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Biomedical subjects

K Mori

Publications and source records attributed to K Mori.

At least 271 records · Page 15Linked to original sources

Convergence of segregated pheromonal pathways from the accessory olfactory bulb to the cortex in the mouse.

The accessory olfactory system mediates intraspecies pheromonal communication. Two subsets of spatially segregated vomeronasal sensory neurons, presumably handling functionally and structurally different sets of ligand molecules, can be distinguished. The two subsets of sensory neurons project their axons to segregated zones of the accessory olfactory bulb (AOB) and connect with zonally separated mitral/tufted (M/T) cells, suggesting that the accessory olfactory system is divided into two distinct pathways up to the level of the AOB. To examine whether the segregation is maintained at the accessory olfactory cortical (AOC) regions, we selectively tracer-labelled mitral/tufted cells located in the rostral, caudal or in both zones of the adult mouse AOB. The results demonstrate that the axonal projection patterns of rostral zone and caudal zone M/T cells were indistinguishable in the AOC regions. Mitral/tufted cell axons from either zone of the AOB covered the entire area of all four AOC regions: the bed nucleus of the accessory olfactory tract, the medial amygdaloid nucleus, the posteromedial cortical amygdaloid nucleus and the bed nucleus of the stria terminalis. Therefore, over the entire area of each AOC region, ensembles of cortical neurons receive input from both zonal subsets of M/T cells of the AOB. However, the present results do not rule out the possibility that individual cortical neurons sample information from M/T cells of a single zone. These results are consistent with the idea that the segregation of zonal pathways collapses in the AOC regions. Clusters of cortical neurons in each AOC region may combine information from both families of pheromone receptors and thus handle signals from structurally and functionally different categories of pheromone molecules.

Animals↗

S-allylcysteine ameliorates doxorubicin toxicity in the heart and liver in mice.

Doxorubicin, a potent anticancer drug, is effective against a wide range of human neoplasms. However, the clinical uses of doxorubicin have been limited due to its serious cardiotoxic effects, which are likely the result of generation of free radicals and lipid peroxidation. S-Allylcysteine (SAC), an organosulfur compound purified from garlic, has been reported to have antioxidant and radical scavenging effects. Thus, we examined the effect of SAC on doxorubicin toxicity in mice. Severe doxorubicin toxicity was induced in mice by a single intraperitoneal injection (15 mg/kg body weight). SAC (30 mg/kg) was injected intraperitoneally daily for 5 days, starting two days prior to the administration of doxorubicin. Body weight was measured every alternate day. A measurement of serum creatine phosphokinase (CPK) and a histopathological analysis of the heart and liver was performed 6 days after the administration of doxorubicin. Death of any of the animals was recorded during the observation period. Doxorubicin injection induced a mortality rate of 58%, with SAC treatment reducing the doxorubicin-induced mortality rate to 30%. The severe body weight loss caused by doxorubicin (13%) was also significantly attenuated by SAC treatment (9%). Although an elevation of the level of serum CPK was observed following doxorubicin injection (5472 +/- 570 i.u./L), treatment with SAC significantly reduced the level of CPK (1923 +/- 635 i.u./L). Histological analysis demonstrated that heart and liver damage was significantly less severe in SAC treated mice than in mice receiving only doxorubicin. These results suggest that SAC research may ultimately lead to a resolution of the adverse effects of doxorubicin treatment in cancer chemotherapy.

Animals↗

Cyclic variation of integrated ultrasound backscatter in the left ventricle during the early neonatal period.

BACKGROUND: Significant changes in the contractility and histologic structure of the ventricular myocardium occur during the early neonatal period. Cyclic variation (CV) of ultrasonic integrated backscatter (IBS) reflects myocardial contractile performance. The aim of this study was to define normal values of and its serial changes in CV of IBS in the left ventricle of normal neonates. METHODS AND RESULTS: We recorded long-axis IBS images in 169 healthy neonates within 14 days after birth (mean 4.6 +/- 4.2 days) and in 84 infants and children (mean age 8.7 +/- 5.2 years). For each, we obtained CV of IBS in the interventricular septum (CV(IVS)) and the posterior wall (CV(PW)). In neonates, there was a significant linear correlation between CV and date after birth in measurements of both the interventricular septum and the posterior wall (r = 0.57 and 0. 60, respectively). In infants and children, there was no significant relation between age and CV(IVS) or CV(PW). In neonates >4 days after birth, the magnitude of CV(IVS) was not significantly different from that in infants or children. By contrast, the magnitude of CV(PW) was still significantly decreased in neonates >9 days after birth compared with that in infants and children (P <. 005). The ratio of CV(IVS) to CV(PW) (CV(IVS)/CV(PW)) was significantly higher in neonates than in infants and children (0.99 +/- 0.29 vs 0.80 +/- 0.22, P <.001). CONCLUSIONS: Both CV(IVS) and CV(PW) in neonates gradually increase after birth, indicating developmental maturation of the left ventricle. High values of CV(IVS)/CV(PW) might reflect the remnant of relatively high contractile performance in the right ventricle during fetal life.

