Femtosecond response of polyatomic molecules to ultra-intense hard X-rays.

X-ray free-electron lasers enable the investigation of the structure and dynamics of diverse systems, including atoms, molecules, nanocrystals and single bioparticles, under extreme conditions. Many imaging applications that target biological systems and complex materials use hard X-ray pulses with extremely high peak intensities (exceeding 1020 watts per square centimetre). However, fundamental investigations have focused mainly on the individual response of atoms and small molecules using soft X-rays with much lower intensities. Studies with intense X-ray pulses have shown that irradiated atoms reach a very high degree of ionization, owing to multiphoton absorption, which in a heteronuclear molecular system occurs predominantly locally on a heavy atom (provided that the absorption cross-section of the heavy atom is considerably larger than those of its neighbours) and is followed by efficient redistribution of the induced charge. In serial femtosecond crystallography of biological objects-an application of X-ray free-electron lasers that greatly enhances our ability to determine protein structure-the ionization of heavy atoms increases the local radiation damage that is seen in the diffraction patterns of these objects and has been suggested as a way of phasing the diffraction data. On the basis of experiments using either soft or less-intense hard X-rays, it is thought that the induced charge and associated radiation damage of atoms in polyatomic molecules can be inferred from the charge that is induced in an isolated atom under otherwise comparable irradiation conditions. Here we show that the femtosecond response of small polyatomic molecules that contain one heavy atom to ultra-intense (with intensities approaching 1020 watts per square centimetre), hard (with photon energies of 8.3 kiloelectronvolts) X-ray pulses is qualitatively different: our experimental and modelling results establish that, under these conditions, the ionization of a molecule is considerably enhanced compared to that of an individual heavy atom with the same absorption cross-section. This enhancement is driven by ultrafast charge transfer within the molecule, which refills the core holes that are created in the heavy atom, providing further targets for inner-shell ionization and resulting in the emission of more than 50 electrons during the X-ray pulse. Our results demonstrate that efficient modelling of X-ray-driven processes in complex systems at ultrahigh intensities is feasible.

Pulse Energy and Pulse Duration Effects in the Ionization and Fragmentation of Iodomethane by Ultraintense Hard X Rays.

The interaction of intense femtosecond x-ray pulses with molecules sensitively depends on the interplay between multiple photoabsorptions, Auger decay, charge rearrangement, and nuclear motion. Here, we report on a combined experimental and theoretical study of the ionization and fragmentation of iodomethane (CH_{3}I) by ultraintense (∼10^{19} W/cm^{2}) x-ray pulses at 8.3 keV, demonstrating how these dynamics depend on the x-ray pulse energy and duration. We show that the timing of multiple ionization steps leading to a particular reaction product and, thus, the product's final kinetic energy, is determined by the pulse duration rather than the pulse energy or intensity. While the overall degree of ionization is mainly defined by the pulse energy, our measurement reveals that the yield of the fragments with the highest charge states is enhanced for short pulse durations, in contrast to earlier observations for atoms and small molecules in the soft x-ray domain. We attribute this effect to a decreased charge transfer efficiency at larger internuclear separations, which are reached during longer pulses.

Tight regulation of transgene expression by tetracycline-dependent activator and repressor in brain.

Methods to temporally and spatially regulate gene mutations will provide a powerful strategy to investigate gene function in the brain. To develop these methods, we have established a tightly regulated system for transgene expression in the forebrain using both a tetracycline (Tc)-dependent transcription activator (rtTA) and a repressor (TetR-Kruppel-associated box). In this system, the repressor binds to the Tc-responsive element (TRE) in the absence of doxycycline (Dox), leading to the repression of leaky activation of TRE-mediated transcription caused by weak binding of rtTA to TRE. Upon Dox administration, only the activator binds to TRE and activates transcription. We tested this system in cultured cells by bicistronically expressing both the regulators using an internal ribosome entry site (IRES). In COS-1, HeLa and SHSY5Y cells, leaky transcription activation led by rtTA in the absence of Dox was repressed without decreasing the level of activated transcription in the presence of Dox. Using this system, transgenic mice were produced that express both the regulators using IRES in the forebrain under the control of the alphaCaMKII promoter and were bred with transgenic mice carrying the TRE-dependent reporter transgene. In reverse transcription-polymerase chain reaction and in situ hybridization analyses of the forebrain in adult double transgenic mice, the treatment of Dox induces reporter mRNA expression, which was not detected before the treatment and after the withdraw of Dox following the treatment. These results indicate that this system allows the tight regulation of transgene expression in a Dox-dependent fashion in the forebrain and will be useful in investigating gene function in the brain.

