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A patient is presented with a large pituitary adenoma that was successfully treated with a Le Fort I osteotomy in combination with mandibulotomy.

Our recent work demonstrated functional Fas expression on human osteoblasts, and the histologic examination of the periarticular osteoporosis region in patients with rheumatoid arthritis (RA) showed apoptosis in osteoblasts. High concentrations of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6--which are thought to increase bone resorption--have been determined in RA synovium. We investigated the effect of these cytokines on the Fas-mediated apoptosis of human osteoblasts. The human osteoblastic cell line MG63 and human primary osteoblast-like cells from bone biopsy specimens were used as human osteoblasts. Fas expression on these cells was examined by flow cytometry, and Fas-mediated apoptosis induced by anti-Fas immunoglobulin M (IgM) was determined by a chromium 51 release assay, the presence of cells with hypodiploid DNA, staining with Hoechst 33258 dye, and the detection of DNA fragmentation on agarose gel electrophoresis. The proliferation of osteoblasts was analyzed by a tritiated thymidine incorporation assay. Spontaneous apoptosis was not found on cultured osteoblasts. The apoptosis of human osteoblasts was not induced by TNF-alpha, IL-1beta, or IL-6 alone in the absence of anti-Fas IgM. In addition, proliferation of the cells was not affected by these cytokines. Fas was constitutively expressed on unstimulated osteoblasts, and treatment of these cells with IL-1beta or TNF-alpha significantly augmented Fas expression. Human osteoblasts were committed to apoptosis with anti-Fas IgM, and the treatment of both IL-1beta and TNF-alpha markedly increased Fas-mediated apoptosis. TNF-alpha augmented both Fas expression and Fas-mediated apoptosis more efficiently than did IL-1beta. In addition, an additive effect on both Fas expression and Fas-mediated apoptosis was demonstrated when TNF-alpha and IL-1beta were added to osteoblasts. IL-6 influenced neither Fas expression nor the Fas-mediated apoptosis of osteoblasts. Furthermore, no synergistic effect of IL-6 with IL-1beta or TNF-alpha was observed. IL-1beta, TNF-alpha, or IL-6 did not change Bcl-2 expression. Our results suggest that IL-1beta and TNF-alpha regulate osteoblast cell number by up-regulating the Fas-mediated apoptosis of osteoblasts, one of the putative mechanisms inducing periarticular osteoporosis in patients with RA.

Previously we reported an original method of visualizing the shape of yeast nuclei by the expression of green fluorescent protein (GFP)-tagged Xenopus nucleoplasmin in Saccharomyces cerevisiae. To identify components that determine nuclear structure, we searched for mutants exhibiting abnormal nuclear morphology from a collection of temperature-sensitive yeast strains expressing GFP-tagged nucleoplasmin. Four anu mutant strains (anu1-1, 2-1, 3-1 and 4-1; ANU=abnormal nuclear morphology) that exhibited strikingly different nuclear morphologies at the restrictive temperature as compared to the wild-type were isolated. The nuclei of these mutants were irregularly shaped and often consisted of multiple lobes. ANU1, 3 and 4 were found to encode known factors Sec24p, Sec13p and Sec18p, respectively, all of which are involved in the formation or fusion of intracellular membrane vesicles of protein transport between the endoplasmic reticulum (ER) and the Golgi apparatus. On the other hand, ANU2 was not well characterized. Disruption of ANU2 (delta anu2) was not lethal but conferred temperature-sensitivity for growth. Electron microscopic analysis of anu2-1 cells revealed not only the abnormal nuclear morphology but also excessive accumulation of ER membranes. In addition, both anu2-1 and delta anu2 cells were defective in protein transport between the ER and the Golgi, suggesting that Anu2p has an important role in vesicular transport in the early secretory pathway. Here we show that ANU2 encodes a 34 kDa polypeptide, which shares a 20% sequence identity with the mammalian epsilon-COP. Our results suggest that Anu2p is the yeast homologue of mammalian epsilon-COP and the abrupt accumulation of the ER membrane caused by a blockage of the early protein transport pathway leads to alteration of nuclear morphology of the budding yeast cells.

We report a 65-year-old woman with thyrotropin (TSH) secreting pituitary adenoma, who was diagnosed based on the lack of inhibition of serum TSH despite an increased serum free thyroxine (T4), a low response of serum TSH to thyrotropin releasing hormone, and a pituitary tumor as revealed by magnetic resonance imaging. The pituitary adenoma was, however, inoperable due to chronic respiratory failure. The treatment with octreotide in a dose of 100 microg b.i.d. resulted in inhibition of serum TSH and free T4 to euthyroid levels and considerable shrinkage of the pituitary tumor. These effects were continued over 8 months after the start of octreotide therapy without any adverse effects. These findings add further evidence that octreotide is useful for treating inoperable TSH secreting pituitary adenoma.

