Biomedical subjects
Ichiro Kobayashi
Publications and source records attributed to Ichiro Kobayashi.
Closure of duodenocutaneous fistula due to recurrent colon cancer with a pedicled jejunal seromuscular flap.
A new approach to closing a malignant enterocutaneous fistula is reported. Transverse colon cancer recurred around the superior mesenteric vein along with a duodenocutaneous fistula, thus causing severe dermatitis. The tumor was partially resected at the fascia level and the fistula measured 2.5 cm in diameter. A left rectus abdominis musculocutaneous flap failed to close the fistula because of graft necrosis. A jejunal flap measuring 8 cm in length was prepared by sacrificing about 15 cm of adjacent jejunum to create the pedicle. The mucosal layer of the flap was removed and the fistula was closed, then the tumor surface was covered. Two weeks later, the skin defect was covered with free skin grafting. The patient died of cancer 6 months after surgery, but there was no recurrence of the fistula.
Epitope mapping of anti-alpha-fodrin autoantibody in juvenile Sjögren's syndrome: difference in major epitopes between primary and secondary cases.
OBJECTIVE: Juvenile Sjögren's syndrome (SS) is an early-onset type of SS. Autoantibody against the N-terminal 120 kDa form of a-fodrin is a specific and sensitive disease marker for both juvenile and adult SS. We investigated the initial and major determinants of a-fodrin in SS. METHODS: Sera were obtained from patients with juvenile SS, 10 with primary SS and 10 with secondary SS. Epitope specificities of IgG antibodies were examined by dot-blot analyses using overlapping fusion proteins of the N-terminal part (561 amino acid residues) of a-fodrin as antigens. RESULTS: All sera from patients with primary SS reacted with amino acid residues 1 to 98 and 36 to 150, but not with 91 to 199. Epitope mapping using fusion proteins with subfragments, each consisting of about 50 amino acid residues, showed reactivity with amino acid residues 27-80 and 79-132, suggesting that at least 2 epitopes are contained in the first 150 amino acid residues. All 3 cases with neurological complications had additional epitope specificities. Sera from patients with secondary SS showed more diversified specificities and strongly reacted with amino acid residues 1-98 and 334-432, whereas the reactivities to 36-150, a major epitope in primary SS, were minimal. CONCLUSION: Major and initial B cell epitopes specifically reside in N-terminal amino acids 36-132 and could be used as a diagnostic tool for primary SS. The epitope subsequently expands to other regions of a-fodrin in association with the development of neurological complications or disease progression. Secondary SS has distinct epitope specificities.
Low-dose cyclosporine A in a patient with X-linked immune dysregulation, polyendocrinopathy and enteropathy.
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Continuous vertical hemimattress suture for biliary-enteric anastomosis.
The continuous hemivertical mattress suture technique for biliary-enteric anastomosis has not been well reported in the literature. We used the technique with a double-armed monofilament absorbable suture (Glycomer 631) for 32 anastomoses in 31 patients. There was one anastomotic leakage (3.1%). The mean follow-up period was 683 days, during which time no patient developed anastomotic stenosis or cholangitis. The technique provided satisfactory results with lower cost than one-layer interrupted sutures.
An analysis of the chest wall motions using the dynamic MRI in healthy elder subjects.
The objective of this study was to compare respiratory motions of the chest wall in the healthy elder subjects (N = 5; mean age, 71 years old) with those in healthy young subjects (n = 9; mean age, 29 years old). Thirty sequential images (scanning time, 0.4s per image) of dynamic MRI on sagittal and coronal planes were obtained while the subjects were deeply breathing. Lung volume change was simultaneously measured with pneumotachometer. In the elder subjects, dimensions of the middle and posterior parts of the diaphragm were linearly related to instantaneous lung volume. There were poor correlation between motion of the anterior diaphragm and transverse motions of the upper rib-cage and lower rib-cage. The contribution of individual part of the chest wall motion to a unit lung volume change, assessed by slope of the linear regression line, in elder subjects were not significantly different from those in young subjects. Either in the elder or young subjects, the middle and posterior parts of the diaphragm moved coordinately. We conclude that chest wall motion in the healthy elder subjects is not different from that in healthy young people and that middle and posterior parts of the diaphragm act as one functional unit during deep breathing.
[Changes in sleep architecture by resumption of CPAP in patients with sleep apnea syndrome].
