Biomedical subjects

H Nakano

Publications and source records attributed to H Nakano.

At least 109 records · Page 6Linked to original sources

PubMed2001

Synthesis of coenzyme A esters of 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oic acids for the study of beta-oxidation in bile acid biosynthesis.

3alpha,7alpha,12alpha-Trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl CoAs were chemically synthesized by the conventional method for the study of side chain cleavage in bile acid biosynthesis. 3alpha,7alpha,12alpha-Triformyloxy- and 3alpha,7alpha-diformyloxy-5beta-cholan-24-als were initially subjected to the Reformatsky reaction with methyl alpha-bromopropionate, and the products were then converted into methyl 3alpha,7alpha,12alpha-triformyloxy- and 3alpha,7alpha-diformyloxy-24-oxo-5beta-cholestan-26-oates. Protection by acetalization of the 24-oxo-group of these methyl esters with ethylene glycol, followed by alkaline hydrolysis, gave 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24,24-ethylenedioxy-5beta-cholestan-26-oic acids. These acids were condensed with coenzyme A by a mixed anhydride method, and the resulting CoA esters were treated with 4M-hydrocholic acid to remove the protecting group to give 24-oxo-5beta-cholestanoic acid CoA esters. The chromatographic behaviors of these CoA esters were also investigated.

Bile Acids and Salts↗

PubMed2001

Conjugation reactions catalyzed by bifunctional proteins related to beta-oxidation in bile acid biosynthesis.

The conjugation reactions of hydration and dehydrogenation catalyzed by the dehydratase and dehydrogenase activities of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (DBP) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein (LBP) in the side chain degradation step of bile acid biosynthesis were investigated using chemically synthesized C27-bile acid CoA esters as substrates. The hydration catalyzed by DBP showed high diastereoselectivity for (24E)-3alpha,7alpha,12alpha-trihydroxy- and (24E)-3alpha,7alpha-dihydroxy-5beta-cholest-24-en-26-oyl CoA to give (24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy- and (24R,25R)-3alpha,7alpha,24-trihydroxy-5beta-cholestan-26-oyl CoAs, respectively, and the dehydrogenation catalyzed by DBP also showed high stereospecificity for the above (24R,25R)-isomers to give 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl CoAs, respectively. On the other hand, the dehydratase activity of LBP displayed a different diastereoselectivity producing the (24S,25S)-isomer, and dehydrogenase activity of LBP was stereospecific for the (24S,25R)-isomer to give the above 24-oxo-derivative. The hydration and dehydrogenation reactions catalyzed by DBP were effectively conjugated to convert (24E)-5beta-cholestenoyl CoA to 24-oxo-5beta-cholestanoyl CoA. However, the reactions catalyzed by LBP were not conjugated. These results indicate that DBP plays an important role in the biosynthesis of bile acid.

17-Hydroxysteroid Dehydrogenases↗

PubMed2001

Diurnal variation of eye movement and heart rate variability in the human fetus at term.

To elucidate diurnal variations in eye movement and fetal heart rate (FHR) variability in the term fetus, we observed these two parameters continuously for 24 h, using real-time ultrasound and Doppler cardiotocograph, respectively. Studied were five uncomplicated fetuses at term. The time series data of the presence and absence of eye movement and mean FHR value for each 1 min were analyzed using the maximum entropy method (MEM) and subsequent nonlinear least squares fitting. According to the power value of eye movement, all five cases were classified into two groups: three cases in the large power group and two cases in the small power group. The acrophases of eye movement and FHR variability in the large power group were close, thereby implying the existence of a diurnal rhythm in both these parameters and also that they are synchronized. In the small power group, the acrophases were separated. The synchronization of eye movement and FHR variability in the large power group suggests that these phenomena are governed by a common central mechanism related to diurnal rhythm generation.

Adult↗

PubMed2001

Diurnal changes in the power spectral characteristics of eye movements and heart rate variability in the human fetus at term.

