritic marker protein. Further confocal microscopic observation demonstrated the colocalization of NAP-22 and either tau or vesicle-associated protein-2 (VAMP-2). A comparison of the time course of the axonal localization of NAP-22 and GAP-43 showed that NAP-22 localization was much later than that of GAP-43. The correlation between the expression of NAP-22 and synaptogenesis in the cerebellar granular layer, particularly in the synaptic glomeruli, was also investigated. There existed many VAMP-2 positive synapses but no NAP-22 positive ones in 1-week-old cerebellum. On sections of 2-week-old cerebellum, accumulation of NAP-22 to the synaptic glomeruli was clearly observed and this accumulation became clearer during the maturation of the synaptic structure. The present results suggest the possibility that NAP-22 plays an important role in the maturation and/or the maintenance of synapses rather than in the process of the axonal outgrowth, by controlling cholesterol-dependent membrane dynamics.

Bullous pemphigoid-like lesions induced by phenacetin. Report of a case and an immunopathologic study.

An 84-year-old man with chronic eczema and ischemic heart disease had bullous pemphigoid-like lesions develop following the oral administration of phenacetin. The diagnosis was confirmed by routine histopathologic studies and by immunofluorescent and electron microscopy. Since rechallenge with phenacetin resulted in bulla formation, phenacetin was considered to be the causative agent. This patient showed several atypical clinical features, compared with patients with idiopathic bullous pemphigoid, including no associated erythematous macules, a positive Nikolsky's sign, painful superficial ulcers, and nonpruritic bullae. Histopathologically, there was lack of polymorphonuclear leukocyte infiltrate. The immunopathologic characteristics, however, were quite typical for those found in bullous pemphigoid. The antigenic sites for the autoantibodies from our patient were, at least in part, different from those of idiopathic bullous pemphigoid.

Optical resolution by high-performance capillary electrophoresis. Micellar electrokinetic chromatography with sodium N-dodecanoyl-L-glutamate and digitonin.

Optical resolution by micellar electrokinetic chromatography with sodium N-dodecanoyl-L-glutamate (SDGlu) and with digitonin-sodium taurodeoxycholate (STDC) mixed micelles was investigated. Addition of sodium dodecyl sulphate, urea and methanol to SDGlu micellar solutions could give improved peak shapes and resolution. With SDGlu, phenylthiohydantoin (PTH) derivatives of five DL-amino acids (alpha-aminobutyric acid, methionine, norvaline, tryptophan and norleucine) were separated from each other and each pair of enantiomers was optically resolved. On the other hand, three PTH-DL-amino acids (norvaline, valine and alpha-aminobutyric acid) were also successfully resolved with a digitonin-STDC-urea solution (pH 2.5).

Selective synthesis of 4-methoxyestrogen from 4-hydroxyestrogen.

The introduction of an oxygen atom into the C-6 position of 4-hydroxyestrogen allowed for the selective methylation of the two phenolic hydroxyl groups. When the 6-oxo derivative of 4-hydroxyestrone was benzylated in ethanol, only the 3-monobenzyl ether was obtained without formation of the 4-monobenzyl ether. Moreover, the 6-carbonyl group was further reduced to methylene almost quantitatively in the reaction of 4-acetoxy-6-oxoestrone 3-benzyl ether derivative with sodium borohydride. Therefore, 4-methoxyestrogen was synthesized by essentially combining these two reactions.

Evaluation of anti-cardiolipin antibody and its cross-reactivity in sera of patients with lepromatous leprosy.

Using a sensitive and modified solid-phase radioimmunoassay for detecting anti-cardiolipin antibodies, sera of 45 patients with lepromatous leprosy were examined. Nine of the 45 (20%) showed positive levels of anti-cardiolipin antibodies. Inhibition tests revealed that these antibodies significantly cross-reacted with double-stranded (ds) DNA, but not with single-stranded (ss) DNA or extractable nuclear antigens (ENA). We describe the unique pattern of antibody cross-reactivity with cardiolipin and dsDNA in sera of patients with lepromatous leprosy.

Intracerebral neurinomas in a case of von Recklinghausen's disease (neurofibromatosis).

We report the third case of intracerebral neurinoma in a patient with von Recklinghausen's disease, who died of recurrent subdural hematomas after head injury. A total of ten tumors were found in the brain. Both by histological and ultrastructural standards the multiple tumors resembled neurinomas. The pattern of positivity for S-100 and myelin basic protein indicated the Schwann cell origin of the tumors. The ultrastructural findings indicated Schwann cells and numerous areas showing a well defined basement membrane surrounding spindle-shaped neoplastic cells and other areas lacking basement membrane with Schwann cells embedded in collagen. The present case may be categorized as a mixed form of peripheral and central neurofibromatosis. It seems safe to assume that perivascular nerves are the site of origin of the tumors.

Transcranial Doppler ultrasonography in patients with moyamoya disease.

