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Biomedical subjects

M Shin

Publications and source records attributed to M Shin.

At least 19 recordsLinked to original sources

Relief of hemiballism from a basal ganglia arteriovenous malformation after radiosurgery.

A patient with a 3-year history of progressive hemiballism presented with an unruptured arteriovenous malformation (AVM) in the contralateral caudate nucleus and putamen. PET demonstrated a matched reduction of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in the basal ganglia and adjacent frontal lobe. The patient underwent radiosurgery for the AVM. After a period of no clinical change for 6 months, the movement disorder resolved by month 7 post-treatment. The AVM was successfully obliterated 2 years after irradiation without any significant change in the regional CBF or CMRO2.

Arteriovenous Malformations

Complex gangliosides are essential in spermatogenesis of mice: possible roles in the transport of testosterone.

Mice, homozygous for disrupted ganglioside GM2/GD2 synthase (EC 2.4. 1.94) gene and lacking all complex gangliosides, do not display any major neurologic abnormalities. Further examination of these mutant mice, however, revealed that the males were sterile and aspermatogenic. In the seminiferous tubules of the mutant mice, a number of multinuclear giant cells and vacuolated Sertoli cells were observed. The levels of testosterone in the serum of these mice were very low, although testosterone production equaled that produced in wild-type mice. Testosterone was found to be accumulated in interstitial Leydig cells, and intratesticularly injected testosterone was poorly drained in seminiferous fluid in the mutant mice. These results suggested that complex gangliosides are essential in the transport of testosterone to the seminiferous tubules and bloodstream from Leydig cells. Our results provide insights into roles of gangliosides in vivo.

Animals

Pyridine nucleotide levels in liver of rats fed clofibrate- or pyrazinamide-containing diets.

Hepatic NAD+, NADH, and NADPH were increased significantly 3 days after feeding rats with a 0.25% clofibrate diet, increased further after 8 days, and stayed at the same levels 14 days after feeding the diet. The NAD+/NADH ratio was decreased significantly by feeding the clofibrate diet for 8 days, while the ratio remained unchanged with a 1% pyrazinamide diet. Hepatic quinolinate phosphoribosyltransferase (QAPRTase) (EC 2.4.2.19) activity was increased to 1.8 and 1.3 times that of the control animals in the clofibrate- and the pyrazinamide-fed rats, respectively, while hepatic aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) (EC 4.1.1.45) activity was decreased to 0 and 19% of that of the control animals. The heat-treated liver homogenate from the pyrazinamide-fed rats contained inhibitory activity toward ACMSDase, while no inhibitory activity was found in the liver homogenate of the clofibrate-fed animals. We conclude that these changes of enzyme activities, which seem due to different mechanisms, may contribute to the increase of pyridine nucleotides in the liver of rats fed clofibrate or pyrazinamide.

Animals

Prognostic factors of renal cell carcinoma: a multivariate analysis.

BACKGROUND AND OBJECTIVES: To establish appropriate therapeutic modalities for renal cell carcinoma (RCC), informations on the factors affecting prognosis of patients are essential. For this purpose, multivariate analysis including a large set of variables is necessary. METHODS: Prognostic significance of 14 clinical factors and 19 histologic factors including counting of silver-stained nucleolar organizer regions (AgNORs) were evaluated in 96 patients. Age of patients ranged from 41 to 85 (median 59) yr with a male to female ratio of 4:1. The tumors were staged based on the TNM classification as follows: 7 in stage I, 58 in stage II, 15 in stage III, and 11 in stage IV. RESULTS: The overall and metastasis-free survival rates in all patients were 80.1% and 72.7%, respectively. Multivariate analysis using Cox's proportional hazards model performed on the factors proved to be significant at the univariate analysis. Univariate analysis revealed four clinical factors including presence of macroscopic hematuria, symptoms such as pain and palpable abdominal mass, anemia, and adjuvant therapy, and nine histologic factors, including AgNOR count, to be significant for survival. Multivariate analysis showed that anemia, pathological stage, and AgNOR count were independent factors for overall survival of patients. The AgNOR count, in particular, is the only predictive factor for metastasis-free survival. CONCLUSIONS: Among various clinicopathological factors, anemia, pathological stage, and AgNOR count are significant prognosticators of RCC. The AgNOR count is also predictive factor for metastasis-free survival.

Adult

Medical decision-making and the patient: understanding preference patterns for growth hormone therapy using conjoint analysis.

