Therapeutic effect and mechanism of repetitive transcranial magnetic stimulation in Parkinson's disease

The therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on clinical performance was assessed by a double-blind study in 9 patients with Parkinson's disease (PD). Nine other patients underwent sham stimulation as controls. The modified Hoehn and Yahr (H&Y) staging scale, the Schwab and England Activities of Daily Living (ADL) scale, and the Unified Parkinson's disease rating scale (UPDRS) were used to assess changes of clinical performance. Patients were assessed prior to and following 2 months of rTMS. In addition, the mechanism of rTMS was investigated by dopamine and homovanillic acid (HVA) in the lumbar cerebrospinal fluid (CSF) of 17 patients before and after therapeutic rTMS for three or four months. rTMS was applied manually to the frontal areas 60 times per session, i. e., 30 times per side using a large circular coil, a pulse intensity of 700 V, and a frequency of 0.2 Hz. Sessions were continued once a week for 2 months. The 9 control patients showed no changes of symptoms between the initial evaluation and that after 2 months of sham rTMS. In contrast, all 9 patients receiving rTMS showed a significant decrease of the modified H&Y and UPDRS scores after 2 months, while the Schwab and England ADL Scale scores increased significantly. In the second CSF sample from patients receiving rTMS, HVA showed a significant decrease These results suggest that rTMS is beneficial for the symptoms of Parkinson's disease and that it may act via inhibition of dopaminergic systems.

     

A case of primary Sj?gren syndrome with repeated purpura]

In Sj?gren syndrome, purpura is one of its various well known eruptions. Although this disease state is assumed to be based on hypergammaglobulinemia, the details of its mechanism are unknown. We experienced a case involving a female patient with primary Sj?gren syndrome showing repeated purpura on the legs, and examined her blood viscosity and histopathology. This girl developed Sj?gren syndrome and was admitted to our hospital at 12-years-old. She underwent steroid treatment because of aggravation of the xerosis state and prominent purpura on the legs. Hypergammaglobulinemia was improved during the course; however, purpura appeared repeatedly. Although her blood viscosity was slightly higher than normal, this had no relation to purpura and serum gamma globulin values. Skin biopsy revealed necrotizing angiitis. These results suggest that the purpura of this case was caused not only by hyperviscosity from the hypergammaglobulinemia but also involvement of vasculitis by the primary disease.     

Establishment and characterization of a spindle cell squamous carcinoma cell line

BACKGROUND: Spindle cell squamous carcinoma (SCSC) is a rare and peculiar biphasic malignant neoplasm that occurs mainly in the upper aerodigestive tract. It consists of sarcomatoid proliferation of pleomorphic spindle-shaped cells and squamous cell carcinoma. METHODS: Here, we established a SCSC cell line from a tumour arisen in gingiva. We characterized the feature of a SCSC cell line by immunohistochemistry. To know the biological feature, we examined the cell growth, invasiveness and epithelial-mesenchymal transition markers of a SCSC cell line in comparison with oral squamous cell carcinoma (OSCC) cell lines. RESULTS: By immunohistochemical analyses, the primary tumour expressed cytokeratin and vimentin, indicating carcinosarcoma-like characters. This tumour also showed overexpression of p53 protein. Cultured SCSC cells resulted in bypass of crisis and maintenance over passage 100. The established SCSC cell line was spindle-shaped and showed identical immunohistochemical characters to those of primary tumour cells. Similar to the primary tumour, the cell line showed p53 overexpression and had p53 mutation at codon 132: AAG (lys)-->AAT (asp). The SCSC cell line grew slower than two other OSCC cell lines (MSCC-1 and HSC-2), whereas SCSC cells had remarkable invasiveness in comparison with these cell lines. Moreover, SCSC cells expressed wnt-5a and vimentin mRNA at high levels, but did not express E-cadherin mRNA. This expression pattern of the markers was similar to that of mesenchymal cells, not of epithelial cells. CONCLUSION: In the present study, we newly established a SCSC cell line with strong invasiveness. This is the first report on the establishment of SCSC cell line. The SCSC cell line can be a useful cell model for the study to know the cytodifferentiation and nature of SCSC.     

