Unstable rocker shoes promote recovery from marathon-induced muscle damage in novice runners.

We recently reported that wearing unstable rocker shoes (Masai Barefoot Technology: MBT) may enhance recovery from marathon race-induced fatigue. However, this earlier study only utilized a questionnaire. In this study, we evaluated MBT utilizing objective physiological measures of recovery from marathon-induced muscle damages. Twenty-five university student novice runners were divided into two groups. After running a full marathon, one group wore MBT shoes (MBT group), and the control group (CON) wore ordinary shoes daily for 1 week following the race. We measured maximal isometric joint torque, muscle hardness (real time tissue elastography of the strain ratio) in the lower limb muscles before, immediately after, and 1, 3, and 8 days following the marathon. We calculated the magnitude of recovery by observing the difference in each value between the first measurement and the latter measurements. Results showed that isometric torques in knee flexion recovered at the first day after the race in the MBT group while it did not recover even at the eighth day in the CON group. Muscle hardness in the gastrocnemius and vastus lateralis showed enhanced recovery in the MBT group in comparison with the CON group. Also for muscle hardness in the tibialis anterior and biceps femoris, the timing of recovery was delayed in the CON group. In conclusion, wearing MBT shoes enhanced recovery in lower leg and thigh muscles from muscle damage induced by marathon running.

Comparisons of the effects of 12-week administration of miglitol and voglibose on the responses of plasma incretins after a mixed meal in Japanese type 2 diabetic patients.

To compare the effects of miglitol [an alpha-glucosidase inhibitor (AGI) absorbed in the intestine] and voglibose (an AGI not absorbed) on plasma glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels, 26 and 24 Japanese type 2 diabetic patients were randomly assigned to receive miglitol or voglibose, respectively. After 12-week administration of both drugs, during 2-h meal tolerance test, plasma glucose, serum insulin and total GIP were significantly decreased and active GLP-1 was significantly increased. Miglitol group showed a significantly lower total GIP level than voglibose group. Miglitol, but not voglibose, significantly reduced body weight (BW). In all participants, the relative change in BW was positively correlated with that of insulin significantly and of GIP with a weak tendency, but not of GLP-1. In conclusion, both drugs can enhance postprandial GLP-1 responses and reduce GIP responses. The significant BW reduction by miglitol might be attributable to its strong GIP-reducing efficacy.

Inhibition of DNA topoisomerase II by ICRF-193 induces polyploidization by uncoupling chromosome dynamics from other cell cycle events.

ICRF-193, a novel noncleavable, complex-stabilizing type topoisomerase (topo) II inhibitor, has been shown to target topo II in mammalian cells (Ishida, R., T. Miki, T. Narita, R. Yui, S. Sato, K. R. Utsumi, K. Tanabe, and T. Andoh. 1991. Cancer Res. 51:4909-4916). With the aim of elucidating the roles of topo II in mammalian cells, we examined the effects of ICRF-193 on the transition through the S phase, when the genome is replicated, and through the M phase, when the replicated genome is condensed and segregated. Replication of the genome did not appear to be affected by the drug because the scheduled synthesis of DNA and activation of cdc2 kinase followed by increase in mitotic index occurred normally, while VP-16, a cleavable, complex-stabilizing type topo II inhibitor, inhibited all these processes. In the M phase, however, late stages of chromosome condensation and segregation were clearly blocked by ICRF-193. Inhibition at the stage of compaction of 300-nm diameter chromatin fibers to 600-nm diameter chromatids was demonstrated using the drug during premature chromosome condensation (PCC) induced in tsBN2 baby hamster kidney cells in early S and G2 phases. In spite of interference with M phase chromosome dynamics, other mitotic events such as activation of cdc2 kinase, spindle apparatus reorganization and disassembly and reassembly of nuclear envelopes occurred, and the cells traversed an unusual M phase termed "absence of chromosome segregation" (ACS)-M phase. Cells then continued through further cell cycle rounds, becoming polyploid and losing viability. This effect of ICRF-193 on the cell cycle was shown to parallel that of inactivation of topo II on the cell cycle of the ts top2 mutant yeast. The results strongly suggest that the essential roles of topo II are confined to the M phase, when the enzyme decatenates intertwined replicated chromosomes. In other phases of the cycle, including the S phase, topo II may thus play a complementary role with topo I in controlling the torsional strain accumulated in various genetic processes.

Vasoactive intestinal peptide and inflammatory cytokines enhance vascular endothelial growth factor production from epidermal keratinocytes.

