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Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 343 records · Page 19Linked to original sources

Aberrant patterns of immunoglobulin levels in Wiskott-Aldrich syndrome.

We have investigated IgM deficiency in Wiskott-Aldrich syndrome patients. From the assessment of T and B cell functions in pokeweed mitogen-induced immunoglobulin (Ig) production, IgM deficiency was chiefly thought to result from B cell dysfunction. The percentages of surface IgM-bearing cells were decreased in peripheral blood mononuclear cells (PBMCs) and the number of IgM-secreting cells was also decreased. Lymphoblast cell lines (LCLs) from the patients have produced IgG and IgA, but never IgM. Moreover the expression of the C mu transcript from the patients' PBMCs and their LCLs were decreased, whereas the C gamma gene was well expressed. No germ-line polymorphism existed between the patients and the controls in the C mu region, and no mutation was detected in the mu s C-terminal and the M exon by nucleotide sequencing. These suggest that the Ig heavy chain (IGHC) isotype switch may be abnormally accelerated in the patients' B cells. While the methylation patterns of the human Ig enhancer gene region were the same between the patient and the control, the methylation patterns of the I gamma 1 region showed less methylation in the patient than in the control, which may cause low IgM expression and high expression levels of other classes located downstream of the IGHC gene.

Adolescent↗

DNA mutation induced in the sequence upstream of the secreted MYU C-terminal coding sequence by ultraviolet irradiation in the cell line of Bloom's syndrome.

Selective IgM deficiency is commonly found in Bloom's syndrome (BS). We reported that membrane-bound mu (micron(s)) mRNA was well transcribed but secreted mu (microseconds) mRNA was not, although there was no mutation or deletion in the sequence including the microseconds C-terminal coding sequence in the patients with BS. Furthermore, we have shown previously, preferential damage to IgM production by ultraviolet (UV) irradiation of the cells of the patient. In the study described here, mutation in the sequence which is upstream of the 5' end of the microseconds C-terminal coding sequence was induced by UV irradiation in the lymphoblastoid cell line (LCL) of BS patient. These results suggest that abnormal repair of DNA damage is present in this LCL, and that preferential damage to IgM production by UV irradiation in this LCL may be due to the abnormal repair of DNA damage.

Adult↗

Methylation patterns of I epsilon region in B cells stimulated with interleukin 4 and Epstein-Barr virus in patients with a high level of serum IgE.

Human IgE synthesis requires the presence of both interleukin 4 (IL-4) and T-cells. However, it is not clear what role IL-4 and T-cells play in the induction of IgE synthesis at the level of gene regulation. B cells that were obtained from patients with a high level of serum IgE and from healthy donors were immortalized by Epstein-Barr virus. We examined IgE production of these B cells stimulated with IL-4. Supernatant IgE levels of patient's B cells cultured with or without IL-4 were higher than those of healthy donor's B cells. Our results indicated that B cells stimulated with IL-4 from patients produced IgE, germline C epsilon transcript, and S mu S epsilon recombination. The germline C epsilon transcript was dose-dependently induced in the presence of IL-4 and related to the supernatant IgE level. In B cell stimulated with IL-4 that were obtained from patients, (some of the) DNA near or within the I epsilon region was (already partly) unmethylated, unlike those from healthy donors, and there was a loss of methyl groups of the DNA upon the addition of IL-4 in B cells from both patients and normal donors. IgE synthesis of B cells stimulated with IL-4 in patients with a high level of serum IgE is due to an accessibility in the immunoglobulin heavy-chain isotype switch, and this may reflect the accessibility in synthesis of germline C epsilon transcript, which may be caused by the increase of opening chromatin structures because of their unmethylation in the I epsilon region.

Asthma↗

Genetic analysis of IgE and the IGHE, IGHEP1 and IGHEP2 genes in atopic families.

