A comparison of gastric emptying of soluble solid meals and clear fluids matched for volume and energy content: a pilot crossover study.

We previously demonstrated that the gastric emptying time of different liquids with the same volume mainly depended on their energy content, regardless of differences in composition. In this crossover study, we investigated whether the same applies when soluble solid foods are ingested with water. Ten healthy volunteers ingested one of five test diets consisting of two test meals (Calorie Mate® 100 and 200 kcal) and three test solutions (water and glucose solutions of 100 and 200 kcal), each given in a volume of 400 ml, and then underwent ultrasonography to measure the gastric antral cross-sectional area every 10 min for 120 min. The gastric emptying time was defined as the time for the antral cross-sectional area to revert to its initial value. When test diets with the same energy content were ingested, the gastric emptying curves were nearly identical, regardless of whether the original form was solid or liquid. The median (IQR[range]) gastric emptying times of Calorie Mate® of 100 kcal with water vs. isocaloric glucose solution were 65 (60-78 [50-80]) vs. 65 (60-70 [50-80]) min (p = 0.58), and for Calorie Mate® of 200 kcal with water vs. isocaloric glucose solution they were 100 (93-108 [90-120]) vs. 105 (90-110 [90-120]) min (p = 0.54). The median (IQR [range]) for water was 40 (30-40 [30-50]) min. Energy content may be a critical determinant of the gastric emptying time when ingesting soluble solid diets with water.

Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS.

Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B, IL6, IL10, TNFA, IL1RN, SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN, the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls (p=0.0067), and A allele at rs4251981 in 5' upstream of IL1RN with borderline significance (p=0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40-10.8, p=0.0057). For SCN1A, no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A, the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance (p=0.011). We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases.

Characterization of SPATA5-related encephalopathy in early childhood.

Mutations in SPATA5 have recently been shown to result in a phenotype of microcephaly, intellectual disability, seizures, and hearing loss in childhood. Our aim in this report is to delineate the SPATA5 syndrome as a clinical entity, including the facial appearance, neurophysiological, and neuroimaging findings. Using whole-exome sequencing and Sanger sequencing, we identified three children with SPATA5 mutations from two families. Two siblings carried compound heterozygous mutations, c.989_991del (p.Thr330del) and c.2130_2133del (p.Glu711Profs*21), and the third child had c.967T>A (p.Phe323Ile) and c.2146G>C (p.Ala716Pro) mutations. The three patients manifested microcephaly, psychomotor retardation, hypotonus or hypertonus, and bilateral hearing loss from early infancy. Common facies were a depressed nasal bridge/ridge, broad eyebrows, and retrognathia. Epileptic spasms or tonic seizures emerged at 6-12 months of age. Interictal electroencephalography showed multifocal spikes and bursts of asynchronous diffuse spike-wave complexes. Augmented amplitudes of visually evoked potentials were detected in two patients. Magnetic resonance imaging revealed hypomyelination, thin corpus callosum, and progressive cerebral atrophy. Blood copper levels were also elevated or close to the upper normal levels in these children. Clinical delineation of the SPATA5-related encephalopathy should improve diagnosis, facilitating further clinical and molecular investigation.

Determinants of liquid gastric emptying: comparisons between milk and isocalorically adjusted clear fluids.

BACKGROUND: Although current preoperative fasting guidelines apply restrictions to drinks containing milk because of delayed gastric emptying, the safe volume of milk that can be consumed up to 2 h before surgery on a theoretical basis has not yet been defined. We aimed to determine whether delayed gastric emptying depended mainly on the total amount of calories irrespective of compositional differences between milk and clear fluids. METHODS: We prepared five beverages with a uniform volume (500 ml) and step-wise increments in calories (0, 220, and 330 kcal), comprised mainly of non-human milk, pulpless orange juice, water, and gum syrup. The gastric emptying rate of each beverage was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by eight healthy fasting volunteers. RESULTS: The emptying rates of 500 ml of orange juice and 330 ml of non-human milk with 170 ml of water (both were 220 kcal) from the stomach were similar. Furthermore, 450 ml of orange juice with 50 ml of gum syrup and 500 ml of non-human milk (both were 330 kcal) left the stomach at similar rates. The 220 kcal beverages emptied faster than the 330 kcal beverages. CONCLUSIONS: There were no significant differences in liquid gastric emptying after drinking equal volumes of either orange juice or milk as long as both had the same amount of calories. Liquid gastric emptying depends chiefly on the total caloric content. CLINICAL TRIAL REGISTRATION: UMIN000012537.