Adolescent↗

Left ventricular wall motion velocities in healthy children measured by pulsed wave Doppler tissue echocardiography: normal values and relation to age and heart rate.

Left ventricular wall motion velocities were measured by pulsed wave Doppler tissue (PWDT) echocardiography in 131 healthy children (mean age 7.5 +/- 5.5 years) at the interventricular septum and the posterior wall in the left ventricular short-axis view, and at the interventricular septum and the lateral wall in the 4-chamber view. The systolic wave (Sw) consisted of 2 components, and the difference between the 2 components was greater in the lateral wall than in the other walls. The peak early diastolic wave (Ew) velocity was also highest in the lateral wall. Most variables during systole correlated with age. The ratio of peak atrial systolic wave (Aw) velocity to peak Ew velocity (Aw/Ew) correlated with heart rate. The Aw/Ew in each wall correlated with the ratio of late (A) to early (E) peak mitral flow, although regression slopes differed among different wall segments. In younger children with increased heart rates, the Aw/Ew ratio increased because the Ew velocity decreased, although the A/E ratio increased because of an increased A velocity. Normal values for the PWDT variables change with heart rate and age in the pediatric population. The data reported in this study can be used as normal values for left ventricular function for PWDT echocardiography.

Adolescent↗

Subglottic airway becomes stable with age in the human infant larynx.

Development of the mucosal defence system and its relationship to the pathogenesis of laryngeal diseases was studied by examining the changes in the laryngeal structures at the level of subglottic larynx of 59 human infants who died within 1 year of birth. By making a transverse section at the level of the cricoid cartilage, the area and diameter of each subglottic structure were examined using an image analysis system. The results were analysed, not only by their age at death, but also based on the total development score. The areas of the whole structure, cricoid ring, subglottic mucosa and inner cavity (available area) increased in close correlation with the total development score. In contrast to the increased diameter of the inner cavity, the thickness of the mucosa was almost the same size. These results indicate the stability of the subglottic airway with advancing age in the human infant larynx.

Age Factors↗

Antitumor effect and peritumoral brain edema formation in relation to MX2, ACNU, and doxorubicin therapy: a comparative analysis using rodent models of gliomas.

The potential antitumor effect of MX2, a new lipophilic morpholino anthracycline, was compared with those of ACNU or doxorubicin (DOX) using two different rodent glioma models. A mouse subcutaneous glioma model (203 glioma) was used to measure the effect of each drug on reducing the glioma size and a rat 9L intracerebral glioma model (9L glioma) was used to assess the antitumor effect on survival rate in a clinically similar fashion. Treatment with ACNU inhibited tumor growth by 94.6% (p < 0.0001) and complete regression of the tumor was observed in 3 of 25 (12.0%) of the ACNU-treated cases. Tumor growth was inhibited by 32.4% with DOX despite a tendency (p < 0.16) and by 59.4% with MX-2 (p < 0.001); neither of these drugs resulted in complete tumor regression. In the intracerebral glioma rats, only ACNU tended to ameliorate survival rate, but there was no statistical significance. These results suggest that ACNU has the most potent effect but MX2 can be an option for chemotherapy of malignant gliomas. Interestingly, all three drugs significantly elevated the brain water content on both the ipsilateral and contralateral sides of the tumor, although they did not induce brain edema in the normal rat brains. Careful management of brain edema might be required regardless of the drug used during chemotherapy to maximize the prognosis of glioma patients.

Animals↗

Actualities in hydrocephalus classification and management possibilities.