The familial occurrence of allergic diseases was studied in 478 individuals and their family members. The results showed that there was pronounced familial clustering. Total serum IgE concentrations of atopic patients and their parents were well correlated. Moreover, the concentration of specific IgE of the patients and their parents was also well correlated, suggesting that IgE production was genetically determined. To determine if major structural abnormalities of IGHE, IGHEP1 and IGHEP2 genes might lead to aberrant control and subsequent increase in IgE concentration, genomic DNAs from 55 individuals, i.e., 31 atopic patients and their family members, were examined. We detected the IGHE, IGHEP1 and IGHEP2 genes in all 55 leukocyte DNAs. We could not find any large deletions or duplications in the IGHE, IGHEP1 and IGHEP2 genes of atopic patients with high serum IgE concentrations.

Adolescent↗

The sweating responses of athletes trained on land and in water.

In order to examine whether different sweating responses of athletes trained on land and in water may be ascribed to changes in the central sudomotor mechanisms and/or those of the peripheral mechanisms of sweat glands, we measured the local sweating rate at the left forearm (mswf) and the left scapula (msws), the frequence of sweat expulsion (Fsw) and body temperatures (mean skin temperature and rectal temperature: Tre) in six runners and five soccer players (R group) and six swimmers (S group) during progressive thermal stress at rest (2 degrees C increase in ambient temperature every 15 min from 35 to 45 degrees C RH = 30-40%). Tre and heart rate at the end of experiment did not differ significantly between the groups (37.31 +/- 0.04 degrees C, 74.5 +/- 7.9 beats.min-1 in the S group and 37.27 +/- 0.07 degrees C, 71.1 +/- 9.0 beats.min-1 in the R group, respectively). The msws and mswf at any given mean body temperature (Tb) were greater in the S group than in the R group. Although the regression line showing the relationship between Fsw and Tb in the S group was shifted to the left of that in the R group, there was no significant difference in the slope of the lines. The msws-Fsw or mswf-Fsw regression line was not different between the two groups. These results indicate that the higher sweating rate in the S group may be ascribed to a difference in the centrally derived sudomotor neural activity, but not to that in the peripheral mechanisms of sweat gland activity.

Adult↗

[Development of new in vitro chemosensitivity test using collagen gel droplet embedded culture and its clinical usefulness].

We developed a new in vitro assay for chemosensitivity test using collagen gel droplet embedded culture and image analysis. In this in vitro assay, we successfully minimized the cancer cell number required for culture to approximately 3-10 x 10(3) cells for each 30 microliters collagen gel droplet, obtained the sufficient growth of cancer cells using serum-free medium while suppressing the growth of fibroblastic cells, and measured the volume of cancer cells by eliminating the contaminating fibroblastic cells by an image processing technique. Anticancer effects of the in vitro assay showed a very good correlation with those of in vivo nude mouse assay using human cancer cell lines. The success rates of the in vitro assay for 141 surgical specimens of primary lung cancers and for 65 of primary breast cancers were 89 and 80%, respectively. The accumulated in vitro assay response rates of MMC, CDDP, VDS and VP-16 for primary lung cancers and of MMC, 5-FU and ADR for primary breast cancers were similar to the respective clinical response rates. These results suggest that this in vitro chemosensitivity test may be practically useful for clinical applications.

Animals↗

T cell proliferation restricted by HLA class II molecules in patients with hen's egg allergy.

We investigated the synergistic effect of anti-HLA class II monoclonal antibodies on proliferative responses to ovalbumin (OA) of T cell line (TCL) cells from five hen's-egg-sensitive patients. Among the five patients, the proliferation of the TCL cells from two patients with AD who have a low immune reaction was restored by the anti-HLA-DQ monoclonal antibodies, and the proliferation of the TCL cells from the other three patients was inhibited by the anti-HLA-DP monoclonal antibodies. These results suggest that a component of the T cell repertoire reactive with OA in hen's-egg-sensitive patients may be restricted by HLA-DP molecules. Furthermore, in hen's-egg-sensitive patients with AD who have a low immune reaction, low responsiveness may be regulated by HLA-DQ molecules.

Animals↗

[Efficacy and safety of percutaneous transluminal coronary angioplasty of other coronary arteries in patients with chronic total occlusion of the left anterior descending artery].

