Delayed resolution of residual hemifacial spasm after microvascular decompression operations.

OBJECTIVE: After microvascular decompression to treat hemifacial spasm (HFS), resolution of the HFS is often gradual. We carefully investigated the course of the gradual resolution of HFS and examined the differences between patients with and without postoperative HFS. METHODS: One hundred seventy-five patients with HFS were monitored, for observation of 1) whether postoperative HFS occurred, 2) when it occurred, and 3) when it disappeared after microvascular decompression. For two groups of patients, with (Group I) and without (Group II) postoperative HFS, we investigated age, sex, spasm side, preoperative facial nerve block (botulinum toxin treatment), decompression material, preoperative HFS period, offender (compressing vessel), temporary and permanent postoperative complications, and electromyographic findings. RESULTS: In Group I (88 patients), postoperative HFS began within 4 days after surgery, a period that we have termed the silent period of postoperative HFS; the median value for the time to resolution was 28 days. The other 87 patients exhibited no postoperative HFS (Group II). There was a significantly higher incidence of postoperative facial weakness in Group II (Group II, 41.3%; Group I, 25.5%; P = 0.02 by logistic regression analysis). In Group I, there was no statistically significant relationship between the investigated parameters and the silent period or the postoperative HFS period, as determined by Cox proportional-hazards regression analysis, except for the number of preoperative facial nerve blocks. Electromyographic investigation of F waves revealed facial paresis during the silent period in a patient. CONCLUSION: Approximately 50% of patients with HFS exhibited residual spasm postoperatively. An immediate postoperative silent period of 4 days without spasm was characteristic. One-quarter, one-half, and 90% of the residual spasm resolved by 1 week, 1 month, and 8 months after surgery, respectively.

Conservative treatment for cervical spondylotic myelopathy. prediction of treatment effects by multivariate analysis.

BACKGROUND CONTEXT: Many studies have suggested only slight effects of conservative treatment on cervical spondylotic myelopathy (CSM), whereas a few reports describe conservative treatment as being effective. This suggested the influence of various factors on treatment outcomes. PURPOSE: We investigated symptomatic changes after conservative treatment in patients based on a clear understanding of the effects and limitations of conservative treatment. STUDY DESIGN: We have encountered cases that showed symptomatic improvement with conservative treatment and became interested in the effectiveness of conservative treatment for CSM and whether other factors affect the results of conservative treatment. PATIENT SAMPLE: We have analyzed the results of conservative treatment for CSM in 69 cases, derived from a population of 101 CSM cases. OUTCOME MEASURES: Symptoms at the time of the first examination were compared with those at the final examination, and the patients were classified into three groups showing improvement, no change or exacerbation. METHODS: Improvement or exacerbation of the symptoms was used as dependent variables and the collected factors as independent variables, and logistic regression was performed on these variables. RESULTS: Multivariate analysis showed significant correlation between clinical outcome and the disease duration and the presence of rigorous conservative treatment. CONCLUSIONS: Conservative treatment for CSM is considered to be effective if it is performed intensively in selected patients. In treating CSM, the therapeutic approach must be selected first in consideration of the patient's disease duration. Conservative treatment must be carried out intensively after sufficient explanation to the patients. Timely surgical intervention is considered to be important if the symptoms show no change or exacerbation with conservative treatment.

Quantitative gated myocardial SPECT: effect of collimation on left-ventricular ejection fraction.

OBJECTIVE: Left-ventricular ejection fraction (LVEF) can be computed from gated myocardial perfusion SPECT studies using quantitative algorithms. The purpose of this study was to compare the LVEF obtained using the conventional high-resolution parallel-hole collimator (HRC) to the Cardiofocal collimator (CFC) (Siemens Medical Systems, Hoffman Estates, IL) using a quantitative LVEF program. METHODS: Thirty-four patients (15 men, 19 women; mean age = 62 y) had either treadmill or pharmacological stress testing with 25-30 mCi 99mTc sestamibi injected at peak stress. Conventional gated SPECT imaging was performed approximately 30 min poststress, first with the HRC collimator, then with the CFC, using the same acquisition parameters on a single-head gamma camera. Traditional (TRAD) determination of LVEF using planar gated blood pool and/or cardiac catherization also was obtained for each patient. RESULTS: The correlation in LVEF between the CFC and HRC acquisitions was excellent, r = 0.99. The correlation between CFC and TRAD LVEF was good, r = 0.95, as was the HRC and TRAD correlation, r = 0.97. The mean LVEF value for HRC was slightly less than TRAD (54% vs. 55.4%), while the CFC mean LVEF was higher (62% vs. 55.4%). Although CFC LVEF correlated well with HRC, mean LVEF value using CFC was higher than HRC. CONCLUSION: The choice of collimator may alter the LVEF obtained from gated SPECT perfusion studies.

