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Biomedical subjects

N Ohsawa

Publications and source records attributed to N Ohsawa.

At least 73 records · Page 4Linked to original sources

Fractal dimension analysis of the oscillated blood flow with a vibrating flow pump.

To analyze the hemodynamic parameters during circulation with oscillated blood flow, nonlinear mathematical analyzing techniques, including fractal theory, were utilized. Vibrating flow pumps (VFP) were implanted as a left heart bypass, and the ascending aorta was clamped to constitute the total left heart circulation with oscillated blood flow in acute animal experiments using 7 adult goats. Using nonlinear mathematical analyzing techniques, reconstructed attractors of the arterial blood pressure waveform in the phase space during natural circulation and oscillated circulation were analyzed. Using the Grassberger-Procaccia correlation dimension analyzing technique, fractal dimension analysis of the reconstructed attractor was performed. During VFP bypass, lower fractal dimensions of the reconstructed attractor were shown compared with those during natural heart circulation. The results suggest that lower dimensional chaotic dynamics contributed to the circulation with oscillated blood flow.

Animals↗

Lymphocytapheresis in combination with immunosuppressive drugs for refractory myasthenia gravis: two-color flow cytometric analysis of changes in peripheral blood lymphocyte subsets.

We carried out lymphocytapheresis (LCP) in combination with the administration of immunosuppressive drugs in patients with myasthenia gravis (MG), who were resistant to conventional immunosuppressive therapy, and examined its efficacy and effects on peripheral blood lymphocyte subsets. LCP was carried out once a week for 1 month (one course, 4 times) using a continuous-flow blood cell separator. Immunosuppressive medication (prednisolone or prednisolone and azathioprine) was continued during the course of treatment. After LCP, clinical improvement was noted in 5 of 6 patients. Anti-AChR antibody titers and the number of lymphocytes were significantly reduced in all patients. A significant decrease in CD4+CD45RA- (memory) T cell level and significant increase in CD4+CD45RA+ (naive) T cell level were also observed. In the patients having good response to LCP, follow-up evaluation showed long-term clinical improvements, as well as the memory T cell level staying at the decreased level. Our study suggests that LCP in combination with the administration of immunosuppressive drugs can suppress the disease activity of MG.

Autoantibodies↗

In situ localization of ribosomal RNAs is a reliable reference for hybridizable RNA in tissue sections.

Assessments of RNA integrity and its hybridizability are essential for successful implementation of in situ hybridization (ISH) for mRNA or viral RNA, particularly when paraffin-embedded specimens from surgical, biopsy, and autopsy cases are used. In this study, we examined the suitability of ISH of 28S ribosomal RNA (rRNA) for this purpose. Oligo-DNA with nucleotide sequences complementary to a well-conserved segment of 28S rRNA with auxiliary adenine-thymine-thymine (ATT) repeats at the 3' and 5' ends was synthesized. The oligo-DNA was made antigenic by converting the adjacent thymines to T-T dimers by UV irradiation and was used as a probe for ISH of 28S rRNA. The T-T dimers were detected by enzyme immunohistochemistry. When the results of ISH rRNA staining and that of total RNA staining by methyl green/pyronin Y were compared for various types of sections prepared from rat and human tissues, the staining intensities of total RNA did not always match those of ISH rRNA staining. In paraffin sections of formalin-fixed tissues, the degree of proteinase digestion influenced the ISH rRNA staining intensity, whereas it had no effect on the total RNA staining intensity. The intensities of ISH rRNA staining agreed well with those of various types of mRNA staining by ISH in 10 cases of paraffin-embedded pathological specimens. We therefore believe that ISH rRNA staining is a convenient parameter for evaluation of levels of hybridizable RNAs in tissue sections.

Animals↗

Assessment of the severity of coronary artery disease by thallium-201 washout rate after dipyridamole infusion--a coronary hemodynamic and metabolic study.

