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In patients with inflammatory conditions such as infection, cytokines induce the production of C-reactive protein(CRP) and serum amyloid A protein(SAA) in hepatic cells. It has been reported that upon viral infection, the serum SAA level increases by a greater degree than the serum CRP level. Procalcitonin (PCT), the precursor of calcitonin, is a new type of inflammatory marker that is specifically induced by bacterial infection, sepsis and lethal multiple organ failure, but not by viral infection, autoimmune diseases, tumors or surgical stress. To evaluate the immunoluminometric assay(LUMI test PCT; Brahms Diagnostics, Berlin, Germany) procedure for determining the PCT level and to study the clinical significance of the serum PCT level, we determined the serum levels of PCT, CRP and SAA in patients with various inflammatory diseases and normal subjects. The serum PCT level in the normal subjects was < 0.3 ng/ml. Among the patients with inflammatory disease who had a high CRP level(CRP > 20000 micrograms/dl), the PCT level was elevated only in those patients with severe bacterial infection. These results suggest that determining the PCT level may be useful in the differential diagnosis of severe bacterial infection. The patients who had a low CRP level(CRP < 150 micrograms/dl), had a PCT level within the normal range. The patients with autoimmune disease, viral infection, and fungal infection did not have an elevated PCT level.

There exist various morphological and biochemical changes closely associated with electrophysiological phenomena which cause epileptic seizures in the brains of epilepsy patients. Recent developments in investigation methods, not only electrophysiological(EEG and MEG), but also neuroimaging involving morphological imaging(CT and conventional MRI) and functional imaging(SPECT, PET, functional MRI and MRS) is able to demonstrate these changes. SPECT and PET can particularly clarify the changes of cerebral blood flow and glucose metabolism between interictal and ictal periods. In our experience of 423 patients who underwent epilepsy surgery for intractable seizures, these interventions provide important information to identify the epileptogenic foci. However, in practice, discordance in the results of these presurgical evaluations is recognized, and invasive intracranial recordings are needed in such cases. These problems in diagnosis were shown especially in patients with mesial temporal sclerosis and focal cortical dysplasia. To detect an epileptogenic focus more clearly, a combination of morphological and functional findings, new functional imaging such as neurotransmitter receptor imaging, EEG-triggered or neuropharmacological functional MRI, as well as, statistical parametric analysis may be needed.

To test the hypothesis that acute inflammatory reaction associates with the development of pressure ulcers in bedridden elderly patients, 40 hospitalized elderly patients suffering from bacterial pneumonia, cerebrovascular disease, and femoral bone fracture were enrolled in this study. All of them were divided into two groups with pressure ulcers (group P; 17 patients) and without one (group N; 23 patients). The blood samples were taken from them within 5 days after the patients being bedridden. Although no significant difference exist in pressure ulcer risk factors (age, gender, Braden scale, underlying diseases, blood pressure, and heart rate) between the two groups, white blood cell, plasma C-reactive protein and fibrinogen in group P increased significantly as compared with those in group N. Besides number of platelets and maximum platelet aggregation rate were significantly higher in group P than in group N. Serum albumin and hemoglobin of both groups decreased after being bedridden, especially hemoglobin in group P was significantly lower than that in group N. While the concentration of serum IL-6 did not indicate a significant difference between both the groups, serum IL-1 beta increased significantly in group P. In conclusion, we suggested that acute inflammatory reaction releasing proinflammatory cytokines affected the development of pressure ulcer in bedridden elderly patients.

Prostate-specific antigen (PSA) is present in blood in free form as well as in complex form with various protease inhibitors such as alpha 2 macroglobulin (alpha 2M) and alpha 1 antichymotrypsin (alpha 1 ACT). We had found that alpha 2M is deficient (below approximately 40 mg/dl) in some patients with prostatic carcinoma. Therefore, we investigated the levels of free and complex form of PSA in patients with prostatic disease and obtained the following results. The HPLC study showed that total (free plus complex) PSA level was much higher in the alpha 2M deficient patients with prostatic carcinoma stage D (n = 7, range 1,530-14,746 ng/ml, median value 6,800 ng/ml) than in the non-deficient patients with stage D (n = 16, range 121.6-4,210 ng/ml, median value 851 ng/ml). In the deficient patients, the complex of PSA with alpha 1 ACT increased extraordinarily while free PSA increased to only some extent. In the more severe cases of prostatic carcinoma, the ratio (complex/total PSA) was higher while the ratio (free/total PSA) was lower. The SDS-PAGE Western blotting showed that complex PSA increased extraordinarily and free PSA increased in sera of the deficient patients which was consistent with the HPLC results. Many bands appeared on the blotting at the positions smaller than alpha 2M molecule, which indicated that many fragments of alpha 2M were present in their sera. These bands were more intense than the bands with sera of controls or benign prostatic hypertrophy. The alpha 2M deficiency may be due to the rapid disappearance of the complex with PSA or any other prostate-originated proteases. The complex may undergo accelerated degradation or catabolism of alpha 2M.

Serum amyloid A protein (SAA), a putative precursor of the AA protein which constitutes amyloid fibrils in secondary amyloidosis, is evaluated as a sensitive acute-phase reactant in serum. At present, SAA concentration in serum is determined by latex nephelometry, but this assay cannot detect SAA in the low concentration range lower than 10 ng/ml. We have developed a sensitive enzyme immunoassay (EIA) for determining low concentrations of SAA. The assay is reproducible, reliable and requires no pretreatment of specimen prior to assay. We measured levels of SAA by this EIA in both cerebrospinal fluid (CSF) and serum of patients with suspected meningitis, measured also levels of albumin, alpha 2 macroglobulin and C-reactive protein (CRP) to investigate if these protein levels are useful for differential diagnoses of meningitis and for indicators damage of blood-CSF barrier. The SAA reference value in CSF is 3.99 +/- 1.74 ng/ml (mean +/- SD for nonmeningitis patients). The CRP concentration in CSF in bacterial meningitis was much higher than in viral meningitis, but CRP in CSF was also high in bacterial infection other than meningitis. On the other hand, SAA concentration in CSF in these patients with any meningitis are significantly higher than the reference values of SAA (p < 0.001). However, the differences in SAA concentrations among the three types (bacterial, viral and mycotic meningitis) of meningitis were not significant.

Leber's hereditary optic neuropathy(LHON) is a maternally inherited mitochondrial disease of an acute or subacute bilateral loss of central vision. G to A substitutions at nucleotide position 11778 in mitochondrial DNA(mt DNA) have been identified in approximately 40% to 90% of patients. In this study, regions containing mt DNA 11778 mutations were analyzed by polymerase chain reaction(PCR), non-RI single strand conformation polymorphisms(SSCP) and direct sequencing. In 26 visually affected patients, mt DNA 11778 mutations were detected in 9 patients (36.4%). In one pedigree of a LHON patient(L-6), four unaffected family members had heteroplasmy of the 11778 mutation using non-RI SSCP. Ratios of the heteroplasmy between wild type and mutant mt DNAs can be detected in non-RI SSCP and accurately quantified by video densitometric analyzer. Two types of novel polymorphisms, 11696 G to A and 11719 A to G, in the mt DNA region were also found in this non-RI SSCP analysis. Non-RI SSCP is an efficient and accurate method for diagnosis of mt DNA 11778 mutations and quantifying heteroplasmy in patients with LHON and pedigrees.