This study included 17 patients (five men and 12 women) with clinical diagnosis of Moyamoya disease from conventional angiograms. Bilateral basal arteries were measured by the transtemporal approach with a 2 MHz pulsed Doppler instrument (TC-2 64B EME). In 28 out of the 34 basal arteries (82.4%), reliable recordings were obtained. These transcranial Doppler ultrasonography (TCD) findings were classified into three patterns: (1) High-high pattern; the mean cerebral blood flow velocity (CBFV) was increased throughout the basal arteries by over 70 cm/s (seven arteries, 25.0%); (2) high-low pattern; the mean CBFV was fastest (over 70 cm/s) at the ICA or proximal MCA and the mean CBFV decreased remarkably distally (15 arteries, 53.6%); and (3) low-low pattern; the mean CBFV was less than 40 cm/s throughout the basal arteries (arteries, 15.4%). These CBFV patterns as assessed by TCD are compared with the patients age, clinical symptoms and angiographical stagings (Suzuki's criteria). The high-high pattern on TCD was predominantly seen in the younger patients and in the earlier stages of the disease. The high-low pattern was the most common pattern of CBFV as assessed by TCD in Moyamoya patients. The low-low pattern on TCD was more common in the later stages following angiographic evaluation by Suzuki's criteria. The above patterns based on TCD findings show a good correlation with the age of the patient and the clinical diagnosis at the onset. TCD appears to be very useful in the evaluation of patients with Moyamoya disease.

[A case of atypical moyamoya disease with a ruptured aneursym on moyamoya vessel].

A 45-year-old female had sudden onset of severe headache, nausea and vomiting without any inducing moments and was transferred to our hospital by an ambulance car. On admission the patient was alert and showed only signs of meningeal irritation. There were no other neurological deficits at all. Immediate CT examination revealed a small high density spot in the area of the right basal ganglia, and a large high density in the frontal horns of both lateral ventricles. Right carotid angiogram showed completely patent carotid siphon with Moyamoya vessels. A small round aneurysmal shadow of 3 mm in diameter was seen in the area of these Moyamoya vessels of the right basal ganglia, and it was thought to be corresponding to the high density spot in the CT examination. Left carotid angiogram showed stenosis of C portion with typical Moyamoya vessels. Therefore, diagnosis of atypical Moyamoya disease with a ruptured aneurysm and ventricular penetration of hematoma was made. The patient was placed on conservative treatment. On 25th day from onset, repeated angiogram showed enlargement of the aneurysmal shadow from 3 mm to 5 mm in diameter. So, on 33rd day, right STA-MCA anastomosis and encephalomyosynangiosis were carried out. Angiogram on 12th day after surgery revealed no aneurysmal shadow. The patient was discharged without any neurological deficit at all. Previous paper, which reported cases of Moyamoya disease with aneurysm, were reviewed. According to the location of the aneurysm, these cases were classified into 3 types angiographically; type I: aneurysm in the area of Moyamoya vessels, type II: aneurysm of cerebral-peripheral artery, and type III: aneurysm of the circle of Willis. It has been generally believed that the Moyamoya disease may be associated with either a true or a pseudoaneurysm in the case of type I. However, pseudoaneurysm in the area of Moyamoya vessels has not been found in postmortem examination but true aneurysms so far. Therefore it may not be denied that the aneurysm of this case was true aneurysm although it showed an enlarging tendency and disappeared rather spontaneously.

[Adult identical twins with moyamoya disease].

Adult identical twins with Moyamoya disease are reported. Laboratory examinations such as blood types, AB, Rh(+), HLA (human leucocytic antigen) analysis [AW26(9), A26(10), BW62(15), BW61(40), CW3], and finger prints, and hairs confirmed that two patients were identical twins. Both had normal serum immunoglobulin levels and no anti-DNA antibodies. Patient No. 1, a 39-year-old female, was admitted to our service with chief complaints of nausea, vomiting and left hemiparesis with sudden onset on Oct 31, 1981. The patient had an episode of tetraplegia that occurred suddenly at 4 years of her age and lasted about a week. Motor weakness had completely disappeared but moderate mental retardation remained. She had been employed just prior to this attack. CT and angiographic examinations revealed ventricular hemorrhage with Moyamoya disease, which had miliary aneurysm in the branch of the right posterior choroidal artery. The operation of encephalomyosynangiosis was performed on her left hemisphere. The postoperative course was uneventful. Patient No. 2, the twin sister of patient No. 1, was in good health and mental state until 19 years of her age, when she suddenly lost consciousness and developed hemiparesis. After this attack, her motor function had recovered well. However, mental ability gradually deteriorated and she was admitted to a psychiatric ward. CT examination and angiographic studies were performed on Oct 12, 1982, and she was diagnosed as having Moyamoya disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental evidence of nonthermal acceleration of relativistic electrons by an intensive laser pulse.