Apoptosis, a physiological process of cell death, may modulate the mass of the thyroid gland. We investigated the role of apoptosis and the possible involvement of Fas/Fas ligand (FasL) system in apoptosis during goiter formation and involution in a rat model of goiter. Rats were fed a low iodine diet and a goitrogen, 6-propyl-2-thiouracil, to induce goiter. Rats with goiter were then fed a high iodine diet to study the phase of involution. We examined the presence of apoptosis by electron microscopy (EM) and terminal deoxy-UTP nick end labeling (TUNEL). We also investigated the association between Fas and FasL expression and thyrocyte apoptosis using immunohistochemistry and Western blotting. To evaluate the proliferation of thyrocytes, proliferating cell nuclear antigen was examined immunohistochemically. The number of apoptotic cells increased during goiter formation and the early stage of involution, which were also associated with increased number of Fas-positive thyrocytes, and some of these cells contained TUNEL-positive nuclei. However, the expression of FasL was almost constant throughout the experiment. Proliferating cell nuclear antigen/TUNEL ratio markedly increased during goiter formation but decreased particularly during the late stage of goiter involution. Our results indicate that apoptosis of thyrocytes is a main factor of cell loss during goiter formation and involution and suggest that the Fas/FasL system is involved in the induction of apoptosis of these cells. Moreover, the delicate balance between apoptosis and cell proliferation may play an important role in the control of thyroid gland mass.

To ascertain the prevalence of childhood and adolescent atopic dermatitis in a Japanese population, we clinically observed the total body of 5 to 6-year-old children (994 cases), 7 to 9-year-old children (1,240 cases), 10 to 12-year-old children (1,152 cases), 13 to 15-year-old children (1,670 cases), and 16 to 18-year-old adolescents (2,159 cases). The examination was performed in the spring of 1994-96, when exacerbation of childhood and adolescent atopic dermatitis most frequently occurs in Japan. Atopic dermatitis was observed in 24% of the 5 to 6-year group, in 19% of the 7 to 9-year group, in 15% of the 10 to 12-year group, in 14% of the 13 to 15-year group, and in 11% of the 16 to 18-year group. The prevalence of atopic dermatitis in 9 to 12-year-old children was two times and in 18-year-old adolescents five times as high as in similar age groups examined 20 years ago.

Thyroid hormone (T3) is essential for normal bone growth and bone metabolism. T3 stimulates bone formation directly through T3 receptors in osteoblasts. T3 also stimulates bone resorption by osteoclasts probably secondary through osteoblasts. In thyrotoxicosis accelerated bone formation and resorption resulted in high turn-over bone loss. Bone metabolic markers elevate reflecting thyrotoxic state. Normalizing thyroid hormone level at least partially restore bone mineral content. In patients under thyroid hormone replacement therapy or TSH suppression therapy TSH and free thyroid hormones should be monitored to prevent unnecessary bone loss. Especially in postmenopausal women with thyrotoxicosis or thyroid hormone therapy the assessment of bone mineral content is required.

Recent studies suggest a protective effect of glucocorticoid against progression of bone erosion and periarticular osteoporosis in patients with rheumatoid arthritis (RA), although this steroid hormone itself is believed to increase bone loss. To understand the antagonistic effect of glucocorticoid for osteopenic process in RA patients, we examined the effect of dexamethasone on Fas-mediated apoptosis of cultured human osteoblasts induced by either anti-Fas IgM or activated peripheral blood mononuclear cells (PBMC). Human osteoblastic cell line MG63 and primary osteoblast-like cells obtained from biopsy specimens were used in this study. PBMC isolated from healthy donors were cultured with or without recombinant interleukin-2 (rIL-2) followed by 12-O-tetradecanoyl-phorbol 13-acetate (PMA) with ionomycin in the presence or absence of dexamethasone. Fas was functionally expressed on MG63 and primary osteoblast-like cells, and treatment of these cells with dexamethasone affected neither Fas expression nor anti-Fas IgM-induced apoptosis. Activated PBMC expressing membrane-type Fas ligand (mFasL) efficiently killed both MG63 and primary osteoblasts-like cells, and the addition of human Fas chimeric protein (hFas-Fc) significantly diminished the cytotoxicity, indicating that interactions between mFasL of activated PBMC and Fas on human osteoblasts induce apoptosis of the latter. Although dexamethasone did not affect apoptosis of MG63 and primary osteoblast-like cells induced by anti-Fas IgM, treatment of activated PBMC with dexamethasone markedly inhibited both mFasL expression and cytotoxicity of these cells against human osteoblasts, suggesting that dexamethasone preferentially acts not on osteoblasts but PBMC. Cultured supernatants from activated PBMC induced apoptosis of human osteoblasts and the addition of hFas-Fc also inhibited the cytotoxicity of the supernatants. In addition, soluble form FasL (sFasL) was detected in the supernatants of activated PBMC. Furthermore, both the cytotoxicity and sFasL concentration of cultured supernatants of activated PBMC incubated with dexamethasone was significantly lower than that in the absence of dexamethasone. Our data suggest that glucocorticoid suppresses the apoptotic process of osteoblasts by inhibiting the expression of both mFasL and sFasL derived from activated PBMC, mediating a protective effect against periarticular bone loss and bone erosion in inflammatory arthritis such as RA.