Cystic lesion at the foramen magnum disseminated from a pituitary adenoma--case report.

A 38-year-old male presented with a cystic lesion at the foramen magnum due to intracranial dissemination from a pituitary adenoma. The primary tumor had required reoperation for regrowth twice. The tumor at the foramen magnum was removed surgically. Two smaller solid tumors were located in the left parietal convexity and the right temporal lobe. The former tumor was also removed surgically and the latter was observed. Histological examination showed the typical characteristics of pituitary adenoma in both surgical specimens. Immunohistochemical staining with MIB-1 and p53 antibodies showed low (< 1%) and negative reaction. Patients with pituitary adenoma, even benign tumors, must be carefully followed up for signs of metastasis.

Intracerebral cystic meningioma--case report.

A 46-year-old female presented with persistent bifrontal headache. Computed tomography revealed a large cystic tumor in the right temporoparietal area, which included a solid component. The tumor had no attachment to the dura. There was no peritumoral edema or mass effect usually found around cystic meningiomas. The solid component was totally removed. Histological examination indicated that the tumor was a fibrous meningioma. Intracerebral meningioma with a large cystic component without dural attachment should be considered in the differential diagnosis of cystic cerebral tumors.

Primary amebic meningoencephalitis due to Naegleria fowleri: an autopsy case in Japan.

Free-living amebas represented by Naegleria fowleri, Acanthamoeba and Balamutia have been known to cause fatal meningoencephalitis since Fowler and Carter (1965) reported the first four human cases. An autopsy case of a 25-year-old female with primary amebic meningoencephalitis (PAM) due to Naegleria fowleri is described. Headache, lethargy and coma developed in this patient, and her condition progressed to death 8 days after the onset of clinical symptoms. Cerebral spinal fluid examination confirmed clusters of amebas, which were grown in culture and identified as Naegleria fowleri. At autopsy, lesions were seen in the central nervous system (CNS) and the ethmoid sinus. The CNS had severe, suppurative meningoencephalitis with amebic trophozoites mingled with macrophages. This case is the first report of PAM due to Naegleria fowleri in Japan.

Efficacy of aquatic exercises for patients with low-back pain.

We have studied 35 patients (25 female and 10 male) with low-back pain who were managed with aquatic exercises after an appropriate period of treatment for their condition in the medical institution. The exercises employed consisted of strengthening exercises for the abdominal, gluteal, and leg muscles, stretching of the back, hip, hamstrings, and calf muscles, walking in water, and swimming. All the patients had been participating in the exercise program for more than 6 months. The frequency of performing exercises was once a week for 7 patients, twice a week for 19, and 3 or more times a week for the remaining patients. The method used in this study was a survey questionnaire which was composed of questions about the patient's physical and psychological condition. Those patients who had performed exercises twice or more in a week showed a more significant improvement in the physical score than those who performed exercises only once a week. More than 90% of the patients felt they had improved after 6 months of participation in the program. The improvement in physical score was independent of the initial ability in swimming. The results obtained suggested that exercises in water may be one of the most useful modes of exercise for a patient with low-back pain.

Parasellar dermoid tumor with intra-tumoral hemorrhage.

We report a case of parasellar dermoid tumor with intra-tumoral hemorrhage. It is rare for a dermoid tumor that hemorrhage was detected as high attenuation on the initial CT. In the present case, the tumor content included a little fat component and mostly cholesterin-rich fluid which resulted in extremely low signal intensity on T2-weighted and high signal on T1-weighted MR images. In addition to this, hemosiderin accumulation in the tumor could be the reason for low signal intensity on T2-weighted images.