Retrospective analysis in co-operative study of hydrocephalus at institutions of members of the Research Committee on Intractable Hydrocephalus sponsored by the Ministry of Health and Welfare of Japan was performed to determine the functional prognosis. For clinico-epidemiological study we classified non-tumoral hydrocephalus into eight types based on its etiology and the time of onset. Analysis of the 1,450 cases of hydrocephalus stored in the database obtained from the study was performed in order to find intractable factors in terms of factors related to patients and management. Analysis of the cases stored in the database revealed that the following types and conditions were found to be intractable factors: 1. Early fetal hydrocephalus. 2. Overt neonatal hydrocephalus. 3. Hydrocephalus associated with such severe brain malformations as hydranencephaly, holoprosencephaly and lissencephaly. 4. Hydrocephalus associated with severe brain damage. 5. Hydrocephalus associated with epilepsy. 6. Hydrocephalus shunted late after detection. 7. Hydrocephalus complicated by a shunting operation. It is impossible to determine prior to treatment whether or not a shunting operation is indicated for the patient with intractable factors, however, they may be a useful pre-operative indicator of prognosis. For the management of hydrocephalus, secondary intractable hydrocephalus may be preventable if we treat it appropriately before it becomes intractable.

Adult↗

Efficacy of temporal musculopericranial flap for reconstruction of the anterior base of the skull.

Since March 1988 the temporal musculopericranial (TMP) flap has been used as our flap of choice to reconstruct defects of the anterior base of the skull that are larger than 2 x 3 cm, including the dura mater, in 33 patients. The primary diseases were malignant head and neck tumours (n = 16), trauma (n = 15), meningioma (n = 1), and teratoma (n = 1). The dura mater was reconstructed with a unilateral TMP flap, after which the cranial and nasal cavities were closed with the opposite TMP flap. In addition, bone was grafted by sandwiching the bone between the two flaps and fixing it to the surrounding residual bone. When a large area was resected, making it impossible to use a TMP flap, a frontal musculopericranial (FMP) flap or a free flap (usually the rectus abdominis myocutaneous flap) was used to close the cranial and nasal cavities. Thirty of the 33 patients recovered with no postoperative complications. Two patients developed extradural abscesses in the anterior base of the skull and one developed mild meningitis, but they were successfully treated conservatively. When bilateral TMP flaps were used for the reconstruction, no patient had aesthetic problems in the forehead region. The TMP flap is extremely effective for the reconstruction of the anterior base of the skull because it is minimally invasive and causes few aesthetic problems in the forehead region.

Adolescent↗

Mitogen-activated protein kinase, ERK1/2, is essential for the induction of vascular endothelial growth factor by ionizing radiation mediated by activator protein-1 in human glioblastoma cells.

Vascular Endothelial Growth Factor (VEGF)/Vascular Permeability Factor plays an important role in angiogenesis and cell proliferation of cancer cells. Glioblastoma cells are most malignant and show resistance to radiation therapy inducing VEGF to cause angiogenesis and brain edema. In the present study, the regulatory mechanism of the expression of VEGF by ionizing radiation was studied in three human glioblastoma cells. Induction of VEGF mRNA by ionizing radiation was dependent on dose and incubation time. Activator protein-1 (AP-1) was activated by 10 Gy of ionizing radiation in 1 h in T98G glioblastoma cells on an electrophoretic mobility shift assay. We constructed chimeric genes containing various regions of the VEGF promoter gene and the coding region for chloramphenicol acetyltransferase (CAT) and transiently transfected them to T98G cells. CAT assay with the VEGF promoter gene containing an AP-1 site demonstrated that the promoter activity of the VEGF gene was enhanced by ionizing radiation. Immunological analysis of the activity of mitogen-activated protein kinase, ERK1/2, showed that this activity is up-regulated by ionizing radiation. These results suggest that ERK1/2 pathway is involved in the up-regulation of VEGF expression ionizing radiation mediated by AP-1, which may lead to further neovascularization and proliferation of glioblastoma cells resistant to radiation therapy.

Blotting, Northern↗

Relationship between intraocular pressure and obesity in Japan.

