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Biomedical subjects

H Nishii

Publications and source records attributed to H Nishii.

At least 19 recordsLinked to original sources

Prevalence of androgen receptor gene mutations in latent prostatic carcinomas from Japanese men.

The incidence rate of clinically apparent prostatic carcinoma is 8-fold higher in the United States than in Japan, while the prevalence of latent prostatic carcinoma, a presumed precursor to clinical carcinoma, is similar in the two countries. The purpose of this study was to investigate the hypothesis that this profound difference in incidence rates of clinical carcinoma reflects distinct profiles of molecular genetic alterations in the latent precursor lesions that occur in the two countries. A significant fraction of latent carcinomas from Japanese men were found to contain inactivating mutations of the androgen receptor gene, while no such mutations were found in latent carcinomas from American men. No mutations were found in clinical carcinomas from either country. These data offer a potential molecular genetic explanation that may partially account for the distinct prostatic carcinoma incidence rates in these two populations.

Amino Acid Sequence

Allelotype of endometrial carcinoma.

An allelotype analysis of endometrial carcinoma was undertaken to identify chromosomal loci that are relevant to this tumor type. A total of 70 highly polymorphic microsatellite markers, distributed among all nonacrocentric chromosome arms, were examined for evidence of loss of heterozygosity or allelic imbalance in DNA samples from matched normal and tumor tissues. An average of 21 informative tumor cases were obtained for each marker. Allelic deletions or imbalance were observed on 31 of 41 chromosome arms with no marker showing an allelic loss ratio of greater than 33%. Those chromosome arms most frequently involved were 3p, 8p, 9p, 14q, 16q and 18q. There was a strong correlation between loss of heterozygosity on chromosome 14q and death from disease. These data indicate that the molecular genetic character of endometrial carcinoma is complex and that a relatively large number of different chromosomal loci are likely to play a role in the etiology and progression of this tumor type.

Chromosomes, Human, Pair 14

Fusion activity of an amphiphilic polypeptide having acidic amino acid residues: generation of fusion activity by alpha-helix formation and charge neutralization.

A sequential polypeptide, poly(Glu-Aib-Leu-Aib) (Aib represents 2-aminoisobutyric acid), was synthesized and the pH-dependence of fusogenic activity of the polypeptide was studied. The polypeptide was designed to take amphiphilic structure upon the formation of alpha-helix. Circular dichroism spectra of the polypeptide showed a negative Cotton effect with double minima, indicative of an alpha-helical conformation. The alpha-helix content was increased with lowering pH and/or increasing the ionic strength. It was found that the polypeptide induces remarkable leakage of calcein from egg-yolk phosphatidylcholine (EYPC) vesicles loaded in the inner aqueous phase with lowering pH and/or increasing ionic strength. The polypeptide caused fusion of EYPC liposomes and dipalmitoylphosphatidylcholine liposomes more strongly with decreasing pH. Moreover, two distinct increases of fusogenic activity of the polypeptide were observed near pH 6.0 and below pH 4.5. The former corresponds to the midpoint of pH-dependent change in helical content of the polypeptide and the latter the pKa of the gamma-carboxyl group of glutamic acid. These results indicate that elevation of the fusogenic activity of the polypeptide is related to the increase in two factors, alpha-helix content and hydrophobicity.

Amino Acid Sequence

Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma.

Previous studies have demonstrated that some human endometrial carcinomas contain an activating point mutation in codon 12 of the Ki-ras protooncogene. To examine the hypothesis that this mutation may occur at an earlier stage of neoplastic progression in the endometrium, we analyzed 89 samples of premalignant endometrial hyperplasia and an additional 84 samples of endometrial carcinoma for point mutations of Ki-ras codon 12. Mutations were found in all three types of endometrial hyperplasia, simple, complex, and atypical, with no clear evidence of a differential distribution in any particular type. Furthermore, the overall incidence of Ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%), indicating that ras mutation may represent an early event in a subset of endometrial carcinomas. When the tissue samples were segregated as to country of origin, the frequency of this mutation was approximately 2-fold higher in hyperplasia and carcinoma samples from Japan than from the United States, where the incidence, clinicopathological characteristics, and risk factors for endometrial carcinoma differ dramatically. There was no apparent correlation, however, between ras mutation and any pathological, histological, or clinical parameter examined, except survival. The presence of a ras mutation was inversely associated with death from disease, suggesting that this molecular feature may characterize a subset of endometrial carcinomas with a good prognosis.