Crucial role of N-terminal residue of binding peptides in recognition of the monoclonal antibody specific for the peptide-HLA-B5, -B35 complex.

The monoclonal antibody (mAb) 4D12 specific for the HLA-B5, -B35 cross-reacting group (CREG) bound to a fraction of HLA-B*3501 and HLA-B*5101 molecules carrying self-peptides. Analysis of the binding of mAb 4D12 to HLA-B*3501 and -B*5101 molecules pulsed with chemically synthesized peptides revealed that this mAb recognizes a restricted number of peptides and that P1 of the bound peptides critically influences its binding. The 4D12 mAb bound only to HLA-B*3501 molecules carrying peptides with Asn, Asp, Glu, Ser, and Val at P1. Analysis using an HLA-B*3501 crystallographic model suggested that 4D12 may recognize the side chain of the P1 residue that is pointing to the solvent. On the other hand, 4D12 bound only to HLA-B*5101 molecules carrying peptides with Asn or Asp at P1, suggesting that the 4D12 epitope formed by Glu, Ser, or Val at P1 and the A-pocket was changed by the substitution of His for Tyr at residue 171 of HLA-B*3501 molecules. This was confirmed by testing the binding of mAb 4D12 to HLA-B*3501 mutant molecules at residue 171 carrying these peptides. These results together suggest that the conformation of the A-pocket and its hydrogen bound network with the P1 residue is also critical for the binding of mAb 4D12. The present study shows the molecular basis of the specificity of 4D12 for the peptide-HLA class I complex.

Localization of aberrant messenger RNA of epidermal growth factor receptor (EGFR) in malignant glioma.

Human gliomas occasionally show rearrangements with deletions (exons II to VII) in the epidermal growth factor receptor (EGFR) gene, resulting in the expression of aberrant EGFR mRNA. This abnormality of EGFR gene expression is closely related to the malignancy of glioma. However, this EGFR gene abnormality has not been demonstrated directly in the glioma cells themselves, as gliomas consist of heterogeneous tissue components. In this study, we used in situ hybridization (ISH) to detect aberrant EGFR mRNA in the tumor cells in 26 human gliomas and 19 human glioma xenografts. We used digoxigenin (DIG)-labeled antisense oligonucleotide probes for ISH, which demonstrated aberrant EGFR mRNA in 2 of the 26 gliomas and in 3 of the 19 human glioma xenografts. ISH with an aberrant EGFR-specific probe (oligo-PA) revealed that EGFR mRNA was absent from multinucleated giant cells and from proliferating endothelial cells, but this transcript was present in small glioma cells. Identical aberrant EGFR mRNA was confirmed in these glioma and human glioma xenografts by Southern blotting. Northern blotting, and by reverse transcription-polymerase chain reaction (RT-PCR). These findings suggest that small tumor cells specifically express the aberrant EGFR mRNA in certain high grade gliomas.

Murine P-glycoprotein on stromal vessels mediates multidrug resistance in intracerebral human glioma xenografts.

Human glioma usually shows intrinsic multidrug resistance because of the blood-brain barrier (BBB), in which membrane-associated P-glycoprotein (P-gp), encoded by the human multidrug resistance gene MDR1, plays a role. We studied drug sensitivity to vincristine (VCR), doxorubicin (DOX) and nimustine (ACNU) in both intracerebrally and subcutaneously xenotransplanted human glioma. We examined the levels of MDR1 and murine mdr3 gene expression in the xenografts by reverse transcriptase polymerase chain reaction and the localization of P-gp by immunohistochemistry. Six of seven subcutaneously transplanted xenografts (scX) were sensitive to the above three drugs. In contrast, all three intracerebrally transplanted human glioma xenografts (icX) were resistant to P-gp-mediated drugs VCR and DOX, but were sensitive to the non-P-gp-mediated drug ACNU. Neither icX nor scX showed any MDR1 expression. Intracerebrally transplanted human glioma xenografts showed an increased level of murine mdr3 gene expression, whereas scX showed only faint expression. The localization of P-gp was limited to the stromal vessels in icX by immunohistochemistry, whereas scX expressed no P-gp. Our findings suggest that the P-gp expressed on the stromal vessels in icX is a major contributing factor to multidrug resistance in human glioma in vivo.