Preoperative therapy with octreotide, a long-acting somatostatin analog, suppresses GH hypersecretion, shrinks GH-producing tumors and leads to an improvement in subsequent surgical remission in acromegalic patients. A continuous infusion of octreotide has demonstrated more persistent suppression of GH secretion than intermittent injections, and only a few studies were reported on the effect of the tumor shrinkage with a continuous infusion of a small dose of octreotide. We therefore investigated the preoperative effects of small doses of octreotide (120-240 micrograms/day) administered continuously (with a subcutaneous infusion pump) over a short period (2 or 4 weeks) in nine untreated acromegalic patients. Octreotide therapy resulted in suppression of serum GH and IGF-1 concentrations in 8 out of 9 patients and reduction in pituitary tumor size measured by MRI in all patients (by 7.9 to 38.5%). In particular, considerable reduction in tumor size (more than 20%) occurred in 6 of 9 patients. In three patients assessed serially throughout the preoperative period, reduction in tumor size was noted within only one week after the start of octreotide therapy and reduction rate more than 20% was obtained within the first two weeks. In one patient, suprasellar tumor expansion totally disappeared after such therapy. Our results indicate that short-term continuous subcutaneous infusion of a small dose of octreotide results in not only inhibition of GH hypersecretion but also shrinkage of tumor size prior to surgery.

We investigated the cellular and humoral interactions between peripheral blood mononuclear cells (PBMCs) and human osteoblasts, leading to apoptosis of osteoblasts. Human osteoblastic cell line MG63 and human primary osteoblast-like cells obtained from biopsy specimens were used in this study. PBMCs were isolated from healthy donors and cultured with or without stimulation by recombinant interleukin-2 followed by 12-o-tetradecanoylphorbol 13-acetate with ionomycin. Fas was functionally expressed on MG63 and primary osteoblast-like cells. Activated PBMCs expressed Fas ligand (FasL) strongly on their surface and killed MG63 and primary osteoblast-like cells. Cultured supernatants of activated PBMCs also induced apoptotic cell death of MG63 and primary osteoblast-like cells. In contrast, both unstimulated PBMCs and cultured supernatants of unstimulated PBMCs did not induce apoptosis of these cells. Furthermore, the cytotoxic effect and induction of apoptosis against MG63 and primary osteoblast-like cells by activated PBMCs and cultured supernatants were inhibited significantly by human Fas chimeric protein. Our data showed that human osteoblasts expressed Fas fuctionally and both membrane-type and soluble form FasL from activated PBMCs induced apoptosis of these cells, providing the one possible mechanism of bone loss in inflammatory diseases such as rheumatoid arthritis.

A 40-year-old woman with adrenal insufficiency was clinically diagnosed and examined with human corticotropin releasing hormone (CRH). This patient with secondary hypo-adrenalism has shown a normal serum cortisol response to exogenous ACTH administration and has been examined with CRH, lysine-vasopressin (LVP) and insulin tolerance test (ITT), respectively. Success in secreting ACTH in response to both CRH and LVP tests, but not ITT, suggests that this disorder was possibly due to a hypothalamic CRH deficiency rather than pituitary corticotroph dysfunction. A combination of the CRH test and ITT has come to play an increasingly significant role in the diagnosis and differential diagnosis of isolated ACTH deficiency syndrome.