Computerized method for estimation of the location of a lung tumor on EPID cine images without implanted markers in stereotactic body radiotherapy.

The purpose of this study was to develop a computerized method for estimation of the location of a lung tumor in cine images on an electronic portal imaging device (EPID) without implanted markers during stereotactic body radiotherapy (SBRT). Each tumor region was segmented in the first EPID cine image, i.e., reference portal image, based on a multiple-gray level thresholding technique and a region growing technique, and then the image including the tumor region was cropped as a 'tumor template' image. The tumor location was determined as the position in which the tumor template image took the maximum cross-correlation value within each consecutive portal image, which was acquired in cine mode on the EPID in treatment. EPID images with 512 x 384 pixels (pixel size: 0.56 mm) were acquired at a sampling rate of 0.5 frame s(-1) by using energies of 4, 6 or 10 MV on linear accelerators. We applied our proposed method to EPID cine images (226 frames) of 12 clinical cases (ages: 51-83, mean: 72) with a non-small cell lung cancer. As a result, the average location error between tumor points obtained by our method and the manual method was 1.47 +/- 0.60 mm. This preliminary study suggests that our method based on the tumor template matching technique might be feasible for tracking the location of a lung tumor without implanted markers in SBRT.

Effect of 8-MHz radiofrequency-capacitive regional hyperthermia with strong superficial cooling for unresectable or recurrent colorectal cancer.

A well-known disadvantage of a radiofrequency-capacitive device for deep-seated tumours is preferential heating of the subcutaneous fat tissue. The authors previously developed the hyperthermia with their own external cooling unit and achieved strong superficial cooling, and reported its usefulness for the reduction of the preferential heating. The purpose of the present study was to evaluate the effect of hyperthermia with strong superficial cooling on the treatment results for unresectable or recurrent colorectal cancers. From 1986 to 2002, 44 patients with primary unresectable or locally recurrent colorectal cancer treated with thermoradiotherapy were analysed retrospectively. The patients with obesity as a subcutaneous fat thickness more than 3 cm, a high age or other serious complications did not undergo therapy. The results were compared between 17 cases with strong superficial cooling treated after 1997 (Group A) and 27 cases without strong superficial cooling treated before 1996 (Group B). Significant differences in thermometry data of T(max), T(ave) and T(min) were noted between Groups A (45.3, 44.4 and 43.6 degrees C, respectively) and B (42.9, 42.0 and 41.1 degrees C, respectively) (p<0.01). Complete response plus partial response rates were better for Group A than for Group B (59 versus 26%, p = 0.05). Multivariate analysis by logistic regression to evaluate the effects of certain factors on complete response plus partial response was strongly correlated with strong superficial cooling (p<0.05). The median survival times for overall survival were 24.3 months for Group A and 17.1 months for Group B (p<0.05). Eight-megahertz radiofrequency-capacitive regional hyperthermia with strong superficial cooling is potentially useful for improving treatment results in unresectable or recurrent colorectal cancers.

[The optimal procedure for chylothorax after operation for thoracic esophageal cancer; reasonable approaches to the thoracic duct from the point of view of routes for esophageal replacement].