Suppression of hematopoiesis by activated T-cells in infectious mononucleosis associated with pancytopenia.

Two patients with primary Epstein-Barr virus (EBV) infection followed by pancytopenia were studied. They showed increased numbers of DR-positive, activated T-cells and serological evidence of persistent EBV infection over a 12 and 18 week period. Bone marrow granulocyte-macrophage colony formation (CFU-GM) was investigated by limiting dilution assay (LDA) and methylcellulose assay. CFU-GM of bone marrow mononuclear cells (BMMNC) was markedly suppressed in both patients during the pancytopenic phase. Removal of bone marrow T-cells by E-rosetting resulted in a significant increase of CFU-GM to normal levels in BMMNC of both patients, while no significant increase was observed in the BMMNC of normal subjects. CFU-GM in BMMNC from Patient 1 in the recovery phase was normal when DR-positive T-cells were within normal levels, irrespective of the presence or absence of T-cells. These results suggest that pancytopenia due to infectious mononucleosis in these patients was due to bone marrow suppression by activated T-cells. In vitro studies with Con A activated T-cells and their culture medium showed that suppression of CFU-GM by T-cells was mediated by a lymphokine.

Prophylactic chemotherapy for primary and recurrent superficial bladder cancer: preliminary results. The Hokkaido University Bladder Cancer Collaborating Group.

A multicenter trial for postoperative prophylaxis of the recurrence of superficial Ta-T1, G1-G2 bladder cancer was performed. Eligible patients with primary or recurrent superficial bladder cancer were randomized into four groups. For the primary cases, intravesical instillation of drugs [group A, 20 mg Adriamycin (ADM) + 200 mg cytosine arabinoside (CA) in 30 ml physiological saline; group B, 10 mg peplomycin (PEP) + 200 mg CA in 30 ml physiological saline; group C, 2 mg neocarzinostatin (NCS) + 200 mg CA in 30 ml physiological saline; and group D, control] was carried out once a week for 2 weeks, once every 2 weeks for 14 weeks, once monthly for 8 months, and, finally, once every 3 months for 1 year. For the recurrent cases, intravesical instillation of 20 mg ADM + 200 mg CA in 30 ml physiological saline as described above and daily oral administration of another drug [group E, 300 mg/day UFT; group F, 200 mg 5-fluorouracil (5-FU)/day; group G, 30 mg ubenimex/day; and group H, no oral drug] was performed. The postoperative follow-up period was 3-36 months. A total of 193 primary cases and 121 recurrent cases of superficial bladder cancer were evaluated. The cumulative 12-month nonrecurrence rates for the primary cases were 86.2% in group A, 78.1% in group B, 82.1% in group C, and 68.4% in group D. The cumulative nonrecurrence rate obtained using ADM+CA (group A) was significantly higher than the control value. On the other hand, no significant difference was found in the cumulative nonrecurrence rates calculated for the recurrent cases, regardless of the oral drug given. Intravesical instillation of ADM+CA for primary superficial bladder cancer was considered to be useful, but the long-term effect of intravesical instillation remains to be elucidated. Further refinement of this regimen is necessary for effective prophylaxis of the recurrence of superficial bladder cancer.

Pyloric opening and closure evaluated by means of strain gauge force transducers.