The acute and long-term outcomes of percutaneous transluminal coronary angioplasty (PTCA) of the right coronary artery (RCA) or left circumflex branch (LCS) in patients with chronic occlusion of the left anterior descending branch (LAD) (group A) were compared with those of sex and age matched patients undergoing PTCA of the RCA or LCX with a normal LAD (group B). Before the procedure, group A had more frequent prior myocardial infarction (96% vs 33%, p < 0.001), and a lower left ventricular ejection fraction (LVEF) (49 +/- 14% vs 71 +/- 13%, p < 0.001). The acute results were similar in the two groups with respect to primary success (group A 90%, group B 91%) and major complications (group A 6%, group B 2%). At 3 months, the rate of restenosis was 33% in group A and 27% in group B. In group A, LVEF increased significantly in patients without restenosis (53 +/- 11% vs 62 +/- 11%, p < 0.01). At long-term follow-up, group A had higher rates of persistent angina but there was no difference in outcome between the two groups. In patients with chronic total occlusion of LAD, PTCA for RCA or LCX can be performed with a low complication rate and provides a significant improvement in LVEF at 3 months in the absence of restenosis. However, at short-term follow-up, these patients have a greater incidence of persistent angina.

Adult↗

Expression of surrogate light chain in common variable immunodeficiency.

VpreB and lambda-like genes encode proteins that can associate to form a light-chain-like structure, the surrogate light chain (SLC). VpreB and lambda-like genes are selectively expressed in human progenitor B and precursor B (pre-B) cells. We analyzed the expression of VpreB and lambda-like genes in seven patients with common variable immunodeficiency (CVI). Gene expression was examined in the peripheral blood mononuclear cells (PBMCs) using the polymerase chain reaction. In four CVI patients, two of whom were brothers, the expression of the VpreB gene was detectable in the PBMCs. In the brothers with CVI, the expression of the VpreB gene was also examined in bone marrow cells, where it was found to be expressed in trace amounts. A number of the brothers' bone marrow cells were stained with mu and kappa antibodies using the avidin-biotin complex method. In lambda 5-gene-deleted mice, B cell development in the bone marrow is blocked at the pre-B stage, but the blockade is leaky. We suggest that expression of the SLC is weak in patients with CVI compared with their normal counterparts, and this may be one of the underlying mechanisms of CVI.

Adult↗

Differences in lymphocyte proliferative responses to food antigens and specific IgE antibodies to foods with age among food-sensitive patients with atopic dermatitis.

BACKGROUND: Clinical symptoms of patients with food-sensitive atopic dermatitis often improve with increasing age. OBJECTIVE: To investigate this tendency and the underlying mechanism. METHODS: We selected and divided 194 food-sensitive atopic dermatitis patients into three age groups. The proliferative responses of peripheral blood mononuclear cells (PBMCs) to food antigens and specific IgE antibodies to foods then were evaluated with respect to age. We also followed up 55 food-sensitive patients with atopic dermatitis and examined their improvement ratio after 1 year. Further, we investigated changes in lymphocyte proliferative responses to food antigens and specific IgE antibodies to foods in food-sensitive patients with atopic dermatitis during elimination diets. RESULTS: Proliferative responses of PBMCs to ovalbumin of patients in the over 6-years-old group were significantly (P < .05) lower than those of the less than 1-year-old group. Proliferative responses of PBMCs to bovine serum albumin of patients in the over 6-years-old group were significantly (P < .05) lower than those in the 1 to 5-year-old group and in the less than 1-year-old group. RAST values for hen egg in the over 6-years-old group were significantly (P < .05) lower than those for the less than 1-year-old group. Improvement was shown by 13 of the 33 hen egg-sensitive patients with atopic dermatitis, an improvement ratio of 39%, and by 9 of the 22 cow milk-sensitive patients with atopic dermatitis, an improvement ratio of 41%. Proliferative responses of PBMCs to food antigens in food-sensitive patients with atopic dermatitis decreased rapidly after patients were placed on elimination diets. CONCLUSION: The PBMC proliferative responses to food antigens and RAST values were higher for young children and lower for older ones who suffered from food-sensitive atopic dermatitis. Oral tolerance, in addition to the development of digestive and absorptive functions, may be responsible for these immunologic changes.

Adolescent↗

[A study on the difference between clinical and neuropathological diagnoses of age-related dementing illnesses; correlations with Hachinski's ischemic score].

