Solitary Epicranial Neurofibroma with Neurofibromatosis Type 1-Related Germline Mutation: Case Report

A 33-year-old male became aware of a painless soft mass in the left occipital region. His medical and family history were unremarkable for neurofibromatosis type 1 (NF1) or other genetic disorders. Physical examination showed no signs of NF1. Neurological and ophthalmological examinations found no abnormality. Cranial computed tomography showed an isodense mass located subcutaneously with irregular deformities in the adjacent occipital bone. Magnetic resonance (MR) imaging demonstrated that the lesion, 7.5 × 5.5 cm in diameter, was hypointense both on T₁- and T₂-weighted images and intensely enhanced after gadolinium infusion. The patient requested to remove the large mass. The subcutaneous tumor was well circumscribed, encapsulated, and less vascular, and resected en bloc. The histological diagnosis was neurofibroma without findings of cell atypia, whereas genomic exploration identified abnormal gains in NF1 gene, and resultant absence of neurofibromin, a protein coded on NF1 gene. Solitary neurofibromas in “clinically” non-NF1 patients may originate from the genomic changes in NF1 gene.     

The combination of external high-frequency oscillation and pressure support ventilation in acute respiratory failure

Background: Effective gas exchange can be maintained in animals by using external high-frequency oscillation (EHFO). The present study evaluates the effect of relatively long-term duration EHFO combined with pressure support ventilation (PSV) in patients with acute respiratory failure.
Methods: Twelve patients were ventilated with EHFO combined with PSV for 8 h at 60 oscillations min^-1, with a cuirass pressure of 36 cm H₂O: -26 to +10 cm H₂O (27 mm Hg: -19.5 to +7.5 mm Hg) and an inspiratory-to-expiratory ratio of 1: 1. Blood gas values and hemodynamic parameters were measured. Results: Significant increases were noted in cardiac index (3.0±0.7 to 3.2±0.7 1 min^-1 m^-2, P < 0.05) and stroke volume index (32±14 to 35±13 ml m^-2, P < 0.05) without changes in pulmonary artery wedge pressure at 1 h after EHFO. PaO₂(kPa)/FiO₂ and PaCO₂ improved from 21.9±7.5 to 26.8±8.0 ( P < 0.05) at 2 h and from 6.9±1.7 to 6.1±0.9 kPa ( P < 0.01) at 30 min after EHFO, respectively. Breath sounds could be heard well throughout the lung fields after institution of EHFO. The mucous rales also decreased.
Conclusions: As a method of ventilation for patients with acute respiratory failure, EHFO combined with PSV may have potential advantages over conventional mechanical ventilation when drainage of secretions is facilitated. Beneficial effects of EHFO may appear after several hours.     

Induction of autoimmune hepatitis and autoantibodies to liver antigens by neonatal thymectomy in mice

We examined development of autoimmune hepatitis in neonatally thymectomized C3H/HeN mice and tried to characterize the nature of liver antigens recognized by the autoantibodies at the molecular level. Autoantibodies to crude liver proteins detected by ELISA were found in 12 (67%) of 18 mice thymectomized 2 days after birth. However, autoantibodies were not detected in mice thymectomized 7 days after birth. The autoantibodies mainly consisted of IgG and reached the maximum level 8 weeks after birth. Hepatic inflammation, mononuclear cell infiltration in the portal area, was seen in 5 (28%) of 18 mice thymectomized 2 days after birth, but not in mice thymectomized 7 days after birth. Most infiltrating cells were Thy-1⁺ lymphocytes. The serum autoantibody level to crude liver proteins in mice with hepatitis was much higher than that in mice without hepatitis. We fractionated crude liver proteins by a Sepharose 6B column and examined the reactivity against the autoantibodies. The autoantibodies of three of five mice with hepatitis reacted with the ≈150 kD liver proteins other than liver-specific protein (LSP). By Western immunoblotting of SDS–PAGE using LSP and fractionated liver proteins, we found that the molecular weights of the target antigens were 52 kD in LSP and 150 kD (strong band), 138, 128, 120 and 110 kD (weak band) in fractionated liver proteins other than LSP. This 150-kD target molecule in crude liver proteins was found only in liver. These results indicate that hepatitis and autoantibodies to liver proteins are induced spontaneously by neonatal thymectomy in mice, and the candidates of autoantigen in this hepatitis model are 52-kD protein in LSP and 150-kD liver proteins different from LSP. Still more, we regard the 150-kD molecule as a new autoantigen related to hepatitis.     