Recently, gastrointestinal motility research and various studies to measure motility have been conducted. However, it is not easy to measure the pyloric sphincter motility, especially its open and closed motility. There are few reports on the opening and closed motility of the pyloric ring. In this study, I examined the pyloric motility with strain gauge force transducers (SGTs). SGTs were implanted onto the antrum, pyloric ring and duodenum of a dog. In order to clarify the relationship between the opening and closed motility of the pylorus and SGTs recordings, the pyloric ring was observed with a gastrofiberscope while measurements were taken using the SGTs in anesthetized dogs. In addition, the pyloric ring was extended mechanically with a balloon and measurement were taken using the SGTs. In conscious dogs, the natural gastropyloroduodenal motility was recorded. Then, cisapride, erythromycin, and Leu13-motilin were administered in the interdigestive state and the motility was recorded. The pyloric opening and closed motility could be monitored using SGTs. The pyloric ring opened when the pyloric motility recorded using the SGTs showed a negative deflection. In addition, in phase III, when intense contraction of the antrum was observed, relaxation and opening of the pyloric ring could be observed. Erythromycin and Leu13-motilin induced phase III-like motility and relaxation of the pyloric ring. However, in cisapride-induced motility, relaxation of the pyloric ring was not observed. The pyloric ring opening and closed motility can be monitored using SGTs and this method is effective for the evaluation of the pyloric function.

Motility of the canine pyloric ring following a pylorus-preserving pancreatoduodenectomy.

Recently, function-preserving operations have become popular, and pylorus-preserving pancreatoduodenectomy (PPPD) is frequently performed for diseases of the head of the pancreas. However, there are only a few basic studies on the pyloric function after PPPD. Using strain gauge force transducers (SGTs), we studied the pyloric motility of normal and PPPD dogs. We prepared three normal and three PPPD dogs in which the SGTs were implanted onto the antrum and pyloric ring, etc. In conscious dogs, the spontaneous gastrointestinal motility was recorded, and the plasma motilin concentration was measured during the interdigestive state. Following the administration of exogenous Leu13-motilin, the motility was again recorded. The relaxation and opening of the pyloric ring was observed synchronously with intense contractions of the antrum during the phase III of normal dogs. Phase III-like motility was recorded in the PPPD dogs, which was not a typical periodic motility. The plasma motilin concentration of one PPPD dog could be measured, and the motilin levels during the phase III-like motility were higher than during phase I. The phase III-like motility was induced by Leu13-motilin in both normal and PPPD dogs. The phase III-like motility recorded in the PPPD dogs was not a typical periodic one, and this aberrant motility was considered to be one of the causes of delayed gastric emptying. Phase III-like motility was induced by the administration of Leu13-motilin; therefore, it is possible that Leu13-motilin improved the motility of the pyloric ring after PPPD.

Structure-activity relationships of (1'S)-1'-acetoxychavicol acetate, a major constituent of a southeast Asian condiment plant Languas galanga, on the inhibition of tumor-promoter-induced Epstein-Barr virus activation.

The structure-activity relationships of (1'S)-1'-acetoxychavicol acetate (ACA), a cancer chemopreventive agent of food origin, were investigated in an inhibitory test of tumor promoter teleocidin B-4-induced Epstein-Barr virus (EBV) activation in Raji cells. Through a test of 16 derivatives, the structural factors regulating activity were found to be as follows: (1) the absolute configuration at the 1'-position does not affect activity; (2) hydrogenation of the terminal methylene group abolishes activity; (3) both the phenolic and alcoholic hydroxyl groups are compulsorily acetylated, and it is necessary that the former is oriented only at the position para to the side chain; (4) an additional acetoxyl group is allowed to locate at the ortho or meta position; and (5) substitution of the hydrogen atom at the 1'-position by a methyl group reduces activity. Upon esterase blockade in Raji cells, (1'R,S)-ACA suppressed EBV activation, the extent of which was the same as tested in the control, suggesting that ACA bearing two acetoxyl groups is an intracellular structure prerequisite for activity exhibition. The present study suggests that nucleophilic attack to the 3'-position is important and involved in the interaction of ACA with an unidentified target molecule(s) participating in the process of EBV activation.