In general, chylothorax after esophagectomy with lymph node dissection under thoracotomy is a rare postoperative complication. We report a 71-year-old man who developed chylothorax following esophagectomy and 3-field lymph node dissection together with reconstruction using stomach through the posterior mediastinum, and discuss ideal approaches that are less invasive and make it possible to provide better exposure of the thoracic duct. In selecting the ideal approach, the most important thing is differences in routes for esophageal replacement. The anatomical relation between the location of a conduit adopted for reconstruction of the resected esophagus and the thoracic duct should be considered in each case. In the case of the retrosternal or antesternal route, a video-assisted thoracoscopic approach allows for easy detection of the thoracic duct while reducing surgical invasiveness, because there is no conduit in the posterior mediastinum. On the other hand, a conduit interrupts the visual field of thoracoscopy in the case of the posterior mediastinal or intrathoracic route. Drawing up of a conduit to gain a good operative field involves some risks in protection of the vascular pedicle. Therefore, a transabdominomediastinal approach is an optimal option. With this approach, we could easily find the thoracic duct and directly ligate it just cranial to the hiatus, resulting in a remarkable decrease in discharge through the thoracic drainage tube. In addition, we present an intelligible intraoperative photograph.

[Postintubation tracheal stenosis; problems associated with choice of management].

We experienced a case with tracheal stenosis due to postintubation damage, or so-called cuff stenosis. A 50-year-old man who attempted suicide by pounding nails into his head and chest using carpenter's tools was treated by endotracheal intubation and immediately underwent emergency surgery in July 2000. The patient was placed on artificial ventilation with oral endotracheal intubation, and a tracheostomy was performed 4 days after the operation. After that, his respiration recovered and he was weaned from the respirator. He was discharged 22 days after surgery with no respiratory symptoms. Two days after discharge, he complained of wheezing and dyspnea. Medical examination revealed that the cervical trachea had a severe circumferential stenosis 2.5 cm from the second tracheal cartilage. On retrospective inspection, the region of stenosis was compatible with the cuff site of the endotracheal tube used for the emergency operation. At first we tried nonoperative treatment, considering his mental state. However, we found that surgical treatment was ultimately necessary. A 2.5 cm sleeve resection of the trachea (5 tracheal cartilage rings) was performed, followed by end-to-end suture using 21 stitches with 4-0 MEDIFIT C thread. Pathologically, the surgical specimen showed degeneration and necrosis of tracheal cartilage with excessive growth of granulation tissue. These findings revealed that the etiologic basis of the tracheal stenosis was attributed to pressure necrosis by the cuff. The postoperative course was uneventful. Sixteen months after the surgery, the granulation tissue had not recurred, and problematic stenosis was not visible in the trachea. In this report, we discussed a reasonable management of postintubation tracheal stenosis. Tracheoplasty has been proposed as the most reliable method for treating tracheal stenosis. However, the best treatment in each case is still somewhat controversial because various nonoperative treatment methods are recently available, including laser phototherapy, argon plasma coagulation, mechanical dilatation, stent replacement, and drug treatment. Therefore, it is very important to judge properly the absolute indication for surgical treatment. If granulations are removed successfully by the above-described nonoperative methods, attempts at repair lead only to regrowth of granulation tissue as long as there is necrotic tracheal cartilage. Thus, the determinant of treatment methods is whether postintubation damage extends to tracheal cartilage or not. For now, there is no accurate diagnostic study for viability of cartilage preoperatively. In the literature, symptoms due to airway stenosis occurred rapidly within one month in the case of patients with necrosis of tracheal cartilage. We concluded that the period between extubation and development of symptoms is very informative in the management of postintubation tracheal stenosis. Surgical approaches should be selected for a patient with a rapid and progressive course after extubation when the patient can tolerate it.

[Reirradiation with brachytherapy for recurrent tongue cancer after initial brachytherapy].

The purpose of this study was to assess the efficacy of reirradiation with brachytherapy in the treatment of patients with tongue cancer that had recurred after initial brachytherapy. A retrospective analysis was performed in 12 patients with tongue cancer treated by reirradiation with brachytherapy using rigid linear sources such as the 226Ra-needle or 192Ir-hairpin at Kyushu University Hospital from 1978 to 1998. The patients included 8 men and 4 women, who ranged in age from 30 to 69 years (mean, 52 years). At the time of reirradiation, 7 patients had stage I cancer, and 5 had stage II cancer, according to the UICC (1997) classification. The median follow-up time of the surviving patients was 92 months. The 5-year relapse-free and cause-specific survival rates were 31% and 64%, respectively. The 5-year cause-specific survival rate varied according to the interval between the first and second course of brachytherapy and was 25% for intervals of less than 12 months and 83% for intervals of more than 12 months. Only 4 patients with local recurrence were recognized after their second course of brachytherapy. Among the 6 patients who survived more than 2 years after reirradiation without local recurrence, symptomatic complications such as soft tissue necrosis and minimal bone necrosis were found in 3 patients, but these side effects were not serious enough to require surgery. Reirradiation with a second course of brachytherapy may be useful in the treatment of patients with tongue cancer that recurs more than 12 months after initial brachytherapy.

