Biomedical subjects

K Yamagata

Publications and source records attributed to K Yamagata.

At least 91 records · Page 5Linked to original sources

PubMed1999

Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset Type I (insulin-dependent) diabetes mellitus.

AIMS/HYPOTHESIS: To determine whether the clinical heterogeneity observed in the development of Type I (insulin-dependent) diabetes mellitus correlates with immunohistochemical differences observed at diagnosis. METHODS: Patients (n = 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I), underwent pancreatic biopsy for immunohistological analysis. These patients were divided into two groups based on the presence or absence of islet immunological abnormalities (insulitis or hyperexpression of MHC class I antigens or both). The patients were also HLA typed and tested for islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD-Ab). All patients were followed monthly for 2 years and their fasting plasma glucose, haemoglobin A1c and daily insulin doses were recorded. The clinical course of patients with islet immunological abnormalities was compared with that of patients without those abnormalities. RESULTS: Patients with and without islet immunological abnormalities did not differ with regard to HLA type or islet cell antibodies. Antibodies to glutamic acid decarboxylase correlated with the presence of insulitis and MHC class I hyperexpression. These local immunological abnormalities were also associated with higher haemoglobin A1c values (p < 0.05) and a trend towards greater insulin requirements. Further, patients with the islet abnormalities had higher fasting plasma glucose concentrations 2 years after the biopsy than at the time of the biopsy (p < 0.05). CONCLUSION/INTERPRETATION: The heterogeneous clinical course observed following diagnosis in patients with Type I diabetes correlates with islet immunological abnormalities. Insulitis and hyperexpression of MHC class I correlate with deteriorating glycaemic control.

Adolescent↗

PubMed1999

Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization.

AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of the type 3 form of maturity-onset diabetes of the young. We examined the clinical features and molecular basis of hepatocyte nuclear factor-1alpha (HNF-1alpha) diabetes. METHODS: Thirty-seven Japanese subjects with early onset Type II (non-insulin-dependent) diabetes mellitus and 45 with Type I (insulin-dependent) diabetes mellitus were screened for mutations in this gene. Functional properties of mutant HNF-1alpha were also investigated. RESULTS: Three new mutations [G415R, R272C and A site of the promoter (+ 102G-to-C)] were found. Insulin secretion was impaired in the three subjects. Insulin and glucagon secretory responses to arginine in the subject with the R272C mutation were also diminished. Molecular biological studies indicated that the G415R mutation generated a protein with about 50% of the activity of wild-type HNF-1alpha. The R272C mutation had no transactivating or DNA binding activity and acted in a dominant negative manner. The + 102 G-to-C mutation in the A site of the promoter activity was associated with an increase in promoter activity and it had 42-75% more activity than the wild-type sequence. CONCLUSION/INTERPRETATION: Mutations in the HNF-1alpha gene may affect the normal islet function by different molecular mechanisms.

Adult↗

PubMed1999

Fas and Fas ligand expression in inflamed islets in pancreas sections of patients with recent-onset Type I diabetes mellitus.

AIMS/HYPOTHESIS: Type I (insulin-dependent) diabetes results mainly from T-cell-mediated autoimmune destruction of pancreatic beta cells. Cytotoxic T lymphocytes destroy target cells via a perforin-based or Fas-based mechanism. Our previous study indicated that the Fas-Fas ligand (FasL) pathway is required for the development of autoimmune diabetes in the NOD mouse. We now investigated whether or not the Fas-FasL system is involved in the beta-cell destruction in human Type I diabetes. METHODS: We immunohistochemically analysed pancreas biopsy specimens of 13 recent-onset patients. RESULTS: Pancreatic islets were identified but showed various degrees of reduction in beta-cell volume in all patients. Out of 13 patients 6 had insulitis. In these 6 patients Fas was expressed in both the islets and infiltrating cells but not in either cell type in the 7 other patients without insulitis. Double immunostaining showed that Fas was positive in 92.2 to 97.7 % of beta cells but only in 17.6 to 46.7 % of alpha cells in Fas-positive, insulin-remaining islets. We found FasL was expressed exclusively in islet-infiltrating cells in patients with insulitis. Double immunostaining revealed that the most prevalent phenotype of FasL-positive cells was CD8, which was followed by macrophages and CD4. CONCLUSION/INTERPRETATION: The interaction between Fas on beta cells and FasL on infiltrating cells might trigger selective apoptotic beta-cell death in inflamed islets, leading to immune-mediated Type I diabetes. [Diabetologia (1999) 42: 1332-1340]

Adolescent↗

PubMed1999

An inverse correlation between serum leptin levels and hemoglobin A1c in patients with non-insulin dependent diabetes mellitus.