This study examined the relationship between the myocardial washout rate (WR) of thallium-201 (201Tl) in dipyridamole scintigraphy and both coronary flow reserve (CFR) and myocardial lactate extraction rate (LER) after dipyridamole infusion in 31 patients with coronary artery disease (CAD) without myocardial infarction and 16 control patients. Patients with CAD demonstrated significantly lower WR (21 +/- 17 vs 43 +/- 10%, p < 0.001), lower CFR (128 +/- 82 vs 242 +/- 89%, p < 0.001) and lower LER (-2 +/- 20 vs 10 +/- 10%, p < 0.05) than did the control patients. WR was significantly correlated with CFR (r = 0.50, p < 0.001) and LER (r = 0.41, p < 0.01) in all of the patients. CAD patients with dipyridamole-induced chest pain demonstrated significantly lower WR (14 +/- 20 vs 27 +/- 12%, p < 0.05), lower CFR (97 +/- 71 vs 162 +/- 82%, p < 0.05) and lower LER (-13 +/- 21 vs 11 +/- 9%, p < 0.001) than did CAD patients without chest pain. CAD patients with dipyridamole-induced ST depression demonstrated significantly lower WR (14 +/- 20 vs 29 +/- 8%, p < 0.05), lower CFR (105 +/- 79 vs 170 +/- 73%, p < 0.05) and lower LER (-8 +/- 21 vs 11 +/- 10%, p < 0.01) than did CAD patients without ST depression. These results suggest that the myocardial washout rate of 201Tl after dipyridamole infusion reflects the severity of coronary artery disease as assessed by coronary hemodynamics, myocardial metabolism, symptoms and electrocardiography.

Aged↗

Serum concentrations of granulocyte colony-stimulating factor (G-CSF) determined by a highly-sensitive chemiluminescent immunoassay during the clinical course of subacute thyroiditis.

Granulocyte colony-stimulating factor (G-CSF) concentrations in serum were determined for the first time by a newly developed and highly sensitive chemiluminescent immunoassay (the limitation of detection, 0.5 pg/ml) in ten patients with subacute thyroiditis, during treatment with glucocorticoid or indomethacin. Before therapy, circulating neurophil counts significantly increased to 5.15 +/- 2.07 x 10(3)/microliters compared with the convalescent phase (2.94 +/- 1.07 x 10(3)/microliters), and the data were correlated with individual serum G-CSF levels (r = 0.854, P < 0.01). Serum concentrations of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were less than the detectable threshold of ELISA. During two weeks of glucocorticoid therapy, although the circulating neutrophil counts increased from 5.15 +/- 2.46 x 10(3)/microliters to 7.73 +/- 1.64 x 10(3)/microliters (P < 0.01), serum G-CSF levels were depressed from 25.1 +/- 15.3 pg/ml to 13.8 +/- 13.9 pg/ml (P < 0.01). These data indicate that G-CSF is one of the mediators of the increase of neutrophils in subacute thyroiditis, while it does not contribute to steroid-induced neutrophilia.

Adult↗

Longitudinal study of serum and cerebrospinal fluid (CSF) class-specific antibodies against Campylobacter jejuni and GM1 ganglioside in Guillain-Barré syndrome.

We report two Guillain-Barré Syndrome (GBS) patients with culture-proven Campylobacter jejuni (Penner19/Lior 7). Elevated anti-C.jejuni IgA antibody declined to the normal range within one month, elevation of anti-C.jejuni IgM antibody lasted for 3 months and the titers of anti-C.jejuni IgG antibody were still elevated at one year after the neurologic onset. Serological criteria for antecedent C.jejuni infection in GBS patients should require 1) high titer of serum IgA and/or IgM antibody against C.jejuni followed by seroconversion of the IgA and/or IgM and 2) a 4-fold decline of IgG serum dilution against C.jejuni. Anti-C.jejuni antibodies in cerebrospinal fluid (CSF) reached the maximum value at one month after their neurologic onset which may not be responsible for the main pathological mechanism in the development of GBS. Anti-GM1 antibodies in serum and CSF were parallel with those of anti-C.jejuni antibodies during the course of the disease.

Adult↗

Herpes simplex virus type 2 infections presenting as brainstem encephalitis and recurrent myelitis.

We describe here 3 patients with central nervous system infection caused by herpes simplex virus type 2 (HSV-2); one patient with brainstem encephalitis and two with recurrent transverse thoracic myelitis. All three patients showed increased IgG antibodies to HSV in the cerebrospinal fluid (CSF). HSV-2 DNA was demonstrated in the CSF by polymerase chain reaction (PCR) amplification. Upon treatment with acyclovir, one patient with myelitis partially recovered and the others completely recovered. It is important to recognize the wide spectrum of clinical manifestations of HSV-2 infection in the central nervous system (CNS).

Adult↗

Varied effects of thoracic irradiation on peripheral lymphocyte subsets in lung cancer patients.