Invasive thymoma associated with lung cancer: report of a case.

We report herein a case of invasive thymoma simultaneously associated with lung cancer. A 64-year-old man presented with a cough and anterior chest pain, and preoperative examinations revealed an anterior mediastinal tumor as well as lung cancer. The patient underwent a total thymectomy, partial resection of the right lung, left lower lobectomy, and mediastinal lymph node dissection, followed by radiotherapy. Although it is well known that thymomas may be accompanied by nonthymic cancers, invasive thymomas occurring coincidentally with lung cancer are rarely reported in Japan. This case is very interesting in its relation to the oncogenesis of thymomas.

[Effectiveness of intra-arterial infusion chemotherapy for solitary bone metastasis from lung cancer with radiotherapy--a case report].

There have been few reports on intra-arterial infusion chemotherapy for metastatic bone cancer because the bone metastasis is multiple in almost all cases. However, selective intra-arterial infusion chemotherapy is thought to be more effective than systemic chemotherapy for solitary bone metastasis. The patient was a 47-year-old man who had been diagnosed with solitary metastasis of the right knee joint from lung cancer on the basis of various imaging studies and biopsy. The metastatic bone cancer showed rapid growth with systemic inflammatory response, and the patient's general condition became progressively worse. Therefore, radiotherapy alone consisting of 3 Gy of fraction x 5 fractions/week was initiated, but the metastatic lesion was a progressive disease (PD) at the middle point of radiotherapy (24 Gy), and we had no choice but to alter the therapy. Angiography showed dense tumor staining, so intra-arterial infusion chemotherapy was contemplated. Subsequently 15 mg/body of CDDP was administered persistently 5 days a week through a catheter placed in the right femoral artery that had been introduced via the left femoral artery. After 8 courses of this therapy (total dose 600 mg), the metastatic bone cancer was remarkably reduced in size and showed nearly a complete response (CR) on CT scan. This result suggests that intra-arterial infusion chemotherapy is very effective if there is only one bone metastasis lesion.

[A case of Marie-Bamberger syndrome caused by growth hormone-producing lung cancer: problems associated with peri- and postoperative management of patients with growth hormone-producing tumors from the standpoint of the "second attack" theory].

Marie-Bamberger syndrome is identical to pulmonary hypertrophic osteoarthropathy, and the causative factors have not been thoroughly clarified yet. Therefore, further studies of each case would seem to be useful to shed some light on the pathogenesis. We reported a 48-year-old man with primary lung cancer associated with clubbing of the fingers and hypertrophic osteoarthropathy. Chest CT portrayed a 10 x 6.5-cm bulky mass with central necrosis in the left upper lobe. The serum level of growth hormone (GH) showed about a twenty-fold increase over the normal upper limit. With the emergence of SIRS (Systemic Inflammatory Response Syndrome), the patient's general condition took a downhill course. We considered this state to be an oncological emergency and performed a semi-urgent operation. Immunohistochemical evaluation revealed a poorly differentiated adenocarcinoma with GH production. After treatment, the serum level of GH normalized and the clubbing and the periosteal changes of the bones resolved, which suggests that GH plays an etiologic role in Marie-Bamberger syndrome. Recent studies have indicated that GH has immunostimulatory effects. From the standpoint of the "second attack" theory, surgical stress seems to act on the immune system already activated by GH (so called "priming") in the form of a second attack, and trigger an excessive inflammatory response leading to postoperative organ injury in patients who suffer from GH-producing tumors. Thus, we should recognize this immanent risk and perform peri- and postoperative management for patients with GH-producing tumors.

