Microsatellite mapping of a susceptible locus within the HLA region for Behçet's disease using Jordanian patients.

Behçet's disease (BD) has been established to be associated with HLA-B51. However, it has not been revealed whether the HLA-B51 gene itself or another gene located near the HLA-B gene is directly involved in the pathogenesis of BD. Previously, using Japanese BD patients, our group has narrowed down a BD-causative gene to 46 kb between the MICA and HLA-B genes by means of fine mapping analysis with eight microsatellite markers distributed within a 1100 kb segment around the HLA-B gene. To know whether this mapping result is generally observed in BD of another population we have investigated repeat polymorphisms of the same microsatellite markers in Jordanian BD patients. Furthermore, we have evaluated these data by Mantel-Haenzel stratified analysis to find out a primarily associated locus for BD. As a result, HLA-B51 was found to be the most strongly and primarily associated marker. This result suggests that the pathogenic gene of BD is HLA-B51 itself, but unlikely to be other genes located in the vicinity of HLA-B.

Rapid and wide-reaching delivery of HIV-1 env DNA vaccine by intranasal administration.

Although the potential of DNA vaccination is now beginning to be greatly appreciated, no detailed study of its localization in tissue or its expression kinetics has been reported. In this study, we investigated these issues using HIV-1 DNA plasmids administered either intranasally or intramuscularly. Fluorescence in situ hybridization (FISH) revealed that the human immunodeficiency virus (HIV) plasmids administered intranasally localized in the alveoli, lung, liver, spleen, regional lymph nodes, kidney, fetus, and esophagus. These HIV plasmids were detected 2 to 4 weeks after administration. We detected messenger RNA production of HIV env gene in the lung, liver and spleen, and human immunodeficiency virus type 1 (HIV-1)-specific proteins were detectable in the lung. These observations may provide important information for understanding the mechanisms of strong immune activation induced by DNA vaccination via the intranasal route. This technology of DNA administration suggests possible practical applications for vaccination and probably for gene therapy.

Strong linkage disequilibrium and haplotype analysis in Japanese pedigrees with Machado-Joseph disease.

To identify the markers tightly linked to Machado-Joseph disease (MJD) and to investigate whether a limited number of ancestral chromosomes are shared by Japanese MJD pedigrees, a detailed linkage analysis employing D14S55, D14S48, D14S67, D14S291, D14S280, AFM343vf1, D14S81, D14S265, D14S62, and D14S65 was performed. The results of multipoint linkage analysis as well as detection of critical recombination events indicate that the gene for MJD is localized in a 4-cM region between D14S280-D14S81. We found strong linkage disequilibria at AFM343vf1 and D14S81, and association of a few common haplotypes with MJD. These results indicate that there is an obvious founder effect in Japanese MJD and suggest the possibility of the existence of predisposing haplotypes which are prone to expansions of CAG repeats.

Age-specific prevalence of open-angle glaucoma and its relationship to refraction among more than 60,000 asymptomatic Japanese subjects.

To clarify the prevalence of open-angle glaucoma (OAG) and its relationship to refraction among a Japanese population with a broad range of ages including children and adolescents, an 1-year epidemiological survey was conducted. The subjects of this study were 64,394 asymptomatic individuals who had attended the glasses and contact lens center in Yokohama, Japan from February 15, 1999 to February 14, 2000 and had been subjected to several optical examinations. The results of this study showed that the overall prevalence of OAG was 1.19% (1.14% for men, and 0.98% for women). Prevalence for children aged 6 to 14 of both sexes was approximately 0.5%. There were significant positive associations between the strength (diopter) of myopic refraction and OAG prevalence among all the examined subjects.

Immune function in aging atomic bomb survivors residing in the United States.

Immunologic parameters were studied among survivors of the 1945 atomic bombs who now reside in the United States. Of all known survivors living in the U.S., about 40% (n = 189) participated in this study. Of those survivors on whom radiation exposure information was available (n = 168), 96% were exposed to less than 50 rad at the time of the bomb (ATB). Survivors were divided into two groups; those exposed to varying low doses of radiation (S+ group, exposed at less than or equal to 2500 m from the hypocenter) were compared with those exposed to "O rad" (S0 group, exposed at greater than 2500 m from the hypocenter). Of the former group, 92% were exposed to less than 100 rad and 89% to less than 50 rad ATB. Cellular immune responses, including natural cell-mediated cytotoxicity (NCMC), interferon production, and the mitogenic response to PHA, tended to be higher among S+ individuals, although only the difference for NCMC was statistically significant. This was suggestive of a trend which was consistent with the higher serum interferon levels and lower frequencies of detectable immune complexes and antimitochondrial antibodies among the S+ group, although these differences were not statistically significant. Other immunologic parameters which showed no trend included frequency of antinuclear antibodies, rheumatoid factor, levels of serum immunoglobulins, levels of isoantibodies and heteroantibodies, and the magnitude of the mixed lymphocyte reaction.