To investigate the influence of thoracic irradiation on immunological competence in patients with lung cancer, we examined the changes in peripheral blood lymphocyte subsets in 15 patients before and after radiation therapy by two-color flow cytometry techniques. After radiation therapy, the percentage and the absolute number of CD4+CD45RA+ cells (naive T cells) and CD56+ and/or CD16+ cells (NK cells) decreased. The percentage of CD4+human leukocyte antigen-DR(HLA-DR)+ cells (activated CD4T cells) and CD8+HLA-DR+ cells (activated CD8T cells) increased, although the absolute number did not change significantly. Naive T cells may be more selectively damaged than memory T cells by thoracic irradiation, through their recirculation behavior. The reduction of natural killer (NK) cells is disadvantageous for anti-tumor immunity. The percentage of HLA-DR positive T lymphocytes was significantly increased, and thus the possibility of HLA-DR enhancement by irradiation cannot be excluded. Therefore, thoracic irradiation has numerous varied effects on the immunological system of lung cancer patients.

Adult↗

Chaotic behavior of hemodynamics with ventricular assist system.

In order to analyze hemodynamic parameters during left ventricular assistance as an entity and not as decomposed parts, non-linear mathematical techniques were utilized. Pneumatically actuated ventricular assist systems (VAS) were implanted as left heart bypasses in acute animal experiments, using healthy adult mongrel dogs. By the use of the non-linear mathematical technique, the arterial blood pressure waveform (AP) was embedded into the four-dimensional phase space and projected into the three-dimensional phase space. The Lyapunov numerical method was used as an adjunct to the graphical analysis of the state space. The phase portrait of the attractor showed a complex structure; a three dimensional solid torus with a screw type structure as a part, suggesting deterministic chaos in the AP without left ventricular assistance. Positive lyapunov exponents confirmed the existence of chaos. During counterpulsation mode left ventricular assistance, the phase portrait of the attractor showed a more complex structure, and positive Lyapunov exponents suggested a greater dimensional deterministic chaos. However, non-structured patterns were seen in the phase space during internal mode VAS driving, suggesting the possibility of dissipative dynamics in the four dimensional phase space. These results suggest that the cardiovascular system with counterpulsation mode VAS driving is in a homeochaotic state, which is thought to be a flexible and intelligent control system. And there is greater dimensional complex dynamics in the circulatory regulatory system with VAD during internal mode assistance.

Animals↗

[Intracranial tuberculoma with spontaneous recovery].

A 57-year-old man was admitted because of headache, nausea, and fever up (38 degrees C). He showed nuchal rigidity slightly. CSF analysis showed 833 white blood cells (WBC) (80% monocyte), protein value of 68 mg/dl, glucose level of 36 mg/dl and ADA level of 11.8 IU/l. Brain pre-contrast CT indicated high density area in right parietal lobe, and it showed slightly homogeneously enhancement with contrast medium. MRI on T2 WI demonstrated hypointense lesion with bright central core in right parietal lobe. The lesion showed isointense on T1WI, and indicated homogeneous enhancement with Gd-DTPA. He was sent to our hospital after one week. With only antibiotics the symptoms were relieved and the CSF findings improved during the previous hospital. However, Mycobacterium tuberculosis (M. tuberculosis) DNA was detected in CSF by PCR amplification, and he recovered completely with anti-tuberculous treatment. This case was interesting to reveal atypical features of spontaneous recovery. Since Shankar's study using polymerase chain reaction (PCR) for detection of M. tuberculosis in cerebrospinal fluid (CSF), the PCR assay have been recognized to be a rapid method for diagnosis of tuberculous meningitis (TBM). But there are problems of PCR sensitivity when dealing with CSF samples containing small amount of M. tuberculosis DNA. Comparing direct PCR with nested PCR, we studied on the evaluation of PCR for diagnosis of TBM. In this study the nested PCR was positive in all CSF specimens from 4 patients with TBM, but we could not detect M. tuberculosis DNA by only the direct PCR. Nested PCR amplification improved the sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Can the artificial heart make the circulation become fractal?