Studies of postoperative transarterial infusion chemotherapy for liver metastasis of colorectal carcinoma after hepatectomy.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of postoperative transarterial infusion chemotherapy (PTIC) for the prevention of metastatic liver cancer recurrence after hepatectomy following curative surgery for colorectal carcinoma. METHODOLOGY: Thirty-eight patients who underwent curative hepatectomy for metastatic liver cancer from colorectal carcinoma were studied. Ten out of the 38 patients received PTIC (experimental group) and 28 patients did not receive chemotherapy (control group). PTIC was performed with an intrahepatic indwelling catheter, which was set-up for 3 weeks and repeated 3 times in two monthly intervals. RESULTS: In the control group, no significant differences were observed in the survival between patients with a single hepatic nodule and those with multiple hepatic nodules. Between patients with hepatic tumors of more than 3 cm in diameter and those with tumors less than 3 cm, and between patients with tumors located at H1 and H2, no significant differences were seen, either. However, the 5-year survival rate of the patients with metachronous liver metastases was 90% which was significantly better than for those patients with synchronous liver tumors (p < 0.05). The 100% of 3- and 100% of 4-year survival rates of the experimental group were significantly better than the 60% and 47% respectively of the control group (p < 0.05). The non-recurrence rate in the remnant liver was also significantly better in the experimental group than that in the control group (p < 0.01). The adverse effect of this protocol was negligible. CONCLUSION: We conclude that PTIC improved the survival and non-recurrence rate in the remnant liver of the patients with liver metastases from colorectal cancer after hepatectomy, and was considered to be safe and an important protective factor for the prevention of recurrence of liver metastases after hepatectomy.

[Effectiveness of tiaprofenic acid on clinical symptoms of acute simple cystitis in women].

Acute simple cystitis is very easily cured by the proper use of an antibiotic. However, at times, such irritation symptoms in the bladder as micturition pain, pollakisuria and pyuria disappear. Consequently, medication to remove these irritation symptoms in the bladder at the earliest possible date, is required. However, there are no established standards for treatment in terms of the administration method and the administration period, etc. We gave a new non-steroid anti-inflammatory drug, tiaprofenic acid (SURGAM) to women suffering from acute simple cystitis who strongly complained of bladder irritation symptoms especially of micturition pain. The administration was carried out concurrently with an antibiotic, and its effectiveness was studied. As a result, micturition pain showed 86% improvement on the 1st day after starting administration, and it is thought that the concurrent use of this product with an antibiotic can probably remove the patients' complaints quickly and prevent the meaningless administration of antibiotics due to the persistence of symptoms and, subsequently, there is the possibility of shortening the period of administration.

[A clinical study of associated bladder cancer in patients with renal pelvic and ureteral cancer].

We reviewed 76 cases of renal pelvic and ureteral cancer, admitted to our hospital between January, 1975 and December, 1988, with special reference to the occurrence of bladder cancer. Bladder cancer was associated with an upper urinary tract neoplasm in 35 of the 76 cases (46.1%), 7 with a preceding bladder cancer, 17 with a coexistent one and 11 with a subsequent one. In case of renal pelvic and upper ureteral cancer the incidence of coexistent or subsequent tumors of the bladder was 28.7% (16 of 56 patients). However, in the cases of lower ureteral cancer the incidence of these tumors was 82.4% (14 of 17 patients). This incidence was significantly higher than that in renal pelvic and upper ureteral cancer. The subsequent bladder cancer was observed in 19 patients including 8 patients who had a recurrence of the bladder cancer after the treatment for a preceding and coexistent bladder cancer. The cancer in most cases occurred within 2 years after the treatment of the upper urinary tract neoplasm. Of 19 patients who had subsequent bladder cancer 11 had primary sites in the renal pelvis and upper ureter. Another 8 patient had primary sites in the lower ureter. Four of the 8 subsequent bladder cancers in patients with lower ureteral cancer occurred just on and around the affected ureteral orifice. All these 4 tumors were high grade and high stage tumors. On the other hand, another 15 patients developed subsequent bladder cancer in a place other than the affected ureteral orifice. Of these 15 patients, 13 cases showed a low grade and low stage tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effective administration of recombinant granulocyte colony-stimulating factor to prevent granulocytopenia due to combination chemotherapy for testicular germ cell tumors].