OBJECTIVES: This study examines two questions that relate to patients' role in medical decision making: (1) Do patients utilize multiple attributes in evaluating different treatment options?, and (2) Do patient treatment preferences evidence heterogeneity and disparate patterns? Although research has examined these questions by using either individual- or aggregate-level approaches, the authors demonstrate an intermediate level approach (ie, relating to patient subgroups). METHODS: The authors utilize growth augmentation therapy (GAT) as a context for analyzing these questions because GAT reflects a class of nonemergency treatments that (1) are based on genetic technology, (2) aim to improve the quality (rather than quantity) of life, and (3) offer useful insights for the patient's role in medical decision making. Using conjoint analysis, a methodology especially suited for the study of patient-consumer preferences but largely unexplored in the medical field, data were obtained from 154 parents for their decision to pursue GAT for their child. RESULTS: In all, six attributes were utilized to study GAT, including risk of long-term side effects (1:10,000 or 1:100,000), certainty of effect (50% or 100% of cases), amount of effect (1-2 inches or 4-5 inches in adult height), out-of-pocket cost ($100, $2,000, or $10,000/year) and child's attitude (likes or not likes therapy). An experimental design using conjoint analysis procedures revealed five preference patterns that reflect clear disparities in the importance that parents attach to the different attributes of growth therapy. These preference patterns are (1) child-focused (23%), (2) risk-conscious (36%), (3) balanced (23%), (4) cost-conscious (14%), and (5) ease-of-use (4%) oriented. Additional tests provided evidence for the validity of these preference patterns. Finally, this preference heterogeneity related systematically to parental characteristics (eg, demographic, psychologic). CONCLUSIONS: The study results offer additional insights into medical decision making with the consumer as the focal point and extend previous work that has tended to emphasize either an individual- or aggregate-based analysis. Implications for researchers and health care delivery in general and growth hormone management in particular are provided.

Adult

Utility of immunohistochemical detection of high molecular weight cytokeratin for differential diagnosis of proliferative conditions of the prostate.

BACKGROUND: Differential diagnosis of adenocarcinoma from other proliferative conditions in the prostate is often problematic. Immunohistochemistry using an antibody (34 beta E12) to high molecular weight cytokeratin, specifically present in basal cells of the prostate, could clearly demonstrate the presence or absence of these cells in the proliferating glands and thus provide an important clue in cancer diagnosis. METHODS: To examine the utility of immunostaining using 34 beta E12, we examined 88 equivocal lesions. Twenty lesions with apparently benign and malignant features were added as controls. We compared the morphologic features of these lesions with their immunoreactivities toward 34 beta E12 on a personal computer display following storage on the MICROPHOT-FXA system. RESULTS: Proliferating glands in all 20 benign lesions had 34 beta E12-reactive basal cells, but none of the malignant lesions did. The equivocal lesions were categorized on morphologic grounds into 2 groups: possibly benign and possibly malignant. Forty-five (51.1%) of the 88 equivocal lesions, were positive for 34 beta E12. These included 35 of the 45 (77.8%) possibly benign lesions and 10 of the 43 (23.3%) possibly malignant lesions. Among the equivocal lesions, 10 considered possibly benign on morphologic grounds showed negative reactivities, and 10 considered possibly malignant showed positive reactivities. Even through comparison on the computer display, no difference in morphology could be discovered between the negative and positive lesions in either group. CONCLUSION: Immunohistochemical procedures using 34 beta E12 are indispensable in the diagnosis of equivocal prostate lesions.

Adenocarcinoma

Effect of thioridazine or chlorpromazine on increased hepatic NAD+ level in rats fed clofibrate, a hypolipidaemic drug.

The effect of the phenothiazines, thioridazine and chlorpromazine, on the increased hepatic NAD+ level of rats fed clofibrate, a hypolipidaemic drug, has been investigated. Short-term (6 days) addition of phenothiazines to the diet negatively affected diet intake and body-weight gain, but increased liver weight and hepatic NAD+ levels, which was synergistic to clofibrate. The phenothiazines were shown to inhibit hepatic peroxisomal fatty acid oxidation in-vivo, as determined by the increased residual catalase activity. In hepatocytes prepared from clofibrate-fed rats, phenothiazines inhibited not only peroxisomal but also mitochondrial fatty acid oxidation to the same extent. In the hepatocytes, NAD+ was maintained at the high level until the phenothiazine concentration was increased to 0.2 mM. The result suggests that the increase of hepatic NAD+ in rats fed clofibrate is not related to peroxisomal fatty acid oxidation.

Animals

NAD+ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa by rat hepatocytes--effect of clofibrate-feeding.