BACKGROUND: Overexpression of vascular endothelial growth factor (VEGF) in epidermal lesions of psoriasis is well documented; however, its underlying mechanisms are largely unknown. We have recently demonstrated that vasoactive intestinal peptide (VIP) induces the production of cytokines such as interleukin-6 and stem cell factor from keratinocytes, thereby contributing to the development of inflammatory dermatoses such as psoriasis. OBJECTIVES: In this study, we attempted to determine whether VIP could increase the production of VEGF in human keratinocytes. METHODS: We examined the expression of VEGF using reverse transcription-polymerase chain reaction, immunocytochemistry, enzyme-linked immunosorbent assay and immunoblotting in normal human epidermal keratinocytes and human epidermal keratinocyte cell line DJM-1 cultured in the absence or presence of VIP and/or inflammatory cytokines. RESULTS: We demonstrate that human keratinocytes produced VEGF in a steady state at both mRNA and protein levels. VIP significantly upregulated the production of VEGF in keratinocytes in a dose- and time-dependent manner. The VIP-mediated production of VEGF was further enhanced by inflammatory cytokines such as interferon-gamma, tumour necrosis factor-alpha and interleukin-4, with maximum enhancement being observed with the combination of VIP and interferon-gamma. CONCLUSIONS: VIP and other cytokines from nerve endings, mast cells and local inflammatory cells are capable of enhancing VEGF production from epidermal keratinocytes, which may underlie excessive angiogenesis and vasodilation in skin lesions of psoriasis.

Stimulation of RNA polymerase II elongation by hepatitis delta antigen.

Transcription elongation by RNA polymerase II (RNAPII) is negatively regulated by the human factors DRB-sensitivity inducing factor (DSIF) and negative elongation factor (NELF). A 66-kilodalton subunit of NELF (NELF-A) shows limited sequence similarity to hepatitis delta antigen (HDAg), the viral protein required for replication of hepatitis delta virus (HDV). The host RNAPII has been implicated in HDV replication, but the detailed mechanism and the role of HDAg in this process are not understood. We show that HDAg binds RNAPII directly and stimulates transcription by displacing NELF and promoting RNAPII elongation. These results suggest that HDAg may regulate RNAPII elongation during both cellular messenger RNA synthesis and HDV RNA replication.

Diurnal changes in urinary excretion of IgG, transferrin, and ceruloplasmin depend on diurnal changes in systemic blood pressure in normotensive, normoalbuminuric type 2 diabetic patients.

Previous studies of diabetic patients indicate that increased urinary excretion of certain plasma proteins (molecular radii <55 A), such as IgG, transferrin, and ceruloplasmin, precede the development of microalbuminuria. Moreover, increases in these urinary proteins predict future development of microalbuminuria. To clarify whether blood pressure changes influence urinary excretion of these proteins, we examined relationships between diurnal blood pressure changes measured by ambulatory blood pressure monitoring and urinary excretion of IgG, transferrin, ceruloplasmin, alpha2-macroglobulin (88 A) and albumin (36 A) measured separately during the day and night in 20 healthy controls and 26 normotensive, normoalbuminuric diabetic patients. Diurnal change in systolic blood pressure was not correlated to urinary excretion of either albumin or alpha2-macroglobulin in either diabetic patients or controls. However, statistically significant correlations between diurnal changes in systolic blood pressure and those of urinary excretion of IgG, transferrin and ceruloplasmin were found in diabetic patients but not in controls. The present findings suggest that urinary excretion of IgG, transferrin, and ceruloplasmin are more easily affected than albuminuria by systemic blood pressure changes in normoalbuminuric diabetic patients. This is supported by our previous finding that urinary excretion of IgG, transferrin and ceruloplasmin increased while albuminuria did not following enhanced glomerular filtration rate after acute protein loading, which causes increased glomerular capillary pressure due to afferent arterioles dilation, mimicking diabetic intra-renal hemodynamics. Taken together, these findings suggest that urinary excretion of IgG, transferrin, and ceruloplasmin may be more sensitive indicators of glomerular capillary pressure change than albuminuria in normoalbuminuric diabetic patients.

The effect of perfusion prior to cold preservation and addition of biliverdin on the liver graft from non-heart-beating donors.

