Hydroxyurea-induced foot ulcer successfully treated with a topical basic fibroblast growth factor product.
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Biomedical subjects
Publications and source records attributed to A Yajima.
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Parathyroidectomy and immediate autotransplantation (PTX-AT) has been shown to decrease bone pain and increase bone mineral density. However, adynamic bone disease (ABD) has been predicted to develop if the serum intact parathyroid hormone (i-PTH) level remains lower than normal for a long period of time. Therefore, we investigated the bone histology of patients whose serum i-PTH levels did not increase over 70 pg/mL for 1 year after PTX-AT. Four chronic hemodialysis patients were investigated. The serum intact osteocalcin (i-OC) level was measured and histomorphometry for cancellous bone was performed 1 year after the operation. Tetracycline hydrochloride was administered in the 12 weeks after PTX-AT. The serum i-PTH levels were 20.5 +/- 15.0 pg/mL and i-OC levels were 19.5 +/- 0.9 ng/mL. Histomorphometric analyses showed the osteoclast surface to be 0.1% in two cases and 0% in the other two cases, the eroded surface was 7.7 +/- 6.1%, and the fibrosis volume and osteoblast surface were 0% in all four cases. Osteoid volume, osteoid surface and osteoid thickness were lower in cases 1-3, but higher in case 4. All tetracycline labelings were in contact with the mineralization front in cases 1 and 3, but some were not in cases 2 and 4. Serum i-PTH and i-OC levels indicated that ABD developed in these four cases. Histomorphometric analyses revealed that ABD developed in case 1, while either ABD or low-turnover osteomalacia developed in cases 2 and 4, and low-turnover osteomalacia was observed in case 3 after PTX-AT. In conclusion, i-PTH should not be maintained at lower levels to avoid low-turnover bone diseases.
'Sarcoidosis-lymphoma syndrome' is known as an association of sarcoidosis with malignant lymphoma. We report a 56-year-old woman with systemic sarcoidosis who was seropositive for antibody against human T cell lymphoma/leukemia virus type I (HTLV-I). This patient showed integration of HTLV-I proviral DNA within cutaneous sarcoid nodules, but not in peripheral blood mononuclear cells. Neither atypical lymphocytes nor a T cell receptor beta1 gene rearrangement were observed in peripheral blood mononuclear cells or in cutaneous nodules, indicating that the patient did not have a smouldering type of adult T cell lymphoma/leukemia. Detection of integration of HTLV-I proviral DNA in cutaneous sarcoid nodules could suggest that the sarcoid nodules might have been generated as a protective response to chronic stimuli of HTLV-I.
Our purpose is to evaluate a model proposed by Stene et al. for estimating the risk of unbalanced progeny at the time of second trimester amniocentesis for 114 pregnancies of 71 couples, who are carriers of a reciprocal translocation. The overall estimated risk was 18%, 1.26 times higher than the observed risk (14%). There were no unbalanced fetuses in the 19 pregnancies of the no-risk group. In the low-risk group, the observed risk was highly correlated with the estimated risk. However, the estimated risks in the medium- and high-risk groups were much higher than the observed risks (2- and 1.5-fold). In the group ascertained through spontaneous abortions, the average estimated risk was 1.9 times higher than the observed risk. Although the model is useful in estimating individual empirical risks, it may be necessary to consider the type of ascertainments and add some modifications to calculate the risks in the second trimester.
A novel pyrrolidine amide (MQ-A3) isolated from the tropical convolvulaceous species was synthesized in 5 steps by starting from commercially available 12-bromododecanol and (S)-2-methylbutylbromide. The absolute configuration of the natural product was confirmed by a comparison of the specific rotation values.