It is well known that 1/f characteristics in power spectral patterns exist in various biological factors including heart rate variability. In the present study, we tried to elucidate the diurnal variation in spectral properties of eye movement and heart rate variability in the human fetus at term, via continuous 24-h observation of both these parameters. Studied were five uncomplicated fetuses at term. We observed eye movement and fetal heart rate (FHR) with real-time ultrasound and Doppler cardiotocograph, respectively, and analyzed the diurnal change in spectral properties, using the maximum entropy method. In four of five cases, the slope values of power spectra for both eye movement frequency and FHR, ranging approximately between 0.5 and 1.8, indicated diurnal variation, where the slopes tended to have high values during the day and low values at night. These findings suggest that, in the human fetus at term, eye movement and FHR are under the control of a common central mechanism, and this center changes its complexity as seen through diurnal rhythm.

Adult↗

PubMed2001

The characterization of superoxide production of human neonatal neutrophil.

To assess the role of neutrophil in neonatal host defense against microbial infection, we characterized the superoxide anion (O(2-)) production of neonatal neutrophil on a biochemical basis. After taking an appropriate informed consent, neutrophils were obtained from cord blood immediately after transvaginal delivery and divided into two groups: the Preterm group, 15 neonates (27-36 weeks' gestation) and the Term group, 15 neonates (37-41 weeks' gestation). Eleven healthy adults served as controls in the Adult group. The value of N-formyl-methionyl-leucyl-phenylalanin (fMLP)-induced O(2-) production activity of neutrophils in the Preterm group using chemiluminescence assay was significantly lower than those values in both the Term and Adult groups (5.77+/-0.53x10(6) vs. 11.1+/-0.94x10(6) and 10.7+/-0.63x10(6) cpm; mean+/-S.E.M., p<0.05). In phorbol 12-myristate 13-acetate (PMA)-stimulation, the values of O(2-) production activity of neutrophils in both the Preterm and Term groups were significantly lower than that in the Adult group (13.0+/-1.66x10(6) and 18.0+/-1.44x10(6) vs. 27.3+/-1.45x10(6) cpm, p<0.05). Scatchard analysis of [(3)H]fMLP binding to neutrophil demonstrated a two-receptor model in each group, and the number of high-affinity receptors per neutrophil in the Preterm group was significantly lower than those in other groups (p<0.05). However, cord blood levels of proinflammatory cytokines, such as interleukin (IL)-6, -8, and tumor necrosis factor-alpha (TNF-alpha) did not differ in either neonatal group. These results indicated that the fMLP-induced O(2-)production activity of neutrophils in the term neonates was enhanced at the level of the receptor and suggested that this enhanced production contribute to the neonatal host defense against microbial infection.

Adult↗

PubMed2001

Doppler velocimetry in the adrenal artery in human fetuses.

BACKGROUND: Fetal hypoxia and/or acidosis causes redistribution of blood flow to the high-priority organs including the adrenal glands. Although this phenomenon is well described in the human cerebral and placental circulations using Doppler velocimetry, there are few reports about the adrenal glands. AIM: To clarify the gestational age-related changes in adrenal blood flow in normal fetuses and fetuses at risk of hemodynamic derangement. MATERIAL AND METHODS: In 153 normal cases, the resistance indices (RIs) calculated from the blood flow velocity waveforms (FVWs) in the middle adrenal artery (MAA) were obtained from 24 weeks to construct nomogram using regression analysis. Twenty-seven complicated cases were divided according to the 5%ile RI values in the MAA, and clinical outcomes were retrospectively compared. RESULT: The RI values in the MAA increased until 31 weeks and decreased thereafter. The 50%ile regression curve was represented as RI=-0.000914 (weeks)(2)+0.0579 weeks-0.181. Of the 27 complicated cases, 13 had RIs in the MAA below the 5%ile. Cases with low RI had significantly higher RI ratio in regard of UA/MCA; higher occurrence of abnormal FHR patterns on observation; higher incidence of cesarean delivery for nonreassuring fetal well-being status; earlier gestational age at delivery; lower birth weights and longer periods of admission to NICU than the cases with normal RI. CONCLUSION: We have described the nomogram for the RI in the MAA. In conditions of fetal hypoxia or acidemia, blood flow redistribution to the adrenal glands may occur and the analysis of the adrenal artery FVWs may be useful in detection of fetal altered hemodynamics.

Adrenal Glands↗

PubMed2001

Repeat liver resection for hepatocellular carcinoma.