Nonthermal acceleration of relativistic electrons is investigated with an intensive laser pulse. An energy distribution function of energetic particles in the universe or cosmic rays is well represented by a power-law spectrum, therefore, nonthermal acceleration is essential to understand the origin of cosmic rays. A possible candidate for the origin of cosmic rays is wakefield acceleration at relativistic astrophysical perpendicular shocks. The wakefield is considered to be excited by large-amplitude precursor light waves in the upstream of the shocks. Substituting an intensive laser pulse for the large amplitude light waves, we performed a model experiment of the shock environments in a laboratory plasma. An intensive laser pulse was propagated in a plasma tube created by imploding a hollow polystyrene cylinder, as the large amplitude light waves propagated in the upstream plasma at an astrophysical shock. Nonthermal electrons were generated, and the energy distribution functions of the electrons have a power-law component with an index of ~2. We described the detailed procedures to obtain the nonthermal components from data obtained by an electron spectrometer.

Surface acceleration of fast electrons with relativistic self-focusing in preformed plasma.

We report an observation of surface acceleration of fast electrons in intense laser-plasma interactions. When a preformed plasma is presented in front of a solid target with a higher laser intensity, the emission direction of fast electrons is changed to the target surface direction from the laser and specular directions. This feature could be caused by the formation of a strong static magnetic field along the target surface which traps and holds fast electrons on the surface. In our experiment, the increase in the laser intensity due to relativistic self-focusing in plasma plays an important role for the formation. The strength of the magnetic field is calculated from the bent angle of the electrons, resulting in tens of percent of laser magnetic field, which agrees well with a two-dimensional particle-in-cell calculation. The strong surface current explains the high conversion efficiency on the cone-guided fast ignitor experiments.

p53 prevents maturation of T cell development to the immature CD4-CD8+ stage in Bcl11b-/- mice.

Signaling pathways such as the pre-TCR and Wnt pathways regulate alpha/beta T cell differentiation in thymus. Mice lacking an essential component of the pre-TCR exhibit arrest at the (CD4(-)CD8(-)) (CD44(-)CD25(+)) stage (DN3) of thymocyte development, and introduction of p53 deficiency into those mice abrogates this arrest, resulting in transition to the (CD4(+)CD8(+)) double-positive (DP) stage. This paper examines the effect of inactivation of p53 on thymocyte development in Bcl11b(-/-) mice that exhibit arrest at the DN3 or (CD4(-)CD8(+)) immature single-positive (ISP) stage. No DP thymocytes were detected in thymocytes of adoptive transfer experiments in scid mice that were derived from p53(-/-)Bcl11b(-/-) precursors but ISP thymocytes increased in the proportion and in the cell number approximately three times higher than those from Bcl11b(-/-) precursors. Consistently, the level of apoptosis decreased to the level of wild-type precursors. These results suggest that inactivation of p53 is sufficient for DN3 thymocytes to differentiate into the ISP, but not to DP, stage of thymocyte development in Bcl11b(-/-) mice. This provides evidence for a novel p53-mediated checkpoint that regulates the transition from the DN3 to ISP stage of thymocyte development.

Plant nuclear tRNA(Met) genes are ubiquitously interrupted by introns.

We have isolated three independent clones for nuclear elongator tRNA(Met) genes from an Arabidopsis DNA library using a tRNA(Met)-specific probe generated by PCR. Each of the coding sequences for tRNAMet in these clones is identical and is interrupted by an identical 11 bp long intervening sequence at the same position in the anticodon loop of the tRNA. Their sequences differ at two positions from the intron in a soybean counterpart. Southern analysis of Arabidopsis DNA demonstrates that a gene family coding for tRNA(Met) is dispersed at at least eight loci in the genome. The unspliced precursor tRNA(Met) intermediate was detected by RNA analysis using an oligonucleotide probe complementary to the putative intron sequence. In order to know whether introns commonly interrupt plant tRNA(Met) genes, their coding sequences were PCR-amplified from the DNAs of eight phylogenetically separate plant species. All 53 sequences determined contain 10 to 13 bp long intervening sequences, always positioned one base downstream from the anticodon. They can all be potentially folded into the secondary structure characteristic for plant intron-containing precursor tRNAs. Surprisingly, GC residues are always present at the 5'-distal end of each intron.

Acute capsular infarction. Location of the lesions and the clinical features.

Sixty-three patients with lacunar-type of acute capsular infarction were treated in our service during the last 2 years. Their lesions were identified by computed tomography (CT) and classified into six types according to their locations: anterior, lateral, posterior, superior, inferior and multiple. The lesions were thought to be in the watershed areas of the regional arterial supplies, and the areas were considered to be prone to ischemia. The clinical course of each type showed characteristic features of ischemic strokes. In the majority of the patients with the lateral type, reversible ischemic neurological deficit (RIND) was seen as the predominant symptom, transient ischemic attack (TIA) was noted in the patients with the superior type, and major completed stroke was observed in those with posterior type.

Cutaneous leiomyoma of the male nipple.

A case of cutaneous leiomyoma of the male nipple is reported. This is the second case reported by dermatologists to the best of our knowledge.