AIM: Our aim was to improve the energy status and viability of a liver graft from a non-heart-beating donor (NHBD), we investigated the effects of perfusion prior to cold preservation and the addition of an antioxidant, biliverdin. METHODS: Rats were divided into five groups: group 1: without 30 minutes warm ischemia (WI) and cold preservation (control group); group 2 without WI and with 6 hours of cold preservation in UW solution (HBD group); group 3 with WI and cold preservation (NHBD group); group 4 with 30 minutes perfusion prior to cold preservation (PRE group); and group 5 with addition of biliverdin to precold preservation perfusion (BV group). Oxygenated Klebs-Henseleit solution was used as the perfusate prior to and after preservation. Portal flow and bile production during reperfusion, energy charge (EC), ATP level, GOT, and TNF-alpha were measured as well as a histological evaluation. RESULTS: Portal flow of the PRE and BV groups during 1 hour of reperfusion was higher than of that the NHBD group. Bile production of the PRE group was also higher than that of the NHBD group, but bile production in the BV group was comparable to the NHBD group. EC of the PRE group was higher than that of the NHBD group prior to and after reperfusion. The EC and ATP levels of the BV group after reperfusion were higher than those of the NHBD and PRE groups. The GOT and TNF-alpha were reduced in the BV group. CONCLUSIONS: Precold preservation perfusion improves the viability of grafts from NHBDs. Furthermore, biliverdin exerted an additive effect to ameliorate energy status.

Effect of melatonin on B16 melanoma growth in athymic mice.

The effect of melatonin on the growth of B16 mice melanoma was examined. Male and female BALB/c athymic mice, inoculated with 7 X 10(4) melanoma cells, were given drinking water containing melatonin (5 micrograms/g body weight/day) and 0.5% ethanol. Compared to control animals the melatonin treated male and female athymic mice had significantly smaller tumors on Day 40. The weights of the testes, the ovaries, and the adrenal glands of melatonin treated mice were significantly reduced compared to control animals. These data indicate that melatonin p.o. significantly inhibited the growth of B16 mouse melanoma and that the antitumor effect of melatonin was associated with a significant decrease in gonadal and adrenal weights.

Inhibition of intracellular topoisomerase II by antitumor bis(2,6-dioxopiperazine) derivatives: mode of cell growth inhibition distinct from that of cleavable complex-forming type inhibitors.

In the accompanying paper (K. Tanabe, Y. Ikegami, R. Ishida, and T. Andoh, Cancer Res., 51: 4903-4908, 1991), we showed that ICRF-154 and -193, dioxopiperazine derivatives, inhibited the activity of purified topoisomerase II, without formation of a cleavable DNA-protein complex. In order to see whether ICRF-154 and ICRF-193 affect cellular topoisomerase II in situ or not, we examined the effect of these drugs on etoposide (VP-16)-induced, topoisomerase II-mediated DNA breaks in RPMI 8402 cells by alkaline sedimentation analysis. When RPMI 8402 cells were exposed to VP-16 in the presence of ICRF-154 or ICRF-193 for 1 h, VP-16-induced DNA strand breaks were greatly inhibited by both ICRF compounds. In parallel with this observation, VP-16-induced growth inhibition was also reversed by ICRF-193. Exposure of cells to ICRF-154 resulted in a progressive accumulation of cells with 4C DNA content. Although mitotic index did not significantly increase, mitotic abnormalities were seen in cells exposed to ICRF-193 or ICRF-154: all mitotic cells exhibited early mitotic figures with fewer condensed and entangled chromosomes. The most sensitive phase of the cell cycle to ICRF-154 was the G2-M. ICRF-154 did not affect the spindle formation. However, abnormally oriented spindles were observed in drug-treated cells in parallel with the appearance of multinucleated cells. The results suggest that ICRF-154 and -193 inhibit topoisomerase II activity in RPMI 8402 cells, and this effect resulted in the appearance of cells in G2 and early M phase with fewer condensed and entangled chromosomes and of cells with multilobed nuclei.

Safety and Effectiveness of Marginal Donor in Living Kidney Transplantation.