Our objective is to investigate the involvement of granule-mediated apoptosis in the cyclic changes of the endometrium. We demonstrated the localization of CD56, perforin, granzyme B and caspase-3 in the endometrium by immunohistochemistry. We also confirmed the localization of perforin by immuno-electron microscopy, and demonstrated apoptosis in endometrial glandular cells by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and electron microscopy. Uterine CD56-positive natural killer (NK) cells expressed perforin and granzyme B in its cytoplasm. Uterine NK cells increased significantly in the endometrial stroma during the secretory phase, and peaked during the late secretory phase. These cells started decreasing in number during the menstrual period. In endometrial glandular cells, caspase-3 and TUNEL-positive cells increased significantly from the late secretory phase, with apoptosis reaching a peak during the menstrual period. Using electron microscopy, we observed uterine NK cells with chromatin rich, segmented nuclei and intracytoplasmic granules in the stroma obtained from late secretory phase endometria. These cells extended projections to the lining of endometrial glandular cells and attached to form a cell-to-cell contact. In addition, nuclear chromatin was observed to have already cohered and small cytoplasmic organelles were beginning to disappear, suggesting that these endometrial glandular cells were undergoing apoptosis. Utilizing immuno-electron microscopy, intracytoplasmic granules in uterine NK cells were stained with anti-perforin antibody. The findings of this study suggest that granule-mediated apoptosis in endometrial glandular cells induced by NK cells expressing perforin and granzyme B may be associated with the onset of menstruation.
AIMS: There have so far been no reports on the changes in bone histology in the early period after parathyroidectomy and autografting (PTX-AG). We investigated the effects of PTX-AG on bone histology during the initial 12 weeks after undergoing these surgical procedures. MATERIALS AND METHODS: We performed bone histomorphometry 3 times (before as well as 4 and 12 weeks after PTX-AG) in 6 patients and 2 times (before and 4 weeks after PTX-AG) in 3 hemodialysis patients. In addition, the circulating parameters of bone metabolism were also assessed before and after PTX-AG in all 9 patients. The changes in the histomorphometric (static) parameters between pre-surgery and 4 weeks after surgery and those between 4 weeks and 12 weeks after surgery were assessed by the t-test while changes in the circulating parameters of bone metabolism were analyzed by Friedman's test. RESULTS: Bone formation parameters including carboxy terminal propeptide of human type I procollagen (PICP), alkaline phosphatase (ALP) and intact osteocalcin (i-OC) were all extremely high before surgery. These parameters initially increased after PTX-AG and thereafter gradually declined. In contrast, the circulating bone resorption parameters including tartrate-resistant acid phosphatase (TRAP) and deoxypyridinoline (Dpyr) were also extremely high at baseline but markedly declined after operation. Osteoid-related parameters including osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid thickness (O.Th) all initially increased at 4 weeks after PTX-AG. In contrast, osteoblast surface (Ob.S/BS), osteoclast surface (Oc.S/BS), eroded surface (ES/BS), and fibrosis volume (Fb.V/TV) all decreased at 4 weeks after surgery, while Ob.S/BS decreased further at 12 weeks in cases 1-6. Although bone mineralization was ongoing at 4 weeks after surgery, both the mineral apposition rate (MAR) and bone formation rate (BFR) remained below the mean for normal individuals. CONCLUSIONS: The circulating bone formation parameters and osteoid-related parameters showed an initial increase after PTX-AG. The concomitant decline in the circulating bone resorption parameters reflected the reduction in bone resorption. BFR decreased, but bone mineralization did not stop after PTX-AG.
Choroidal metastasis from recurrent ovarian cancer is extremely rare. To our knowledge, this report is the first such case of endometrioid adenocarcinoma. A 30-year-old pregnant woman presented to an ophthalmologist in January 1999 because of a rapid visual deterioration. Ophthalmologic evaluation revealed a metastatic choroidal tumor from ovarian cancer which had been diagnosed 10 years ago. After cesarean section, multiple metastases were found including the choroid, scalp, bone, and lung, and she received four courses of single agent carboplatin chemotherapy. She died of disease in July 1999. This case highlights the need to investigate the etiology of visual complaints in patients with a history of ovarian cancer even in the early stage.
