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Biomedical subjects

H Nishitani

Publications and source records attributed to H Nishitani.

At least 19 recordsLinked to original sources

[Intracranial MR imaging of achondroplasia].

Intracranial MR imaging was performed in five patients with achondroplasia. All patients had narrowing of the subarachnoid space at the level of the foramen magnum that was mainly due to protrusion of the posterior aspect. Three patients had compressive deformities of the brainstem and/or upper cervical spine. Among them, two patients had deformities of the pons. Relative upward displacement of the brainstem was seen in all patients. Hydrocephalus was seen in three patients.

Achondroplasia

tsBN75 and tsBN423, temperature-sensitive x-linked mutants of the BHK21 cell line, can be complemented by the ubiquitin-activating enzyme E1 cDNA.

tsBN75 and tsBN423 are independently isolated temperature-sensitive (ts) mutants of the BHK21 cell line for cell growth. Both tsBN75 and tsBN423 belong to the same complementation group and show G2 block at the nonpermissive temperature. Both were efficiently transformed to ts+ cells with the mouse and human cDNA encoding the ubiquitin-activating enzyme, E1. While no transformants of tsBN423 cells had a DNA content greater than the parental 2C, several ts+ transformants of tsBN75 cells acquired a multiploid DNA content. These data thus demonstrate the function of the human and mouse E1 cDNAs and further suggest that E1 functions in more than one step in cell cycle progression.

Animals

Impaired metabolism of high density lipoprotein in uremic patients.

We measured lipoproteins, apolipoproteins, lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), lecithin: cholesterol acyltransferase (LCAT) and parameters of calcium metabolism to evaluate the roles of these enzymes and hypertriglyceridemia for impaired high-density lipoprotein (HDL) metabolism in chronic renal failure, and to examine the impact of altered calcium homeostasis on the lipoprotein-regulating enzymes. The subjects were 25 healthy volunteers and 66 uremic patients, 24 treated with hemodialysis (HD) and 42 with continuous ambulatory peritoneal dialysis (CAPD). Lipoprotein analysis revealed: (1) reduction in HDL cholesterol especially in HDL2 subfraction; (2) increase in HDL triglyceride; and (3) decreased ratio of HDL2 cholesterol to HDL3 cholesterol in both HD and CAPD patients. Simple regression analysis showed: (1) a positive correlation between VLDL triglyceride and triglyceride/cholesterol ratio of HDL; (2) positive correlations of LPL level in post-heparin plasma to cholesterol concentrations in HDL2, HDL3 and total HDL, and to apolipoproteins A-I and A-II; and (3) inverse correlations of HTGL to HDL2 cholesterol and to the ratio of HDL2 cholesterol/HDL3 cholesterol. Multiple regression analysis of HDL cholesterol indicated positive association with LPL and inverse correlation with VLDL triglyceride. Four variables including LPL, HTGL, LCAT and VLDL triglyceride explained 51.5% of the variation of HDL cholesterol. HDL2 cholesterol was associated positively with LPL and negatively with VLDL triglyceride in the model. HDL3 cholesterol was associated positively with LPL, HTGL and LCAT and inversely with VLDL triglyceride. Stepwise multiple regression analysis indicated that independent predictors of HTGL were gender, parathyroid hormone levels by a mid-portion assay, ionized calcium and age, and that those of LCAT were ionized calcium and age.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins

Chromosome condensation caused by loss of RCC1 function requires the cdc25C protein that is located in the cytoplasm.

We cloned the hamster cdc25C cDNA by using the human cdc25C cDNA as a probe and prepared an antibody to Escherichia coli-produced hamster cdc25C protein that is specific to the human cdc25C protein. The microinjected antibody inhibited a chromosome condensation induced by tsBN2 mutation, indicating that the cdc25C protein is required for an activation of p34cdc2 kinase caused by loss of RCC1 function. The hamster cdc25C protein located in the cytoplasm, prominently in a periphery of the nuclei of cells arrested with hydroxyurea, and seemed to move into the nuclei by loss of RCC1 function. Also, we found a molecular shift of the cdc25C protein in cells showing premature chromosome condensation (PCC), in addition to normal mitotic cells. This molecular-shift appeared depending on an activation of p34cdc2 kinase.