Mechanism of action and therapeutic indication of prosthetic mandibular advancement in obstructive sleep apnea syndrome

Abstract Prosthetic mandibular advancement (PMA) was applied to nine patients with obstructive sleep apnea syndrome (OSAS) and its therapeutic usefulness, mechanism of action, and clinical indication were discussed based on polysomnographic findings and serial examination of upper airway before and during PMA treatment. Apnea hypopnea index significantly decreased during PMA treatment compared with the value before treatment ( P < 0.01) and the rate of the treatment responder counted 78.1%. Cephalometric variables indicated forward and inferior advancement of mandible in our subjects. Magnetic resonance imaging of the upper airway during sleep revealed a marked improvement of velopharyngeal obstruction in most subjects. In addition, intraesophageal negative pressure during sleep decreased significantly. Our results confirmed the high therapeutic efficacy of PMA for OSAS and indicated forward advancement of the mandible and decrease of negative pressure loading on upper airway with PMA might suppress velopharyngeal collapse. Thus, PMA was regarded as one of the treatments of choice for OSAS occurring based on with velopharyngeal narrowing.     

Regulation of G1 cyclin-dependent kinases in liver regeneration

The liver serves as a suitable model for studying tissue regeneration. Although various growth factors have been implicated in the promotion of this process, their precise role in liver regeneration remains to be elucidated. Whatever the extracellular signals may be, they all converge on cell cycle regulators in the nucleus, where the sequential activation of cyclin-dependent kinases (Cdk) takes place. The activities of Cdk are regulated positively through their association with cognate cyclins, and negatively via interactions with Cdk inhibitors. In this review article, our recent data as well as results of previous reports on how these cell cycle regulators trigger and/or terminate the process of liver regeneration are summarized. The authors believe that ‘knockout’ mice, in which specific genes are deleted, will be useful for providing further insight into the positive and negative regulation of liver regeneration.     

Ultrastructural observation on 'transitional tubules' in human oviductal ciliogenic cells

In the human oviduct epithelium during ciliogenesis, short tubular structures were found in the transitional zone between the basal body and cilium. The tubules, termed transitional tubules from their location, were 34–36 nm in diameter and 0.13±0.06 μm in length; the number around a basal body was variable, but usually 4–6. The cytoplasmic leaflets of the tubule membranes were coated by electron-dense material and appeared to be connected to alar sheets. The transitional tubules existed transiently during ciliogenesis. The exact role of transitional tubules is unknown, but considering their location, they may fix the basal body in the apical cytoplasm during ciliary elongation and/or may be related to formation of alar sheets.     

Failure of autologous mixed lymphocyte reaction in patients with auto-immune chronic active hepatitis

T cells are effectively stimulated by DR -antigens on the surface of autologous non-T cells. This phenomenon, referred to as an autologous mixed lymphocyte reaction (AMLR), is reported to be impaired in several auto-immune diseases. In the present study, both AMLR and allogeneic mixed lymphocyte reaction (allo-MLR) activities of peripheral blood mononuclear cells were examined from patients with auto-immune chronic active hepatitis. AMLR activity in these patients was much lower than that of controls, while allo-MLR activity of the same patients revealed no abnormality with regard to either stimulator or responder activities in comparison to controls. Furthermore, co-culture experiments using cells from patients and their HLA-identical siblings suggested that the defect resided in the responder T cells rather than in the stimulator non-T cells.     