Fetal somatic cell gene therapy could become an attractive solution for some congenital genetic diseases or the disorders which manifest themselves during the fetal period. We performed adenovirus-mediated gene transfer to mice and guinea pig fetuses in utero and evaluated the efficiency of gene transfer by histochemical analysis and a quantitative TaqMan-polymerase chain reaction (TaqMan-PCR) assay. We first injected a replication-deficient recombinant adenovirus containing the Escherichia coli LacZ gene driven by a CAG promoter (AxCALacZ) into pregnant mice through the amniotic space, placenta, or intraperitoneal space of the fetus. Histochemical analysis showed limited transgene expression in fetal tissues. We then administered AxCALacZ to guinea pig fetuses in the late stage of pregnancy through the umbilical vein. The highest beta-galactosidase expression was observed in liver followed by moderate expression in heart, spleen, and adrenal gland. The transgene expression was also present in kidney, intestine, and placenta to a lesser degree. No positively stained cells were observed in lung, muscle, or pancreas except in the vascular endothelium of these organs. Quantitative measurement of recombinant adenoviral DNA by the TaqMan-PCR assay showed that the vast majority of the injected viruses was present in liver. The current study indicated that adenovirus-mediated gene transfer into guinea pig fetus through the umbilical vein is feasible and results in efficient transgene expression in fetal tissues. The experimental procedures using pregnant guinea pigs might serve as a good experimental model for in utero gene transfer. Since our TaqMan-PCR assay detects the LacZ gene, one of the most widely used reporter genes, it may be generally applicable to adenovirus quantification in various gene transfer experiments.
To investigate X-chromosome inactivation (XCI) in human trophoblasts during early pregnancy, trophoblast genomic DNA was extracted and analyzed for a Bst XI restriction endonuclease site polymorphism in the X-linked phosphoglycerate kinase gene, after digestion with methylation-sensitive Hpa II (control samples were digested instead with Afa I). Six villous trophoblast DNA samples were informative for the polymorphism (ie, heterozygous) and were derived from women homozygous for the polymorphism. These samples were then evaluated for XCI. In five of the six samples with Hpa II predigestion, the sizes of the two heterozygous band peaks differed; maternal X-chromosome (X(M))-derived alleles showed smaller peak sizes than paternal X-chromosome (X(P))-derived alleles, but the differences varied in degree. In samples obtained by microdissection from formalin-fixed, paraffin-embedded tissues (30 samples from different anchoring villi, and 38 samples from different branch villi), monoclonal band patterns of X(P)-derived alleles were observed more frequently than those of X(M)-derived alleles, but almost half of the samples showed polyclonal patterns. Our results suggest that a skewing of XCI exists in the human trophoblast; however, the degree of nonrandomness due to predominant X(P) inactivation appears to be restricted. It is probable that transcription of the X inactivation center (XIC) begins earlier in mice than in humans.
OBJECTIVE: To describe the case of a Japanese woman with combined 17alpha-hydroxylase/17,20-lyase deficiency (congenital adrenal hyperplasia type V) and to discuss possible therapeutic procedures in such patients. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 26-year-old woman with secondary amenorrhea and primary sterility. INTERVENTION(S): Nucleotide sequencing of the P45017alpha gene (CYP17), induction of endometrial maturation with steroid hormone replacement, and ovulation induction with gonadotropin. MAIN OUTCOME MEASURE(S): Nucleotide sequence of CYP17, endometrial thickness and follicle diameter measured by transvaginal ultrasonography, and histologic evaluation of the endometrium. RESULT(S): Two different mutations were detected on CYP17: One was a deletion of the phenylalanine codon (TTC) at either amino acid 53 or 54 in exon 1, and the other was a missense mutation with the substitution of histidine (CAC) by leucine (CTC) at position 373 in exon 6. Repeated histologic evaluations performed during treatment with P consistently revealed an unripe endometrium with glands of the early secretory phase and markedly scanty stroma. Ultrasound examination revealed follicular growth and ovulation after gonadotropin administration, but insufficient thickness of the endometrium. CONCLUSION(S): Ovulation induction was possible in this patient with 17alpha-hydroxylase/17,20-lyase deficiency, but the endometrial response to steroid hormone replacement was extremely poor.