NAD+ biosynthesis from tryptophan in the presence of nicotinic acid or vice versa by rat hepatocytes was investigated. In the control hepatocytes, NAD+ synthesis from tryptophan was not affected by nicotinic acid from 0.026 to 0.26 mM. NAD+ synthesis from nicotinic acid was slightly inhibited with varying concentrations of tryptophan from 0.1 to 1.0 mM. In the clofibrate-treated hepatocytes, NAD+ synthesis from tryptophan was greatly increased (234% of the control), while that from nicotinic acid was decreased (71.2% of the control). Both, NAD+ synthesis from tryptophan and that from nicotinic acid were decreased by the coexisting nicotinic acid or tryptophan. Total amount of NAD+ synthesized from tryptophan and nicotinic acid at their physiological concentrations was significantly higher than that in the control hepatocytes as a result of a large increase of NAD+ synthesized from tryptophan. When the metabolic flux of 0.1 or 0.5mM tryptophan was investigated, the glutarate pathway was suppressed in the clofibrate-treated hepatocytes, the quinolinic acid-NAD+ flux being elevated. Similarly to clofibrate, DEHP and CPP revealed an increase in NAD+ synthesis from tryptophan. Mutual relationship of NAD+ biosyntheses from tryptophan and nicotinic acid in rat hepatocytes is discussed and the relevance with peroxisomal proliferation is suggested.

Animals

[Detection of receptor mRNAs using nonradioactive in situ hybridization].

To understand better the regulatory mechanism of cell function through bioactive substance such as hormones and cytokines, analysis of the gene expression of their receptors at the individual cell level is required. Since the presence of specific mRNA is a good index of gene expression, in situ hybridization (ISH) has been recognized as a powerful tool. Especially, nonradioactive ISH with synthetic oligodeoxynucleotide probe is a safe, quick and highly sensitive method. We have developed a unique method with thymine-thymine (T-T) dimer as a nonradioactive labeling, in which adjacent thymines are dimerized by ultraviolet light irradiation. The T-T dimers in hybrids are immunohistochemically recognized using an anti-T-T dimer antibody. In this article, we will present an example of ISH protocol, which works very well both T-T dimer and digoxigenin-labeled probes.

Animals

Different patterns of p53 mutations in prostatic intraepithelial neoplasia and concurrent carcinoma: analysis of microdissected specimens.

Prostatic intraepithelial neoplasia (PIN) is characterized by intraluminal proliferation of epithelial cells and can be divided into high-grade (HGPIN) and low-grade (LGPIN) lesions. HGPIN is regarded as the most likely precursor of prostatic carcinoma (PCA). Microdissected DNA selectively extracted from paraffin-embedded sections of 29 cases of PCA and 1 benign prostatic hypertrophy were analyzed for p53 mutation by single-strand conformation polymorphism (SSCP) of polymerase chain reaction (PCR)-amplified DNA fragments followed by direct sequencing. These patients had received total prostatectomy (27 cases) or transurethral resection (3 cases). Under direct microscopic observation, DNA was microdissected from 108 lesions: 67 lesions from 22 cases of PIN (55 HGPIN and 12 LGPIN), 29 from 22 cases of PCA, and 12 from 11 cases of adjoining benign glands. Analysis revealed 13 mutations in 10 lesions from six cases. All 13 were point mutations: 7 missense, 5 silent, and 1 nonsense. Mutations were detected in 3 cases (14%) of PIN and 5 cases (25%) of PCA. PIN lesions with p53 mutations were all categorized as HGPIN. Neither LGPIN nor benign glands adjoining PIN and/or PCA had mutations. Two PIN and one PCA lesion in each of two cases had mutations that were different from each other. G-to-A transition was the commonest mutation pattern. The current findings showed that HGPIN, but not LGPIN, and PCA are similar with regard to p53 mutation. The diverse patterns of p53 mutation among HGPIN and PCA lesions suggested multiclonal development of prostatic precancerous lesions.

Amino Acid Substitution

Incidence of prostatic intra-epithelial neoplasia in Osaka, Japan.

High-grade prostatic intra-epithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic carcinoma. A high incidence of its association with cancer has been reported in Western countries. On the other hand, information regarding its incidence is limited in Japan, where the mortality due to prostate cancer is much lower. We reviewed 53 clinical stage T2 or T3 prostatic cancers of Japanese patients living in Osaka, Japan (mean age, 67.2 years). These cases were subdivided into a pre-operatively non-castrated group (34 cases) and a medically or surgically castrated group (19 cases). HGPIN was found in 27 cases. The incidence of HGPIN was significantly lower in the castrated group (21.0%) compared with the non-castrated group (67.6%). In the non-castrated group, patient age, pathological stage, Gleason score, tumor size and serum prostate-specific antigen showed no significant correlation with HGPIN. Advanced pathological stage and tumor size tended to decrease the incidence of HGPIN, although this was not statistically significant. When the study group was limited to stage T2 tumors of the non-castrated group, the incidence of HGPIN was 81.0%. HGPIN in Japan may also be clinically and etiologically significant as a precursor of clinical cancer.