BACKGROUND: We evaluated the safety and feasibility of living kidney transplantation from marginal donors. PATIENTS AND METHODS: Between June 2006 and March 2015, we performed 61 living related renal transplantations at two renal transplantation centers. Marginal donors were defined as those who were older than 70 years or who had hypertension, reduced renal function, body mass index greater than 30 kg/m(2), or mildly impaired glucose tolerance. We retrospectively compared renal function and graft survival between marginal and standard living donor kidney transplantations. To evaluate renal function, creatinine clearance (CCr) was preoperatively used for donors, and estimated glomerular filtration rate (eGFR) was postoperatively used for donors and recipients. RESULTS: Among 61 donors, 14 (23%) met the marginal criteria, the major reason being hypertension (91%). The mean age tended to be higher in the marginal group. Preoperative eGFR was significantly lower in the marginal group, whereas postoperative renal function decline ratio at two years was not significantly different between the groups (67% vs 67%, P = .960). Five-year graft survival rates were not significantly different between the two groups. However, recipient eGFR 1 year after kidney transplantation was lower in the marginal group than in the standard group (44 ± 8 vs 55 ± 9 in eGFR, P = .003). CONCLUSIONS: No significant differences were observed between the groups regarding donor renal function. Careful marginal donor selection can be safe and feasible for donors and recipients of living kidney transplantation; however, it may have a negative impact on recipient renal function.

Differential expression of fos and jun family members in the developing chicken gastrointestinal tract.

We have analysed the expression patterns of all the known fos/jun family genes, which encode the components of the transcription factor AP-1, in the chicken embryonic digestive tract that develops into the esophagus, proventriculus, gizzard, small intestine, ceca and large intestine. From soon after formation of the tubular structure, each gene transcript was localized in distinct domains of the epithelium and mesenchyme in all of these major gastrointestinal organs, independently of the anterior-posterior axis. fra-2 was expressed predominantly in epithelium, which also expressed junD, while low-level expression of junD was also detected in smooth muscle cell precursors in mesenchyme. Expression of c-jun and c-fos was detectable in both mesenchyme and epithelium through the whole tract. In the differentiated proventriculus, the developed glandular epithelium expressed c-jun and junD, but not fra-2, while luminal epithelium expressed fra-2 and junD, but not c-jun. These results suggest that distinct Fos/Jun protein heterodimers play important roles in maintaining the epithelial-mesenchymal interactions. Similar expression patterns to those of fra-2 and junD were established from earlier stages by Sonic hedgehog gene and the Indian hedgehog gene, respectively, both of which are important in forming the inductive network between epithelium and mesenchyme of the digestive tract.

Gene expression profile in rat pancreatic islet and RINm5F cells.

To clarify tissue-specificity of pancreatic beta cells, comparison of mRNA expression in various conditions of the tissue of multiple organisms is important. Although the developed methodologies for mRNA monitoring such as microarray, rely on the growth of dbEST (database of expressed sequence tag), a large number of unknown genes in the genome, especially in the rat, have not been shown to be expressed. In this study, we have established the first database of ESTs from rat pancreatic islet and RINm5F cells. Two cDNA libraries were constructed using mRNAs from rat pancreatic islet and RINm5F cells to cover a wider spectrum of expressed genes. Over 40,000 clones were randomly selected from the two libraries and partially sequenced. The sequences obtained were subjected to BLAST database analyses. This large-scale sequencing generated 40,710 3'-ESTs. Clustering analysis and homology search of nucleotide and peptide databases using both 3'- and 5'-ESTs revealed 10,406 non-redundant transcripts representing 4078 known genes or homologs and 6328 unknown genes. To confirm actual expression, the unknown sequences were further subjected to dbEST search, resulting in the identification of 5432 significant matches to those from other sources. Interestingly, of the remaining sequences showing no match, 779 were found to be encoded by exon-intron organization in the corresponding genomic sequences, suggesting that these are newly found as actually expressed in this study. Since many genes are up- or down-regulated in differing conditions, applications of the expression profile should facilitate identification of the genes involved in cell-specific functions in normal and disease states.

Large-scale isolation of ESTs from medaka embryos and its application to medaka developmental genetics.

The medaka is becoming an attractive model organism for the study of vertebrate early development and organogenesis and large-scale mutagenesis projects that are aimed at creating developmentally defective mutants are now being conducted by several groups in Japan. To strengthen the study of medaka developmental genetics, we have conducted a large-scale isolation of ESTs from medaka embryos and developed tools that facilitate mutant analysis. In this study, we have characterized a total of 132,082 sequences from both ends of cloned insert cDNAs from libraries generated at different stages of medaka embryo development. Clustering analysis with 3-prime sequences finally identified a total of 12,429 clusters. As a pilot analysis, 924 clusters were subjected to in situ hybridization to determine the spatial localization of their transcripts. Using EST sequence data generated in the present study, a 60-mer oligonucleotide microarray with 8,091 unigenes (Medaka Microarray 8K) was constructed and tested for its usefulness in expression profiling. Furthermore, we have developed a rapid and reliable mutant mapping system using a set of mapped EST markers (M-marker 2003) that covers the entire medaka genome. These resources will accelerate medaka mutant analyses and make an important contribution to the medaka genome project.