BACKGROUND: Although hepatectomy has been accepted as a therapeutic option for the primary tumor of hepatocellular carcinoma (HCC), what role the second liver resection will play in the clinical care of patients with intrahepatic recurrence of HCC after the initial resection has not been well evaluated. STUDY DESIGN: In a retrospective review of the 6-year period between January 1991 and December 1996, records were examined of 94 patients who underwent curative liver resection for HCC. Of these, 57 patients had isolated recurrent disease to the liver; 12 of the 57 patients underwent repeat surgical resection and 45 patients received nonsurgical ablative therapy. Clinical data for these patients were reviewed for operative morbidity and mortality, survival, disease-free survival, and pattern of failure. RESULTS: There were no perioperative deaths during repeat liver resections for recurrent HCC. Operative morbidity in the second resection was comparable to the initial resection. The disease-free survival rate after the second hepatectomy was 31% at 2 years, significantly lower than that after initial hepatectomy (62%) (p = 0.009). The overall survival rate after the second hepatectomy was 90% at 2 years, in contrast to 70% after nonsurgical ablative treatment for recurrent HCC (p = 0.253). CONCLUSIONS: Although the second liver resection for recurrent HCC can be performed safely and may improve survival, the disease-free survival rate after such resection therapy is low. This likelihood of further recurrences encourages studies for the selection of patients who may benefit from repeat liver resection.

Aged↗

PubMed2001

Congestion of superior mesenteric veins and small bowel mucosal injury after endoscopic treatment of esophageal varices in patients with portal hypertension.

We investigated treatment-induced changes in venous return from the small bowel and small bowel intestinal mucosal injury induced by the treatment of esophageal varices in patients with portal hypertension. A total of 14 patients (age 59.8+/-9.5 years, five women and 9 men) who received prophylactic treatment of esophageal varices between December 1998 and March 1999 were investigated. Diamine oxidase (DAO) activity was measured before and after treatment. Changes in blood flow of the portal and superior mesenteric veins were investigated by Doppler ultrasonography in six patients. A significant decrease in DAO activity was observed three days after treatment (11.5+/-1.6 units/liter prior to treatment versus 8.6+/-1.6 units/liter three days after treatment; P < 0.001). Decreases in superior mesenteric and portal venous flow velocity were observed in four and three patients, respectively. In two patients with an increase in the cross-sectional area of the superior mesenteric vein with delayed venous return, a marked decrease in DAO activity was observed three days after treatment. In patients with portal hypertension, rapid reduction of pooling of portal flow caused by the treatment of esophageal varices can induce transient congestion of the mesenteric venous system which can produce some small bowel mucosal injury.

Amine Oxidase (Copper-Containing)↗

PubMed2001

Cytotoxic effects of soluble factor in preeclamptic sera on human trophoblasts.

Evidence indicating abnormal biological behavior of trophoblasts has been seen in preeclamptic patients, but the mechanism is still unknown. We have previously shown that endothelial injury and neutrophil activation are induced by certain factors in preeclamptic sera. We investigated the effect of sera from eight preeclamptic and 11 normal pregnant women on cellular proliferation and viability of trophoblasts using 3H-thymidine incorporation and the trypan-blue dye exclusion test, respectively. Five of eight preeclamptic sera, but none of the normal pregnant sera, inhibited 3H-thymidine incorporation. The trypan-blue test revealed the sera reduced cellular viability. Gel permeation showed that the greatest growth-inhibitory activity corresponded to a molecular weight of 50 kDa. The serum-mixing test revealed this permeation and inhibitory preeclamptic sera suppressed the growth-promoting activity of normal pregnant sera in a dose-dependent manner. These results suggested the presence of certain factors in some preeclamptic sera that can affect cellular behavior of human trophoblasts.

Adult↗

PubMed2001

Characterization of EP receptor subtypes responsible for prostaglandin E2-induced pain responses by use of EP1 and EP3 receptor knockout mice.