YM17E (1,3-bis[[1-cycloheptyl-3-(p-dimethylaminophenyl)ureido]methyl]ben zene dihydrochloride) was found to be a potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT) in rabbit liver and intestine microsomes. Dixon plot analysis revealed that YM17E inhibited microsomal ACAT in a non-competitive manner. YM17E induced a marked decrease in serum cholesterol, especially in non-high-density lipoprotein (HDL) fractions, in cholesterol-fed rats and rats fed normal chow. Measurement of bile secretion after oral administration of YM17E in cholesterol-fed rats showed that the drug markedly accelerated the secretion of bile acids and neutral sterols. Furthermore, absorption of [3H]cholesterol from the gut of cholesterol-fed rats was significantly inhibited by YM17E. From these results, the hypocholesterolemic activity of YM17E in these animals resulted from both a decrease in cholesterol absorption from the gut and the stimulation of excretion of cholesterol from the liver into bile. However, YM17E caused secretory diarrhea in beagle dogs at near lipid lowering doses. When YM17E was administered at the same total dosage but divided into 5 daily administrations, the incidence of diarrhea was significantly reduced while its cholesterol lowering effect became stronger. These results suggest that the inhibition of intestinal and/or liver ACAT increases the risk of diarrhea development which, however, can be avoided by controlled drug administration in beagle dogs.

We report a 50-year-old female who suffered from reversible hypothyroidism accompanied by isolated ACTH deficiency. There were no findings indicating a complication of autoimmune thyroiditis. Replacement of maintenance dose of glucocorticoid not only led to improvement of thyroid function, but also caused a transient decrease in T3 and an increase in reverse T3, suggesting that chronic cortisol deficiency may impair thyroid function, and that the maintenance dose, as well as pharmacological doses of glucocorticoids may influence T4 deiodination. The findings of this case suggest that thyroid function should be re-evaluated to avoid unnecessary replacement of thyroid hormone, a few months after glucocorticoid replacement.

The purpose of this study was to evaluate the distribution of parathyroid hormone-related peptide (PTHrP) in human thyroid tissues. The presence of PTHrP was studied immunohistochemically in 107 consecutive patients with human thyroid tumours. PTHrP expression was revealed in 97.6 per cent of carcinomas, but not in paranodal normal thyroid epithelial cells. Although there were no differences in the incidence of PTHrP positivity among papillary, follicular, and anaplastic carcinoma cases, PTHrP expression levels were correlated with the growth pattern of thyroid cancer. Strong immunopositivity was detected in 67.3 per cent of papillary growth tissues in papillary carcinomas. A tissue growth pattern consisting of colloid-absent follicles had a high incidence of strong immunopositivity irrespective of the histological type of tumour. Anaplastic carcinoma without colloid production also showed strong immunoreactivity in all cases. In contrast, a growth pattern of colloid-rich follicles did not show strong immunopositivity in either papillary or follicular carcinomas. Follicular adenomas showed positive immunostaining in only one case, and no adenomatous goitres showed PTHrP antigens. In situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) revealed strong PTHrP mRNA in thyroid cancer tissues, but not in normal thyroid tissues. PTHrP expression was not associated with metastasis, calcification, or hypercalcaemia in thyroid cancers. These results suggest that the expression of PTHrP in human thyroids is closely related to the malignant alteration of normal thyroid epithelial cells, especially in the growth pattern of thyroid carcinoma tissues.

To examine whether suppressive doses of thyroxine have any adverse effects on bone, we evaluated various bone metabolic markers (lectin-precipitated alkaline phosphatase, osteocalcin, carboxyl-terminal region of type I collagen propeptide, tartrate-resistant alkaline phosphatase, and urinary excretion of hydroxyproline and pyridinium crosslinks), incidence of vertebral deformity, total body and regional (lumbar spine and radius) bone mineral densities (BMDs), and rates of bone loss in 24 late postmenopausal (more than 5 years after menopause) women who were treated with levothyroxine (L-T4) after total thyroidectomy for differentiated carcinoma. Depending on the clinical records, including serum TSH levels measured by immunoradiometric assay, these patients were divided into two groups. One group of patients was given suppressive doses of L-T4 (TSH < 0.1 mU/L, n = 12) and the other group was given nonsuppressive doses of L-T4 (TSH > 0.1 mU/L, n = 12). There was no difference in bone metabolic markers and incidence of vertebral deformity between the groups. In patients with TSH suppression, Z-scores of BMDs calculated from age-matched healthy women (n = 179, aged 55 to 80) were nearly in the zero range of values (0.077 at total body, 0.228 at lumbar spine, and -0.117 at trabecular region of lumbar spine). The rate of bone loss in TSH-suppressed patients (-0.849 +/- 0.605%/year) was not significantly different from that of nonsuppressed patients (-0.669 +/- 0.659). These prospective and cross-sectional data suggest that long-term levothyroxine therapy using suppressive doses has no significant adverse effects on bone.

Parathyroid hormone-related peptide (PTHrP) expression is associated with the histological type in pituitary tumor, but not in thyroid carcinoma. However invasive and metastatic tumors showed intense PTHrP staining in both pituitary and thyroid tumors. Analysis of the established metastatic rat pituitary tumor cell line showed that PTHrP plays a crucial role in in vivo cell proliferation closely related to worsening of malignant transformation and neovascularization in a paracrine fashion.