In this study, clinical diagnosis and results of neuropathological examination were analyzed on 55 demented patients serially autopsied in a geriatric hospital. Based on clinical observations including Hachinski's ischemic score and CT scan, 30 cases were diagnosed as vascular dementia (VD), 16 cases as Alzheimer-type dementia (ATD), 6 as mixed-type dementia (MD), and 5 as other types of dementias. On the results of neuropathological examination, 25 cases were diagnosed as ATD, 19 cases as VD, 5 as diffuse Lewy body disease (DLBD), 4 as MD, and 2 as other types of dementias. The accuracy of the clinical diagnosis for ATD was 78.6%, and that for VD was 53.3%. Thus, misdiagnosis was more frequent on VD. Clinically, VD cases were rarely misdiagnosed as ATD, while ATD or MD cases were more frequently misdiagnosed as VD. Therefore, it is suggested that VD is overdiagnosed. One of the reasons is that risk factors of cerebrovascular disorders increase and Hachinski's ischemic score also becomes higher with the age of the patients. ATD is clinically diagnosed only after excluding other dementing illnesses. More detailed analysis of clinical features including cognitive function and brain images is required for more accurate clinical diagnosis of age-related dementing illnesses. Also in our series, DLBD was the second most frequent degenerative dementia following ATD, although all DLBD cases were clinically misdiagnosed as ATD or VD.

Aged↗

Paraquat tolerance of transgenic Nicotiana tabacum with enhanced activities of glutathione reductase and superoxide dismutase.

Transgenic tobacco with enhanced cytosolic activities of glutathione reductase and superoxide dismutase were generated by cross-fertilization. Leaves of the hybrids exhibited further increased tolerance to a O2-.-generating herbicide paraquat than those of their parents. This result indicates the efficiency of manipulating more than one gene in improving resistance of plants to photooxidative stress.

Drug Resistance↗

Prevalence of and risk factors for allergic diseases: comparison of two cities in Japan.

BACKGROUND: Differences in the prevalence of allergic diseases and the effects of genetic and environmental factors on these diseases in two areas of the same country have not been examined by multiple logistic regression. OBJECTIVE: To determine whether the effects of genetic and environmental factors on allergic diseases differ between two areas. METHODS: A questionnaire was distributed in March 1991 to children less than 16 years old attending kindergarten, elementary, or junior high school in two Japanese cities; Gifu, with a temperate climate, and Itoman, with a subtropical one. The number of subjects analyzed were 1243 in Gifu and 1953 in Itoman. Multiple logistic regression analysis was performed using SAS. RESULTS: The prevalence of allergic diseases and atopic dermatitis in Gifu were significantly higher than in Itoman (P < .05). In contrast, the prevalence of bronchial asthma in Itoman was significantly higher than in Gifu (P < .05). Multiple logistic regression analysis showed that in both cities children of families with allergic histories have significantly higher risk of contracting an allergic disease and atopic dermatitis. The prevalences of allergic diseases and atopic dermatitis were higher in Gifu than in Itoman, even after being controlled for genetic and environmental factors. CONCLUSIONS: The increased risk of contracting an allergic disease and atopic dermatitis for the children in Gifu may be due to such factors not included in the study as climate, eating habits, or the level of air pollution.

Adolescent↗

Cardiovascular complications following liver transplantation.

