Biomedical subjects
Publications and source records attributed to Y T Chang.
Primary cutaneous plasmacytoma arising in the skin is very rare. The case of a young man suffering from primary cutaneous plasmacytomas, without an underlying disorder, is reported. The clinical, histopathological, electron microscopical and laboratory findings from the case are described.
1. Presynaptic activity in the inhibitory network impinging on the Mauthner (M-) cell was investigated in the goldfish medulla in vivo using extra- and intracellular recordings. The inhibitory presynaptic volley elicited by stimulation of the contralateral vestibular nerve consisted of multiple successive peaks at high frequency (up to 1,000 Hz). Less pronounced multicomponent responses were recorded after antidromic activation of the M-cell. Such high-frequency "oscillatory" field potentials also occurred spontaneously. 2. In intracellular recordings, a subset of inhibitory interneurons showed evoked and spontaneous burst discharge. Burst action potentials were correlated with the peaks in the extracellular volley, suggesting that repetitive firing of these cells is synchronized. Nonbursting cells, on the other hand, fired single action potentials in response to vestibular stimuli and were not activated via the M-cell collateral network. 3. Bursting cells were determined morphologically to be part of the feedback inhibitory circuit. Their responses to stimulation of the contralateral vestibular nerve thus suggest the existence of a crossed excitatory pathway to these interneurons. 4. Vestibular-evoked excitatory postsynaptic potentials (EPSPs) in bursting interneurons had a short latency of 0.781 +/- 0.08 ms (mean +/- SD, n = 18) but reached threshold at 2.25 +/- 1 ms (n = 21). These characteristics are suggestive of a chemically mediated EPSP. Indeed, the evoked synchronous repetitive activity of these cells was prevented by superfusion with excitatory amino-acid receptor antagonists. 5. Bursting neurons showed several characteristics that differentiate them from nonbursting cells, including brief action potentials, plateau responses, and intense spontaneous subthreshold activity. 6. With extracellular recordings, tetanization of contralateral vestibular primary afferents evoked a long-lasting potentiation of oscillatory population responses in 11 of 27 cases. Furthermore in three experiments, the frequency of occurrence of spontaneous bursts was enhanced and a similar facilitation was detected at the intracellular level. 7. We conclude that a subset of interneurons in this inhibitory network is capable of repetitive discharges and that evoked as well as spontaneous firing in this population is synchronized. Although electrical coupling between interneurons may mediate synchronization and intrinsic membrane properties may promote burst activity, our data suggest strongly that repetitive firing requires chemically mediated transmission. Furthermore they indicate that the mechanisms underlying evoked as well as spontaneous bursting in this population show activity-dependent plasticity.
We report mutations of the type II 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) gene in two siblings, male and female, with congenital adrenal hyperplasia caused by classical nonsalt-losing 3 beta HSD deficiency. During childhood, the male sibling, born with ambiguous genitalia, and the female sibling, born with normal genitalia, both manifested symptoms of mild androgen excess; both apparently had normal zona glomerulosa function. Gonadal dynamic study at puberty showed the presence of partial gonadal 3 beta HSD deficiency in both siblings despite their spontaneous pubertal maturation. The 5'-region as well as exons I-II, III, and IV and portions of the adjacent introns of the type II 3 beta HSD gene were amplified by polymerase chain reaction and sequenced. In both siblings and their mother, an identical single nucleotide substitution mutation in intron III, six bases up-stream from exon IV, was identified in one allele. This mutation, G to A at nucleotide 6651, may create a new splicing junction and affect the normal splicing of the messenger ribonucleic acid. In the other allele of both siblings, a missense mutation from GGG (Gly) to AGG (Arg) at codon 129 (G129R) in exon IV was found. We assessed the effect of the G129R missense mutation on enzymatic activity by in vitro analysis of the mutant recombinant enzyme generated by site-directed mutagenesis after its transient expression in COS-1 cells. Using homogenates from transfected cells, the G129R 3 beta HSD enzyme showed a Km value for pregnenolone of 10 +/- 2 mumol/L compared with 1.00 +/- 0.03 mumol/L for the wild-type type II 3 beta HSD enzyme. When dehydroepiandrosterone was used as substrate, the Km value for G129R3 beta HSD was 14 +/- 2 mumol/L compared with 2.1 +/- 0.2 mumol/L for the wild-type II 3 beta HSD enzyme. In addition to an apparent decrease in affinity, the G129R mutation caused a marked decrease in the apparent relative specific activity, thus leading to apparent relative specific efficiencies (relative specific activity/Km) of 2.0% and 4.7% that of the normal type II 3 beta HSD using pregnenolone or dehydroepiandrosterone as substrate, respectively. It appears likely that this low level of activity is sufficient to prevent salt loss, but it is also possible that part of the enzymatic activity comes from the putative remaining percentage of correctly spliced n6651 allele in these patients.