In order to analyze the hemodynamic parameters in prosthetic circulation as an entity and not as decomposed parts, non linear mathematical analyzing techniques, including the fractal dimension analyzing theory, were utilized. Two pneumatically actuated ventricular assist devices were implanted, as biventricular bypasses (BVB), in chronic animal experiments, using four healthy adult goats. For the comparison between the natural and prosthetic circulation in the same animals, the BVB type complete prosthetic circulation model with ventricular fibrillation, was adopted. All hemodynamic parameters with natural and prosthetic circulation were recorded under awake conditions, and calculated with a personal computer system. Using the non-linear mathematical technique, the arterial blood pressure waveform was embedded into the return map as the beat-to-beat time series data and fractal dimension analysis were performed to analyze the reconstructed attractor. By the use of the Box counting method, fractal dimension analysis of the hemodynamics was performed. Return map of the hemodynamics during natural and artificial circulation showed fractal characteristics, and fractal dimension analysis of the arterial blood pressure revealed the fact that lower dimensional fractal dynamics were evident during prosthetic circulation. Fractal time series data is suggested to have robustness and error resistance, thus our results suggest that the circulatory regulatory system with an artificial heart may have these desired characteristics.

Animals↗

[A case of primary thyroid T-cell lymphoma with infiltration of lymphoma cells in peripheral blood: diagnosed by DNA analysis].

A 57-year-old woman came to our hospital with complaints of neck swelling and headache in 1991. She was diagnosed as having chronic thyroiditis in euthyroidism because she had a diffuse goiter with both antithyroglobulin antibody (TGHA) and antimicrosomal antibody (MCHA). In 1992, she complained of the rapid growth of her thyroid gland and a swallowing disturbance. Atypical lymphocytes were observed in 16.5% of leukocytes in peripheral blood and similar atypical cells were found in bone marrow. Although an ultrasound scan of the thyroid gland revealed a symmetrical enlargement without a pseudocystic appearance, cytological study with fine needle aspiration biopsy of the thyroid gland demonstrated an abundance of atypical lymphoid cells. A whole body scintigram with 67gallium citrate showed no significant accumulation except in the thyroid gland. With a diagnosis of suspected primary thyroid lymphoma, total thyroidectomy was performed. However the diagnosis of malignant lymphoma was not confirmed histologically. A study of lymphocytes subset with two-color flow cytometry, which was performed for both lymphocytes in peripheral blood and infiltrating lymphocytes in the resected thyroid gland, revealed abnormal increased CD4 positive T cells and decreased HLA-DR expression. Additionally, southern blot DNA analysis for abnormal lymphocytes using restriction enzymes, EcoRI and BamHI, demonstrated rearrangement of the T-cell antigen receptor, which indicates a monoclonal proliferation of lymphocytes. After total thyroidectomy, atypical lymphocytes in peripheral blood decreased, and circulating autoantibodies including TGHA and MCHA disappeared. From these data, this patient was finally diagnosed as having a primary T-cell lymphoma of the thyroid gland, which is a very rare type of thyroid lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Mitochondrial diabetes mellitus: prevalence and clinical characterization of diabetes due to mitochondrial tRNA(Leu(UUR)) gene mutation in Japanese patients.

Mutations in the mitochondrial gene were recently identified in a large pedigree of diabetes mellitus and deafness. As the mitochondrial gene is materially inherited, Japanese diabetic patients whose mothers were also diabetic were screened, using peripheral leucocytes, for an A to G transition at nucleotide pair 3243 of the mitochondrial gene, a tRNA(Leu(UUR)) mutation. This mutation was identified in four pedigrees from among 300 unrelated patients who were screened. Diabetes co-segregated with the mutation, except in one young subject, and was maternally inherited. The apparent onset of disease occurred between 11 and 68 years of age. Some of the affected members developed hearing impairment and congestive heart failure due to cardiomyopathy, though generally long after the onset of diabetes, and these patients had therefore not been diagnosed as having a specific form of diabetes. The duration of sulphonyl-urea treatment was not more than 8 years in these pedigrees and affected members were prone to progression to insulin-requiring diabetes. Thus, these patients were secondary sulphonylurea failures. Long-term follow-up revealed that the underlying disorder in affected members is a progressive impairment of insulin secretion. Some were initially diagnosed as having IDDM based on an apparent acute onset in youth and the clinical severity of their diabetes. Others were regarded as having MODY with an aggressive course. The mitochondrial gene mutation or diabetes is not transmitted to all offspring of the affected mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sequence analysis of the thyrotropin (TSH) receptor gene in congenital primary hypothyroidism associated with TSH unresponsiveness.