OBJECTIVE: To evaluate the expression of estrogen receptor (ER)-alpha and ER-beta messenger RNA (mRNA) in ovarian endometriosis. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with endometriosis and patients with uterine leiomyoma or carcinoma in situ. INTERVENTION(S): A sample of ovarian endometriotic cyst tissue was obtained from each of the 32 patients during laparoscopic cystectomy. Samples of ovarian tissue and endometrium were obtained from 15 patients during or just after surgery. MAIN OUTCOME MEASURE(S): Expression of mRNA for ER-alpha and ER-beta with use of the reverse transcription-polymerase chain reaction (RT-PCR) and nonradioactive in situ hybridization (ISH) techniques. RESULT(S): Expression of mRNA for ER-alpha and ER-beta was observed in all of the control tissues from the normal endometrium and normal ovaries in the RT-PCR and ISH analyses, although the distribution of positive signals changed in the ISH analysis during different phases of the menstrual cycle. Messenger RNA for ER-alpha was detected in all of the ovarian endometriotic cysts analyzed (19 of 19), but mRNA for the ER-beta was limited (12 of 19) in the RT-PCR analysis. The ISH analysis confirmed the RT-PCR results and revealed that the two estrogen receptors were localized in both epithelial and stromal cells of endometriotic tissues. CONCLUSION(S): The results suggest that predominant expression of ER-alpha in both glandular epithelial and stromal cells may be essential to the development and growth of ovarian endometriosis.
OBJECTIVE: To determine differences between growth patterns of monochorionic and dichorionic twins, and of concordant and discordant twins of both chorionicities. METHODS: We studied 70 cases of concordant twins (24 monochorionic, 46 dichorionic) and 45 cases of discordant twins (25 monochorionic, 20 dichorionic). In each case, growth was measured longitudinally by ultrasound biometry and the growth pattern was depicted. RESULTS: There were no differences in incremental growth between concordant monochorionic and dichorionic twins. The growth curve of concordant twins of both chorionicities was almost the same as that of a singleton until 34 weeks' gestation. However, in the discordant twins, the growth of the larger twin matched the growth curve of a singleton or concordant twin, but the growth of the smaller twin gradually decreased to the range of growth restriction. The growth curves for monochorionic discordant twins appeared to be representative of two groups, one of which had onset of discordancy before 24 weeks. CONCLUSION: It is clinically important to determine chorionicity early in twin pregnancies, to calculate the percentage of discordancy between the fetuses, and to examine longitudinal fetal growth curves in each chorionicity.
We report a case of endomyometriosis arising in the left uterosacral ligament of a 29-year-old woman. The central cavity of the uterine-like mass was lined by pseudo-stratified columnar epithelium and endometrial stroma. The wall of the cyst consisted of bundles of smooth muscle cells. Immunohistochemical analysis demonstrated both alpha-estrogen receptor and progesterone receptor immunoreactivities in the epithelial, stromal and smooth muscle cells. A relatively high proliferating activity was also demonstrated in these cells by Ki-67 immunostaining. These findings suggest that the mass was hormone dependent and had a relatively rapid evolution.
Human epithelial ovarian carcinoma is well-known as a sex steroid-dependent neoplasm, but the possible biological significance of progesterone receptor (PR) in this cancer remains controversial. Recently, two isoforms of human PR, PRA and PRB, have been characterized and different functional characteristics have been reported for these two isoforms. We therefore examined immunohistochemistry (107 cases) and reverse transcription-polymerase chain reaction (RT-PCR) (16 cases) for PRA, PRB, and oestrogen receptor-a (ER-a). Labeling indices (LI) for PRA and PRB were 2.4 and 43.6, respectively, and the difference was statistically significant. PRB LI, but not PRA LI, as well as performance status, stage, and residual tumour turned out to be independent prognostic factors following multivariate analysis. There was also a significant correlation between ER-a LI and PRB LI (r = 0.595, P < 0.0001), suggestive of a possible interaction between these two receptors. RT-PCR also detected the expression of PR isoform transcripts in the same pattern as was observed with immunohistochemistry. Results of these studies indicate that PRA and PRB both mediate distinct pathways of progesterone action in ovarian carcinoma. Moreover, it is important to examine PRB LI as a prognostic factor in the cases of human epithelial ovarian carcinoma.