BACKGROUND: Breast cancer developing during pregnancy or lactation is such an infrequent problem that, when it occurs, physicians are confronted with ethical and therapeutic challenges. Moreover, there are very few references to compare or discuss breast cancer in pregnant women in Taiwan. We hope that data from this review will add to our understanding of such difficult problem as well as help improve the treatment of our patients. METHODS: Between 1979 and 1988 the charts of 21 women, who were pregnant or postpartum within one year of the breast cancer diagnosis, were analyzed retrospectively. All of the patients were followed until Dec. 1990. Patients with pregnancy-associated breast cancer were compared with nonpregnant women (199 cases) of similar age who were treated at the same hospital and during the same period. RESULTS: We found no statistical differences in the overall 5-year survival rate between pregnant (57.1%) and nonpregnant (69.6%) groups. It is noteworthy that the time lag was significantly longer in the pregnant group than in the nonpregnant group. A stage-by-stage comparison showed equivalent survival rates between pregnant and nonpregnant patients. The pregnant patients at stage II had a somewhat lower survival rate; however, there was no statistical significance. CONCLUSIONS: The rule of cancer treatment, "early diagnosis followed by aggressive management," is still a key principle to improve the treatment in pregnant women with breast cancer.
Androgen insensitivity syndromes represent one cause of human male pseudohermaphroditism related to defects in the androgen receptor. The formation of a biologically active androgen receptor complex with testosterone and 5 alpha-dihydrotestosterone is required for normal androgen action during fetal development and differentiation of the internal accessory sex glands and external genitalia. Cloning of the human androgen receptor complementary DNA and genetic screening of human subjects with the clinical and biochemical features of androgen insensitivity using the polymerase chain reaction, denaturing gradient gel electrophoresis and nucleotide sequencing techniques have led to the identification of molecular defects in the androgen receptor. The complexity of phenotypic presentation by affected subjects with the complete or partial forms of androgen insensitivity is represented by the heterogeneity of androgen receptor gene mutations which include deletions and point mutations, with the latter causing inappropriate splicing of RNA, premature termination of transcription and amino acid substitutions. The naturally occurring mutations in the androgen receptor of subjects with androgen insensitivity represent a base upon which we can increase our understanding of the structure and function of the androgen receptor in normal physiology and disease.
Inherited adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency is most likely caused by a mutation of the type II 3 beta-HSD gene. Cloning and sequencing of exons I-II, III, and IV and portions of the adjacent introns, amplified by polymerase chain reaction using primers specific for the type II gene, in one male pseudohermaphrodite with salt-wasting classic 3 beta-HSD deficiency congenital adrenal hyperplasia revealed the same mutation in all nine clones of exon IV consisting of a missense mutation at codon 248 [GTC(Val)-->AAC(Asn)] followed by a frameshift mutation at codon 249 [CGA (Arg)-->TA], resulting in a stop codon TAG, and normal sequences of exon I-II and III and the adjacent portions of introns. The same codon 248 and 249 mutations were found on one clone of his mother's DNA, but two other clones revealed normal sequences. These data indicate a homozygous combined missense/frameshift mutation in exon IV of the type II 3 beta-HSD gene resulting in severe salt-wasting adrenal and gonadal 3 beta-HSD deficiency in the patient.