BACKGROUND: As the indications for liver transplantation broaden to include older and more critically ill patients, the likelihood of encountering unsuspected cardiovascular disease increases. PURPOSE: This study examined the frequency, type, and subsequent outcome of intra- and postoperative cardiovascular complications that occurred during the first 6 months following liver transplantation. METHODS: The records of 146 consecutive patients who underwent primary liver transplantation were reviewed retrospectively to determine the occurrence of major (myocardial infarction or reversible ischemia, pulmonary edema, cardiogenic shock, symptomatic rhythm disturbances, or pulmonary embolism) and minor (transient hypertension, hypotension, atrial or ventricular premature beats) cardiac events. The relation between such events and actuarial patient survival was evaluated. Stepwise logistic regression analysis was also employed to identify those pre-operative variables that predicted an increased risk of postoperative events or mortality. RESULTS: Cardiac events directly caused or contributed to 4 deaths (2.7%). Ventricular tachycardia/fibrillation was the most frequent intra-operative cardiac complication (3.4%); transient hypotension (post-reperfusion syndrome) was the most common minor event (20%). Thirty-four recipients (23%) developed a major postoperative cardiac complication including pulmonary edema (9%), myocardial ischemia or infarction (5.4%), new dilated cardiomyopathy (3.4%), and ventricular tachycardia (2.7%). Pre-existing cardiac disease and older age (mean age 49 +/- 8 years) at transplantation were the only independent predictors of a major complication. Major cardiac events did not affect 6 month survival but were associated with a lower 5-year survival rate (event: 32% vs event-free: 52%; p = 0.04). The frequency of major intraoperative (21% vs 2%; p = 0.0005) and postoperative (57% vs 17%; p = 0.0001) cardiac complications was significantly higher for recipients with known heart disease (Group A) compared with those without pre-existing heart disease (Group B). Five-year survival in Group A patients was 36% versus 50% for Group B patients; p = 0.45. CONCLUSION: One or more cardiovascular complications occurred in over 70% of liver transplant recipients. Major events were associated with a lower likelihood of long-term survival. Older patients, particularly those with pre-existing but compensated heart disease, are at greatest risk for a major cardiac event and may require more extensive pre-operative risk assessment.

Adolescent↗

A recurrent case of spontaneous mediastinal emphysema.

The first case of spontaneous mediastinal emphysema was reported by Hamman et al. in 1939. It is a rare condition that primarily occurs in young adults. In many instances, spontaneous mediastinal emphysema is caused by yelling, shouting or active exercise, but the cause is often unknown. It is rare for cases of spontaneous mediastinal emphysema to recur. Recently, we experienced a recurrent case of spontaneous mediastinal emphysema in a patient with a duodenal ulcer. Vomiting appeared to be the cause of the recurrence in our patient. Of the 58 patients with spontaneous mediastinal emphysema who have been reported in Japan so far, recurrences were documented only in our patient and two others.

Adult↗

One subspecies of the red junglefowl (Gallus gallus gallus) suffices as the matriarchic ancestor of all domestic breeds.

The noncoding control region of the mitochondrial DNA of various gallinaceous birds was studied with regard to its restriction fragment length polymorphism (RFLP) and sequences of the first 400 bases. Tandem duplication of the 60-base unit was established as a trait unique to the genus Gallus, which is shared neither by pheasants nor by quails. Unlike its close ally Gallus varius (green junglefowl), the red junglefowl Gallus gallus is a genetically very diverse species; the 7.0% sequence divergence was seen between those from Thailand (G. g. gallus and G. g. spadiceus) and the other from the Indonesian island of Java (G. g. Bankiva). Furthermore, the divergence increased to 27.83% if each transversion is regarded as an equivalent of 10 transitions. On the other hand, a mere 0.5-3.0% difference (all transitions) separated various domestic breeds of the chicken from two G. g. gallus of Thailand, thus indicating a single domestication event in the area inhabited by this subspecies of the red junglefowl as the origin of all domestic breeds. Only transitions separated six diverse domesticated breeds. Nevertheless, a 2.75% difference was seen between RFLP type I breeds (White Leghorn and Nagoya) and a RFLP type VIII breed (Ayam Pelung). The above data suggested that although the mitochondrion of RFLP type V was the main contributor to domestication, hens of other RFLP types also contributed to this event.

Animals↗

Normal sequences of muscarinic acetylcholine receptors (m1 and m2) in patients with Alzheimer's disease and vascular dementia.

The genes for muscarinic acetylcholine receptors, m1 and m2, were studied in autopsied brains from nine Alzheimer's disease, six vascular dementia and three control. The genes were amplified by the polymerase chain reaction and sequenced by the dideoxy method. Although one DNA polymorphism was found in m1, the deduced amino acid sequences of the muscarinic acetylcholine receptor were unchanged. The amino acid sequences of m1 and m2 in Alzheimer's disease and vascular dementia were intact.

Alzheimer Disease↗