Are tuberculosis advisory committees well-functioning?

PURPOSE: To evaluate the function status of TB advisory committee to assess treatments of tuberculosis. OBJECT AND METHOD: Estimate by questionnaire sheets to public health nurses attending to seminars on tuberculosis at Research Institute of Tuberculosis. RESULT: 137 answers are available for analysis. Of these, 57 (41.6%) TB advisory committees are estimated not to assess treatments of tuberculosis at all and/or to assess treatments without necessary informations on drug sensitivity in more than around half of the cases. In 13 (16.3%) committees of the other 80, many cases are in fact self-assessed. Number of committees that are estimated to functioning well is only 44 (32.1%). CONCLUSION: Many TB advisory committees are estimated to be malfunctioning from the stand point of assessments of treatment. As TB advisory committee is one of key agency to control drug-resistant tuberculosis, its reform and revitalization are urgently needed.     

Cell distribution differences of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in patients with kawasaki disease

The interaction of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metalloproteinase-1 has been implicated in the formation of coronary aneurysms in Kawasaki disease. MMP-9 and tissue inhibitor of matrix metalloproteinase-1 were distributed predominantly in the granulocytes and platelets, respectively, in patients with Kawasaki disease. The plasma values of MMP-9 correlated positively with the circulating neutrophil count. Inhibiting the activity of granulocytes and maintaining the platelet activity might prevent coronary aneurysms.     

An autopsy case of clinically un‐diagnosed autosomal recessive polycystic kidney disease in 77‐year‐old male

Autosomal recessive polycystic kidney disease (ARPKD) is caused by genetic mutations of the gene encoding fibrocystin, and is characterized by the collecting duct cysts and congenital hepatic fibrosis. We report an autopsy‐proven case of ARPKD in a 77‐year‐old male who presented with rapidly progressive renal and liver dysfunction. He had refused hemodialysis, and died 4 months later. At autopsy, both kidneys were enlarged with numerous small cysts throughout the cortex, which were revealed immunohistochemically to be the collecting ducts. Liver involvement was characterized by ductal plate malformation accompanied with portal fibrosis. The morphological appearances were compatible with ARPKD and the negative immunostaining for fibrocystin in the collecting ducts and bile ducts confirmed the diagnosis. ARPKD is known to occur in the neonatal period or in infancy with a high mortality rate. Although some patients who survive infancy are expected to live longer into young adulthood, most patients with ARPKD die of renal and hepatic failure in their childhood. The present case is extremely exceptional, in that no clinical symptoms suggestive of ARPKD were noticed until old age, and suggests that the disease spectrum of ARPKD is variable, and that a slowly progressive form of ARPKD may not be diagnosed until old age.     

Ubiquitin-related proteins in neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

Recent studies have shown that eosinophilic intranuclear inclusions (INI) in the brain of patients with intranuclear inclusion body disease (INIBD) are immunopositive for ubiquitin and ubiquitin-related proteins (URP). However, the extent and frequency of URP-immunoreactive inclusions in INIBD are uncertain. We immunohistochemically examined the brain, spinal cord and dorsal root ganglia from five patients with INIBD, using a virtual slide system with sequential staining of the same sections with hematoxylin and eosin and by immunolabeling with antibodies against ubiquitin and URP (NEDD8, NUB1, SUMO-1 and SUMO-2). Intranuclear inclusions were widely distributed in neurons and glial cells in all the cases. Sequential staining revealed that 100% of INI in neurons and glial cells were positive for ubiquitin. Moreover, the majority or a significant proportion of INI were positive for NEDD8, NUB1, SUMO-1 and SUMO-2. However, the proportions of NEDD8-, NUB1- and SUMO-1-positive inclusions were significantly higher in neurons than in glial cells (P < 0.05). These findings suggest that proteins related to ubiquitination and proteasomal degradation are involved in the formation of INI in INIBD.     

Myelodysplastic syndrome in a child with 15q24 deletion syndrome

15q24 deletion syndrome is a recently-described chromosomal disorder, characterized by developmental delay, growth deficiency, distinct facial features, digital abnormalities, loose connective tissue, and genital malformations in males. To date, 19 patients have been reported. We report on a 13-year-old boy with this syndrome manifesting childhood myelodysplastic syndrome (MDS). He had characteristic facial features, hypospadias, and mild developmental delay. He showed neutropenia and thrombocytopenia for several years. At age 13 years, bone marrow examination was performed, which showed a sign suggestive of childhood MDS: mild dysplasia in the myeloid, erythroid, and megakaryocytic cell lineages. Array comparative genomic hybridization (array CGH) revealed a de novo 3.4?Mb 15q24.1q24.3 deletion. Although MDS has not been described in patients with the syndrome, a boy was reported to have acute lymphoblastic leukemia (ALL). The development of MDS and hematological malignancy in the syndrome might be caused by the haploinsufficiency of deleted 15q24 segment either alone or in combination with other genetic abnormalities in hematopoietic cells. Further hematological investigation is recommended to be beneficial if physical and hematological examination results are suggestive of hematopoietic disturbance in patients with the syndrome.     

Effects of unilateral jaw clenching on cerebral/systemic circulation and related autonomic nerve activity

Jaw clenching (clenching) is the result of an isometric contraction of jaw closing muscles. Because of the location of working muscles and afferent information during tooth contact, the effect of clenching on the cerebral and systemic circulation might differ from that of isometric limb exercise. This study aimed to investigate the characteristic changes in cerebral and systemic circulation during jaw clenching by comparing those during handgrip exercise. Subjects were 17 right-handed men. Bilateral middle cerebral arterial blood flow velocity (MCAV), electromyography (EMG) of contracting muscles, heart rate (HR) and blood pressure (BP) were measured during unilateral handgrip exercise and clenching tasks. Autonomic nerve activity was evaluated by analyzing fluctuations in HR and BP. MCAV was significantly increased during the task with significantly higher values on the non-working than working side irrespective of unilateral handgrip or unilateral jaw clenching. Changes in HR during jaw clenching were lower than those during handgrip exercise, and changes in vaso-motor sympathetic nerve activity during left jaw clenching were lower than those during left handgrip exercise. The present results indicate that, compared with handgrip exercise, unilateral jaw clenching promotes bilateral activation of MCAV with smaller effects on cardiac output and sympathetic nervous system activity.