Identification of multiple HIV-1 cytotoxic T-cell epitopes presented by human leukocyte antigen B35 molecules.

OBJECTIVE: To identify HIV-1 cytotoxic T lymphocyte (CTL) epitopes presented by human leukocyte antigen (HLA)-B35 molecules that are associated with the accelerated progression of AIDS using a reverse immunogenetic approach. METHODS: 8-mer to 11-mer sequences carrying two anchor residues at position 2 and the carboxy-terminus were selected from HIV-1SF2 strain. Sixty-four peptides matched to these sequences were synthesized and tested by a peptide binding assay using RMA-S-B*3501 cells. Peripheral blood lymphocytes (PBL) from two HIV-1-infected donors carrying HLA-B35 were stimulated once-weekly with each HLA-B*3501 binding peptide. The CTL activity of the cultured cells for the HLA-B35-positive target cells loaded with the corresponding peptides was examined after the second and fourth stimulation. Furthermore, the CTL activity of the cultured cells possessing HLA-B*3501-restricted HIV-1 peptide-specific CTL activity were examined for the HLA-B*3501-positive target cells infected with the recombinant vaccinia virus containing corresponding HIV-1 gene. RESULTS: HIV-1 peptide-specific HLA-B*3501-restricted CTL was induced in PBL of HIV-1 infected donors by in vitro stimulation with 11 out of 27 HLA-B*3501-binding HIV-1 peptides. The specific CTL induced with 10 peptides killed the cells infected with recombinant vaccinia virus expressing the corresponding HIV-1 proteins. Out of these HIV-1 peptide epitopes, two epitopes were also presented by HLA-B51 molecules. CONCLUSION: In addition to the four HLA-B35-restricted HIV-1 CTL epitopes that have been previously reported, nine HLA-B35-restricted HIV-1 CTL epitopes were identified in the present study. These multiple epitopes will be useful in studies for immunopathogenesis of AIDS.

Role of HLA-B*5101 binding nonamer peptides in formation of the HLA-Bw4 public epitope.

HLA-Bw4 is one of two HLA-B public epitopes which are discriminated by specific alloantisera and mAb. It is believed that the 77-83 of HLA-B molecules form the Bw4 epitope recognized by specific antibodies. This epitope is also recognized by NKB1 receptors on NK cells. We investigated the role of a peptide bound to HLA-B molecules on the formation of the Bw4 epitope recognized by two HLA-Bw4-specific mAb, TU109 and TU48, which recognized the difference of the Bw4 epitope among HLA-B52, -B52 and -B53. Recognition of the HLA-B*5101-peptide complex by these mAb was examined using a panel of HLA-B*5101 binding nonamer peptides. The sequence of HLA-B*5101 binding peptides has a minimum influence on the binding of TU48 mAb to HLA-B*5101 molecules. In contrast, the binding of TU109 mAb to HLA-B*5101 molecules was critically influenced by the sequence of a peptide bound to HLA-B*5101 molecules. TU109 mAb did not recognize HLA-B*5101 binding peptides carrying small or negatively charged residues at P8. The results were confirmed by a panel of mutant peptides at P8. Taken together, these results indicate that a positively charged or neutralized side chain of P8 is critical for the epitope formation of Bw4 recognized by this mAb.

[A case of de novo aneurysm of the distal posterior inferior cerebellar artery with intraventricular hemorrhage].