A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.

[DNA ploidy of testicular germ cell tumors in childhood; difference from adult testicular tumors].

It is well known that there are various differences in the biological characteristics and clinical behavior between prepubertal testicular germ cell tumors and adult ones. We analyzed the nuclear DNA ploidy of testicular tumors in childhood using DNA flow cytometry for clarifying those biological features and shedding some insights in the pathogenesis of testicular germ cell tumors. Formalin-fixed, paraffin-embedded specimens of primary tumors taken from 9 boys with histological evidence of yolk sac tumors and 8 with prepubertal teratoma treated in our clinic were used for flow cytometry analysis with some modification of the Hedley's technique. The results were compared with those of adult testicular tumors which we previously reported. All specimens in children showed "DNA euploid"; DNA diploid in all teratomas and 6 yolk sac tumors, DNA tetraploid in other 3 yolk sac tumors. Neither distinct DNA aneuploidy nor DNA heterogeneity were detected in children. Our previous study proved that the vast majority of adult testicular tumors contain DNA aneuploid stemlines. Although prepubertal yolk sac tumor and teratoma are histologically identical with those in adults, this study apparently reveal the different DNA stemline ploidy in prepubertal testicular tumors compared with that in adult ones. It has been known that carcinoma in situ (CIS) of the testis is a precursor of adult testicular germ cell tumors and the CIS cells in precancerous state already shows aneuploid DNA histogram patterns. Moreover, CIS has never been observed in children. The current results are in agreement with the hypothesis that the pathogenesis of prepubertal testicular tumor is different from that of adult ones.(ABSTRACT TRUNCATED AT 250 WORDS)

[Flow cytometric analysis of the DNA content of the urinary bladder cancers--study on the DNA heterogeneity in bladder cancers].

PURPOSE: To evaluate the clinical relevance between the DNA ploidy and histopathology, and the incidence of the DNA heterogeneity in patients with bladder cancers. METHODS: Flow cytometry (FCM) was used to study the DNA ploidy in 63 patients who underwent total cystectomy. The DNA ploidy and DNA index were analyzed by FCM in total 328 paraffin embedded samples (5.2 samples per case on the average). RESULTS: The DNA ploidy of 52 bladder cancers, that had coexisted after total cystectomy, showed that 24 cases, 46% were DNA aneuploid and 18 cases, 35% had DNA heterogeneity. The DNA ploidy of 11 cases that were eradicated after cystectomy was all DNA diploid. There were significantly good correlation among DNA ploidy pattern and intravesical involvement (lymph duct involvement and venous involvement), but were not among the DNA ploidy pattern and tumor grade and stage. With regard to the evaluation of two vertical divided samples of tumors, DNA aneuploid had been not always recognized in the deeper sample, therefore, we did not determine that there was good correlation between the DNA ploidy and the tumor invasion. CONCLUSION: These data suggest that although the incidence of DNA heterogeneity in bladder cancers (35%) is thought to be relatively small, the DNA ploidy will be able to the important prognosticating factor in bladder cancers.

[Flow cytometric analysis of DNA content of urinary bladder cancers--study on primary tumors and metastasized lymph nodes].

PURPOSE: This study was designed to evaluate DNA ploidy patterns and metastatic patterns between primary tumors and metastatic lymph nodes in bladder tumor patients with lymph node metastases. METHODS: Flow cytometry (FCM) was used to study the DNA ploidy. The DNA ploidy patterns in 16 lymph node metastases in relation to the degree of ploidy in the primary bladder tumor were evaluated in 63 patients who underwent total cystectomy. RESULTS: The primary tumor that had metastasized was G3 tumor in grade and over pT2 in stage in many cases. Thirty-nine diploid tumors had given raise to lymph node metastases in only 5 cases (13%), whereas 11 cases (46%) of aneuploid tumors had metastasized (p < 0.01). With regard to ploidy patterns between primary tumors and the corresponding lymph node metastases, four patterns were noted, namely D-->D (5 cases), D + A-->D (4), A-->A (5) and A-->D (2) (D: DNA diploid, A: DNA aneuploid). The DNA index between the primary tumors and the corresponding lymph node metastases was the same in all but 2 cases (14/16.88%). In cases with lymph node metastases, the prognosis was very poor whether or not the DNA ploidy of the primary tumors or the metastatic tumors was DNA aneuploid. CONCLUSION: These data suggest that a malignant cell on the primary tumor metastasized to the lymph node in many cases.