We report pubertal maturation and dynamic studies of gonadotropin and gonadal hormone secretion in long term glucocorticoid-treated siblings with nonsalt-wasting classic adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) deficiency. The 18-yr-old female siblings spontaneously developed thelarche and menarche at 10 and 12 yr, respectively, and manifested irregular menses, hirsutism, and polycystic ovaries at 17 yr. The 16-yr-old male sibling spontaneously developed secondary sex characteristics at age 11 yr and exhibited Tanner IV-V pubic hair, a 6.5 x 3.0-cm surgically repaired penis, and enlarged nonnodular testes. Overnight (2200-0700 h) plasma gonadotropin (every 20 min) and gonadal steroid levels (every 2 h) under ACTH adrenal suppression revealed the following. In the male sibling, there were overall normal Tanner V male LH (3-21 mIU/mL) and FSH (1.2-13 mIU/mL) levels, normal peak frequency and amplitude of LH (70 +/- 62 min and 15 +/- 3 mIU/mL, respectively) and FSH (65 +/- 28 min and 13 +/- 3 mIU/mL), and low normal Tanner V testosterone (T) levels (11.4-17.9 nmol/L). In the female sibling, there were normal follicular phase range LH (10-28 mIU/mL) and FSH (5.1-17.2 mIU/mL) levels, normal peak frequency and amplitude of LH (96 +/- 17 min and 22 +/- 4.5 mIU/mL, respectively) and FSH (62 +/- 27 min, 13 +/- 4 mIU/mL), and early follicular phase estradiol (E2) levels (100-170 pmol/L). The LH-releasing hormone-stimulated LH response was in the normal adult range in the male and normal for the early follicular phase in the female. In contrast, ACTH and adrenal delta 5-steroid responses to CRH administration were elevated in each sibling. Gonadal suppression via Norlutin administration (30 mg/day for 3 days) after prolonged adrenal suppression by dexamethasone resulted in suppression of dehydroepiandrosterone (DHEA) and E2 in the female and DHEA and T in the male. Gonadal stimulation via hCG administration (5000 IU/day for 3 days, im) during continuous adrenal suppression resulted in a low E2 response in the female (200 pmol/L; control, 295-660 pmol/L) and a low T response in the male (15.3 nmol/L; control, 17-39 nmol/L), whereas delta 5-17-hydroxypregnenolone and DHEA levels rose 2- to 4.7-fold in each sibling. In conclusion, despite partial gonadal 3 beta HSD deficiency, the dynamics of gonadotropin and gonadal hormone secretion in these siblings indicate the absence of increased LH secretion, in contrast to the markedly increased ACTH secretion resulting from adrenal 3 beta HSD deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
A 60-year-old uremic patient treated with hemodialysis for 13 years developed acute hypotension during hemodialysis and overt heart failure subsequently in a period of relatively mild hypocalcemia after parathyroidectomy. Blood pressure during hemodialysis was maintained by continuous calcium infusion alone. Cardiomegaly was improved by normalization of serum calcium. The cardiac complication is considered to be exacerbation of the underlying myocardial dysfunction by the acute decline of serum calcium which might be a feature of the 'hungry bone' syndrome. Latent myocardial dysfunction might be exacerbated by only mild hypocalcemia after parathyroidectomy in long-term hemodialysis patients.