We measured serum leptin concentrations in 70 patients with diabetes mellitus to investigate the relationship between serum leptin levels and glycemic control. A positive correlation between serum leptin levels and body mass index or plasma insulin was obtained as reported previously. The present study also demonstrated an inverse association of serum leptin levels with hemoglobin A1c (HbA1c). Multiple regression analysis revealed that HbA1c was an independent determinant of serum leptin levels. These results suggest that HbA1c may be a factor to influence serum leptin levels and that hyperglycemia for a long period or poorly controlled diabetes may reduce leptin levels.

Adult↗

PubMed1999

Electromyographic examination of jaw muscles in relation to symptoms and occlusion of patients with temporomandibular joint disorders.

Clinical/occlusal scores and jaw-muscle EMGs were recorded in 24 TMD symptomatic (group S) and 20 normal (group N) subjects to evaluate the significance of EMG parameters and their clinical associations. Results indicated: (1) integrated EMG activity (IEMG) was larger at the rest position (RP) in anterior temporalis (Ta) but smaller at maximal voluntary clenching (MVC) in masseter (Ma) and Ta, and the ratios of IEMG at 70%MVC to the corresponding bite force (70%BF) were greater in group S; (2) mean power frequency (MPF) were almost the same in both groups but its shift was more rapid in group S; (3) silent period duration (SPD) was longer in group S; (4) asymmetry indices for SPD and silent period latency (SPL) were larger in group S; (5) muscle pain was associated negatively with IEMG at MVC and 70%BF but positively with IEMGs at RP and 70%MVC, and impaired jaw movements were associated negatively with the above EMG values; (6) muscle pain was positively associated with SPD in Ma, while joint pain and sound showed positive and negative associations with SPD, respectively; (7) associations between occlusion and EMG parameters were found more in group N. These findings verify: (1) jaw elevators in TMD may have hyper-tonic activities and a weak functional efficiency; (2) jaw muscles in TMD may become easily fatigued following a functional effort, and less relaxed following a muscle twitch; (3) the severity of pain could not be reflected in EMG activities, but impaired jaw movement may increase tonic activity and decrease functional effort; (4) TMD symptoms may alter the functional adaptation of jaw-muscle activities and occlusion.

Adaptation, Physiological↗

PubMed1999

In vitro assessment of a chemically synthesized Shiga toxin receptor analog attached to chromosorb P (Synsorb Pk) as a specific absorbing agent of Shiga toxin 1 and 2.

A synthetic analog of Shiga toxin (Stx) receptor (Synsorb Pk) was quantitatively assessed to determine whether it can protect human renal adenocarcinoma cells (ACHN cells) from the cytotoxicity of Stx1 and Stx2 by coincubation experiments. Coincubation of 100 and 20 ng of Stxl and Stx2 with 50 mg of Synsorb Pk for 1 hr at 37 C in 1 ml of Eagle's Minimum Essential Medium supplemented with 1% (v/v) non-essential amino acid and 10% (v/v) fetal calf serum protected 50% of the cells from the cytotoxic effect. Chromosorb P, an inert matrix control, did not absorb the Stxs at all. Heat-treatment (boiled for 10 min) to Synsorb Pk caused a 50% decrease in Stx2-binding activity, but did not effect the Stx1 binding. Further, Stxs bound to Synsorb Pk could be demonstrated. When 20 mg of Synsorb Pk was coincubated for 30 min at 37 C in 1 ml of phosphate-buffered saline with 1 and 10 ng or more of Stx1 or Stx2, respectively, the toxins could be detected on the surface when the bound toxins on Synsorb Pk were used as the solid phase in enzyme immunoassay. The amount of 100 ng/ml of both Stxl and Stx2 appeared to saturate 20 mg/ml of Synsorb Pk after coincubating for 30 min at 37 C. While assessing the Stxs' binding activity to Synsorb Pk, it was demonstrated that Stxl had a higher affinity to Pk trisaccharide than Stx2. These observations provide useful information on the effectiveness of Synsorb Pk to trap and eliminate free Stxs produced in the gut of patients infected by Stx-producing Escherichia coli, and to prevent the progression of hemorrhagic colitis to hemolytic uremic syndrome.