Amino Acid Sequence

Metabolism of tegafur in rat liver observed by in vivo 19F magnetic resonance spectroscopy and chromatography.

Metabolism of tegafur in the rat liver was observed by in-vivo 19F magnetic resonance spectroscopy (MRS). After MRS observation, tegafur and q-fluorouracil (5-FU) in the liver were determined by a chromatographic method for comparison with the results of 19F-MRS. Rats were divided into 3 groups: 1) CCl4-induced liver injury group, 2) uracil combined group, 3) control group. Catabolism to fluoro-beta-alanine was suppressed in both the liver injury group and the uracil combined group. Low peaks of 5-FU and fluoronucleotides could be found only in the uracil combined group. The result of 19F MRS observation of each group was in agreement with the result of determination of tegafur and 5-FU by chromatography. This showed that substances which could be observed by 19F-MRS were in proportion to all intracellular fluoro-containing substances. 19F-MRS can provide direct information on the metabolism of fluoropyimidines non-invasively and it might be a useful aid in choosing suitable chemotherapy for patients.

Alanine Transaminase

RCC1, a regulator of mitosis, is essential for DNA replication.

Temperature-sensitive mutants in the RCC1 gene of BHK cells fail to maintain a correct temporal order of the cell cycle and will prematurely condense their chromosomes and enter mitosis at the restrictive temperature without having completed S phase. We have used Xenopus egg extracts to investigate the role that RCC1 plays in interphase nuclear functions and how this role might contribute to the known phenotype of temperature-sensitive RCC1 mutants. By immunodepleting RCC1 protein from egg extracts, we find that it is required for neither chromatin decondensation nor nuclear formation but that it is absolutely required for the replication of added sperm chromatin DNA. Our results further suggest that RCC1 does not participate enzymatically in replication but may be part of a structural complex which is required for the formation or maintenance of the replication machinery. By disrupting the replication complex, the loss of RCC1 might lead directly to disruption of the regulatory system which prevents the initiation of mitosis before the completion of DNA replication.

Animals

Nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of parkinsonian patients. Final report.

Final results of the 5-year multicentric collaborative study on the long-term effects of bromocriptine in the patients with Parkinson's disease are reported. This prospective study started in May 1985 in order to see whether the early combination therapy with bromocriptine and levodopa is really superior to the levodopa monotherapy with regard to the late side effects of levodopa in the treatment of parkinsonian patients. Another project of the study was to see the therapeutic efficacy of bromocriptine monotherapy without concomitant use of levodopa. For these purposes, a total of 702 patients with Parkinson's disease were enrolled into three groups: Group 1 (n = 286) with bromocriptine monotherapy, Group 2A (n = 216) with early combination of bromocriptine and levodopa, and Group 2B (n = 200) with levodopa alone. At the end of the 5-year study, 48 patients in Group 1 (16.8%) were still continuing bromocriptine monotherapy with satisfactorily good therapeutic effects. About half (49.1%) of the Group 2A patients remained on the combined therapy, and the comparable number of the Group 2B patients (46.0%) were also kept on the initial mode of therapy, while 13.5% of the latter group with levodopa monotherapy needed bromocriptine to be added in order to assure the good therapeutic effects. Moreover, significant differences were seen between group 2A and Group 2B with regard to the incidence of wearing-off phenomenon and dyskinesias. Disappearance rate of dyskinesias which were present at the time of enrollment was significantly higher in Group 2A than in Group 2B. No significant difference was noted as to the incidence of untoward symptoms and the death rate among all three therapeutic groups. These results support the view that the early combination of bromocriptine with levodopa is superior to levodopa alone in the treatment of Parkinson's disease.

Activities of Daily Living

Nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of parkinsonian patients: analysis on the maintenance and the change of the original mode of treatment.

