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Biomedical subjects

M Koga

Publications and source records attributed to M Koga.

At least 181 records · Page 10Linked to original sources

[Chronic sensory ataxic neuropathy associated with IgM antibody against b-series gangliosides including GD1b].

We described a 62-year-old man with a 10 years history of chronic sensory ataxic neuropathy. His laboratory investigations revealed elevated serum IgM with IgM kappa paraproteinemia, IgM antibody against b-series gangliosides including GD3, GD2, GD1b, GT1b, GQ1b, GQ1b alpha, and high titer of cold agglutinin. The clinical and serological features in our patient were compatible with the diagnosis of CANOMAD (chronic ataxic neuropathy with ophthalmoplegia, M-protein, agglutination, and disialosyl antibodies), proposed by Willison et al. IgM antibody against b-series gangliosides including GD1b appeared to play an essential role in developing autoimmune sensory ataxic neuropathy.

Ataxia↗

[A case of Bickerstaff's brainstem encephalitis during pregnancy].

Here we present a case of 23-year-old woman with Bickerstaff's brainstem encephalitis (BBE) during 13 weeks of pregnancy. After symptoms of the upper respiratory tract infection, she developed somnolence, marked disturbance of extraocular eye movements, cerebellar ataxia, hyperreflexia and spasticity of the lower limbs. An electroencephalogram revealed slow waves and brainstem auditory evoked potential disclosed prolongation of III-V interpeak intervals. Serum IgG anti-GQ1b antibody was detected. Plasma exchanges (PE) were performed four times. Although no patient with BBE during pregnancy has ever been reported, in the literatures the pregnant patients with Guillain-Barré syndrome had four sessions of plasmapheresis with safe. Neurological symptoms gradually improved after the PE. No serious adverse effects were noted. Although no definite therapy for BBE has been established, PE may be one of the selections even if the patients is pregnant.

Adult↗

Guillain-Barré and Fisher's syndromes subsequent to Campylobacter jejuni enteritis are associated with HLA-B54 and Cw1 independent of anti-ganglioside antibodies.

The frequencies of human leukocyte antigens (HLA)-class I (A, B and Cw) were determined serologically and those of HLA-class II (DRB1 and DQB1) at the genomic level in 35 Japanese patients with Guillain-Barré syndrome (GBS), 58 with Fisher's syndrome (FS), and 112 healthy controls. HLA-B54 and -Cw1 antigens were found in GBS and FS patients from whom Campylobacter jejuni had been isolated more often than found in the healthy controls. No HLA types were related to GBS or FS as a whole, except for the B54 antigen which often was significant in the entire GBS group. This relation, however, may depend on the high population of C. jejuni-isolate patients in our GBS group. There were no relationships between the frequencies of HLA types and the presence of serum IgG antibodies to GM1, GQ1b, GD1a, or GalNAc-GD1a. Our findings suggest that HLA types are associated with the onset of GBS and FS after C. jejuni enteritis and that the HLA types in distinct GBS and FS subgroups of a single etiological origin need to be examined.

Antibodies↗

Is IgG anti-GT1a antibody associated with pharyngeal-cervical-brachial weakness or oropharyngeal palsy in Guillain-Barré syndrome?

The pharyngeal-cervical-brachial variant (PCB) of Guillain-Barré syndrome (GBS) has clinical features similar to those of botulism and diphtheria. Mizoguchi et al. (1994) [Mizoguchi, K., Hase, A., Obi, T., Matsuoka, H., Takatsu, M., Nishimura, Y., Irie, F., Seyama, Y., Hirabayashi, Y., 1994. Two species of antiganglioside antibodies in a patient with a pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. J. Neurol. Neurosurg. Psychiatry 57, 1121-1123] reported a patient with PCB-like symptoms who had serum IgG anti-GT1a antibodies which did not cross-react with GQ1b. We assumed that PCB is associated with anti-GT1a antibodies that do not have reactivity to GQ1b and made a serological study of a PCB patient. We searched for PCB patients prospectively and found one with PCB. This patient had IgG anti-GT1a antibodies which were not absorbed with GQ1b in an absorption study, whereas IgG anti-GT1a antibodies from Fisher's syndrome patients were. The frequency of positive IgG anti-GT1a antibody did not differ in patients with and without bulbar palsy. Our findings indicate that IgG anti-GT1a antibodies which do not cross-react with GQ1b are specifically detectable in PCB and can be used as a diagnostic marker of PCB.

Adult↗

Relationship between circulating vascular cell adhesion molecule-1 and microvascular complications in type 2 diabetes mellitus.