Interferon therapy for patients more than 60 years of age with chronic hepatitis C

Abstract Nineteen patients aged > 60 years with chronic hepatitis C (CHC) received interferon (IFN) therapy and a complete response (CR) was achieved by five of them (26%). The incidence of CH with severe fibrosis in this elderly group was significantly higher than in another 52 patients with CHC who were < 60 years of age (the younger group; P < 0.05). There was no significant difference in the hepatitis C virus (HCV) genotype distribution between the elderly group and the younger group. However, the HCV-RNA titre was significantly higher in the elderly group than in the younger group ( P < 0.05). There was no significant difference in the efficacy rate of IFN in the elderly and younger groups after standardization of the background factors. In the elderly group, the HCV-RNA titre was significantly lower in the patients achieving CR than in those with no response ( P < 0.05). These data suggest that elderly patients with a low HCV-RNA titre can still respond well to IFN therapy.     

Lower urinary tract dysfunction in type 1 familial amyloidotic polyneuropathy in Kumamoto, Japan

OBJECTIVE: To evaluate lower urinary tract dysfunction of type 1 familial amyloidotic polyneuropathy (FAP) patients in Kumamoto, Japan. METHODS: Lower urinary tract symptoms were evaluated in FAP patients. Urodynamic studies were evaluated in FAP patients as compared to those in control subjects. The location and distribution of amyloid deposits were evaluated in the urinary bladder in an autopsy case. RESULTS: In lower urinary symptoms, 86%, 19% and 38% patients showed difficulty in urination, urinary frequency and urinary incontinence. In detrusor function during filling cystometry, 14% patients showed detrusor overactivity. Moreover, 43% patients showed low compliance bladder, 62% and 38% patients showed normal and reduced bladder sensation, respectively. First desire to void (FDV), strong desire to void (SDV) and post-voided residual urine (PVR) were increased in FAP patients as compared to those in control subjects. In the urethral pressure profilometry, 71%, 10% and 19% patients showed incompetent, normal functional and overactive urethral closure mechanism, respectively. Maximum urethral pressure (MUP), maximum urethral closure pressure (MUCP) and functional profile length (FPL) were decreased in FAP patients compared to those in control subjects. CONCLUSION: Autonomic, somatic nerve systems and bladder detrusor musculature might be impaired in lower urinary tract of type 1 FAP patients in Kumamoto, Japan.     

Significance of the progression of respiratory symptoms for predicting community‐acquired pneumonia in general practice

Background and objective: Early diagnosis improves outcomes in patients with community‐acquired pneumonia (CAP). However, prediction of CAP based on symptoms and signs is difficult. The present study investigated the evaluation of progression of symptoms as a factor for predicting the occurrence of CAP in general practice. Methods: Consecutive patients (n = 406) suspected of having CAP on routine clinical examination were studied retrospectively. Selection of patients with suspected CAP was based on progression of symptoms after 5 days, as well as published criteria. Diagnostic yields for the recommended criteria and our proposed criteria were then compared. Scoring systems for the prediction of CAP were designed, based on the results of multiple regression analysis. The diagnostic performance of these systems, including or excluding symptom progression, was compared using the areas under receiver operating characteristic curves. Results: The sensitivity and specificity of the recommended criteria and our proposed criteria were 0.75 and 0.44, and 0.93 and 0.38, respectively. Sputum production, dyspnoea, fever > 38°C, heart rate > 100 beats/min, decreased breath sounds, coarse crackles and progression of symptoms significantly increased the likelihood of CAP. Areas under receiver operating characteristic curves analysis showed that the diagnostic prediction of CAP was significantly improved when the scoring system included progression of symptoms. Conclusions: Progression of symptoms was a significant factor for predicting CAP and selecting patients who required CXR. Inclusion of progression of symptoms among the other recommended criteria, namely, dyspnoea, fever > 38°C, heart rate > 100 beats/min and abnormal chest findings, improved prediction of the incidence of CAP in general practice.