Bacterial Toxins↗

PubMed1999

Genetic vulnerability of cortical neurons isolated from stroke-prone spontaneously hypertensive rats in hypoxia and oxygen reperfusion.

Severe hypertension and cerebrovascular diseases develop in stroke-prone spontaneously hypertensive rats (SHRSP). Cortical neurons from SHRSP are more vulnerable than those from Wistar Kyoto rats (WKY) to the effects of nitric oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. Growth factors, idebenone, and nilvadipine (a Ca2+ channel blocker) can reduce neuronal damage caused by hypoxia or neurotoxic agents. This study was designed to determine 1) whether cortical neurons from SHRSP are more vulnerable than those from WKY and 2) whether neuronal damage is minimized by the so-called neuroprotective agents in cells exposed to hypoxia and oxygen reperfusion. We demonstrated that 6 to 24 h of hypoxia did not increase cell death in either WKY or SHRSP, whereas 36 h of hypoxia significantly increased cell death in SHRSP (p < 0.01). Furthermore, 6 to 36 h of hypoxia and 1.5 to 5 h of reperfusion heavily damaged cells from both strains of rats, and most cells became apoptotic or necrotic. We also verified that the ability to protect neurons in hypoxia and oxygen reperfusion was as follows: idebenone > insulin-like growth factor-1 (IGF-1) > nilvadipine. These data indicate that oxygen radical generation occurs and the free radicals heavily damage neurons in hypoxia and oxygen reperfusion. SHRSP neurons are weaker than WKY neurons in these conditions. Furthermore, we surmise that idebenone, an antioxidant, decreases free radicals, and IGF-I attenuates p53-mediated apoptosis and thereby prevents cell death. We conclude that antioxidants are more potent than IGF-1 in protecting cortical neurons from damage caused by hypoxia and oxygen reperfusion, although both are very useful in minimizing damage to cortical neurons.

Animals↗

PubMed1999

Immunohistochemical localization of betacellulin, a new member of the EGF family, in normal human pancreas and islet tumor cells.

Betacellulin (BTC) purified from mouse beta cell tumor (betaTC-3) is a new member of the epidermal growth factor (EGF) family which can bind receptor tyrosine kinase, EGF receptor (erbB1) and erbB4. It has been demonstrated that proBTC mRNA was abundantly expressed in human pancreas tissue, and that BTC converted amylase-secreting rat acinar cell line (AR42J) into insulin-secreting cells, suggesting that BTC might be important for the growth and/or differentiation of islet cells. However, the cell type producing BTC in the pancreas has not been clarified. In this study, we examined the localization of BTC in human pancreas and islet cell tumors. Immunohistochemistry using specific antibodies to human BTC revealed that this protein was produced in alpha cells and duct cells, and probably in beta cells in normal adult pancreas. Furthermore, strong immunoreactivity to BTC was detected in primitive duct cells of the fetal pancreas, and both insulinoma and glucagonoma cells also showed positive immunoreactivity to BTC. EGF receptor (erbB1) and erbB4 were expressed mainly in islet and duct cells, and duct cells, respectively. These results demonstrate the localization of BTC and its receptors, and suggest that BTC may be one of the factors that have physiologically important roles such as growth and differentiation of islet cells in the human pancreas.

Adenoma, Islet Cell↗

PubMed1999

Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats.

Cerebral ischemia followed by oxygen reperfusion induced apoptosis in hippocampal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats. Oxygen radicals were involved in reoxygenation injury after hypoxia in hippocampal slices. Vitamin E inhibited the reoxygenation injury in cultured cortical neurons. In addition, the temporal cortices in Alzheimer's disease have increased sensitivity to oxygen radicals, and Vitamin E slowed the progression of the disease. Thus we fed Wistar Kyoto and SHRSP rats either a normal diet or a high Vitamin E diet for 3 weeks. We measured Vitamin E concentrations of plasma and brain by applying the HPLC method. Vitamin E increased its concentration in plasma, cerebral cortex, and hippocampus (p < 0.01) during a 3-week pretreatment. In addition, we clipped both common carotid arteries in these rats for 30 minutes. After the blocking, the rats were reperfused for 6 and 9 days, respectively, and then killed. We cut the brains coronally, removed the hippocampal CA1 regions, and examined the neurons using an electron microscope. SHRSP rats with normal cerebral circulation had 30.4+/-8.0 apoptotic neurons per 1000 neurons. Cerebral ischemia followed by 6 and 9 days of reperfusion, respectively, increased apoptotic neurons in SHRSP rats fed a normal diet (6 days: 542.5+/-154.1 per 1000 neurons; 9 days: 657.5+/-110.2 per 1000 neurons). In contrast, apoptotic neurons in SHRSP rats fed a high Vitamin E diet were significantly (p < 0.01) small in number (6 days: 41.3+/-27.5 per 1000 neurons; 9 days: 35.5+/-19.7 per 1000 neurons) even though the rats were treated in the same way. These data demonstrate that oxygen radical generation occurs after reperfusion and that free radicals heavily damage the neurons in SHRSP rats. Vitamin E reacts with the radicals and prevents neuronal apoptosis caused by cerebral ischemia and reperfusion. Therefore, Vitamin E seems to be an important agent in lowering radical damage to hippocampal neurons.