The soluble form of the vascular cell adhesion molecule-1 (VCAM-1) is detectable in human sera and is elevated in diabetic patients, with unknown clinical significance. In the present study, the relationship between serum soluble VCAM-1 and diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) was evaluated in 95 Japanese patients with Type 2 diabetes mellitus (DM). Serum soluble VCAM-1 concentration was higher in patients with more advanced stages of retinopathy as well as nephropathy. There was a significant correlation between soluble VCAM-1 and log10 (urinary albumin excretion) in 69 patients with normal serum creatinine levels (r = 0.51, p < 0.0001) and a significant correlation between soluble VCAM-1 and log10 (serum creatinine) in all the patients (r = 0.83, p < 0.0001). Soluble VCAM-1 concentration was also elevated in patients with neuropathy. There was a significant correlation between soluble VCAM-1 concentration and the number of microvascular complications (r = 0.59, p < 0.0001). However, multivariate regression analysis revealed that only diabetic nephropathy, was associated with the soluble VCAM-1 concentration. The elevation of circulating VCAM-1 level in diabetic nephropathy may result from underlying systemic endothelial dysfunction, increased VCAM-1 production in damaged renal tubular or glomerular epithelial cells and/or decreased renal clearance of this molecule, depending on the stage of nephropathy.

Analysis of Variance↗

IgG anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in Guillain-Barré syndrome.

To investigate the pathophysiological role of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor or acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patients), or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathophysiological mechanisms in IgG anti-GM1-positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.

Adult↗

A father and son with Turcot's syndrome: evidence for autosomal dominant inheritance: report of two cases.

Typical Turcot's syndrome is characterized by the association of a brain glioma together with multiple colonic polyposis, in which the number of polypoid lesions is small and the association of colonic cancer occurs at a younger age than in familial adenomatous polyposis. We describe a family in which both the father and his son presented with typical Turcot's syndrome without parental consanguinity. This is the first report of a family that is considered to follow an autosomal dominant inheritance. After reviewing 25 documented cases in which the average age of death was 20.3 years old, it was learned that the major cause of death was brain tumor (76 percent) and the minor cause was colon cancer (16 percent). Patients were very young and, therefore, unlikely to have produced a child before their death. These facts seem to support the theory that Turcot's syndrome is an autosomal dominant disorder.

Adenomatous Polyposis Coli↗

[Two cases of mitral restenosis occurring eight years after percutaneous balloon mitral commissurotomy (PTMC)].

A 63-year-old man and a 49-year-old man who underwent PTMC eight years before were admitted in our hospital because of regurgitation and restenosis of the mitral valve. Both of them had ulcer like lesion on the anterior leaflet near the commissure of the mitral valve. These changes were made by PTMC and likely caused thrombosis. Long-term follow up data of PTMC is essential to chose the correct operative method for treating mitral stenosis.

Catheterization↗

Individual pharmacodynamics assessed by antilymphocyte action predicts clinical cyclosporine efficacy in psoriasis.

BACKGROUND: Cyclosporine (INN, ciclosporin) use for psoriasis has been proposed and clinically examined. However, individual variation in cyclosporine efficacy is currently observed. To evaluate individual therapeutic potency of cyclosporine, pharmacodynamic approaches were performed with use of peripheral blood mononuclear cells (PBMCs) from patients with psoriasis. METHODS: Cyclosporine effects on PBMC-blastogenesis were examined in 33 patients with psoriasis. The drug concentration that gave 50% inhibition of mitogen-stimulated PBMC proliferation in vitro (IC50, in nanograms per milliliter) was evaluated in each patient. Cyclosporine was administered at an initial dose of 5 mg/kg/day, and the dose was tapered for 16 weeks to 3 mg/kg/day. The recovery rate in the psoriasis area and the severity index (PASI) 16 weeks after cyclosporine therapy began was measured. RESULTS: Cyclosporine IC50 values in 33 patients deviated widely, from 0.1 to 120.6 ng/ml. We classified these patients into two groups on the basis of their PBMC sensitivity to cyclosporine with use of the median cyclosporine IC50 (3.0 ng/ml) of these patients as the cutoff point. The PASI recovery rate after cyclosporine therapy in the patients with high sensitivity was significantly higher than that in the patients with low sensitivity (p < 0.0007). Moreover, a significant negative correlation between the IC50 and the PASI recovery rate was observed in these 33 patients (r = -0.73; p < 0.0001). Blood trough levels and side effects of cyclosporine were not significantly different between the two patient groups. CONCLUSIONS: The results showed that we could use PBMCs to pharmacodynamically predict the patients with a poor response to cyclosporine therapy. These patients may require larger doses of cyclosporine or alternative approaches to treatment. The patients with PBMCs sensitive to cyclosporine should be evaluated for treatment with smaller doses of the drug to avoid serious side effects.