Prostaglandin E2 (PGE2) is known to be the principal pro-inflammatory prostanoid and play an important role in nociception. To identify PGE receptor (EP) subtypes that mediate pain responses to noxious and innocuous stimuli, we studied them by use of EP1 and EP3 knockout (EP1(-/-) and EP3(-/-)) mice. PGE2 could induce mechanical allodynia in EP1(+/+), EP3(+/+) and EP3(-/-) mice, but not in EP1(-/-) mice. N-methyl-D-aspartate (NMDA), the substrate of nitric oxide (NO) synthase L-arginine, or the NO donor sodium nitroprusside administered intrathecal (i.t.) could induce allodynia in EP3(-/-) and EP1(-/-) mice. Activation of EP1 receptors appears to be upstream, rather than downstream, of NMDA receptor activation and NO production in the PGE2-induced allodynia. Although PGE2 produced thermal hyperalgesia over a wide range of dosages from 50 pg to 0.5 microg kg(-1) in EP3(+/+) mice, it showed a monophasic hyperalgesic action at 5 ng kg(-1) or higher doses in EP3(-/-) mice. The selective EP3 agonist, ONO-AE-248, induced hyperalgesia at 500 pg kg(-1) in EP3(+/+) mice, but not in EP3(-/-) mice. Saline-injected EP1(-/-) mice showed hyperalgesia, which was reversed by i.t. PGE2 in a dose-dependent manner. There was no significant difference in the formalin-induced behaviours between EP1(-/-) or EP3(-/-) mice and the cognate wild-type mice. These results demonstrate that spinal EP1 receptors are involved in the PGE2-induced allodynia and that spinal EP3 receptors are involved in the hyperalgesia induced by low doses of PGE2. However, the formalin-induced pain cannot be ascribed to a single EP receptor subtype EP1 or EP3.

Animals↗

PubMed2001

Mechanism of trypsin-induced contraction in the rat myometrium: the possible involvement of a novel member of protease-activated receptor.

1. The mechanism of trypsin-induced contraction in the rat myometrium was investigated using front-surface fluorimetry on fura-PE3-loaded strips. The expression of protease-activated receptors (PARs) in the rat myometrium was determined by reverse transcription polymerase chain reaction (RT - PCR). 2. In non-pregnant rats, 10 microM trypsin developed a force of up to 30.5 +/- 5.1% of that obtained during the 40 mM K(+)-depolarization-induced contraction. In pregnant rats, the maximal level of the cytosolic Ca(2+) concentration and tension obtained with 3 microM trypsin was 143.2 +/- 6.0% and 63.2 +/- 7.9%, respectively. The depletion of the extracellular Ca2+ abolished the trypsin-induced contraction. 3. Trypsin-induced contraction was abolished by the pre-treatment of a serine protease inhibitor. PAR1-activating peptide (PAR1-AP) caused a potent contraction of the myometrium, while neither PAR2-AP nor PAR4-AP induced any contraction. 4. RT - PCR analysis detected the expression of PAR1 mRNA. However, neither PAR2 nor PAR4 mRNA was detected in the rat myometrium. 5. Once the strips were stimulated with thrombin, the subsequent application of thrombin failed to induce any contraction, while trypsin induced a contraction similar to that observed without the pre-stimulation with thrombin. Once the strip was stimulated with trypsin, neither trypsin nor thrombin induced any contraction. The response to PAR1-AP remained after the pre-stimulation with thrombin and trypsin. 6. In conclusion, PAR1 was the only known receptor for trypsin expressed in the rat myometrium, but it was suggested to be cleaved and inactivated by trypsin. Trypsin was thus suggested to contract the rat myometrium via a novel type of PAR, which might be upregulated during pregnancy.

Animals↗

PubMed2001

NMDA receptor-mediated modulation of ventilation in obese Zucker rats.