Personal identification from dentures is one of the main method used in the field of forensic odontology. When examining whether a denture left at investigation scene belongs to an unknown set of skeletal remains, it is not difficult to establish identity between the partial denture and the jaw of the skull by comparison of the number and kind of defective teeth and the degree of fit of the retainer to the abutment teeth. However, it is more troublesome to demonstrate identity between a complete denture and a skull since the morphological characteristics of the denture base, including the arrangement of the artificial teeth, have to be compared with those of the surfaces of the jawbones, which cannot be observed from the outside. In cases like this, superimposition and X-ray computed tomography are effective for establishing proof of identity. The method of superimposition involves taking an impression of the upper jaw to prepare a plaster model. A photograph of the denture applied to the plaster model is then taken and another photograph of the plaster model is obtained after removal of the denture under the same conditions. The former photo is printed on a transparent film and then superimposed on the latter. This method is useful for comparison between the arrangement of artificial teeth and the crest of the alveolar ridge, and between the shape of the polished (external) surface of the denture and the shape of the alveolar ridge.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexamethasone regulation of PTHrP expression has been studied in an epidermal squamous cancer cell line COLO 16, which secretes immunoreactive PTHrP into conditioned medium. Dexamethasone was found to suppress PTHrP expression in a time- and dose-dependent manner, which was reversible upon removal of dexamethasone. The half-maximal effective concentration of dexamethasone was 1 nM and an effect of dexamethasone on PTHrP mRNA was first observed after 2 h of treatment, with maximal inhibition by 6 h. Dexamethasone action on PTHrP expression was steroid specific since progestin, 5alpha-dihydroxytestosterone and oestrogen did not regulate PTHrP expression in COLO 16 cells. The gluocorticoid/progesterone receptor antagonist RU486 inhibited the dexamethasone effect, indicating glucocorticoid receptor-mediated regulation of PTHrP expression. The half-life of PTHrP mRNA in COLO 16 cells was approximately 120 min and was not altered by treatment of cells with dexamethasone. Nuclear run-on assays revealed that dexamethasone reduced PTHrP gene transcription in COLO 16 cells. Transient transfection assays with a series of reporter gene constructs encompassing 3.5 kb of the 5' end of the PTHrP gene failed to identify a region of the gene responsible for glucocorticoid down-regulation. PCR of reverse-transcribed RNA from COLO 16 cells revealed that dexamethasone down-regulated transcripts driven from all three promoters (i.e., the TATA promoters 5' to exons I and IV and the GC-rich promoter 5' to exon III) of the human PTHrP gene.

Aldolase deficiency of red blood cell is a rare cause of hereditary hemolytic anemia and now there exists only three patients in the world. We had a 24-year-old man operated on for gallbladder stone secondary to this uncommon disease. He underwent a cholecystectomy under general anesthesia combined with thoracic epidural block, using isoflurane, fentanyl, vecuronium, midazolam and lidocaine. During the surgery serum concentrations of bilirubin, free hemoglobin and LDH showed no change, suggesting a lower incidence of drug-induced hemolysis in the case of aldolase deficiency than in other enzyme deficiency. This fact also provides a useful guide to the choice of anesthetics and related agents. In the postoperative period, however, we found a hemolytic response to fever with a drop in hemoglobin level to 2.5 g.dl-1. Aldolase activity of his red cell is heat labile and an increase in body temperature may aggravate a disturbance in the glycolytic pathway leading to hemolytic crisis. It is thus important to prevent the body temperature from rising when a patient is suffering from hemolytic anemia due to red cell aldolase deficiency.

The regulation of PTHrP expression and production by transforming growth factor-beta (TGF beta) has been investigated in an epidermal squamous cancer cell line COLO 16. TGF beta 1 treatment increased steady-state levels of PTHrP mRNA and concentrations of PTHrP immunoreactivity in conditioned medium in a time- and dose-dependent manner with a half-maximal effect at 40 pM. An effect of TGF beta 1 on PTHrP mRNA was observed first after 4 h treatment and continued to increase up to 48 h with a concomitant increase in PTHrP immunoreactivity in the culture medium. TGF beta 1 was found to stabilize PTHrP mRNA as assessed by actinomycin C1 experiments. In addition, a direct effect of TGF beta to increase PTHrP transcription was indicated by nuclear run-on and transient transfection experiments using a CAT promoter/expression construct encompassing the region -1100 bp to -20 bp from the initiating AUG of the human PTHrP gene. The conditioned medium from COLO 16 cells was also shown to contain both latent and active TGF beta at concentrations of 160 pM and 16 pM, respectively, in 72 h conditioned medium. A neutralizing antibody to TGF beta 1 (and TGF beta 2) decreased the level of immunoassayable PTHrP in the medium.