Metabolism, 45Ca uptake and insulin releasing capacities of glucose and mannose.

A detailed dose-response study relating mannose and glucose oxidation with the induction of 45Ca uptake and insulin release was performed using in vitro incubation of collagenase digested rat islets of Langerhans. The threshold value for 14C-U-D-glucose oxidation, glucose-stimulation of 45Ca uptake, and insulin release was about 5.5 mM. The half maximal response for these 3 parameters occurred at 13.4 mM, 11.6 mM, and 12.2 mM, respectively. Their maximal responses were obtained at approximately 20 mM. The threshold level for mannose oxidation, induction of 45Ca uptake and insulin release was about 11.0 mM, with half maximal responses obtained at 24.6 mM, 20.5 mM, and 22.2 mM, respectively. The maximum response of the 3 parameters to mannose was obtained at 38.8 mM and appeared to reach the same level obtained for glucose. These results suggest that hexose degradation has a significant role in controlling Ca uptake and subsequent insulin release. A lower rate of mannose oxidation appeared to account for its weaker stimulating efficacy for Ca uptake and insulin release.

Cervical intradural disc herniation.

STUDY DESIGN: A case report of anterior en bloc resected cervical intradural disc herniation and a review of the literature. OBJECTIVE: To discuss the pathogenesis of cervical intradural disc herniation. SUMMARY OF BACKGROUND DATA: Including this study case, only 17 cases of cervical intradural disc herniation have been reported. There have been few detailed reports concerning the pathogenesis of cervical intradural disc herniation. METHODS: A cervical intradural disc herniation at C6-C7, with localized hypertrophy and segmentally ossified posterior longitudinal ligament, is reported in a 45-year-old man who had Brown-Sequard syndrome diagnosed on neurologic examination. Neuroradiologic, operative, and histologic findings, particularly the pathology of the anterior en bloc resected posterior vertebral portion of C6 and C7, were evaluated for discussion of the pathogenesis. RESULTS: Adhesion of dura mater and hypertrophic posterior longitudinal ligament was observed around a perforated portion of the herniated disc, and histologic study showed irregularity in fiber alignment accompanied by scattered inflammatory cell infiltration and hypertrophy in the posterior longitudinal ligament. The cervical intradural disc herniation was removed successfully and followed by C5-Th1 anterior interbody fusion with fibular strut graft. Neurologic recovery was complete except for minor residual sensory disturbance in the leg 7 years after the surgery. CONCLUSIONS: Cervical intradural disc herniation is an extremely rare condition. The pathogenesis remains obscure. Only 16 cases have been reported in the literature, and there has been little discussion concerning the local pathology of the herniated portion. The pathogenesis of the disease in the patient reported here was considered to be the adhesion and fragility of dura mater and posterior longitudinal ligament. This was caused by hypertrophy, with chronic inflammation and ossification of the posterior longitudinal ligament sustaining chronic mechanical irritation to the dura mater, leading to perforation of the herniated disc by an accidental force.

Dorsal root ganglia morphologic features in patients with herniation of the nucleus pulposus: assessment using magnetic resonance myelography and clinical correlation.