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A very rare case of a tubular adenoma of the breast is reported. The patient, 59-year-old woman, was admitted to hospital because of a large, left breast tumor. The tumor, 11 cm in diameter, was adhered to the surface skin. Because a malignancy was suspected, an incisional biopsy was first carried out. A pathologic examination revealed it to be a tubular adenoma, and a simple mastectomy was chosen as the operative procedure because a latent malignancy was not ruled out. The removed tumor was grossly cystic and a histological examination supported the finding that it was a non-malignant tubular adenoma.
Intraoperative staining with methylene blue was employed during parathyroid surgery on 50 glands from 13 patients, 5 with primary and 8 with secondary hyperparathyroidism. Forty-seven out of the 50 glands (94 per cent) were visualized by the staining and 2 out of the 13 patients were revealed to have supernumerary parathyroid glands. Since we started using this technique, there have been no cases of persistent hypercalcemia. The results of this study support the clinical usefulness of this staining procedure for detecting hyperplastic parathyroid glands in both primary and secondary hyperparathyroidism.
Ascending excitatory inputs from the periphery to the ventral dendrite of the goldfish Mauthner (M)-cell are characterized in this report. Direct stimulation of the spinal cord, at strengths suprathreshold for antidromic activation of the M-axon, evoked a graded excitatory postsynaptic potential (EPSP) in the distal ventral dendrite of the cell. This localization was demonstrated by multiple intracellular recordings from the soma and dendritic loci. The EPSP had a relatively long latency (mean = 3.6 ms) and contained multiple components. Furthermore, the EPSP amplitudes were extremely sensitive to frequency, being reduced by more than 50% at frequencies of 1-2 Hz and maximal with interstimulus intervals of 30-60 s. The spinal input is, therefore, likely to be mediated by a polysynaptic pathway. Direct stimulation of the skin surface evoked similar EPSPs, in terms of latency, wave form, graded nature, frequency dependence and spatial distribution on the M-cell ventral dendrite. Thus, the spinal cord and skin inputs probably relay somatosensory information from the trunk to the M-cell ventral dendrite. This notion was further confirmed by an interaction study of the EPSPs evoked from the two sites. We also report that the ventral dendrite does not support active spike electrogenesis, as indicated by the spatial profile of the M-cell antidromic impulse amplitude.
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Nineteen human volunteers with normal pulmonary function and no history of asthma were exposed on two separate days to clean air and to an atmospheric mixture containing ozone (O3), 0.37 ppm, sulfur dioxide (SO2), 0.37 ppm, and sulfuric acid aerosol (B2SO4), 100 micrograms/m3. Subjects were exposed under carefully controlled conditions for two hours. During this period, the subjects alternately exercised for 15 minutes, at a level calculated to double minute ventilation, and rested for 15 minutes. The experimental goal was to determine whether the presence of the copollutants, H2SO4 and SO2, would significantly enhance the irritant potential of ozone, or cause decrements in pulmonary function on the order of 10 - 20 percent. Statistical analysis of the group averaged data suggested that the mixture may have been slightly more irritating to the subjects than was O3 alone. A large percentage of the subjects exhibited small decrements in pulmonary function. The group averaged FEV1.0 (forced expiratory volume in one second) on the exposure day was depressed 3.7 percent from the control value. One might expect O3 alone to depress FEV1.0 by about 2.8 percent under similar exposure conditions.
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Burn mortality statistics may be misleading unless they account properly for the many factors which may influence outcome. In reviewing such factors in our patients, we identified age, total burn area, third degree burn area, prior bronchopulmonary disease, abnormal Pao2, and airway edema as the factors present on admission which best distinguished survivors from nonsurvivors. Using multifactorial probit analysis, we then calculated the contribution of each to the probability of fatal outcome. The resultant six-factor model significantly improved estimation of the probability of fatal outcome when compared to probit analysis based only on the traditional factors of age and total burn area. It also revealed a spectrum of mortality probabilities varying with the additional factors present. Although crucial in comparing different approaches to burn care, consideration of such prognostic factors will not eliminate the need for randomized treatment trials, because other factors, some of which are obscure, may also influence mortality rates in burned patients.
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