Adult

Mutation of the p53 tumor-suppressor gene is not a feature of endometrial hyperplasias.

OBJECTIVE: Mutation and overexpression of the p53 gene occur in approximately 20% of endometrial carcinomas. To determine whether alteration of the p53 gene is an early event in endometrial carcinogenesis, we examined the p53 gene in endometrial hyperplasias. STUDY DESIGN: Genomic deoxyribonucleic acid was extracted from 117 endometrial hyperplasias (36 simple, 40 complex, 41 atypical) and 30 endometrial cancers. Exons 5 through 8 of the p53 gene were amplified by means of the polymerase chain reaction. Mutations in the p53 gene were sought with single-stranded conformation polymorphism analysis and confirmed by direct deoxyribonucleic acid sequencing. RESULTS: None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in three of 30 (10%) endometrial cancers (p < 0.02). The p53 mutations seen in three cancers were confirmed by direct sequencing (codons 157, 180, 272). CONCLUSION: Because it does not appear to be a feature of endometrial hyperplasias, mutation of the p53 gene may represent a relatively late event in endometrial carcinogenesis.

Base Sequence

[Diffusely increased uptake in the skull in normal bone scans].

Diffusely increased skull uptake (a hot skull) is often seen in patients with bone metastases and metabolic diseases. This finding is also, however, noticed in normal bone scans of aged women. To determine whether the hot skull could be considered a normal variant in elderly women and is associated to menopause, we studied 282 normal bone scans (166 women and 116 men without metabolic and hormonal disease; age range 11 to 84 yr). We divided the patients into eight age groups--ages 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 yrs. Measurements of skull uptake were obtained from anterior total body views using contrast-to-noise ratio (CNR). CNR for the skull was calculated using the following equation: (counts skull - counts femur)/square root of counts skull+counts femur, where the denominator signifies a measure of the noise and the numerator represents the contrast between the skull and the midfemur. Counts skull and femur are the number of average counts per one pixel recorded over the skull and midfemur, respectively. The sex dependent difference in skull uptake began to develop in the age group 30-39 yrs (p less than 0.05). The skull showed greater activity in women than in men for age groups from 30-39 to 80-89 yrs. In the age groups 50-59 and 60-69, the difference was particularly large (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Studies on the effect of thyroid hormone and epidermal growth factor on the cultured human cytotrophoblast.

We have previously reported that human placental cytotrophoblasts (C-cells) contain nuclear 3,5,3'-triiodo-L-thyronine (T3) receptors. Using a C-cell culture system, the present study was undertaken to clarify some of the effects of T3 and EGF on trophoblastic cells. C-cells were purified from human term placenta by treatment with trypsin-DNAse and percoll gradient centrifugation aggregated, then fused, differentiating into multinuclear syncytiotrophoblasts (S-cells) with incubation times up to 96 h in vitro. As the incubation time increased, the number of immunocytochemically reactive cells with antibodies to hCG-alpha, hCG-beta and hPL increased. Anti-EGF antibody reacted only with the initial C-cells, while anti-EGF receptor antibody reacted only with fused S-cells. Maximum secretion of hCG and hCG-alpha by the cultured cells was evident only when the cells were cultured in T3 (10(-8)M) or EGF (10 ng/ml) containing medium. When the initial cells were exposed to 10(-8) M T3 from 0 to 48 h of incubation, the secretion in 48-96 h was significantly accelerated. However, exposure from 48 to 96 h had no effect on peptide excretion. Although an exposure of these cells to 10 ng/ml EGF during 48-96 h of incubation stimulated the secretion of hCG and hCG-alpha, 0-48 h exposure did not produce any positive effect regardless of incubation time. These results indicated that the main target cell of T3 is the C-cell, while that of EGF is the S-cell. Furthermore, it is suggested that the interaction between T3 and its receptor facilitated functional cell differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured

[A case report of descending thoracic aortic aneurysm associated with anterior spinal artery syndrome despite no marked ESP changes].