Alteration of glycosaminoglycans induced by cadmium in cultured vascular smooth muscle cells

Alteration of glycosaminoglycans (GAGs) in cultured bovine aortic smooth muscle cells after exposure to cadmium was investigated. It was revealed that cadmium increased the accumulation of GAGs metabolically labeled with [³H]glucosamine but decreased that with [³⁵S]sulfate in the cell fraction, the cell surface fraction and the medium fraction. This suggested that cadmium stimulated the biosynthesis of GAGs but inhibited their sulfation in the cells. A similar alteration was observed in cadmium-treated human aortic smooth muscle cell layer. Of tested cations including cadmium, bismuth, cobalt, copper, lead, manganese, nickel and zinc, only cadmium stimulated [³H]glucosamine incorporation, with a strong inhibition of the [³⁵S]sulfate incorporation in the bovine cells. Characterization of bovine smooth muscle GAGs showed that the cadmium-induced increase in the [³H]glucosamine incorporation was mainly observed in heparan sulfate; the inhibition of the [³⁵S]sulfate incorporation occurred non-selectively. Cadmium accumulated in bovine vascular smooth muscle cells in a dose-dependent manner with an increase in the leakage of lactate dehydrogenase into the medium. The present data suggest that vascular smooth muscle cells respond to the cytotoxicity of cadmium and promote the GAG synthesis with a reduction of their sulfation. It is postulated that this response may be a defensive one to the damage of the vascular tissue caused by cadmium but would be a component of the metal-induced atherosclerosis. Received: 19 January 1994/Accepted: 5 May 1994     

Pseudoaneurysm of the extracranial vertebral artery; a case report

Traumatic injury of the vertebral artery is rare and only a few reports have been presented. We treated a case of iatrogenic pseudoaneurysm of the extracranial vertebral artery. A 65-year-old man complained of headache and had a pulsating mass in the soft tissue of the neck which had continued for one month after evacuation of hypertensive cerebellar hemorrhage. The left VAG revealed a large pseudoaneurysm at the third portion of the vertebral artery and the right retrograde VAG revealed agenesis of the vertebral artery. To select the proper treatment was a dilemma. This case was treated by embolization using an occluding spring embolus with direct transcutaneous puncture of pseudoaneurysm. Following this treatment, the mass and associated symptoms resolved without neurological deficit.     

Assessment of mycobacterial interspersed repetitive unit-QUB markers to further discriminate the Beijing genotype in a population-based study of the genetic diversity of Mycobacterium tuberculosis clinical isolates from Okinawa, Ryukyu Islands, Japan

The present investigation focused on genetic diversity and drug resistance of 101 Mycobacterium tuberculosis strains isolated between July 2003 and February 2005 in the Okinawa prefecture, Ryukyu Islands, Japan. A high rate of clustering (87%, eight clusters, 2 to 69 strains/cluster) was observed upon spoligotyping; most of it was due to the lower discriminatory power of this method for the Beijing lineage (n = 72; 71.3% of the isolates). The remaining diversity was limited to seven clusters (two to five isolates/cluster), with the following distribution of major lineages: ill-defined T (n = 13; 12.8%), ancestral East African-Indian (n = 6; 5.9%), Haarlem (n = 4; 4%), Latin American-Mediterranean (n = 2; 2%), X1 (n = 1; 1%), and a total absence of the central Asian clade. Three remaining strains could not be classified on the basis of their spoligotype pattern and were labeled "unknown." Subtyping with mycobacterial interspersed repetitive units (MIRUs) in association with additional QUB minisatellites was performed to discriminate among the Beijing strains. Based on an "in-house" spoligotyping/MIRU database (n = 694 Beijing strains), eight highly discriminative MIRU loci for Beijing strains were selected (loci numbered 10, 16, 23, 26, 27, 31, 39, and 40). The highest discriminatory power (h) observed in our sample (n = 72; M-26, 0.385; M-10, 0.38; M-31, 0.255; M-16, 0.238) was too low, and 73.6% of the Beijing strains from Okinawa remained clustered. Typing of Beijing strains with additional QUB loci (with the exception of "one-copy" QUB-1451) resulted in higher discriminatory powers: QUB-11b, 0.68; QUB-11a, 0.656; QUB-26, 0.644; QUB-18, 0.553; QUB-4156, 0.5; and QUB-1895, 0.453. A definitive algorithm on the use of QUB markers to subtype Beijing isolates in expanded studies would shed light on their hypervariability, which may sometimes blur recognition between epidemiologically linked Beijing isolates. The total absence of multiple drug resistance among Beijing isolates from Okinawa, as well as the relatively older ages of the patients (majority above 60 years), shows that tuberculosis (TB) is a declining disease in Okinawa, and an adequate TB control program has successfully avoided both the emergence and the spread of multidrug-resistant TB in this insular setting.     

Clinical and Immunological Characterization of ICF Syndrome in Japan

Objective

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive primary immunodeficiency. Hypogammaglobulinemia is a major manifestation of ICF syndrome, but immunoglobulin replacement therapy does not seem to be effective for some ICF patients. Therefore, we aimed to reassess the immunological characteristics of this syndrome.

Methods

Eleven Japanese patients with ICF syndrome were enrolled. We performed whole-exome sequencing in four cases and homozygosity mapping using SNP analysis in two. We evaluated their clinical manifestations and immunological status.