Animals↗

PubMed1999

[A case of nephrotic syndrome associated with myasthenia gravis and malignant thymoma].

A 26-year-old woman who presented facial and lower leg edema associated with massive proteinuria was admitted to our hospital in February 1992. Nine months before this admission, she exhibited myasthenia gravis and malignant thymoma, and underwent total thymectomy. On admission, there was no symptom of myasthenia gravis. She was diagnosed as having nephrotic syndrome and the first renal biopsy was performed. The histological findings showed membranous nephropathy. Immunofluorescent microscopy revealed that IgG and C3 were stained in a granular pattern in the periphery, and subepithelial deposits were observed in the basement membrane of the glomerulus by electron microscopy. With the administration of prednisolone, proteinuria disappeared and the nephrotic syndrome remitted. She was admitted again in January 1993 due to proteinuria and lower leg edema following cystitis. The findings of the second renal biopsy were unremarkable. She was administered cyclosporin A to improve the nephrotic syndrome and to reduce the side effects of prednisolone. The proteinuria disappeared again and this effect was dependent on the dose of cyclosporin A. Since the first administration, no symptoms of myasthenia gravis or malignant thymoma have been observed. The relationships among myasthenia gravis, malignant thymoma and nephrotic syndrome were examined. Although the first renal biopsy findings showed membranous nephropathy, from the therapeutic responses of both prednisolone and cyclosporin A, the main course of proteinuria in this case may have been due to minimal change nephrotic syndrome. We consider this case of nephrotic syndrome to be important considering its etiology and the relationship between the histological findings and its clinical course.

Adult↗

PubMed1999

[A case of extragonadal germ cell tumor with inferior vena caval tumor thrombus].

We report a case of retroperitoneal extragonadal germ cell tumor with tumor thrombus in the inferior vena cava. The patient referred to our hospital with lumbago. Computed tomography (CT) showed a bulky mass in the retroperitoneum. The levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-HCG) in the serum were elevated. Histological examinations indicated embryonal cell carcinoma. Bilateral testicles did not contain any palpable mass upon careful palpation. No tumor mass was detected in the bilateral testicles on ultrasonography. Clinically, the diagnosis was a retroperitoneal extragonadal germ cell tumor associated with para-aortic lymph-node involvement. After the combination chemotherapy (BEP 1 course and EP 3 courses), the tumor mass was reduced in size and the tumor marker was normalized. Retroperitoneal lymph node dissection (RPLND) was performed and tumor thrombus in the inferior vena cava was resected. There was no involvement of the viable cells in the resected tumor. The patient has been in good condition with no evidence of disease.

Adult↗

PubMed1998

Bloom's and Werner's syndrome genes suppress hyperrecombination in yeast sgs1 mutant: implication for genomic instability in human diseases.

Bloom's syndrome (BS) and Werner's syndrome (WS) are genetic disorders in which an increased rate of chromosomal aberration is detected. The genes responsible for these diseases, BLM and WRN, have been found to be homologs of Escherichia coli recQ and Saccharomyces cerevisiae SGS1 genes. Here we show that yeast Sgs1 helicase acts as a suppressor of illegitimate recombination through homologous recombination and that human BLM and WRN helicases can suppress the increased homologous and illegitimate recombinations in the S. cerevisiae sgs1 mutant. The results imply a role of BLM and WRN helicases to control genomic stability in human cells. Similar to Sgs1 helicase, BLM helicase suppressed the cell growth in the top3 sgs1 mutation background and restored the increased sensitivity of the sgs1 mutant to hydroxyurea, but the WRN helicase did not. We discussed differential roles of BLM and WRN helicases in human cells. BLM- and WRN-bearing yeasts provide new useful models to investigate human BS and WS diseases.