Enhanced absorption of insulin and (Asu(1,7))eel-calcitonin using novel azopolymer-coated pellets for colon-specific drug delivery.

The objective of this study was to estimate colon-specific delivery of insulin and (Asu(1,7))eel-calcitonin using novel azopolymer-coated pellets. In vitro drug-release experiments from the azopolymer-coated pellets containing fluorescein isothiocyanate dextran (MW 4400; FD-4) were carried out by the Japanese Pharmacopoeia (J.P.) XIII rotating basket method with some slight modifications. Little release of FD-4 from the pellets was observed in phosphate buffered saline. However, the release of FD-4 was markedly increased in the presence of rat cecal contents. The intestinal absorption of insulin and (Asu(1,7))eel-calcitonin after oral administration of the azopolymer-coated pellets containing these peptides with camostat mesilate was evaluated by measuring the hypoglycemic and hypocalcemic effects, respectively. A slight decrease in plasma glucose levels was observed following the oral administration of these pellets containing 12.5 IU of insulin compared with the same dose of insulin solution. Camostat mesilate, a protease inhibitor that is incorporated with insulin in these pellets, further decreased the plasma glucose levels in a dose-dependent manner. Similar results were also obtained with the oral administration of pellets containing (Asu(1,7))eel-calcitonin. These findings suggest that azopolymer-coated pellets may be useful carriers for the colon-specific delivery of peptides including insulin and (Asu(1,7))eel-calcitonin.

Relapse patterns of localized non-Hodgkin's lymphoma of the head and neck after clinical remission: results of a strict follow-up procedure.

BACKGROUND: No effective follow-up strategy for non-Hodgkin's lymphoma (NHL) has been identified to date. The aim of this study was to assess the value of a strict follow-up procedure in patients with NHL after they showed clinical remission. METHODS: One hundred and twenty-one patients with localized NHL of the head and neck who had achieved clinical remission after radiation therapy and/or chemotherapy were followed with a strict follow-up strategy (consisting of a schedule of frequent office visits, imaging studies, and blood tests, even if the patient was asymptomatic). RESULTS: Thirty-nine patients relapsed after remission. Twenty-two (56.4%) of the relapses were associated with symptoms. In the 17 patients with asymptomatic relapses (43.6%), an abnormal physical examination result initially indicated relapse in 10 patients. The other tests that initially indicated relapse included scheduled computed tomography scans (3 patients), scheduled gallium scans (2 patients), and serum lactate dehydrogenase levels (2 patients). According to the Ann Arbor stage at relapse, 72.7% of the patients with symptomatic relapses were stage III or IV, while 70.6% of the patients with asymptomatic relapses were stage I or II. CONCLUSIONS: These results indicate that a strict follow-up procedure is effective in detecting asymptomatic relapses, which generally involve a smaller tumor load than symptomatic relapses.

Stabilizing and solubilizing effects of sulfobutyl ether beta-cyclodextrin on prostaglandin E1 analogue.

PURPOSE: Parent cyclodextrins are known to accelerate the degradations such as dehydration and isomerization of E-type prostaglandins in neutral and alkaline solutions. The objective of this study was to attempt the stabilization and solubilization of E1-type prostaglandin analogue in aqueous solution by biocompatible cyclodextrin derivatives. METHODS: The interaction of an E1-type prostaglandin, methyl 7-[(1R,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-4-(m-methoxymethylphenyl)1-butenyl]-5-oxocyclopentyl]-5-thiaheptanoate (MEester) with cyclodextrins (CyDs) was studied by spectroscopies and the solubility method. The degradation of MEester was monitored by high-performance liquid chromatography. RESULTS: 1H-nuclear magnetic resonance spectroscopic studies indicated that MEester forms 1:1 inclusion complexes with alpha-, beta-, and gamma-CyDs in solutions, where alpha-CyD interacts with the a-side chain containing methyl ester moiety of the drug, whereas beta- and gamma-CyDs preferentially include around the five-membered ring and both side chains of the drug. Parent alpha-CyD and hydrophilic derivatives, such as 2-hydoxypropyl-alpha- and -beta-CyDs, sulfobutyl ether beta-CyD (SBE-beta-CyD) and maltosyl beta-CyD showed higher solubilizing abilities against MEester over parent beta- and gamma-CyDs. SBE-beta-CyD and 2,6-dimethyl-beta-CyD (DM-beta-CyD) significantly decelerated the degradation of MEester, particularly the base-catalyzed dehydration, in neutral and alkaline solutions, whereas other CyDs accelerated the degradation. The acid-catalyzed degradation of MEester (pH < 3) was decelerated by the addition of CyDs, especially alpha-CyD. CONCLUSIONS: SBE-beta-CyD with low hemolytic activity and low toxicity is useful as a pharmaceutical carrier for the preparation of injectable MEester, because of its higher stabilizing and solubilizing effects on MEester. Furthermore, SBE-beta-CyD can be useful as a stabilizing agent for drugs, that are subject to base-catalyzed degradations, probably because of the electric repulsion between anionic charges of the sulfobutyl moiety and catalytic anionic species such as hydroxide ion.