Adult↗

Inhibition of signal transduction by a splice variant of the growth hormone-releasing hormone receptor expressed in human pituitary adenomas.

We have previously shown that some of human growth hormone (GH)-producing pituitary adenomas preferentially express a larger transcript of GH-releasing hormone (GHRH) receptor (GHRH-R). This transcriptional variant is presumed to be produced by alternative messenger RNA splicing and contains premature stop codon in frame, predicted to yield a truncated GHRH-R. Functional expression study indicated that the variant receptor was unable to transduct GHRH signals. To determine the functional relationship between the splice-variant and the wild-type GHRH-R, the expression vector for the variant GHRH-R transcript was transfected into COS-7 cells together with or without that for the wild GHRH-R transcript. In cells transfected with both GHRH-R expression vectors, GHRH-dependent cyclic adenosine monophosphate (cAMP) induction was decreased to 39% of that in the cells transfected with the wild-type GHRH-R expression vector alone. This inhibition was found to be irrespective of the concentration (10(-8) to 10(-5) mol/L) of GHRH. These findings suggest that the splice variant form of GHRH-R functions as a dominant-negative modulator in GHRH-induced cellular signaling.

Adenoma↗

Close association of IgA anti-ganglioside antibodies with antecedent Campylobacter jejuni infection in Guillain-Barré and Fisher's syndromes.

IgA has an important function in the gastrointestinal immune system. We investigated IgA anti-ganglioside antibodies in Guillain-Barré syndrome (GBS) and Fisher's syndrome (FS) subsequent to Campylobacter jejuni enteritis. In previous studies, serological diagnosis of C. jejuni infection was based on the detection of IgG, IgA, and IgM anti-C. jejuni antibodies. Our study, however, showed that the detection of IgG anti-C. jejuni antibody alone was sufficient for the serological diagnosis of antecedent C. jejuni enteritis in GBS and FS, when the cut-off level was defined for results of sera from C. jejuni-isolated patients. Serological evidence of C. jejuni infection was found in 62 (31%) of 201 GBS patients and 12 (18%) of 65 FS patients. IgA anti-GMI antibody was detected in sera from 33 (16%) of the GBS patients, 1 (2%) of the FS patients, and none of the 46 normal control subjects. IgA anti-GM1 antibody titers were significantly higher in the GBS patients with positive C. jejuni serology than in those with negative serology (P < 0.0001) or the FS patients with positive C. jejuni serology (P = 0.007). IgA anti-GQ1b antibody was detected in sera from 18 (28%) of the FS patients, 9 (4%) of the GBS patients, and none of the normal control subjects. FS patients with positive C. jejuni serology had significantly higher titers of IgA anti-GQ1b antibody than those with negative serology (P = 0.01) or the GBS patients with positive C. jejuni serology (P < 0.0001). We conclude that anti-GM1 and anti-GQ1b IgA antibodies are closely associated with antecedent C. jejuni enteritis in GBS and FS, respectively.

Antibodies, Bacterial↗

Peripheral blood monocytes in psoriatic patients overproduce cytokines.

Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) production by peripheral monocytes in 15 patients with psoriasis vulgaris and 13 healthy controls were investigated using an enzyme-linked immunosorbent assay. Polymorphonuclear leukocytes, mononuclear leukocytes, monocytes, lymphocytes and serum were isolated and cultured for 1, 12, 24 and 48 h in RPMI 1640 medium without fetal calf serum to release the cytokines. All cytokine levels in serum were very low in both psoriatic patients and the controls. However, a significant increase in the IL-1 alpha levels in the monocyte culture supernatants was observed in the psoriatic patients compared with that of the controls. IL-1 beta and IL-8 levels in the monocyte supernatants were also significantly increased in the psoriatic patients compared with the controls. TNF-alpha levels in the 12-h supernatants of the monocytes increased in some samples from psoriatic patients but not in the 48-h supernatants. Our study confirmed the overproduction of cytokines in the peripheral monocytes of the psoriatic patients and suggest the activation of monocytes in the patients with psoriasis.

Adult↗

Mild exercise activates renal dopamine system in mild hypertensives.