Base Sequence↗

PubMed1998

Two novel testicular serine proteases, TESP1 and TESP2, are present in the mouse sperm acrosome.

To identify a novel candidate(s) for acrosomal proteins that act on the sperm/egg interaction, a DNA fragment was PCR-amplified from a cDNA library of acrosin-deficient mouse testis and then used as a probe to screen a mouse testis cDNA library. Complementary DNA clones encoding each of two similar but different serine proteases, TESP1 and TESP2, have been identified. The nucleotide sequences of these clones indicate that mouse TESP1 and TESP2 are initially synthesized as preproproteins of 367 and 366 amino acids, respectively. Comparison of the two TESP sequences with those of typical serine proteases suggests that each TESP zymogen is probably converted into a two-chain mature enzyme consisting of light and heavy chains covalently linked by a single pre-existing disulfide bond. The conversion may be accomplished by another protease(s) with a trypsin-like cleavage specificity, since it is unlikely that the mature TESP1 and TESP2 are capable of splitting the Lys-Ile bond between the light and heavy chains. Northern blot analysis of total cellular RNA demonstrates that the TESP1 and TESP2 genes are expressed only in the testis, and the transcripts are abundantly present in the haploid round spermatids. Moreover, immunocytochemical analysis of mouse cauda epididymal sperm using affinity-purified antibodies reveals that these two TESPs are both localized in the sperm acrosome and are released during the acrosome reaction induced by calcium ionophore A23187. These findings provide additional clues for elucidating the mechanisms involved in the sperm/egg interactions, including penetration of the zona pellucida by sperm.

Acrosome↗

PubMed1998

Acrosin accelerates the dispersal of sperm acrosomal proteins during acrosome reaction.

Using homologous recombination, we have previously produced male mice carrying a disruptive mutation (Acr-/-) in the acrosin gene. Although Acr-/- mouse sperm lacking the acrosin protease activity still penetrated the zona pellucida and fertilized the egg, the mutant sperm exhibited a delay in penetration of the zona pellucida solely at the early stages after insemination. To further elucidate the role of acrosin in fertilization, we have examined the involvement of acrosin in the acrosome reaction of sperm using the Acr-/- mutant mice. When the ability of sperm to adhere (attach) and bind to the zona pellucida of cumulus-free eggs was assessed in vitro, no significant difference was observed among Acr+/+, Acr+/-, and Acr-/- mouse sperm. Immunocytochemical analysis demonstrated that the release of several acrosomal proteins from the acrosome of Acr-/- mouse sperm was significantly delayed during the calcium ionophore- and solubilized zona pellucida-induced acrosome reaction, despite normal membrane vesiculation. These data indicate that the delayed sperm penetration of the zona pellucida in the Acr-/- mouse results from the altered rate of protein dispersal from the acrosome and provide the first evidence that the major role of acrosin is to accelerate the dispersal of acrosomal components during acrosome reaction.

Acrosin↗

PubMed1998

"Physiological" age as an outcome predictor for abdominal surgery in elderly patients.

It would seem that a large discrepancy exists between the "chronological" age and "apparent" age of elderly patients, and we often observe that the latter reflects the results of surgical procedures very well. In the present study, we reviewed 258 patients aged 70 years or older who underwent elective abdominal operations under general anesthesia, to evaluate an outcome predictor representing their "physiological" age. A total of 24 preoperative variables were compared between patients who left the hospital in a satisfactory condition, being survivors, and those who died in hospital despite the operative procedure performed, being nonsurvivors. In the group of patients aged between 70 and 79 years, there was no significant difference between the survivor and nonsurvivor groups for any of the variables examined; however, in the group of patients aged over 80 years old, the oldest of whom was 93 years, there were significant differences in the total lymphocyte count (TLC) and the performance status (PS), as well as in age, between the survivor and nonsurvivor groups. Utilizing the three variables of age, PS, and TLC, a computer-generated discriminant function analysis yielded an equation which discriminated survival with 97% accuracy, and mortality with 83% accuracy. These findings indicate that the PS and TLC scores added to the chronological age should be considered when deciding whether a surgical procedure is appropriate for an elderly patient.

Age Factors↗

PubMed1998

Cyclooxygenase-2 is induced in brain blood vessels during fever evoked by peripheral or central administration of tumor necrosis factor.