[An elderly woman with breast cancer and multiple liver metastasis that responded well to combination therapy of fadrozole and tamoxifen].

Few reports suggest a clinical benefit from combination treatment of fadrozole and tamoxifen for advanced breast cancer in elderly patients. We report the case of an 82-year-old breast cancer patient with multiple liver metastasis. After mastectomy, combination treatment of fadrozole and tamoxifen was added. Two months after the start of this treatment, there was a remarkable reduction in the size of metastatic lesions that continued over 6 months. CT examination revealed the largest lesion was reduced from 8.0 cm to 5.0 cm in largest diameter. The other two lesions were reduced from 3.0 cm to 2.0 cm. The reduction rate was 36%, indicating PR in the Response Evaluation Criteria in Solid Tumors (RECIST). The tumor marker CEA was remarkably reduced from 318 to 85 (ng/ml), and CA15-3 was reduced from 430 to 150 (U/ml). Tumor marker reduction continued over the 6 months corresponding to CT findings. No adverse effect was experienced. This combination therapy was useful and safe against metastatic breast cancer in a patient over 80 years of age.

Esophageal carcinoma with nonrecurrent inferior laryngeal nerve.

Occurrence of a nonrecurrent inferior laryngeal nerve is quite rare. We present the case of a 70-year-old man with carcinoma of the esophagus. An abnormal right subclavian artery was detected preoperatively. This anomaly suggested that the right inferior laryngeal nerve branched directly from the vagal trunk. A carcinoma of the esophagus was resected, and lymph nodes were dissected. The right inferior laryngeal nerve was fully preserved, and the esophagus was primarily repaired.

Up-regulation of genes encoding glycosylphosphatidylinositol (GPI)-attached proteins in response to cell wall damage caused by disruption of FKS1 in Saccharomyces cerevisiae.

FKS1 and FKS2 encode alternative catalytic subunits of the glucan synthases that are responsible for synthesis of beta-1,3-glucan in the Saccharomyces cerevisiae cell wall. Disruption of FKS1 reduces the glucan content of the cell wall, increases chitin content and activates the expression of CWP1, which encodes a glycosylphosphatidylinositol (GPI)-dependent cell wall protein. These cellular responses have been regarded as compensating for cell wall damage in order to maintain cell wall integrity. Here, we report the identification, by genome-wide screening, of 22 genes that are transcriptionally up-regulated in fks1delta cells. Among them, five genes were found to encode GPI-attached proteins, three of which are covalently associated with the cell wall. Deletion and replacement analysis of the promoter regions identified Rlm1-binding sequences as being responsible for the up-regulation following disruption of FKS1. Using the rlm1delta tetOp-FKS1 strain, in which the expression of FKS1 can be repressed by doxycycline, we examined the requirement for Rlm1 for the transcriptional up-regulation of these five genes. Three of the five genes were not up-regulated by doxycycline, indicating that Rlm1 mediates their up-regulation when FKS1 is inactivated. The remaining two genes were up-regulated by doxycycline, suggesting that a transcription factor other than Rlm1 is involved in their response to disruption of FKS1.