[Flow cytometric analysis of DNA content in testicular seminomas--correlation to mitotic count].

The DNA ploidy of testicular seminomas was studied by flow cytometry using paraffin embedded samples. The mitotic count and DNA index (DI) for 27 seminomas were analyzed in 80 samples with a mean of 3.0 samples per case. Six anaplastic seminomas which were with 3 or more mitoses per a high power field were distinguished from 21 typical seminomas. DNA ploidy pattern was aneuploid in all seminomas except one case of anaplastic seminoma, and clonal heterogeneity in DNA content was found in 3 of 20 (15%) cases of which 2 or more samples were analyzed. Although the DI had no significant difference between those two groups of seminomas classified by mitotic count, the DI in anaplastic seminomas was ranged from 1.5 to 2.0 (median DI = 1.70), otherwise the DI in typical seminomas ranged from 1.5 to 3.5 (median DI = 1.89), particularly 9 cases in 21 (43%) typical seminomas distributed in hypertetraploid region. The median DI of stage I seminomas was 1.88 and that of stages II + III seminomas was 1.75, though there was also no significant correlation between DI and clinical stages. In general, it is postulated that the higher DI is paralleled to the more malignant nature of neoplasms, nevertheless this study suggested that the higher DI in seminomas is not always related to high malignant potentiality determined by histological type and clinical stage.

[Flow cytometric analysis of the DNA content in the urinary bladder cancers treated by radical cystectomy and pre-operative irradiation].

The DNA ploidy of bladder cancers treated by radical cystectomy following pre-operative irradiation was analyzed by flow cytometry using paraffin embedded samples. The DNA ploidy and its changes by irradiation were studied. We used flow cytometry in 30 patients with transitional cell carcinoma of the bladder who received pre-operative irradiation (40 Gy in 24 patients, 20 Gy in 5 patients and 60 Gy in one) with follow-up for at least 3 years. Total 140 paraffin embedded samples (4.6 samples per one patient) were available. The effects of therapy were related to the DNA patterns before irradiation and to the DNA ploidy changes after irradiation. 1. Eight DNA diploid tumors and twenty-two DNA aneuploid ones were detected before irradiation. Although diploid group didn't change its DNA ploidy after irradiation, of 22 aneuploid tumors 18 were changed to DNA diploid and 4 were not changed in their ploidy. 2. The tumor eradicating effect of irradiation was shown to be higher (p < 0.05) in the diploid group (5 of 8, 63%) than in the aneuploid group (5 of 22, 23%). 3. Overall survival rates were discussed in 3 groups (A, B and C), the group A was 10 of tumor free and 3 diploid tumors after irradiation, the group B was 13 of aneuploid tumors which changed to diploid ones and the group C was 4 of persistent aneuploid tumors. Each of 5 year survival rate was 100% (A), 58% (B) and 0% (C). Overall survival for C group was significantly shorter than for other groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Flow cytometric analysis of DNA content in adult testicular germ cell tumors].