Cyclooxygenase-2 (COX-2) is an inducible type of enzyme that is involved in prostaglandin biosynthesis. In the present study, we examined whether or not COX-2 is involved in fever that is induced by tumor necrosis factor-alpha (TNF-alpha) and, if so, where in the brain COX-2 is induced by this factor. Intraperitoneal (i.p.) injection of TNF-alpha into rats evoked a fever that started 1 h after the TNF injection, peaked 3 h after the injection, and then gradually declined. The fever was suppressed by pretreatment with a COX-2-specific inhibitor. With a time course similar to that of fever, COX-2 mRNA was induced in brain blood vessels. On the other hand, in some of the telencephalic neurons, COX-2 mRNA was constitutively expressed under the normal condition; but its level gradually decreased during the course of fever. Fever was also evoked by an intracerebroventricular (i.c.v.) injection of TNF-alpha. This febrile response was also suppressed by a COX-2 specific inhibitor and was associated with the induction of COX-2 mRNA in the brain blood vessels. On the other hand, the telencephalic neurons did not show consistent change in COX-2 mRNA level after i.c.v. injection of TNF-alpha or saline. COX-2-like immunoreactivity was found in some cells of the brain blood vessels 3 h after the TNF-alpha injection by either i.p. or i.c.v. route. Most of the COX-2-like immunoreactive cells were endothelial cells since COX-2-like immunoreactivity was colocalized with von Willebrand factor, an endothelial cell marker, in the same cells. These results suggest that the brain blood vessels are the major sites where TNF-alpha enhances PG biosynthesis after peripheral as well as after central injection, and provides further evidence supporting the hypothesis that COX-2 induced in the brain blood vessels is involved in fever.

Animals↗

PubMed1998

p-Aminobenzamidine-sensitive acrosomal protease(s) other than acrosin serve the sperm penetration of the egg zona pellucida in mouse.

It has been reported that a significant delay in protein dispersal from the acrosomal matrix is observed in wild-type sperm by adding p-aminobenzamidine, a trypsin/acrosin inhibitor, to the incubation medium. The pattern of this delayed release was similar to that of the acrosin-deficient mutant mouse sperm (Yamagata et al., J. Biol. Chem., 273, 10470-4, 1998). In the present study, no further delay in protein dispersal was found when the acrosin-deficient sperm were treated with p-aminobenzamidine, indicating that among the p-aminobenzamidine-sensitive protease(s) only acrosin may function to accelerate this process. Although the acrosin-deficient sperm penetrated the zona pellucida (Baba et al., J. Biol. Chem., 269, 31845-9, 1994), the addition of p-aminobenzamidine to the fertilisation medium caused a significant inhibition of fertilisation in vitro. This indicates that there is a p-aminobenzamidine-sensitive protease(s) other than acrosin participating in the zona penetration step. Indeed, we demonstrated that a non-acrosin protease with a size of 42 kDa was present in the supernatant of the acrosome-reacted sperm suspension. The enzyme was inhibited by p-aminobenzamidine, diisopropyl fluorophosphate and N alpha-tosyl-L-lysine chloromethyl ketone, and was apparently activated by acrosin.

Acrosin↗

PubMed1998

Gastrointestinal cancer metastasis and lymphogenous spread: viewpoint of animal models of lymphatic obstruction.

Primary gastrointestinal cancer frequently spreads to the mesentery, omentum and other parts of the peritoneum and these deposits are generally considered to be induced by intraperitoneal seeding from the primary lesion. In this work, we examined the spread of gastrointestinal cancer from the viewpoint of lymphogenous metastasis using a rat model of mesenteric lymph vessel obstruction. With these models, we carried out mesenteric lymphangiography on the fourth and sixth postoperative days (five animals each) to examine morphological changes in the lymph vessels and lymph flow. In model animals with mesenteric lymph vessel obstruction, re-celiotomy, performed on the fourth postoperative day, revealed marked mesenteric edema and enlargement of the mesenteric lymph nodes, suggestive of lymph retention. We also carried out mesenteric lymphangiography and obtained images of extensive mesenteric lymph vessels and reflux of lymph distal to the obstruction point in all five animals. On the sixth postoperative day, we obtained lymphangiographic images of lymphatico-venous communication in the mesentery in all five animals. Thus in animals with lymph vessel obstruction, the lymph flow appeared to change to lymphatico-venous communication or reverse lateral flow. In clinical cases, it is conceivable that lymph retention and reflux of lymph induced by lymph vessel obstruction sometimes play a role in the mechanism of intraperitoneal cancer dissemination and hematogenous metastasis.

Animals↗