A nation-wide collaborative study to evaluate the long-term effects of bromocriptine in patients with Parkinson's disease was completed as described in the accompanying paper. The present study analysed the same data by paying attention to a group of patients who maintained the original mode of therapy and to a group of patients who changed the mode of treatment by adding levodopa or bromocriptine to the original drug. Surprisingly, 48 among 286 patients in a group of bromocriptine monotherapy maintained the original mode of therapy. This group has particular features of a short duration of illness and a low grade of Hoehn-Yahr's scale. It is noteworthy that this group of patients did not show wearing-off phenomenon. The effects of additional bromocriptine to levodopa for a 5-year period were analysed by comparing two groups of combination therapy and levodopa alone therapy maintained for 5 years, with 106 and 92 patients, respectively. Results were essentially the same as those obtained from the accompanying paper, i.e., in general, treatment by combination with bromocriptine may be more suitable than treatment by levodopa alone. In order to find the best timing of the combination of levodopa and bromocriptine, results of 3 groups were compared, i.e. a group of patients who started with bromocriptine alone and later added with levodopa (82 patients), a group of patients who maintained the combination for 5 years (106 patients) and a group of patients who started with levodopa alone and later added bromocriptine (27 patients). The best results were obtained in the group of 5-year combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living

Clinical effects of long-term use of neutralized dialysate for continuous ambulatory peritoneal dialysis.

The long-term effects of neutralized dialysate used in continuous ambulatory peritoneal dialysis (CAPD) were evaluated in 8 well-controlled patients. Twelve milliliters of 8.4% sodium bicarbonate was added to Dianeal PD-1 immediately before every administration. The final pH was 6.8 and the concentration of sodium bicarbonate was 6 mmol/l. The final sodium level was 138 mEq/l. This dialysate was used for 5 months. For 2 months before and 3 months after this period, Dianeal PD-2 was used as the dialysate for comparison. Blood bicarbonate levels significantly improved during the use of the neutralized dialysate. Blood sodium, chloride and magnesium levels and the effluent volume significantly increased. Sodium balance improved during the period when neutralized dialysate was used. Total leukocyte counts in the effluent decreased, and leukocyte viability increased. Abdominal distention, abdominal pain during instillation, nausea and headache improved. No side effects, including peritonitis, occurred during the trial of neutralized dialysate. The results suggest that this dialysate was less irritating to the peritoneal membrane than the control dialysate and that the therapeutic effects were satisfactory.

Blood Urea Nitrogen

Protein p67. A calcium-binding protein localized at the sarcolemma of secretory atrial myocytes.

Bovine heart 67-kd protein (p67) was coisolated with calpactin I complex by cycles of Ca(2+)-dependent precipitation followed by solubilization with EGTA-containing buffer. Using affinity-purified anti-p67 antibody and anti-p36 (36-kd subunit of calpactin I) antibody, we examined the localization of the two proteins in secretory atrial myocytes and other endocrine tissues of adult rats. Immunofluorescence microscopy showed that p67 was expressed both in the atrial myocytes in situ and in cultured atrial myocytes in which we failed to detect p36 and that p67 appeared to be closely associated with the cell surface. We also found that p67 was colocalized with p36 in the thyroid follicle epithelium and zona reticularis of the adrenal gland. On the other hand, neither p67 nor p36 was detectable in pancreas islet cells. Immunoelectron microscopy revealed that p67 was localized at the sarcolemma in the atrial myocytes in situ. The p67, which was shown to be a globular molecule with a diameter of 18-25 nm by a low-angle rotary shadowing method, bound radioactive Ca2+ on a nitrocellulose membrane. The results suggest that Ca(2+)-binding proteins expressed in endocrine cells seem to vary from tissue to tissue and that p67 may function in Ca(2+)-mediated events at the plasma membrane of secretory atrial myocytes and some types of endocrine cells expressing this protein.

Amino Acids

Evidence for the presence of differently glycosylated forms of prorenin in the plasma of anephric man.

Previously, we unexpectedly observed that plasma inactive renin (trypsin-activatable renin) in bilaterally nephrectomized rats is not prorenin. To determine whether plasma inactive renin in anephric man is prorenin, we examined the immunological and biochemical properties of plasma inactive renin from five anephric patients. There were significant concentrations of inactive renin (5.33 +/- 2.08 ng/L.s) in plasma of anephric patients, while active renin was negligible (0.06 +/- 0.01 ng/L.s). The inactive renin from anephric patients could be immunoprecipitated 97 +/- 1% by specific antiserum against the prosegment portion of prorenin. Specific antimature renin serum completely inhibited the angiotensin-I-generating activity of inactive renin induced by trypsin treatment. The molecular mass of inactive renin from anephric patients (49.0 +/- 0 kDa), estimated by gel permeation high performance liquid chromatography, was similar to that of normal human plasma prorenin (48.2 +/- 0.8 kDa). These results indicate that plasma inactive renin in anephric man is prorenin, findings different from our previous observations obtained in anephric rats. Concanavalin-A chromatography separated inactive renin from anephric patients into three forms, including the column-unbound form, the loosely bound form, and the tightly bound form. Thus, in anephric man, differently glycosylated multiple forms of prorenin are released into the circulation from an extrarenal organ(s).