Autologous dendritic cells or cells expressing both B7-1 and MUC1 can rescue tumor-specific cytotoxic T lymphocytes from MUC1-mediated apoptotic cell death.

We attempted to induce MUC1-specific cytotoxic T lymphocytes (CTLs) by mixed-lymphocyte tumor cell culture (MLTC) using two allogeneic MUC1-positive cancer cell lines, T-47D and MCF7. The induced CTLs exhibited MUC1-specific cytotoxicity 16 days after the initial stimulation. However, these CTLs underwent apoptotic death within 16 days. To examine whether the B7-1 molecule is required for the expansion of the responder cells, a B7-1(+)/MUC1(-) cell line was transfected with MUC1 cDNA, and the resulting transfectant was employed as a stimulator in an autologous MLTC. The CTLs exhibited MUC1 specificity but also continued to propagate. In parallel, autologous dendritic cells (DCs) were added to an MLTC containing peripheral blood lymphocytes (PBLs) and the allogeneic MUC1-positive stimulators. The CTLs demonstrated MUC1 specificity and their number increased. This suggests that the B7-1 molecule is required for rescuing CTLs from MUC1-mediated apoptotic death, but not for the induction of MUC1-specific responsiveness. This strategy to obtain the CTLs efficiently may be useful for adoptive immunotherapy against cancer.

Excessive portal flow causes graft nonfunction in small size liver transplantation: an experimental study in pigs.

We investigated the effects of portocaval shunt (PCS) on excessive portal flow in producing sinusoidal microcirculatory injury in small-for-size liver transplants in pigs. The posterior segment of a whole liver (25%) was transplanted orthotopically. The pigs were divided two groups: group A, graft with PCS (n = 11), and group B, graft without PCS (n = 11). The PCS was a side-to-side anastomosis of the portal vein and the inferior vena cava. In group A, eight pigs survived for more than 4 days; all pigs except for one died of graft nonfunction within 24 hours in group B. The portal flow after reperfusion decreased in group A, but increased about three times greater in group B than that before the operation (P < .01). In group B, destruction of the sinusoidal lining and bleeding in the periportal areas were observed after reperfusion, findings that were not recognized in group A. These results suggest that graft nonfunction after small-for-size liver transplantation may be attributable to excessive portal flow producing sinusoidal microcirculatory injury.

Abnormality in urinary protein excretion in Japanese men with impaired glucose tolerance.

OBJECTIVE: To examine whether subjects with impaired glucose tolerance (IGT) for more than 2 years have any abnormality in the kidney. RESEARCH DESIGN AND METHODS: We measured urinary excretion rate and clearance of various plasma proteins with different molecular radii and different isoelectric points in 22 Japanese men with IGT (IGT group) and 37 age-matched healthy control subjects (control group). RESULTS: Clearance of ceruloplasmin (molecular radius approximately 45 A; isoelectric point 4.4), IgG4 (molecular radius 55 A; isoelectric point 5.4), and IgG (molecular radius 55 A; isoelectric point 7.4) was significantly higher in the IGT group than in the control group, whereas there were no significant differences in urinary excretion rate of albumin (molecular radius 36 A; isoelectric points 4.8-5.2) and clearance of alpha 2-macroglobulin (molecular radius 88 A; isoelectric point 5.4) between the two groups. CONCLUSIONS: In the present study, we found that clearance of neutral-charged IgG, negatively charged IgG4, and ceruloplasmin with molecular radii of approximately 45-55 A was selectively increased in IGT subjects. This finding does not seem to be explained by impairment of charge and pore-size selectivity in the glomerulus. Therefore, considering the present result together with our recent finding that enhanced glomerular filtration rate (GFR) after acute protein loading in healthy subjects induced a selective increase in clearance of IgG, IgG4, and ceruloplasmin, we suggest that increased intraglomerular hydraulic pressure, although enhanced GFR was not demonstrated, may be at work in these mildly hyperglycemic subjects.

Lower expression of activating transcription factors 3 and 4 correlates with shorter progression-free survival in multiple myeloma patients receiving bortezomib plus dexamethasone therapy.