BACKGROUND: Some cross-sectional studies have suggested that age, systolic blood pressure and obesity are positively related to intraocular pressure (IOP), but few longitudinal studies have examined this relationship. This study was carried out to evaluate the association between intraocular pressure and obesity by cross-sectional and longitudinal analyses in a large Japanese population. METHODS: Data were collected from annual health examinations between 1989 and 1997 and reviewed retrospectively. Subjects of the cross-sectional analysis were 70 139 males and females aged 14-94 years. Among these subjects, 25 216 males and females who had undergone IOP measurements more than three times were analysed longitudinally. The association between IOP and obesity was examined cross-sectionally and longitudinally. RESULTS: Cross-sectional analysis: The mean IOP at the last visit was 11.6 mmHg. The IOP decreased gradually with age and was significantly higher in males than in females in almost all age groups. Body mass index (BMI) significantly correlated with IOP after controlling for age, gender and blood pressure. Longitudinal analysis: There was a significant association between longitudinal change in IOP and change in weight. This relationship remained significant after controlling for initial BMI, initial blood pressure, change in blood pressure, gender and age. CONCLUSION: This study showed a significant association between IOP and obesity in both cross-sectional and longitudinal analysis. These findings suggest that obesity is an independent risk factor for increase in IOP.

Adolescent↗

Computed tomographic fluoroscopy-guided transthoracic needle biopsy for diagnosis of pulmonary nodules.

BACKGROUND: The purpose of this study was to evaluate the usefulness of computed tomographic (CT) fluoroscopy-guided transthoracic needle biopsy (TTNB) with an 18-gauge automatic biopsy gun for the diagnosis of pulmonary nodules. METHODS: Between March 1996 and January 1998, 50 patients in whom pulmonary lesions could not be diagnosed cytopathologically with fiberoptic bronchoscopy or were not clearly visualized with fluoroscopy underwent CT fluoroscopy-guided TTNB. RESULTS: Final pathological diagnoses were 23 lung carcinomas, five pulmonary metastases and 22 benign lesions. Sufficient tissue for analysis was obtained from 48 of the 50 lesions (96%). The overall diagnostic yield of CT fluoroscopy-guided TTNB was 90%. The sensitivity, specificity and accuracy for malignancy were 89%, 100% and 94%, respectively. In 20 of the 22 cases (91%) of benign lesions, histological analysis yielded correct and specific diagnoses. Complications occurred in 22 of the 50 cases (44%). The most common complication was pneumothorax, which occurred in 21 of the 50 cases (42%). Chest tube insertion was required in 6 (12%). CONCLUSIONS: Although CT fluoroscopy could not decrease the complication rate, CT fluoroscopy-guided TTNB with an automatic biopsy gun appears to be a promising technique for diagnosing pulmonary lesions, particularly benign lesions.

Adenocarcinoma↗

Polymorphic CAG repeats of the androgen receptor gene in Japanese male patients with ankylosing spondylitis.

OBJECTIVE: In view of a possible role of androgens in the pathogenesis of ankylosing spondylitis (AS), we investigated the association between Japanese male patients with AS and CAG microsatellites of the androgen receptor (AR) gene which related to the AR transactivation function. METHODS: Peripheral blood was collected from 39 men with AS and 305 male control subjects. The number of CAG repeats in exon 1 of the AR gene was determined. RESULTS: CAG repeat lengths in AS patients were significantly shorter than those in the controls (median value 22 vs 23; P = 0.03). However, there was no significant difference in CAG repeats between HLA-B27-positive and -negative patients (median value 22 vs 22; P = 0.78). CONCLUSIONS: Shorter CAG repeats of the AR gene, presenting high levels of transactivation activity, may play a role in male AS.

Adolescent↗

Methanocalculus pumilus sp. nov., a heavy-metal-tolerant methanogen isolated from a waste-disposal site.

A mesophilic hydrogenotrophic methanogen, strain MHT-1T, was isolated from the leachate of a sea-based site for solid waste disposal (the port of Osaka, Japan). Strain MHT-1T was found to be an irregular coccus and was able to use H2/CO2 and formate as energy sources. Acetate was required for growth. The optimum temperature and pH for growth were 35 degrees C and 6.5-7.5, respectively. Strain MHT-1T was resistant to high concentrations of several heavy metals such as CdCl2 and CuSO4. The G+C content of the DNA was 51.9 mol%. Analysis of the 16S rRNA gene revealed that the isolate was a member of the genus Methanocalculus but distinct from its nearest neighbour, Methanocalculus halotolerans, there being a sequence similarity of 98.9%. DNA-DNA hybridization analysis revealed 51% relatedness with the DNA of M. halotolerans strain SEBR 4845T. The optimum NaCl concentration was 1.0%, whereas the optimum in M. halotolerans was 5.0%. A new species, Methanocalculus pumilus, is proposed for strain MHT-1T. The type strain is MHT-1T (= DSM 12632T = JCM 10627T).