Results

We newly diagnosed six ICF patients who had tentatively been diagnosed with common variable immunodeficiency. We identified two novel mutations in the DNMT3B gene and one novel mutation in the ZBTB24 gene. All patients showed low serum IgG and/or IgG₂ levels and were treated by periodic immunoglobulin replacement therapy. Three of the six patients showed worse results of the mitogen-induced lymphocyte proliferation test. Analyses of lymphocyte subpopulations revealed that CD19⁺CD27⁺ memory B cells were low in seven of nine patients, CD3⁺ T cells were low in three patients, CD4/8 ratio was inverted in five patients, CD31⁺ recent thymic emigrant cells were low in two patients, and CD19⁺ B cells were low in four patients compared with those in the normal controls. ICF2 patients showed lower proportions of CD19⁺ B cells and CD16⁺56⁺ NK cells and significantly higher proportions of CD3⁺ T cells than ICF1 patients. T cell receptor excision circles were undetectable in two patients. Despite being treated by immunoglobulin replacement therapy, three patients died of influenza virus, fatal viral infection with persistent Epstein–Barr virus infection, or JC virus infection. One of three dead patients showed normal intelligence with mild facial anomaly. Two patients presented with autoimmune or inflammatory manifestations. Infectious episodes decreased in three patients who were started on trimethoprim–sulfamethoxazole and/or antifungal drugs in addition to immunoglobulin replacement therapy. These patients might have suffered from T cell immunodeficiency.

Conclusion

These results indicate that patients with ICF syndrome have a phenotype of combined immunodeficiency. Thus, to achieve a better prognosis, these patients should be treated as having combined immunodeficiency in addition to receiving immunoglobulin replacement therapy.

     

Outpatient chemotherapy and clinical pathway for non-small cell lung cancer]

We investigated the usefulness of outpatient chemotherapy in 54 cases of non-small cell lung cancer in which outpatient chemotherapy was performed between August 1999 and October 2001. This chemotherapy accounted for 67% of all chemotherapy. Assessment of therapeutic effect revealed a PR in 14 of the 54 cases, and the efficacy rate was 26%. Therapeutic effect according to chemotherapy regimen revealed the highest efficacy rate, 50%, for paclitaxel + CBDCA. The median survival time was 14.7 months, and the 1-year survival rate was 61.1%. On the basis of the above results, a 16-day inpatient clinical pathway using weekly paclitaxel + CBDCA was devised for non-small cell lung cancer. The aim was to shorten the number of inpatient days, standardize treatment, and introduce outpatient chemotherapy. The clinical pathway was introduced in 8 patients with recurrent non-small cell lung cancer between August and October 2002. Variance was found only in one patient whose hospital discharge had to be postponed by two days because of a Grade 3 side effect. Introduction of a clinical pathway with weekly paclitaxel + CBDCA successfully reduced the inpatient days to an average of 16.3 days.     

Effect of physical exercise training on health-related quality of life and exercise tolerance in patients with left ventricular dysfunction

OBJECTIVES: The improvement of exercise tolerance and quality of life (QOL) are essential in the treatment of patients with heart failure. The influence of physical exercise training on QOL was investigated in patients with left ventricular dysfunction. METHODS: Health-related QOL was evaluated using the Medical Outcomes Study Short-Form 36 Health Status Survey (SF-36) before and 3 months after individualized exercise training determined by cardiopulmonary exercise testing in 65 patients. The 44 patients who could carry out more than two-thirds of the prescribed exercise were classified into two groups: Group A (11 patients)with left ventricular ejection fraction < 40% and Group B (33 patients) with left ventricular ejection fraction > or = 40%. The remaining 21 patients served as the control group. RESULTS: The mean value of SF-36 improved significantly with exercise training only in Group A (50.8 +/- 25.3 to 62.1 +/- 22.2, p < 0.05). Group A also had an increase in peak Vo2 (18.9 +/- 3.5 to 21.4 +/- 3.6 ml/min/kg, p < 0.005) and a decrease in brain natriuretic peptide. The 24 patients (9 in Group A, 15 in Group B) with improved SF-36 values after the exercise training showed a negative correlation between the change of the mental component summary and the peak Vo2 (r = - 0.606, p < 0.05). CONCLUSIONS: Exercise training improves both the QOL, especially the mental component, and the exercise tolerance in patients with left ventricular dysfunction.     

Association between salivary flow rate and depressive symptoms with adjustment for genetic and family environmental factors in Japanese twin study

Clinical Oral Investigations - The association between salivary flow rate (SFR) and depressive symptoms have been inconclusive. The present study aimed to investigate the association between SFR...