OBJECTIVE: The appearance of the sinusoidal heart rate pattern found on fetal cardiotocograms has not been fully explained, either physiologically or clinically. In this study we performed power spectral analysis on the sinusoidal heart rate pattern obtained by administration of arginine vasopressin and atropine sulfate to investigate its frequency components in fetal lambs with long-term instrument implantation. STUDY DESIGN: Eleven tests were performed in 4 fetal lambs at 120 to 130 days' gestation. An artificial sinusoidal heart rate pattern was obtained by administration of atropine sulfate and arginine vasopressin in 9 tests. An autoregression model was used to compare the spectral patterns before and during the sinusoidal heart rate pattern. RESULTS: Marked decreases in low-frequency (0.025-0.125 cycles/beat) and high-frequency (0.2-0.5 cycles/beat) areas were observed in the presence of the sinusoidal heart rate pattern. However, there were no significant changes in the very-low-frequency area (0.01-0.025 cycles/beat), which corresponds to the frequency of the sinusoidal heart rate pattern. CONCLUSION: The sinusoidal heart rate pattern may represent a very low-frequency component inherent in fetal heart rate variability that appears when low- and high-frequency components are reduced as a result of strongly suppressed autonomic nervous activity.
Survivin is a novel inhibitor of apoptosis. It has been reported that survivin is expressed during fetal development and in cancer tissues, but its expression has not been reported in adult tissues. We investigated the expression of survivin in the endometria of women with regular menstrual cycles using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, and compared these findings with Bcl-2, an apoptosis inhibitor. Survivin mRNA was detected by RT-PCR in all samples (nine of nine) of endometrium during the secretory phase, but in only four out of seven samples from endometrium during the proliferative phase, and in none of the atrophic endometrium. Immunohistochemistry demonstrated a survivin protein expression that was strongest in the nuclei of glandular epithelial cells during the late secretory phase. In the proliferative phase, glandular epithelial cells were not stained for survivin. The cyclic changes of survivin and Bcl-2 showed an inverse relationship, with Bcl-2 expression being strongest in the proliferative phase and survivin expression being strongest in the secretory phase. The up-regulation of survivin expression may be due to the concurrent rise in progesterone concentrations during the normal menstrual cycle. Moreover, survivin could play an important role independent of Bcl-2 in physiological homeostasis in the normal endometrium.
Estrogens play important roles in the pathogenesis of the great majority of endometrial endometrioid adenocarcinoma. Recently, a novel estrogen receptor (ER), ER beta, has been characterized, but little is known about the status of ER beta in endometrial carcinoma. We therefore examined expression of both ER alpha and ER beta in 45 cases of endometrioid endometrial adenocarcinoma using mRNA in situ hybridization, reverse transcription and polymerase chain reaction (RT-PCR), and immunohistochemistry. We also correlated the findings with various clinicopathologic parameters in these cases to examine their possible biologic significance. Accumulation of mRNA hybridization signals for both ER alpha and ER beta was detected predominantly in the cytoplasm of carcinoma cells, and to a lesser extent in some stromal cells. ER beta mRNA was detected in 16/45 cases (35.6%), and ER alpha mRNA hybridization signals were detected in 36/45 cases (80.0%). Among the 16 ER beta positive cases, 15 cases also had ER alpha mRNA hybridization signals. In the cases that expressed both ER alpha and ER beta, ER alpha mRNA hybridization signals were more widely distributed than ER beta mRNA. In 21 cases, carcinoma cells had ER alpha mRNA hybridization signals but not ER beta mRNA. There was a statistically significant positive correlation between the results of mRNA in situ hybridization and semiquantitative RT-PCR or immunohistochemistry for both ER alpha and ER beta. There were no significant correlations between ER beta mRNA expression and PR labeling index, Ki67 LI, age, or histologic grade. The results from our study indicate that ER beta is coexpressed with ER alpha, and that the estrogenic effects occur predominantly through ER alpha in endometrial carcinomas.