The fluorine introduced analog of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 [26,27-F6-1,25-(OH)2D3] is 5-10 times more potent than 1,25-(OH)2D3 in vitamin D-deficient rats and chicks. In this study we established cultures of human bone cells in order to elucidate the mechanisms responsible for the higher activity of this compound. The effects of 26,27-F6-1,25-(OH)2D3 and 26,26,26,27,27,27-hexafluoro-1,23(S),25-trihydroxyvitamin D3[26,27-F6-1,23(S),25-(OH)3D3], the postulated main metabolite of 26,27-F6-1,25-(OH)2D3, were assessed by the response of alkaline phosphatase (ALP) activity. 26,27-F6-1,25-(OH)2D3 increased ALP activity in a dose-related fashion, from a concentration of 10(-11) M and caused a 3-fold elevation at a concentration of 10(-9) M. To achieve the same stimulating effect on ALP activity, the required dose of 26,27-F6-1,25-(OH)2D3 was 100 times less than that of 1,25-(OH)2D3. Analysis of the receptors of these cells revealed that they have specific receptors for 1,25-(OH)2D3, which have a dissociation constant of 0.9 x 10(-10) M. The competitive binding assays of 26,27-F6-1,25-(OH)2D3 on these receptors showed that binding ability of 26,27-F6-1,25-(OH)2D3 is almost the same as that of 1,25-(OH)2D3. Therefore, receptor binding affinity does not account for the higher potency of 26,27-F6-1,25-(OH)2D3. The trihydroxylated compound, 26,27-F6-1,23(S),25-(OH)3D3 revealed almost the same stimulatory activity on ALP activity in these cells. The most likely explanation for the higher activity of 26,27-F6-1,25-(OH)2D3 than 1,25-(OH)2D3 is that 26,27-F6-1,25-(OH)2D3 is metabolized to 26,27-F6-1,23(S),25-(OH)3D3, which has almost the same activity as 26,27-F6-1,25-(OH)2D3 in target tissues, whereas 1,25-(OH)2D3 is degraded to less active metabolites such as 1,24,25-(OH)3D3.

26,27-F6-1,25(OH)2D3 has a higher potency both in vivo and in vitro systems, and longer duration of action in vivo, instead of almost equal binding to 1,25(OH)2D3 receptor and comparatively short serum half-life. To date, the mechanism of higher action is not known, but using these analogues as a mirror we might be able to elucidate the mechanism of action or the metabolism of the kidney hormone, 1,25(OH)2D3.

Our statistical study revealed that testicular neoplasms seemed to increase in incidence during a 28-year-period from 1950 to 1977 in Japan. Annual deaths from testicular neoplasm were approximately 50 in the first 4 years of the period and increased to approximately 200 in the last 3 years. Age-adjusted mortality rate increased from 1.2 per million to 3.3 per million during the period. Untoward effects of CDDP were surveyed among 47 patients with urogenital malignancy who received anticancerous chemotherapies of CDDP alone or in combination with other drugs at the Kyoto University Hospital or its affiliates in the recent 3 years. About 95% of the patients suffered from such gastro-intestinal ailments as loss of appetite and vomiting. Bone marrow suppression was confirmed by laboratory studies among a third of the patients. Nephrotoxicity indicated by 25 to 50% reduction in creatinine clearance was induced in 6 patients-transitory in 4 and permanent in the remaining. Fifty percent survival rate was 18 months and 5 survived more than 2 years with NED among 21 patients with stage II or stage III testicular cancer treated at the Hospital or its affiliates since 1975, while the rate was 6 months among 10 patients during the period from 1965 to 1974. These improvements was thought to be brought in by adopation of VAB or PVB chemotherapy.

Acute ethanol ingestion (5 g/Kg) led to an acceleration of lipid peroxidation and reduction in non-proteinic free sulfhydryl (NPFSH) levels in the rat liver and kidney. In the liver, progressive changes of these phenomena were inversely related, and maximal effects were observed 6 hr after ethanol ingestion. Unlike the liver, in the kidney, there was a rapid fall in NPFSH content followed by constantly reduced levels during ethanol intoxication, whereas acceleration of lipid peroxidation was detected only after 6-8 hr of ethanol. In addition, a lower dose (2 g/Kg) which caused no significant change in the liver, was effective in reducing renal NPFSH, but not in enhancing lipid peroxidation. These results suggest that acceleration of lipid peroxidation may not be required for the NPFSH decrease, at least in case of kidney.