STUDY DESIGN: Morphologic features of the dorsal root ganglia were investigated in patients with herniation of the nucleus pulposus by means of magnetic resonance myelography. OBJECTIVES: This study was undertaken to assess morphologic changes of the dorsal root ganglia in patients with herniation of the nucleus pulposus and to determine the relations between the morphologic features of the dorsal root ganglia and clinical features. SUMMARY OF BACKGROUND DATA: It has recently been reported that application of the nucleus pulposus to a nerve root induces edema in the rat dorsal root ganglion. Edema in the human dorsal root ganglion resulting from lumbar disc herniation has not been discussed in the literature, to the authors' knowledge. METHODS: Eighty-three consecutive patients (average age 42.1 years; range 17 to 77 years) with monoradicular symptoms were examined. Dorsal root ganglion morphologic features, i.e., indentations and swelling, were evaluated by magnetic resonance myelography. The dorsal root ganglion swelling at each level was quantitatively expressed as a ratio of the dorsal root ganglion width on the involved side to that of the contralateral side and was termed dorsal root ganglion ratio. Eighty-three uninvolved levels were chosen as controls in a randomized manner. Factors possibly contributing to the morphologic changes in the dorsal root ganglion were investigated. Neurologic symptoms, evaluated by the Japan Orthopaedic Association scoring system, were correlated to the morphologic changes. The morphologic features were followed up for 1 year after treatment in a small group of patients. RESULTS: Dorsal root ganglion indentations were always found in the narrowed intervertebral foramens. The incidence of indentations was significantly higher at the involved nerve roots (10.8%) than at the uninvolved nerve roots (4.0%) (P = 0.026). Patients with dorsal root ganglion indentations were significantly older (P = 0.0008). Leg pain scores in patients with indentations were significantly poor (P = 0.007). The dorsal root ganglion ratios were significantly higher at the involved levels than at the uninvolved levels (P = 0.001); the means +/- SD were 1.19 +/- 0.25 and 1.08 +/- 0.13, respectively. Patients with lateral herniated nucleus pulposus had significantly higher dorsal root ganglion ratios than those with central herniated nucleus pulposus (P = 0.0001); the mean ratios +/- SD were 1.48 +/- 0.32 and 1.10 +/- 0.12, respectively. A moderate positive correlation was found between dorsal root ganglion ratio and age (Pearson's correlation coefficient = 0.313). There was moderate negative correlation between the dorsal root ganglion ratio and leg pain, gait, motor, and total Japan Orthopaedic Association score (correlation coefficients were = -0.385, -0.350, -0.422, and -0.358, respectively). The dorsal root ganglion ratios were significantly diminished at 1-year follow-up (P = 0.001); the means +/- SD were 1.22 +/- 0.22 and 1.09 +/- 0.07, respectively. Indentations observed before treatment disappeared after treatment. CONCLUSIONS: Swelling and impingement in the involved dorsal root ganglion were clearly visualized by magnetic resonance myelography. The swelling and indentations were well correlated with severity of leg pain. These findings have important value in understanding the pathophysiology of the nerve roots in herniated nucleus pulposus.

Cervical posterior fusion with wave-shaped rod under local anesthesia for cervical spondylotic myelopathy: review of 12 patients.

STUDY DESIGN: Clinical evaluation of cervical interspinous fusion under local anesthesia in elderly patients with cervical spondylotic myelopathy. OBJECTIVES: To evaluate the effectiveness of cervical posterior fusion with wave-shaped rods inserted under local anesthesia for elderly high-risk patients with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: A substantial number of patients cannot undergo surgical interventions under general anesthesia because of their general medical complications. Although such patients would become unable to walk, which might induce a worsening of their general condition, conservative treatments had been adopted as the only treatment for these patients. The authors have obtained satisfactory results by means of posterior interspinous fusion under local anesthesia even in the high-risk patients with severe cervical spondylotic myelopathy. The aims of this surgical technique were to adjust cervical alignment and to stabilize the motion segment(s) without decompression. PATIENTS AND METHODS: Between May 1989 and August 1998, 12 elderly patients (3 men and 9 women) with cervical spondylotic myelopathy were treated with posterior interspinous fusion using wave-shaped rods inserted under local anesthesia. The average age at the surgery was 76.9 years. The average follow-up period was 5 years 6 months. All patients were unable to walk without any assistance because of their advanced myelopathy. It was felt that all of them would be unable to accept general anesthesia because of their generally poor medical conditions. Preoperative severity of the clinical symptoms and postoperative recovery were evaluated by a scoring system proposed by the Japanese Orthopaedic Association, which had 17 points at full mark. RESULTS: The average duration of the surgical procedure was 122.8 minutes. The average total blood loss was 118.6 g. No instrument failures were denoted. Neither neural deterioration nor major complication was observed relating to the surgery. Radiographic bony union of the grafted bone was achieved in all patients. Progression of myelopathy was arrested in all 12 patients, and clinical symptoms were improved in 10 patients. The mean Japanese Orthopaedic Association scores had increased from 5.0 to 10.2 points. CONCLUSIONS: Twelve high-risk patients with cervical spondylotic myelopathy were treated with posterior interspinous fusion using wave-shaped rods inserted under local anesthesia. This method was evaluated as an effective surgical salvage without any mortal complications even in the elderly high-risk patients.