Base Composition↗

Automated anatomical labeling of the bronchial branch and its application to the virtual bronchoscopy system.

This paper describes a method for the automated anatomical labeling of the bronchial branch extracted from a three-dimensional (3-D) chest X-ray CT image and its application to a virtual bronchoscopy system (VBS). Automated anatomical labeling is necessary for implementing an advanced computer-aided diagnosis system of 3-D medical images. This method performs the anatomical labeling of the bronchial branch using the knowledge base of the bronchial branch name. The knowledge base holds information on the bronchial branch as a set of rules for its anatomical labeling. A bronchus region is automatically extracted from a given 3-D CT image. A tree structure representing the essential structure of the extracted bronchus is recognized from the bronchus region. Anatomical labeling is performed by comparing this tree structure of the bronchus with the knowledge base. As an application, we implemented the function to automatically present the anatomical names of the branches that are shown in the currently rendered image in real time on the VBS. The result showed that the method could segment about 57% of the branches from CT images and extracted a tree structure of about 91% in branches in the segmented bronchus. The anatomical labeling method could assign the correct branch name to about 93% of the branches in the extracted tree structure. Anatomical names were appropriately displayed in the endoscopic view.

Algorithms↗

Effect of age on the relationship between gastric cancer and Helicobacter pylori. Tokyo Research Group of Prevention for Gastric Cancer.

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10-year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20 - 29, 14.5 for those aged 30 - 39, 9.1 for those aged 40 - 49, 3.5 for those aged 50 - 59, and 1.5 for those aged 60 - 69 (trend in odds ratios: P < 0.01). However, there was no such age-dependent trend for early diffuse-type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P = 0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age-class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age-dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age-independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and / or irreversible damage to gastric mucosa in childhood or the teenage years.

Adult↗

Suppression of acute viremia by short-term postexposure prophylaxis of simian/human immunodeficiency virus SHIV-RT-infected monkeys with a novel reverse transcriptase inhibitor (GW420867) allows for development of potent antiviral immune responses resulting in efficient containment of infection.

A nonnucleoside reverse transcriptase (RT) inhibitor, GW420867, was tested for postexposure prophylaxis (PEP) in rhesus macaques experimentally infected with 100 50% tissue culture infective doses of a chimeric simian/human immunodeficiency virus (SHIV) containing the RT gene of HIV-1 (SHIV-RT). Animals were either mock treated, or treated for 4 weeks starting at 8 or 24 h postinfection (p.i.) with GW420867. While such therapy led to undetectable plasma viremia in three of six monkeys, a transient plasma viremia was noted in the other three treated animals at 2 to 4 weeks following cessation of therapy. Following this transient viremia all drug-treated animals showed low or undetectable levels of plasma viremia up to the last sample examined at 90 weeks p.i. Despite low and/or undetectable viremia, virus-specific cytotoxic T lymphocyte and viral Env-specific proliferative responses were seen in the peripheral blood mononuclear cells of both mock- and drug-treated animals as early as 3 weeks p.i. Such virus-specific cellular responses, however, were better maintained in the drug-treated animals than the mock-treated animals. In contrast to the virus-specific cellular response, the magnitude and kinetics of virus specific humoral responses appeared to correlate with the detection of viremia. These data support the view that a short-term PEP with GW420867 permits the generation and maintenance of long-lasting virus-specific cell-mediated immune responses while markedly reducing viral loads to undetectable levels for a prolonged period of time (90 weeks) and leads to long-term disease protection. This model provides a unique means to define mechanisms and correlates of disease protection.

Animals↗

Mechanisms for adaptation of simian immunodeficiency virus to replication in alveolar macrophages.