BACKGROUND: Ventilation in response to hypoxia is reduced in some obese humans and is believed to represent part of the pathogenesis of obesity hypoventilation syndrome (OHS). Ventilation in response to hypoxic exposure is closely related to the release of excitatory neurotransmitters, in particular glutamate, acting specifically on N-methyl-D-aspartate (NMDA) receptors. OBJECTIVES: The aim of the present study was to investigate whether NMDA receptor-mediated mechanisms are responsible for the altered ventilatory response to sustained hypoxia observed in obese Zucker (Z) rats. SUBJECTS: Seven lean and seven 15-week-old obese male Z rats were studied. MEASUREMENTS: Ventilation ([V](E)) at rest and during 30 min sustained hypoxic (10% O(2)) exposure was measured by the barometric method. [V](E) was assessed following the blinded-random administration of equal volumes of either saline (vehicle) or dextromethorphan (DM, 10 mg/kg), a non-competitive glutamate NMDA receptor antagonist. RESULTS: DM had no effects on resting [V(E) in both lean and obese rats during room air breathing. Lean rats treated with DM exhibited a significant (P<0.05) depression in [V](E), V(T), and V(T)/T(I) during either the early (5 min) or the late phase (30 min) of ventilatory response to sustained hypoxia. In contrast, DM administration in obese rats did not change [V(E), V(T), or V(T)/T(I) during the early phase of ventilatory response to hypoxia. During the late phase of ventilatory response to hypoxia. obese rats treated with DM exhibited a similar depression in [V](E) and V(T) as observed in lean rats, but had no significant change in V(T)/T(I) during the 30 min hypoxic exposure. CONCLUSION: Our findings indicate that altered glutamatergic mechanisms acting on NMDA receptors are partially responsible for a blunted early phase of ventilatory response to hypoxia noted in obese rats and also contribute to their reduced neural respiratory drive.

Animals↗

PubMed2001

A new and simple Doppler method for measurement of fetal cardiac isovolumetric contraction time.

OBJECTIVES: The fetal cardiac isovolumetric contraction time is defined as the interval between mitral valve closure and aortic valve opening. The objective of this study was to develop a simple and reliable Doppler method for measuring fetal isovolumetric contraction time using a digital filtering and processing system. METHODS: Cardiac Doppler signals were recorded from 40 fetuses at 18-40 weeks' gestation using a continuous-wave ultrasound transducer. The raw signal was digitized, filtered and divided into five different frequency ranges: 250-375, 375-500, 500-750, 750-1000 and 1000-1500 Hz. To determine the most suitable filter setting for detecting mitral valve closure and aortic valve opening signals, we examined whether they were detected clearly in each filter range. RESULTS: Both mitral valve closure and aortic valve opening signals were detected clearly in the 500-1000 Hz range. The atrioventricular flow and outflow noises in the 250-500 and 1000-1500 Hz ranges helped us to identify the signals. It was found that dividing the raw signals into three ranges of 250-500, 500-1000 and 1000-1500 Hz was the most suitable digital-filter setting for measuring isovolumetric contraction time. CONCLUSIONS: We have developed a simple Doppler method for measuring fetal isovolumetric contraction time. The advent of digital processing has simplified the equipment and the simultaneous multidisplay of three different filtered signals enables easy and accurate measurement.

Aortic Valve↗

PubMed2001

Characterization of mouse mammary tumour virus-induced migration of lymphoid cells into lymph nodes.

We previously found that Mtv-2+ lymph nodes (LN) implanted into Mtv-2- mice underwent marked hyperplasia owing to the influx of lymphocytes. LN grafts infected with exogenous mouse mammary tumour viruses (MMTV), MMTV(FM) transmitted by FM mice and MMTV-2 produced by Mtv-2, also swelled in MMTV-free recipients. Mtv-3 and Mtv-7 also displayed this capability. Mtv-2-induced LN hyperplasia was earlier in onset and greater in extent when major histocompatibility complex (MHC) class II I-E was expressed than unexpressed. Mtv-3-induced LN hyperplasia was suppressed completely by Mtv-3 from a different mouse strain and partially by Mtv-6 slightly different from Mtv-3 in superantigen (SAg) Vbeta specificity. LN hyperplasia occurred bidirectionally in LN transplantation between mice carrying Mtv-2 and Mtv-3, which are different SAg Vbeta specificity. LN hyperplasia induced by MMTV-2 carrying SAg responsive to Vbeta14 alone and MMTV(FM) carrying SAg responsive to Vbeta14 and Vbeta8.2 was completely but partially suppressed by MMTV(FM) and MMTV-2, respectively. CD4+ T cells were essential for MMTV-induced LN hyperplasia. LN in situ also underwent significant hyperplasia when infected with MMTV. Thus, MMTV SAg may entice circulating lymphocytes into lymphoid organs and contribute to more efficient dissemination MMTV in vivo. Secondary lymphoid tissue chemokine (SLC) may not be directly involved in this event.