A case is presented of a de novo aneurysm of the distal posterior inferior cerebellar artery with intraventricular hemorrhage. A 67-year-old woman was admitted to our hospital with sudden onset of severe headache and loss of consciousness. Computed tomography (CT) scans showed subarachnoid hemorrhage. Angiography demonstrated three aneurysms: an aneurysm of the right vertebral-posterior inferior cerebellar artery, an aneurysm of the bifurcation of the basilar artery, and an aneurysm of the left middle cerebral artery. Considering the distribution of the hemorrhage on CT scans, we concluded that the cause of the hemorrhage was rupture of the vertebral-posterior inferior cerebellar aneurysm. The vertebral-posterior inferior cerebellar aneurysm and the middle cerebral aneurysm were successfully clipped, postoperative angiograms showing the complete clippings. At that time, however, there were no abnormal findings in the left posterior inferior cerebellar artery. Six years later, she was readmitted to our hospital because of sudden onset of headache, nausea, and vertigo. CT scans showed an intraventricular hemorrhage, especially in the fourth ventricle, although subarachnoid hemorrhage was not clearly found. Angiography revealed an aneurysm of the left distal posterior inferior cerebellar artery. She underwent clipping of the aneurysm verified by postoperative angiograms. However she had bacterial meningitis and died from pneumonia and disseminated intravascular coagulopathy. De novo aneurysms of the anterior circulation have often been reported. Carotid, ligation, smoking, the use of oral contraceptives, congenital anomalies and hypertension are major risk factors in the formation of aneurysms. A de novo aneurysm of the distal posterior inferior cerebellar artery is, however, extremely rare. In this case, the right posterior inferior cerebellar artery disappeared when the de novo aneurysm was found. So it is supposed that hemodynamic changes caused by the clipping of the right vertebral-posterior inferior cerebellar aneurysm and the left middle cerebral aneurysm had contributed to the formation of the de novo aneurysm of the left distal posterior inferior cerebellar artery. In the present study, we review the literature on the aneurysm at the distal posterior inferior cerebellar artery and on the de novo aneurysm of the vertebrobasilar artery, and discuss the radiological findings and features.

Binding of nonamer peptides to three HLA-B51 molecules which differ by a single amino acid substitution in the A-pocket.

The interaction between 9-mer peptides and HLA-B51 molecules was investigated by quantitative peptide binding assay using RMA-S cells expressing human beta2-microglobulin and HLA-B51 molecules. Of 147 chemically synthesized 9-mer peptides possessing two anchor residues corresponding to the motif of HLA-B*5101 binding self-peptides, 27 peptides bound to HLA-B*5101 molecules. Pro and Ala at position 2 as well as Ile at position 9 were confirmed to be main anchor residues, while Gly at position 2 as well as Val, Leu, and Met at position 9 were weak anchor residues for HLA-B*5101. The A-pocket is suspected to have a critical role in peptide binding to MHC class I molecules because this pocket corresponds to the N-terminus of peptides and has a strong hydrogen bond formed by conserved Tyr residues. Further analysis of peptide binding to HLA-B*5102 and B*5103 molecules showed that a single amino acid substitution of Tyr for His at residue 171(B*5102) and that of Gly for Trp at residue 167 (B*5103) has a minimum effect in HLA-B51-peptide binding. Since previous studies showed that some HLA-B51 alloreactive CTL clones failed to kill the cells expressing HLA-B*5102 or HLA-B*5103, these results imply that the structural change of the A-pocket among HLA-B51 subtypes causes a critical conformational change of the epitope for TCR recognition rather than influences the interaction between peptides and MHC class I molecules.

Polymorphism of human minor histocompatibility antigens: T cell recognition of human minor histocompatibility peptides presented by HLA-B35 subtype molecules.

To investigate the polymorphism of human minor histocompatibility (mH) antigens, PBLs from 23 Japanese individuals and 25 German individuals with HLA-B35 were studied by using four human mH antigen-specific, HLA-B35-restricted CTL clones. The CTL clones killed PHA-stimulated PBLs from all 23 Japanese individuals. On the other hand, they killed the PHA-stimulated PBLs from 19 of 25 German individuals and partially killed the PHA-stimulated PBLs from three German individuals (CTL weakly sensitive cell line); those from another three individuals (CTL-resistant cell line) were not killed by the CTL clones. All of three CTL weakly sensitive cell lines carry HLA-B*3503 molecules, whereas the three CTL-resistant cell lines carry HLA-B*3502, B*3507, and B*3508 molecules. The cytotoxicity of the CTL clones for three CTL weakly sensitive cell lines was enhanced by stimulation of human mH peptides isolated from HLA-B*3501 molecules purified from C1R-B*3501 cells. Small amounts of human mH peptides were isolated from B*3503 molecules purified from these three CTL weakly sensitive cell lines. Taken together, these results indicate that weak recognition by the CTL clones of three CTL weakly sensitive cell line results from a small amount of the human mH peptides presented by B*3503 molecules. The CTL-resistant cell line carrying B*3507 loaded with the human mH peptides was killed by four CTL clones, whereas the cell lines carrying B*3502 or B*3508 loaded with the peptides were not. The human mH peptides were not isolated from B*3507 molecules purified from the cell lines expressing this subtype, whereas small amounts of the human mH peptides were isolated from B*3502 and B*3508 molecules purified from the cell lines expressing the subtypes. These results indicate that failure of the CTL recognition of the cell line carrying B*3507 is due to a lack of human mH antigens in this cell line. The failure of the CTL recognition of the cell lines carrying B*3502 and B*3508 is not explained by only the amount of the human mH peptides binding to these B35 subtype molecules because the amount of the human mH peptides eluted from B*3502 and B*3508 molecules purified from the cell lines carrying these B35 subtypes is almost the same as that eluted from B*3503 molecules purified from the cell lines carrying B*3503.(ABSTRACT TRUNCATED AT 400 WORDS)