Long-term follow-up results of anterior interbody fusion applied for cervical myelopathy due to ossification of the posterior longitudinal ligament.

STUDY DESIGN: A long-term follow-up study was carried out in 30 patients who underwent anterior interbody fusion for cervical myelopathy associated with ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To investigate whether anterior interbody fusion without decompression is an appropriate surgical method for long-term relief of cervical OPLL myelopathy. SUMMARY OF BACKGROUND DATA: Several studies of operative results after posterior decompression for cervical myelopathy due to ossification of the posterior longitudinal ligament have been reported. There has been no report about anterior interbody fusion without decompression. The postoperative results of this treatment method applied in cervical OPLL myelopathy have been evaluated by the authors of the present study for more than 10 years. No reports on such a long-term follow-up study have been published in the literature. METHODS: Thirty patients who underwent anterior interbody fusion for cervical OPLL myelopathy were evaluated clinically and radiographically. The mean follow-up period was 14.7 years (range, 10-23 years). RESULTS: Clinical results were evaluated according to Okamoto's classification. At the time of the final follow-up evaluation, 16 patients had improved in functional score by two grades, and their surgical results were regarded as excellent; eight patients improved by one grade, and their clinical outcomes were regarded as good; five patients showed no change; and the condition of one patient deteriorated. As for radiographic analysis, the type of ossification had changed in four cases. Ossification width and thickness increased in 26 patients. Postoperative alignment of the cervical spine showed kyphosis in three patients, straight spine in 11 patients, and lordosis in 16 patients. CONCLUSION: Anterior interbody fusion without decompression is an effective treatment for cervical OPLL myelopathy that resulted in stable long-lasting conditions.

Hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification: a cervical myelopathy case report.

STUDY DESIGN: A histopathologic examination of a specimen that showed hypertrophy of the posterior longitudinal ligament of the cervical spine. OBJECTIVES: To illustrate the possibility of hypertrophy of the posterior longitudinal ligament as a prodromal condition to ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Despite much study, the pathology of ossification of the posterior longitudinal ligament still remains unclear. Hypertrophic change often is seen in the part of the ossified ligament; however, there have been few histopathologic reports on hypertrophy of the posterior longitudinal ligament. Some reports have suggested that hypertrophy of the posterior longitudinal ligament is a prodrome of ossification of the posterior longitudinal ligament. METHODS: A 64-year-old man was admitted to the hospital because of gait disturbance and developed oliguria. In a plain radiograph, segmental ossification of the posterior longitudinal ligament was found at C4, C5, and C6. Computed tomograph myelogram revealed a soft tissue shadow, maximum 3.8 mm in diameter, on the dorsal side of the ossification of the posterior longitudinal ligament at C5 and C6. Magnetic resonance T1-weighted image (T1WI) showed an equivalent signal with the intervertebral disc on the dorsal side of ossification of the posterior longitudinal ligament. This lesion was enhanced with Gd-DTPA and confirmed as hypertrophy of the posterior longitudinal ligament. Cervical anterior decompression and fusion were performed using Yamaura's technique. The ossified and thickened lesion was elevated and removed en bloc. Then, hematoxylin-eosin and toluidine blue staining was performed to detect metachromasia. RESULTS: Macroscopic examination of the specimen revealed that soft tissue formation was connected with the C4-C5 intervertebral space and extended downward to C6-C7. Histopatholgically, collagen fibers were proliferating in the long-axis direction on both ventral and dorsal sides. This was surrounded by extended nucleus pulposus-like chondrocyte tissue, where endplate cartilage was detected around the C4 pedicle. Roux staining was low, and partial vascular and cellular infiltration was observed, although it was not marked. CONCLUSION: The herniated nucleus pulposus involving endplate cartilage from C4-C5 was limited to the superficial layer, and proliferation of nucleus pulposus-like chondrocytes occurred in the herniated tissue, where they might undergo a change in cell phenotype. The results of the present study support the hypothesis that hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification of the posterior longitudinal ligament.