Aged

Thiocyanato and Iodo Complexation of Cadmium(II) Ions in Micellar Solutions of a Nonionic Surfactant Triton X-100

Complexation of the cadmium(II) ion with thiocyanate and iodide ions have been studied by precise titration calorimetry in micellar solutions of a nonionic surfactant Triton X-100 containing 0.4 mol dm-3 NaClO4 as a constant ionic medium at 298 K. With regard to the Cd(II)-SCN- system, the formation of [Cd(NCS)]+ and [Cd(NCS)(SCN)] in aqueous solution and [Cd(NCN)2(SCN)]- in micelles was established, though the complexation in micelles is not extensive. With the Cd(II)-I- system, the formation of [CdI]+, [CdI3]-, and [CdI4]2- was established in aqueous solution together with the formation of [CdI2], [CdI3]-, and [CdI4]2- in micelles. It is revealed that the complexation in micelles is accompanied by relatively large and negative enthalpies, which is ascribed to the enthalpies of transfer of [CdI3]- and [CdI4]2- from aqueous solution to micelles. This suggests that a hydrophobic complex with no capacity to form strong hydrogen bonds in water is favored in micelles.

Journal Article

[Examination of scanning technique for lung cancer screening with helical CT].

As a new application of helical CT scanning we evaluated the parameters for lung cancer screening with an extremely low doses and large helical pitch. On the phantom studies, the image quality obtained with the low dose parameter was not inferior to that of the usual screening technique but artifacts were increased with the large helical pitch. A scanning technique using 120 kv, 40-60mA, 10mmth, 20mm/ sec, and a reconstruction pitch of 2 was used for lung cancer screening (screening parameters) (50 cases), and comparison was made between the detectability of the screening parameters and the routine parameters (120 kv, 200mA, 10mmth, 10-13mm/sec, and a reconstruction pitch of 1-1.3). Detectability with the screening parameters was as follows: nodular lesions (< 5mm in size: 76%. 5-10mm: 90-93% 10mm < 100%), linear lesions: 94-95%, infiltrations: 93-100%. There were no false negative lesions, when the reconstruction pitch of the screening parameters was changed from 1 to 0.25. In conclusion, reconstruction pitch had the most influence on lesion detectability.

Adult

Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system.

Gangliosides, sialic acid-containing glycosphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to lay essential roles in establishment of the nervous system, especially in neuritogenesis and synaptogenesis. However, this has never been tested directly. Here we report the generation of mice with a disrupted beta 1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase; EC 2.4.1.92) gene. The mice lacked all complex gangliosides. Nevertheless, they did not show any major histological defects in their nervous systems or in gross behavior. Just a slight reduction in the neural conduction velocity from the tibial nerve to the somatosensory cortex, but not to the lumbar spine, was detected. These findings suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain. The higher levels of GM3 and GD3 expressed in the brains of these mutant mice may be able to compensate for the lack of complex gangliosides.

Animals

NAD+ biosynthesis and metabolic fluxes of tryptophan in hepatocytes isolated from rats fed a clofibrate-containing diet.

Hepatocytes were isolated from rats fed a diet with or without 0.25% clofibrate, and NAD+ synthesis by the hepatocytes was determined using either [carboxyl-14C]nicotinic acid or [5-3H]tryptophan. NAD+ and total pyridine nucleotides synthesized from [14C]nicotinic acid by the clofibrate-treated cells were not significantly different from those synthesized by the control cells when expressed on the basis of nanomoles per hour per milligram of DNA. On the contrary, NAD+ synthesized from [3H]tryptophan was significantly higher in the clofibrate-treated cells (158% of the control cells) on the basis of nanomoles per hour per milligram of DNA. Clofibrate was inhibitory to tryptophan metabolism as a whole, affecting the glutarate pathway more (decreased to 37% of control) than the kynureninase flux (decreased to 64% of control). As a result, the quinolinate-NAD flux, estimated as the difference in the amounts of tryptophan metabolized by the two metabolic pathways, increased in the clofibrate-treated hepatocytes. The increase in quinolinate during the incubation was 8 times more in the clofibrate-treated cells than in the control cells, which confirmed alteration in the metabolic fluxes of tryptophan in the clofibrate-treated cells. Hepatic quinolinate phosphoribosyltransferase (EC 2.4.2.19) activity increased with dietary clofibrate and returned to the control level 1 week after removing clofibrate from the diet. Nicotinate phosphoribosyltransferase (EC 2.4.2.11) and NAD+ glycohydrolase (EC 3.2.2.5) activities remained unchanged with dietary clofibrate.

Animals