In contrast to the simian immunodeficiency virus SIVmac239, which replicates poorly in rhesus monkey alveolar macrophages, a variant with nine amino acid changes in envelope (SIVmac239/316E) replicates efficiently and to high titer in these same cells. We examined levels of viral DNA, RNA, antigen, and infectious virus to identify the nature of the block to SIVmac239 replication in these cells. Low levels of viral antigen (0.1 to 1.0 ng of p27 per ml) and infectious virus (100 to 1,000 infectious units per ml) were produced in the supernatant 1 to 4 days after SIVmac239 infection, but these levels did not increase subsequently. SIVmac239 DNA was synthesized in these macrophage cultures during the initial 24 h after infection, but the levels did not increase subsequently. Quantitation of the numbers of infectious cells in cultures over time and the results of experiments in which cells were reexposed to SIVmac239 after the initial exposure indicated that only a small proportion of cells were susceptible to SIVmac239 infection in these alveolar macrophage cultures and that the vast majority (>95%) of cells were refractory to SIVmac239 infection. In contrast to the results with SIVmac239, the levels of viral antigen, infectious virus, and viral DNA increased exponentially 2 to 7 days after infection by SIVmac239/316E, reaching levels greater than 100 ng of p27 per ml and 100,000 infectious units per ml. Since SIVmac239/316E has previously been described as a virus capable of infecting cells in a relatively CD4-independent fashion, we examined the levels of CD4 expression on the surface of fresh and cultured alveolar macrophages from rhesus monkeys. The levels of CD4 expression were extremely low, below the limit of detection by flow cytometry, on greater than 99% of the macrophages. CCR5(+) cells were profoundly depleted only from alveolar macrophage cultures infected with SIVmac239/316E. High concentrations of an antibody to CD4 delayed but did not block replication of SIVmac239/316E. The results suggest that the adaptation of SIVmac316 to efficient replication in alveolar macrophages results from its ability to infect these cells in a CD4-independent fashion or in a CD4-dependent fashion even at extremely low levels of surface CD4 expression. Since resident macrophages in brains and lungs of humans also express little or no CD4, our findings predict the presence of human immunodeficiency virus type 1 that is relatively CD4 independent in the lung and brain compartments of infected people.

Adaptation, Physiological↗

Sli2 (Ypk1), a homologue of mammalian protein kinase SGK, is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast.

ISP-1 is a new type of immunosuppressant, the structure of which is homologous to that of sphingosine. In a previous study, ISP-1 was found to inhibit mammalian serine palmitoyltransferase, the primary enzyme involved in sphingolipid biosynthesis, and to reduce the intracellular pool of sphingolipids. ISP-1 induces the apoptosis of cytotoxic T cells, which is triggered by decreases in the intracellular levels of sphingolipids. In this study, the inhibition of yeast (Saccharomyces cerevisiae) proliferation by ISP-1 was observed. This ISP-1-induced growth inhibition was also triggered by decreases in the intracellular levels of sphingolipids. In addition, DNA duplication without cytokinesis was detected in ISP-1-treated yeast cells on flow cytometry analysis. We have cloned multicopy suppressor genes of yeast which overcome the lethal sphingolipid depletion induced by ISP-1. One of these genes, SLI2, is synonymous with YPK1, which encodes a serine/threonine kinase. Kinase-dead mutants of YPK1 did not show any resistance to ISP-1, leading us to predict that the kinase activity of the Ypk1 protein should be essential for this resistance to ISP-1. Ypk1 protein overexpression had no effect on sphingolipid biosynthesis by the yeast. Furthermore, both the phosphorylation and intracellular localization of the Ypk1 protein were regulated by the intracellular sphingolipid levels. These data suggest that the Ypk1 protein is a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. The Ypk1 protein was reported to be a functional homologue of the mammalian protein kinase SGK, which is a downstream kinase of 3-phosphoinositide-dependent kinase 1 (PDK1). PDK1 phosphotidylinositol (PI) is regulated by PI-3,4,5-triphosphate and PI-3,4-bisphosphate through the pleckstrin homology (PH) domain. Overexpression of mammalian SGK also overcomes the sphingolipid depletion in yeast. Taking both the inability to produce PI-3,4, 5-triphosphate and PI-3,4-bisphosphate and the lack of a PH domain in the yeast homologue of PDK1, the Pkh1 protein, into account, these findings further suggest that yeast may use sphingolipids instead of inositol phospholipids as lipid mediators.

Fatty Acids, Monounsaturated↗