Exercise intensity determines the magnitude of IOP decrease after running.

The effects of the intensity, duration and quantity (intensity x duration) of exercise on the reduction of intraocular pressure (IOP) in healthy and physically fit individuals were studied. Five minutes after 15 minutes of exercise at 70%, 55% and 40% of maximum exercise load (%HRmax) the IOP decreased 4.3 +/- 0.7 mmHg, 2.2 +/- 0.7 mmHg and 0.6 +/- 0.5 mmHg, respectively. The magnitude of IOP reduction increased with exercise load. Running for 7.5 minutes at 70%HRmax decreased IOP comparable to 15 minutes of running at the same exercise load (4.4 +/- 0.6 mmHg). Twenty-five minutes of running at 40%HRmax is almost the same quantity of exercise as 15 minutes of running at 70%HRmax. However, the former did not result in IOP reductions to equal the latter (2.3 +/- 0.5 vs 4.4 +/- 0.6 mmHg). The amount of IOP reduction after short-term exercise seems to depend on the intensity of exercise, not on the duration of exercise or the quantity of exercise.

An indirect method of estimating VO2 from work load using arm-cranking in adult hemiplegic patients.

The purpose of this study was to develop an oxygen consumption (VO2) measurement for adult hemiplegic patients during an incremental exercise arm-cranking test. Fifty-five adult hemiplegic patients performed a three-stage arm-cranking exercise test while VO2 was measured. The control group consisted of thirteen healthy elderly persons who performed a similar arm-cranking test until exhaustion. The results indicated that there was a significant difference in VO2 during rest periods between the adult hemiplegic and control groups. Based on data analysis, we developed an equation to estimate the VO2 for adult hemiplegic patients: VO2(ml/min) = (kgm/min x 4.2 ml/kgm) + ((4.2 ml/kg/min x kg body weight) + 105.6 ml/min) (r = 0.847), while the equation for the controls was VO2(ml/min) = (kgm/min x 4.3 ml/kgm) + ((2.9 ml/kg/min x kg body weight) + 105.5 ml/min) (r = 0.932). There was no significant difference between the estimated VO2 for the new equations (nVO2) and the measured VO2 (mVO2) in the two groups at any stage. In our data analysis, based on an estimated VO2 from the American College of Sports Medicine (ACSM) equation (aVO2), the nVO2 and mVO2 at each stage showed lower aVO2 than either nVO2 or mVO2 in each subject (p < 0.05). These findings suggest that the ACSM equation is unlikely to be applicable for estimating VO2 for one hand arm-cranking exercise. In conclusion, the new equations established in this study, when used with a specific prescribed exercise testing protocol, would allow us to estimate VO2 more accurately for both adult hemiplegic patients and healthy elderly persons.

The main factor causing prolonged reaction time on force producing process following anterior cruciate ligament reconstruction.

This study investigated the electromechanical properties of atrophied human quadriceps femoris muscle during a voluntarily elicited maximal isometric contraction (MVC) and a peripherally stimulated twitch contraction. Nineteen patients were recruited 2-3 months following a unilateral anterior cruciate ligament (ACL) reconstruction. Both the involved leg as well as the uninvolved leg were studied. Maximal twitch response was elicited and surface electromyograms (EMG) were recorded from the vastus lateralis. Total reaction time (TRT) for both MVC and twitch on involved leg was prolonged (251.47 msec, 26.01 msec). This prolongation suggests an extended lag in avoiding injury such as during sports. Pre-motor time during both MVC and twitch (PMTmvc, PMTtwitch) did not differ between both groups. Electromechanical delay during MVC (EMDmvc) was prolonged on involved leg (53.42 msec), and also evoked twitch EMD (EMDtwitch) (20.04 msec) as compared to the opposite side. Prolonged EMDtwitch may be due to a decrease in stiffness of the series elastic component, changes of peripheral muscle composition to containing more slow type muscle fibers, or a decrease in function of the excitation-contraction (E-C) coupling process. A prolonged EMDtwitch can also explain the prolonged EMDmvc. These findings also suggested that prolonged TRTmvc to visual stimulus during MVC in atrophied human quadriceps femoris muscle after disuse was principally due to prolongation of EMDmvc. Prolonged EMDmvc may have resulted from decreased muscle stiffness, which was evident in the prolongation of the EMDtwitch.