A 67-year-old man underwent graft replacement for the descending thoracic aortic aneurysm with the aid of temporary external bypass. Intraoperative evoked spinal potentials (ESPs) were monitored to detect the spinal cord ischemia. Incomplete paraplegia with sensory dissociation was developed in this patient after surgery, despite well maintained ESPs throughout the aortic cross-clamping. ESPs have been widely used as a mean of detecting early impairment of spinal neural conduction during aortic surgery. However, ESPs are principally mediated through posterior and lateral column pathways and they are not always a reliable monitor to predict paraplegia in aortic surgery.

Aged

[Clinical experience of adjustable pulmonary artery banding].

Pulmonary artery banding has been a useful palliative procedure for infants with congenital cardiac anomalies associated with excessive pulmonary blood flow. We have experienced some cases that the band was not sufficient enough to reduce the pulmonary artery pressure in complex cardiac anomalies. Therefore, we developed a new adjustable pulmonary artery banding system which can be re-adjusted extrathoracically without reoperation. We used this system in seven infants with congenital cardiac lesions and obtained good results.

Heart Defects, Congenital

Studies on the nuclear 3, 5, 3'-triiodo-L-thyronine binding sites in cytotrophoblast.

Human placental trophoblasts contain 3, 5, 3'-triiodo-L-thyronine (T3) nuclear receptors not only at term but all throughout pregnancy. We determined which of the trophoblast, cytotrophoblast (C-cell) or syncytiotrophoblasts (S-cell) respond to thyroid hormone, and whether the T3 binding capacity changes with placental aging. Nuclear protein of mononuclear cells purified from term chorionic tissue by enzymatic digestion and Percoll gradient centrifugation had an apparent association constant (Ka) of 5.2 x 10(9)M-1 and a binding capacity of 445 fmol T3/mg DNA, 8 times greater than that of term trophoblasts. Primary harvested mononuclear cells reacted against neither anti-hCG-beta nor anti-hPL antibodies, although some of them reacted immunocytochemically against anti-hCG-alpha antibody. These cells aggregated with each other and transformed into multinuclear cells in culture after 96 hrs of incubation, showing that these primary harvested cells were C cells that had morphologically transformed into S cells. The transformed cells secreted hCG and hPL and immunocytochemically stained for these markers, suggesting that the C cells had functionally transformed into S cells. Nuclear binding of T3 in trophoblastic tissue is present not only at term but throughout pregnancy. Although each nuclei had a similar Ka value, the binding capacity decreased towards term. These findings suggest that nuclear T3 receptors of placental trophoblast change with placental aging and this change is mainly due to the change in the C/S cell ratio. We concluded that the cytotrophoblast is an active target cell of thyroid hormone.

Antibodies, Monoclonal

[Axillary vertical incision thoracotomy sparing pectoralis major muscle and latissimus dorsi muscle: an approach for patent ductus arteriosus].

The technique of an axillary vertical incision thoracotomy sparing pectoralis major muscle and latissimus dorsi muscle for a closure of patent ductus arteriosus is presented. After an mid-axillary vertical incision, serratus anterior muscle is incised on the third intercostal space between pectoralis major muscle and latissimus dorsi muscle. The space between serratus anterior muscle and rib cage (Spatium intermusc. thoracale) is dissected with a finger, through this space the 3rd intercostal thoracotomy is performed in the axillary and dorsal portion. The ventral part of intercostal muscle is incised from inside of the thoracic cavity for sparing the pectoralis major muscle. We performed this technique in two patients aged 1 year, and secured equally good operative fields as could be secured by the original axillary vertical incision thoracotomy described by Browne.

Axilla