Bortezomib (BTZ), a proteasome inhibitor, is widely used in the treatment of multiple myeloma (MM), but a fraction of patients respond poorly to this agent. To identify factors predicting the duration of progression-free survival (PFS) of MM patients on BTZ treatment, the expression of proteasome and endoplasmic reticulum (ER) stress-related genes was quantified in primary samples from patients receiving a combination of BTZ and dexamethasone (BD). Fifty-six MM patients were stratified into a group with PFS<6 months (n=33) and a second group with PFS⩾6 months (n=23). Of the 15 genes analyzed, the expression of activating transcription factor 3 (ATF3) and ATF4 was significantly lower in patients with shorter PFS (P=0.0157 and P=0.0085, respectively). Chromatin immunoprecipitation analysis showed that these ATFs bind each other and transactivate genes encoding the pro-apoptotic transcription factors, CHOP and Noxa, which promote ER stress-associated apoptosis. When either ATF3 or ATF4 expression was silenced, MM cells partially lost sensitivity to BTZ treatment. This was accompanied by lower levels of Noxa, CHOP and DR5. Thus low basal expression of ATF3 and ATF4 may attenuate BTZ-induced apoptosis. Hence, ATF3 and ATF4 could potentially be used as biomarkers to predict efficacy of BD therapy in patients with MM.

An adenosine receptor agonist-induced modulation of TSH-dependent cell growth in FRTL-5 thyroid cells mediated by inhibitory G protein, Gi.

Adenosine has been shown to modulate the TSH-induced DNA synthesis in FRTL-5 thyroid cells. The mechanism of this adenosine action has been somewhat controversial because both A1 adenosine receptor-mediated and non-receptor-mediated mechanisms have been proposed. We have now reexamined our preliminary finding of the inhibitory action of a non-metabolizable adenosine derivative, N6-(L-2-phenylisopropyl)adenosine (PIA), on the TSH-induced DNA synthesis to clarify the adenosine-dependent mechanism of cell growth modulation. PIA dose-dependently inhibited the TSH-induced DNA synthesis expressed by [3H]thymidine incorporation into DNA. This adenosine derivative also prevented the TSH-induced entry of the cell cycle to the S phase at 24 h of culture and the increase in cell number at 48 h. These PIA actions on different aspects of TSH-dependent cell growth were abolished by the treatment of the cells with pertussis toxin, suggesting the involvement of Gi in the PIA action mechanism. Dibutyryl cAMP-induced DNA synthesis was not influenced by PIA. In concert with our previous finding that PIA in a similar concentration range inhibited TSH-induced cAMP production through the adenosine A1 receptor, the present results strongly support the idea that the major pathway of adenosine signaling for the inhibition of the TSH-induced cell proliferation is through the A1 adenosine receptor-Gi system.

Expression profile of mRNAs from human pancreatic islet tumors.

In order to understand the tIssue specificity of the endocrine pancreas, it is important to clarify the expression profile of mRNAs in various states of the tIssue. A total of approximately 9000 non-redundant expressed genes from human pancreatic islets and insulinoma have so far been determined as expressed sequence tags (ESTs) and deposited in public databases. In the present study towards the identification of a complete set of genes expressed in human pancreatic islets, we have determined 3'-ESTs of 21267 clones randomly selected from a cDNA library of human pancreatic islet tumors. Clustering analysis generated 6157 non-redundant sequences comprising 2323 groups and 3834 singletons. Nucleotide and peptide database searches show that 3103 of them represent known human sequences or homologs of genes identified in other species and 58 are new members of structurally related families. The sequences were classified on the basis of the putative protein functions encoded, and were assigned to the respective chromosome by database analysis. The sequences were also compared with the EST databases (dbEST and EPConDB) including ESTs from normal pancreatic islet, insulinoma, and fetal pancreas. Since 3384 genes were newly found to be expressed in human pancreatic islets and 587 of them were unique to the islets, this study has considerably expanded the catalog of genes expressed in the endocrine pancreas. The larger collection of pancreatic islet-related ESTs should provide a better genome source for molecular studies of differentiation, tIssue-specific functions, and tumorigenesis of the endocrine pancreas as well as for genetic studies of diabetes mellitus.

Peutz-Jeghers syndrome with adenomas and adenocarcinomas in colonic polyps.

A case of Peutz-Jeghers syndrome is reported in which 52 colonic polyps were resected endoscopically. Of these, 49 were hamartomatous and showed no adenomatous or carcinomatous changes. In the other three polyps, adenomatous change and foci of adenocarcinoma were present. The investigation of the sites of adenomas and carcinomas in this case and others previously reported indicates that such neoplastic changes are found on the luminal surfaces of the polyps of Peutz-Jeghers syndrome.