Flow cytometric DNA analysis was carried out in 54 patients with testicular germ cell tumors (GCTs) experienced at our hospital, to evaluate the clinical relevance of DNA index (DI) and provide some insight into the pathogenesis of testicular GCTs. Histological types with their incidences were seminomas in 31 patients and nonseminomatous germ cell tumors (NSGCTs) in 23 adults. DNA ploidy and DI were analyzed by flow cytometry in 158 paraffin embedded samples; 2.9 samples per case on the average. This study revealed that 52 cases (96%) of evaluable 54 adult GCTs were DNA aneuploid, while DNA diploid tumors were observed in only each one case of NSGCT and seminoma. There was a significant difference (p less than 0.01) between the distribution of DIs in adult NSGCTs (median DI = 1.50) and that in pure seminomas (median DI = 1.85). Although we found no significant correlation between DI and clinical staging of Japanese Urological Association, on the basis of Indiana University staging system, the median DI in NSGCT patients of the advanced extent was lower than those of the other extents. DNA heterogeneity was observed only in 4 of 23 NSGCT patients (17%) and 3 of those 4 patients were assigned to advanced extent. These data suggest that the lower DI and the presence of DNA heterogeneity may have prognostic relevance for NSGCTs.

[Tumor size and DNA ploidy changes in renal cell carcinomas--flow cytometric analysis of DNA content in renal cell carcinomas associated with von Hippel-Lindau disease].

BACKGROUND: Renal cell carcinomas (RCCs) develop in 8-63% of von Hippel-Lindau disease (VHL) patients, and loss of 3p segments, chromosome aberrations found in 90% of sporadic RCCs, has also been observed in RCCs associated with VHL. In fact, comparative analysis showed that the chromosome aberrations in RCCs associated with VHL are similar to those found in sporadic RCCs. VHL patients have the whole spectrum of tumors from small early lesions to large ones in the same kidney, providing a unique opportunity to analyze tumors in different stages of development. Subsequently deoxyribonucleic acid (DNA) content in RCCs of VHL patients was examined and correlated to their tumor size to gain some insight in the progression of sporadic RCCs. METHODS: From 1988 to 1991, we have experienced 6 cases of RCCs associated with VHL who underwent partial or radical nephrectomy. A total number of 52 paraffin-embedded samples from 33 RCCs from 6 patients with VHL was analyzed by flow cytometry. RESULTS: The sizes of tumors ranged from 0.2 to 8.2 cm. DNA aneuploid patterns demonstrated in none of 9 tumors less than 1.6 cm, 4 of 14 tumors (29%) as large as 1.6 to 2.5 cm, and 5 of 10 tumors (50%) larger than 2.5 cm (p < 0.05). Twelve tumors less than 1.8 cm showed DNA diploid, so the smallest size of aneuploid tumors was 1.8 cm. CONCLUSION: These data suggest that DNA ploidy change (diploid to aneuploid) in RCCs probably takes place as tumors grow approximately 1.8 cm in size.

[A study on sex chromosome mosaicism--endocrinological and immunohistochemical findings with glutathion S-transferase in the gonads].

In order to clarify the clinical aspects of sex chromosomal mosaicism, we evaluated the karyotypes, the anatomy of external genitalia and internal ductal system, the pituitary-gonadal function, and the histopathology of the gonads by immuno-staining for glutathion S-transferase (GST) in 5 patients who had been all raised as female. Three patients have the 45, X/46, XYq- karyotype in the initial lymphocyte culture or the subsequent culture of skin fibroblasts. Another two karyotypes were 45, X/46, XYq-/47, XYq-, Yq- and 45, X/46, XdicY. Thus, Y chromosome of all patients retained short arms in which the testis determining factor is encoded. Three prepubertal patients were referred to us for their ambigious external genitalia and two postpubertal patients were for the short statures. Although the vaginal orifice was separated from the urethral meatus in all of them, the phallic enlargement was noted in 4 patients and the posterior labial fusion in 2 patients. The oldest patient had a normal female appearance of external genitalia except the vaginal septum. Serum gonadotrophin (GnH) levels were basically high in the postopubertal patients and the responses of GnH to LH-RH were significantly increased in the prepubertal patients. Serum testosterone levels to hCG stimulation ranged from no response to low normal response. All patients underwent the exploratory laparotomy together with the feminizing genitoplasty. The gonads in 3 patients, diagnosed as mixed gonadal dysgenesis (MGD), consisted of a unilateral testis and a contralateral streak gonad. Two patients had variants, including one with bilateral dysgenetic testis and another with bilateral streak gonads.(ABSTRACT TRUNCATED AT 250 WORDS)