A 51-year-old man was admitted with the complaint of left scrotal swelling (11 x 5 x 5 cm). He had undergone left nephrectomy and removal of tumor thrombus in inferior vena cava due to renal cell carcinoma. Nine months after the nephrectomy, left scrotal enlargement was noticed. Left high orchiectomy was performed on January 20, 1988. A clear cell carcinoma was present in spermatic cord and pampiniform plexus histologically but testis and epididymis were intact. Renal cell carcinoma seemed to disseminate retrograde through the spermatic vein to spermatic cord. The metastatic tumor of spermatic cord from renal cell carcinoma is very rare and this case is the fifth case in the Japanese literature.

A statistic survey was carried out on the patients, diseases, and operations experienced at the urological ward of Kyoto University Hospital during the years of 1977 to 1982.

Between June, 1984 and May, 1988, 22 cases of renal injury were treated. There were 13 males and 9 females. The most frequent causes were traffic accidents (13 cases) and the next were falls (7 cases). Associated injuries were seen in 9 cases, including bone fractures, head injuries, liver lacerations, hemothorax and splenic laceration. Out of the 22 patients, there were 13 cases of renal contusion, 6 cases of renal laceration, 1 case of renal rupture and 2 cases of pedicle injury. Evaluation was made by IVP, CT, arteriography and so on. Arteriography was the most useful method whether immediate surgery should be done or not. Three cases were treated surgically (2 nephrectomies for rupture and pedicle injury, 1 drainage for laceration). The other cases were treated conservatively and no complications have been seen.

Adjuvant chemotherapy mainly consisting of cisplatin, adriamycin and mitomycin C was administered to 17 patients after cystectomy for bladder tumor (chemotherapy group). Seventeen concurrently treated patients did not receive adjuvant chemotherapy (control group). From the comparison of survival curves of these two groups, the following results were obtained. 1) Survival curves of the patients in all stages did not differ significantly between chemotherapy and control groups. 2) Among patients in stage pT3, pT4 and/or N+, survival of the chemotherapy group seemed to have some advantage over that of the control group, but the survival curves did not differ significantly between these two groups. 3) Among patients in N+, survival of the chemotherapy group was far better than that of the usual cases. Review of the literature on adjuvant chemotherapy after cystectomy for bladder tumor revealed the necessity of randomized study to determine whether adjuvant chemotherapy is effective.

Recently, the study of the physiological role of the essential trace elements is being emphasized. Some environmental and disease factors has been demonstrated to perturb trace element homeostasis. A number of recent studies have described alterations in serum copper levels (SCLs) and serum zinc levels (SZLs) in human cancer patients and the relationship between the magnitude of their perturbation and disease activity. This report describes SCLs, SZLs and SCL/SZL ratios in patients with malignant neoplasms of the urogenital tract at various clinical stages and the relationship of the levels of these trace elements to disease activity. According to SCLs before treatment, patients with renal cell carcinoma appeared to be separated into two groups, normal SCL group and higher SCL group. In the higher SCL group, patients generally displayed increased erythrocyte sedimentation rate, CRP, alpha 2 globulin, beta 2 microglobulin, ferritin and CEA. In this group, SCL was a useful index of disease activity. In the normal SCL group, SCLs remained within normal limit even in patients with advanced disease. In renal cell carcinoma, SZLs did not reflect disease activity. In transitional cell carcinoma of the upper urinary tract, patients with metastasis had significantly elevated SCLs and significantly decreased SZLs, compared with normal controls or patients without metastasis. In transitional cell carcinoma of the bladder, no distinct relationships were observed between these trace elements and extent of malignancy. But there was a trend toward increasing SCLs and decreasing SZLs with progressing stage and SCL/SZL ratios fairly reflect stage of disease. Patients with prostatic cancer had nearly normal SCLs and SZLs, although there were a few exceptions. Testicular cancer patients with distant metastasis had significantly elevated SCLs and initially high SCLs decreased in patients responding to therapy and increased again in relapse. SZLs and, hence, SCL/SZL ratios had no relationship to activity of testicular cancer. Currently there is no satisfactory way of following the progress of malignancies of the urogenital tract except prostatic cancer with elevated acid phosphatase and non-seminomatous testicular tumors until the secondary tumor can be detected radiographically. Our study suggests that these trace element might be a useful indicator of disease activity of some of the urogenital malignancies.

Cisplatin was administered to 11 patients as a continuous infusion, 25 mg/m2/day for 1 to 4 days. Total and filterable platinum in plasma were monitored for 12 courses and a pharmacokinetic study was carried out in 7 patients by computerized nonlinear least-squares analysis. Following interruption of the infusion, the decrease of plasma filterable platinum was biphasic, with initial and terminal half-life of 21.6 +/- 11.4 min and 31.7 +/- 27.1 hr. Filterable platinum was still detectable in plasma 24 hours after the end of infusion. The total AUC exposure of filterable platinum for 24 hrs, 48 hrs and 96 hrs infusion were 3.67 micrograms.hr/ml, 13.68 micrograms.hr/ml and 14.75 micrograms.hr/ml, which were at least 3-fold higher than that observed for the short-term infusion of equal dose in literature. Gastrointestinal toxicity was evaluated and compared with short-term infusion of equal dose. In the continuous-infusion patients, the reduction of vomiting was observed but the duration of nausea was not shortened.