OBJECTIVE: The role of renal dopamine in the early depressor effect of exercise was evaluated in hypertensives. METHODS: After a general clinical observation period of 4 weeks, 29 essential hypertensives were divided into two groups. The exercise group (n=16) underwent blood lactate threshold exercise using a cycle ergometer for 60 min three times a week for 4 weeks. RESULTS: In the non-exercise group (n=13), blood pressure (BP) and humoral variables did not change significantly (from 150+/-3/93+/-2 to 145+/-2/94+/-1 mm Hg). In the exercise group (n=16), resting BP was significantly reduced from 158+/-2/92+/-2 at week 0 to 145+/-3/85+/-3 mm Hg at week 4. The increase in urinary free dopamine excretion (from 248+/-14 to 276+/-24 ng/mg Cr) at week 4 was significantly higher than that in the non-exercise group (from 220+/-31 to 196+/-27 ng/mg Cr). In the exercise group, urinary kallikrein activity also increased significantly from 173.0+/-35.4 at week 0 to 320.3+/-63.3 ng bradykinin/min/mg Cr at week 4. These changes in urinary free dopamine excretion and urinary kallikrein activity were negatively correlated with the change in BP. The change in urinary sodium excretion was also negatively correlated with the change in plasma volume index. Moreover, the change in urinary free dopamine excretion was positively correlated with the changes in urinary kallikrein activity and urinary sodium excretion. The change in renal decarboxylation rate of DOPA (3,4-dihydroxyphenylalanine) positively correlated with the changes in urinary free dopamine excretion and urinary sodium excretion, and was negatively correlated with the change in systolic BP. CONCLUSION: These results suggest that exercise triggered renal dopamine generation and activation of renal kallikrein-kinin system, resulting in natriuresis and BP reduction in the early phase (4 weeks) of mild exercise.

Adult↗

Plasma renin activity could be a useful predictor of left ventricular hypertrophy in essential hypertensives.

To clarify the ability of clinical and laboratory parameters to reflect target organ damage, especially left ventricular hypertrophy (LVH), we investigated which of these parameters might correlate to LVH as determined by electrocardiographic voltage at the first clinic visit in 108 (53 males and 55 females, average age 52 +/- 10 years) untreated essential hypertensives. The sum of the amplitude of the S wave in lead V1 plus that of the R wave in lead V5 or V6 (SV1 + R(V5, V6)) was correlated with blood pressure in both males and females. In subjects with LVH (SV1 + R(V5, V6) > or = 3.5mV), a stepwise multiple regression analysis revealed that SV1 + R(V5, V6) was associated with plasma renin activity (PRA) in both males and females, and with creatinine concentration (Cr) in males. These results suggest that PRA at the first visit could be a useful predictor of LVH in patients with essential hypertension.

Biomarkers↗

Screening of hybridoma clones producing antibodies against plasma membrane-associated materials.

We have developed a novel method for screening hybridoma clones producing antibodies against plasma membrane-associated materials. The method is based on the binding of cells by antigen-antibody complex formation to immobilized antibodies. The monoclonal antibodies (MAbs) were trapped by goat anti-mouse immunoglobulin antibodies, which were coated on the surface of 96-well plastic plates. Cells to be tested were then added to these plates and the number of bound cells was quantified by the activity of phosphatase of bound cells. This method allows quick and reliable screening of hybridoma clones without resorting to the use of expensive instruments such as a flow cytometer. We immunized mice with two different kinds of cells and obtained two interesting but contrasting MAbs reacting to cell-surface antigens: one interacts quite specifically with neuroblastoma cells and the other reacts equally with various cells with the exception of GOTO, a neuroblastoma cell.

Animals↗

Possible involvement of Fas-mediated apoptosis in eye muscle tissue from patients with thyroid-associated ophthalmopathy.

In order to investigate the possible involvement of apoptosis in the pathogenesis of thyroid-associated ophthalmopathy (TAO), we studied the expression of Fas, Fas ligand (FasL), and Bcl-2 in extraocular muscle tissues from patients with TAO by immunohistochemistry using monoclonal antibodies against Fas, FasL, and Bcl-2. Apoptosis was detected by in situ end-labeling of fragmented DNA. Apoptosis was detected in extraocular muscle tissues from 17 of 19 patients with TAO and, to a smaller degree in 4 of 7 normal control subjects. The mean percentages of apoptotic nuclei were 12.1% in TAO eye muscle fibers and 16.4% in TAO interstitial cells, compared with 2.2% and 0.4% in normal eye muscle fibers and interstitial cells, respectively. The percentage of apoptotic nuclei in eye muscle fibers correlated with the enlargement of eye muscle tissue (r = 0.47, p < 0.05). Fas was demonstrated on the surfaces of extraocular muscle fibers in 11 of 18 patients with TAO, but not in normal extraocular muscle tissues. Neither TAO nor normal extraocular muscle tissues expressed Bcl-2. FasL was detected in infiltrating mononuclear cells in extraocular muscle tissue from a patient with TAO. These data suggest that Fas-mediated apoptosis may occur in extraocular muscle tissue from patients with TAO and may be involved in the late stage of TAO.

Adult↗

Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS: Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS: Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS: DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype.

Adrenal Gland Neoplasms↗