Fine tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues.

The prerequisites of peptide HLA-B*3501 interactions have been revisited by quantitative peptide binding assays with 190 chemically synthesized peptide possessing two anchor residues corresponding to the HLA-B*3501 peptide motif and a statistical residue-position analysis of binding and nonbinding peptides. According to the peptide motif of HLA-B*3501, aliphatic hydrophobic (Leu, Ile, and Met) or aromatic residues (Tyr and Phe) specify the main anchor at the C terminus, and position 2 renders an auxiliary anchor for proline. The importance of these residues was confirmed as a minimum requirement for peptide binding. Moreover, we demonstrated that high affinity peptide binding requires more than one favorable position of positions 3, 4, and 7. Aliphatic hydrophobic residues and residues that contain -OH or -SH side chains in position 3, 7, and 4 significantly enhance binding. Positions 1 and 5, or 7 may deteriorate peptide binding if these positions are held by proline and small residues (Ala and Gly) or basic residues carrying positively charged side chains (Arg and Lys), respectively. Positions 6 and 8 were statistically free of constrains. Yet, bulky aromatic residues and basic residues with a positively charged side chain at position 8 decreased the binding affinity. These findings were used to assess the predictability of binding and nonbinding peptides. Our binding predictions of 28 nonamers were verified by experimental data. Taking into account the importance of anchor and nonanchor positions in peptide binding and their practical value in peptide binding prediction, the search for peptide epitopes becomes more efficient.

Isolation of a human allo-peptide presented by HLA-B51 molecules.

Recent studies have demonstrated directly that alloreactive mouse CTL recognize peptides presented by MHC class I molecules. However, there is no direct evidence that human alloreactive CTL recognize peptides presented by HLA class I molecules. We have isolated an HLA-B51 alloreactive CTL clone, 2B3, that did not kill the TAP defective cell lines T2 and .174, whereas it killed the TAP-positive cell line T1 and .174 cells transfected with TAP genes. These findings suggested that this clone recognizes a TAP-dependent allo-peptide. We attempted to isolate the human allo-peptide recognized by the 2B3 clone from HLA-B51 molecules. A naturally occurring HLA-B*5101 binding peptide isolated from T1 cells was recognized by the 2B3 clone. The peptide was also isolated from HLA-B*5101 molecules purified from C1R-B*5101 cells. In the present study, we directly demonstrated that a human alloreactive CTL clone recognizes peptide presented by HLA class I molecules.

Inhibition of angiogenesis and growth of human non-malignant and malignant meningiomas by TNP-470.

Meningiomas are relatively common (22%) vascular brain tumors. 3-11% of meningiomas are malignant, and defy currently available therapy. Inhibition of neovascularization is one potential strategy for treating these hypervascular tumors. Inhibition of tumor-induced angiogenesis by TNP-470 (previously termed AGM-1470), a synthetic analogue of fumagillin, was tested on the growth of human non-malignant and malignant meningiomas in nude mice. TNP-470 significantly inhibited tumor neovascularization and tumor growth of both non-malignant and malignant meningiomas. TNP-470 is now in human trial and should be tested for efficacy in treating malignant or recurrent aggressive meningiomas.