Adult

Intraarterial lymphocyte-injection therapy for lymphedema of the leg: an examination using indium-111 oxine labeled autologous lymphocytes.

A 58-year-old female patient with lymphedema of the left leg was treated by repeated intraarterial lymphocyte-injection therapy. To elucidate whether the injected lymphocytes act at the affected site of the leg, we examined the distribution of the In-111 oxine labeled lymphocytes injected into the proximal artery to the affected leg in comparison with the distribution in the other, healthy, leg. The radioactivity of the affected leg was almost two times higher than that of the healthy leg during the first 30 min after injection, and it remained higher even after 24 hours. The circumference of the affected leg of the patient decreased steadily during her hospital stay. These results, together with the clinical findings, suggest that some of the intraarterially-injected lymphocytes remained in the affected leg at least 24 hours and might play some role in reducing the volume of lymphedematous fluid.

Blood Component Transfusion

Accuracy of the results measured by in vivo 1H-MRS using model solutions.

In in vivo 1H-MRS of human brain, main three metabolites such as N-acetyl-L-aspartate (NAA), creatine/phosphocreatine (PCr/Cr), and choline (Cho) have been observed. In this paper an accuracy of the results measured by in vivo 1H-MRS using above model solutions was discussed. 1.0 mmol/l choline and 1.5 mmol/l creatine/phosphocreatine saline solutions were measured with STEAM method (echo time 270 msec). The peak area of Cho was larger than that of PCr/Cr against their concentrations and was linearly increased with its concentration in the range of 5.8 and 29 mumol/27 cm3. Although both peak areas of Cho and Cr/PCr were varied with Volume-of-interest (VOI) coordinates, the ratio of Cho to PCr/Cr was approximately 1.6.

Brain

Quantified application of MRI for diagnosis of head and neck tumors.

We evaluated T/M ratios and T2 values of 6 malignant lymphomas and 8 squamous cell carcinomas in the head and neck in order to differentiate these two entities. T/M ratios were calculated by dividing intensity of tumor by that of muscle in same slice images. T2 values were calculated from T2-weighted images and proton-weighted images. Statistical difference of T/M ratios was found between malignant lymphomas and squamous cell carcinomas, but no difference of T2 values was seen between two groups. T/M ratio was considered to be a useful and quantified index for evaluation of head and neck tumor.

Carcinoma, Squamous Cell

High serum lipoprotein(a) concentrations in uremic patients treated with continuous ambulatory peritoneal dialysis.

We measured serum lipoprotein(a) [Lp (a)] concentrations in 50 uremic patients treated on continuous ambulatory peritoneal dialysis (CAPD) and compared them with those in 29 uremic patients on hemodialysis (HD) and those in 62 normal controls. The median values were 47.9 mg/dl in CAPD patients, 25.2 mg/dl in HD patients, and 11.7 mg/dl in controls, respectively. These differences were statistically significant when assessed by Kruskal-Wallis test (p < 0.0001). Thirty-five out of 50 patients on CAPD (70%) and 12 out of 29 patients on HD (41%) had Lp(a) concentrations above 30 mg/dl, whereas these high values were observed in only 15% of normal controls. This difference in prevalence of high Lp(a) was also significant by 2 x 3 chi-square test (p < 0.01). There was a significant positive correlation between Lp(a) and apolipoprotein B (r = 0.517, p < 0.0001). In CAPD patients, 9 with ischemic heart disease had a significantly higher median Lp(a) than those without it (67.4 vs 40.9 mg/dl, p < 0.01 by Mann-Whitney U-test). These results suggest that high levels of serum Lp(a) might contribute to an increased risk for ischemic heart disease in CAPD patients, and that there may be a relationship between Lp(a) and apolipoprotein B metabolism in CAPD patients.

Adult