A case of rhabdomyosarcoma of the right kidney is presented. A 78-year-old man was admitted with the complaint of abdominal pain and abdominal fullness on March 15, 1985. Radiological examination showed a giant tumor of the right kidney. Radical nephrectomy and right hemicolectomy were performed. Histological findings were embryonal rhabdomyosarcoma of the kidney. Residual tumor in the duodenal area recurred and he died of peri-duodenal abscess 2 months after admission. This case is the 17th case of rhabdomyosarcoma of the kidney in Japan. The literature is reviewed and discussed.

Thyroid epithelial cells (thyrocytes) in autoimmune thyroid disease have been found to express DR antigens on their surfaces, and interferon-gamma (IFN gamma) induces DR antigen expression. This study was undertaken to determine the effect of IFN gamma on the response of human thyrocytes to TSH stimulation and the relationship between the response to TSH and the expression of DR antigen induced by IFN gamma, using monolayer cultures of Graves' thyrocytes. When confluent thyrocyte monolayers were incubated with TSH or Bu2cAMP (DBcAMP) for 7-9 days, T3 and thyroglobulin concentrations in the culture medium increased gradually in a dose-dependent manner. However, when TSH or DBcAMP was added after the cells had been cultured for 4 days with IFN gamma, T3 and thyroglobulin secretion in response to both 10 mU/mL TSH and 1 mM DBcAMP was significantly inhibited. The inhibition by IFN gamma was dose dependent and correlated with the number of DR antigen-positive thyrocytes present on the last day of culture. IFN alpha and -beta did not affect the response of thyrocytes to TSH or DBcAMP stimulation. These results suggest that DR antigen-positive thyrocytes fail to respond to TSH stimulation at a site located distal to cAMP formation.

We examined the capabilities of scintigraphic phase imaging in detecting the site of the onset of ventricular activation and the pattern of ventricular activation sequence. ECG-gated equilibrium cardiac blood pool scintigraphy was obtained in the left anterior oblique (LAO) and right anterior oblique (RAO) projections. The standard 12-lead electrocardiograms (ECG) were recorded in 29 cases with various conditions. These included seven normal subjects as controls, eight patients (pts) with complete right bundle branch block (CRBBB), one with CRBBB and left axis deviation (LAD), two with complete left bundle branch block (CLBBB), one with the Wolff-Parkinson-White (WPW) syndrome (B-type), six with right ventricular apical endocardial pacemakers, one with a right ventricular anterior wall myocardial pacemaker, and three with left ventricular apical myocardial pacemakers. Phase image analysis was performed using the first harmonic of the Fourier transform to fit a cosine curve to the time-activity curve of each pixel in the cardiac blood pool study. The results were as follows: In pts with WPW syndrome (B-type) and artificial pacemakers, the site of the earliest phase angle corresponded to the site of the onset of ventricular activation as predicted by ECG and chest radiographs, respectively. However, in normal subjects and in pts with CRBBB, the site of the earliest phase angle was observed at the basal (upper) interventricular septum, which was different from the site of the onset of ventricular activation previously reported by Sodi-Pallares et al and Durrer et al. This discrepancy may have been caused by the paradoxical motion of the basal (upper) interventricular septum in those cases. A similar discrepancy was also observed in pts with CLBBB. Although the site of onset of ventricular activation was predicted to be near the insertion of the anterior papillary muscle of the right ventricle by ECG and electrophysiology, the pixels showing early phase angle were distributed widely along the interventricular septum in those pts with CLBBB. This error in the phase image may have been caused by the extensive paradoxical motion of the interventricular septum. Thus, caution should be exercised in estimating the site of the onset of ventricular activation by phase images. The main direction of phase changes corresponded well to the ventricular activation sequence estimated using ECG in all subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

The renal pelvis of ten patients with ileal or colonic conduit was punctured with a 22G spinal needle under fluoroscopic guidance. Renal pelvic urine was obtained from nine patients. Two patients temporarily developed gross hematuria as a complication due to this procedure. The obtained renal pelvic urine was investigated bacteriologically. Direct renal pelvic puncture was concluded to be a useful and safe technique for locating urinary tract infection. Reflux of infected urine into the renal pelvis did not occur in any of the nine patients who had no obstruction of the ileal or colonic conduit.