Animals↗

PubMed2001

Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-alpha for Crohn's disease in Japan: evaluation by rapid turnover proteins, and radiologic and endoscopic findings.

BACKGROUND: Several studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)-alpha (Infliximab) is extremely valuable in the treatment of Crohn's disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohn's disease. METHODS: A 12-week multicenter, open trial of Infliximab was carried out and involved 25 patients with moderate to severe Crohn's disease who were resistant to conventional treatment. Patients received a single 2-h intravenous infusion of Infliximab at a dose of 1, 3, 5 or 10 mg/kg bodyweight. Clinical evaluation of this treatment response was defined as a reduction in the index of the inflammatory bowel disease (IOIBD) and of the Crohn's disease activity index scores (CDAI), and in serum levels of C-reactive protein (CRP) at 2, 4, 8 and 12 weeks, and as an increase in serum levels of rapid turnover proteins as well as improvement of radiologic and endoscopic findings at 4 weeks. RESULTS: The IOIBD score was reduced after 4 weeks in 66.7% of the group receiving 1 mg/kg Infliximab, 71.4% in the group receiving 3 mg/kg, 80.0% in the group receiving 5 mg/kg, and 85.7% in the group receiving 10 mg/kg. Improvement was better maintained over 12 weeks in the 5 and 10 mg/kg groups compared with the 1 and 3 mg/kg groups. Similar results were obtained for the CDAI scores. Serum levels of rapid turnover proteins significantly increased to within the normal ranges after infusion in all groups. Seven of the 11 (63.6%) patients evaluated showed improvement of radiologic and endoscopic findings. CONCLUSIONS: A single infusion of Infliximab was effective for the treatment of Japanese patients with Crohn's disease. Serum rapid turnover proteins reflected the clinical response to antibody for TNF-alpha well.

Adult↗

PubMed2001

Mycobacterium tuberculosis infection within Warthin's tumor: report of two cases.

We report two patients with Warthin's tumor who were also infected with Mycobacterium tuberculosis. Case 1 was a 75-year-old woman with Warthin's tumor and multiple small epithelioid granulomas with caseous necrosis involving the submandibular gland. This patient died of tuberculous meningitis 4 months after biopsy. Case 2 was a 78-year-old man with a 10-year history of a parotid mass which had enlarged rapidly over 2 months. Surgical excision revealed Warthin's tumor and epithelioid granulomas involving the left parotid gland. DNA extracted from paraffin sections was amplified by nested polymerase chain reaction (PCR) with primer sets for the mycobacterial 65-KDa antigen gene. Restriction enzyme digestion of the PCR products could differentiate Mycobacterium tuberculosis from other mycobacteria in both cases. Although the histogenesis of lymphoid components of Warthin's tumor is controversial, the frequent prevalence of inflammation or necrosis and our present findings suggest these components have a similar behavior to regional lymph nodes.

Adenolymphoma↗

PubMed2001

Hypoxic ventilatory depression in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.

We describe a case of a 21-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.

Adenosine↗

PubMed2001

Papillon-Lefèvre syndrome: mutations and polymorphisms in the cathepsin C gene.

The Papillon-Lefèvre syndrome, inherited in an autosomal recessive pattern, manifests with palmoplantar keratoderma and early, destructive periodontitis. Recently, mutations in the gene encoding cathepsin C have been disclosed in a limited number of families with Papillon-Lefèvre syndrome. We have examined two multiplex families with Papillon-Lefèvre syndrome, and evaluated the gene encoding cathepsin C for mutations. The mutation detection strategy consisted of polymerase chain reaction amplification of all seven exons and flanking intronic sequences, followed by direct nucleotide sequencing. This strategy identified two missense mutations, W39S and G301S, affecting highly conserved amino acid residues within the cathepsin C polypeptide. The affected individuals were homozygotes whereas heterozygous carriers of the mutations were clinically unaffected, confirming the recessive nature of the mutations. Addition of these cathepsin C gene mutations into the expanding Papillon-Lefèvre syndrome mutation database allows further development of genotype/phenotype correlations towards understanding this severe genodermatosis.

Cathepsin C↗