Congenital primary hypothyroidism due to thyrotropin (TSH) unresponsiveness is a very rare disorder and only a few cases have been documented previously. To elucidate whether structural abnormalities in the TSH receptor (TSHR) could be a primary underlying mechanism of this disorder, we analyzed nucleotide sequence of the entire coding region of the TSHR gene in three patients diagnosed with congenital primary hypothyroidism associated with TSH unresponsiveness. Diagnosis of TSH unresponsiveness was largely made based on the following criteria: (a) congenital primary hypothyroidism with autosomal recessive inheritance, (b) a nongoitrous thyroid gland in a normal position with low thyroidal radioactive iodine uptake, (c) normal in vitro TSH bioactivity or absent in vivo response to exogenous TSH, and (d) absence of thyroid autoantibodies. The TSHR cDNA was successfully obtained from RNA of peripheral mononuclear leukocytes with reverse transcription and polymerase chain reaction, and was sequenced directly. Comparison of these nucleotide sequences with the normal TSHR sequence revealed no difference in the predicted amino acid sequence with a heterozygous polymorphism in codon 601 in one patient, indicating absence of TSHR structural abnormalities in these patients. Our results indicate that congenital primary hypothyroidism associated with TSH unresponsiveness is unlikely to be due to mutations in the TSHR-structure gene.

Adult↗

Fluctuations of the sympathetic nerve discharges in animals without natural heartbeat.

To assess the effect of artificial circulation on the circulatory regulatory system, rhythmical fluctuations in the cardiovascular system and autonomic nerve discharges were analyzed in animal experiments using adult mongrel dogs. Two pneumatically actuated ventricular assist devices were implanted as total biventricular bypass (BVB) under general anesthesia; then, the natural heart was electrically fibrillated to constitute the BVB part of the complete prosthetic circulation model. All hemodynamic data and sympathetic nerve discharges were recorded and calculated in the computer system by the use of spectral analyzing methods. In the power spectrum of the arterial blood pressure waveform during prosthetic circulation, the Mayer wave peak was significantly decreased though the respiratory wave peak was not significantly changed. However, the Mayer wave peak in sympathetic nerve discharges was significantly increased though the respiratory wave peak was not significantly changed. These results suggest that rhythmical fluctuations are a necessary response of the circulatory regulatory system including the autonomic nervous system. However, sympathetic nerve discharges respond to the artificial heart without rhythmical fluctuations.

Animals↗

[An adult case of tethered cord syndrome with lipoma and thoraco-lumbar syringomyelia presenting slow progressive muscular atrophy in the lower limbs].

A 23-year-old man developed slowly progressive muscle weakness from the age of 10, followed by paresthesia and urinary disturbance. The physical examination showed bilateral muscular atrophy in the lower limbs and dissociated sensory disturbance below Th8. Although there was normal appearance of spinal X-P, MRI revealed conus medullaris at S2 involved thoraco-lumbar syringomyelia with extramedullary lipoma. After the operation for laminectomy of L5-S2 and untethering without direct surgery for syringomyelia, post-operated MRI exhibited definite shrinkage of the syrinx. It suggested that thoraco-lumbar syringomyelia in the present case was not congenital anomaly, but secondary outcome to tethered cord syndrome.

Adult↗

[Cerebral blood flow patterns in patients with leukoaraiosis and lacunar infarction].

We compared the incidence of risk factors (such as hypertension, diabetes mellitus, hyperlipidemia, hematocrit, atrial fibrillation) and local cerebral blood flow between patients with lacunar infarction associated with leukoaraiosis (LA) in the centrum semiovale (LACS) and those with periventricular white matter lesions (PVWMLs) on magnetic resonance imagings (MRI). Only atrial fibrillation was more frequently seen in LACS (p < 0.05), but the incidence of other risk factors for cerebrovascular disease was not different between the two patient groups. Demented patients were older than those with preserved intelligence in both groups. Local cerebral blood flow was compared between patients with and without dementia by single photon emission computed tomography using N-isopropyl-p-123I iodoamphetamine (IMP). The cerebral: cerebellar IMP uptake ratio (%) was used as a measure of relative cerebral perfusion. Compared with normal controls the demented patients with PVWMLs showed a significant reduction in local cerebral blood flow in the parietal area (p < 0.05) and the basal gray region (p < 0.05), and those with LACS in the frontal area (p < 0.05) and the basal gray region (p < 0.05). A significant positive correlation was found between local cerebral blood flow and dementia rating scales in the temporal and parietal areas in PVWMLs, and in the frontal area in LACS. These results suggest that most patients with LACS may represent vascular dementia of Binswanger type, and some demented patients with PVWMLs may have Alzheimer type dementia.

Aged↗