It is known that application of continuous positive airway pressure (CPAP) improves sleep architecture in patients with sleep apnea syndrome (SAS). In contrast, there have been only a few studies which deal with deterioration of sleep architecture by discontinuation of CPAP. In the present study we analyzed changes of sleep architecture by temporary removal of CPAP. The subjects were 41 patients who underwent polysomnography (PSG) for diagnosis of SAS. The patients chose either a 1-night study in which only PSG was done, or a 2-night study in which, after treatment with CPAP for one month, PSGs with and without CPAP at night were done. The mean ages, heights, and weights between the 1-night group and the 2-night group were not statistically different The mean AHI of the 1-night group (38.9 +/- 5.0/hr; mean +/- SE) and that of the 2-night group (45.7 +/- 5.4/hr) were not significantly different. The mean AHI profoundly decreased (4.4 +/- 0.9) by CPAP therapy on the second night. Percents of each sleep stage in the 1-night group were as follows; stage 1, 31.8%; stage 2, 50.0%; stage (3 + 4), 2.8%: REM, 15.7%. In the 2-night group, stage 1 was 43.6%, significantly higher than that in the 1-night group, while stage 2 was 39.9%, which was significantly smaller. There were no significant difference in stage (3 + 4) and REM. When CPAP was again applied to the 2-night patients, stage 1 significantly decreased to 15.5%, while stage 2 (55.6%), stage (3 + 4) 6.7%, and REM (22.3%) increased significantly. Therefore, cessation of CPAP shifts the sleep stage from stage 2 to stage 1. Since stages 1 and 2 occupy approximately 80% of total sleep duration, the shift may have some physiological significance. Resumation of CPAP may have improved quality of life and day-time sleepiness by decreasing stage 1 sleep and increasing stages of deeper sleep and REM.
Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells.
AIE-75 has been known as a 75-kDa autoantigen detected in the serum of autoimmune enteropathy (AIE) and as a colon cancer-related antigen, and now designated as a gene causative of Usher syndrome type 1C hereditary syndromic hearing loss. It binds to a novel putative tumor suppressor MCC2 that is homologous to MCC (mutated in colon cancer) through a PSD-95/Dlg/ZO-1 (PDZ) domain. To clarify the functional role in colon cancer cells, we transfected AIE-75 gene into SW480 colon cancer cells which do not express AIE-75. Expression of AIE-75 suppressed growth of SW480 cells in vitro in correlation with the expression levels. It was due mainly to G2/M phase cell cycle arrest associated with mitotic slippage, resulting in emergence of hyperploid giant-nucleated or multi-nucleated cells. Screening of proteins that bound to PDZ domains of AIE-75 by a yeast two hybrid system showed that three serine/threonine phosphatase catalytic subunits (PP2AC-alpha, PP2AC-beta, and PPP6C) could bind to AIE-75. Since PP2AC is known to regulate G2/M checkpoint, we suggest that AIE-75 interacts with PP2AC and prevent cells to transit mitotic phase.
Dermatologic and immunologic findings in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.
BACKGROUND: The immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare genodermatosis associated with dermatitis, enteropathy, type 1 diabetes, thyroiditis, hemolytic anemia, and thrombocytopenia. IPEX results from mutations of FOXP3, a gene located on the X chromosome that encodes a DNA-binding protein required for development of regulatory T cells. If untreated, affected males die early in life from malabsorption and other complications. To our knowledge, this syndrome has never been described in the dermatology literature. OBSERVATIONS: We studied an 11-year-old boy with IPEX. Mutation analysis revealed a G-->A transition (1150G>A) in exon 11, resulting in a putative substitution of Ala-->Thr at residue 384, within the DNA-binding site. Histopathologic examination of an active skin lesion revealed psoriasiform dermatitis. The lesions improved with clobetasol ointment. The patient also displayed alopecia universalis, which had been present since age 18 months, accompanied by longitudinal ridging of the nails. Lymphocyte challenge tests revealed a profound inability to synthesize interferon gamma (INF-gamma) and dysregulated production of other cytokines. CONCLUSIONS: IPEX is an often fatal genodermatosis associated with multiple autoimmune disorders. Cutaneous findings may include dermatitis, bullae, urticaria, alopecia universalis, and trachyonychia. Recognition of this life-threatening disorder is crucial for optimal treatment and genetic counseling.
Pedicled ileal flap to repair large duodenal defect after right hemicolectomy for right colon cancer invading the duodenum.
Although right-sided colon cancer occasionally invades the second part of the duodenum, there is no standard procedure for reconstructing a large duodenal defect after resection. This report describes a new approach we recently devised. After resecting the right hemicolon and the involved duodenum, a segment of terminal ileum was isolated on the vascular pedicle, sacrificing the adjacent ileum. We created a flap by opening the segment along the antimesenteric border, and used this flap to cover the defect. This method does not create a nonanatomical bypass and fewer intestinal anastomoses are required than for Roux-en-Y reconstruction.
Parasympathetic neural control of canine tracheal smooth muscle.
The middle segment of the trachea is innervated by the recurrent laryngeal and pararecurrent nerves. This study determined the pathway that mediated descending commands to the tracheal smooth muscle. Animals used were seven paralyzed and tracheostomized dogs. Tracheal contraction induced either by apnea, mechanical stimulation of the tracheal bifurcation or hypercapnia was always composed of tonic and rhythmic components. The rhythmic contraction developed in synchrony with rhythmic bursts on phrenic nerve activity (PNA). The respiratory-related bursts were also observed on the recurrent laryngeal nerve activity (RNA) and pararecurrent nerve activity (ParaRNA). During apnea there was no tonic activity neither on RNA or PNA, whereas ParaRNA had both tonic and rhythmic activities. Bursts on RNA preceded to correspondent PNA-bursts by 90+/-13 ms. In contrast, ParaRNA-burst always developed later than PNA-burst and it started at almost the same time as that of tracheal rhythmic contraction. During mechanical stimulation of the trachea or CO2-loading, though RNA did not include tonic component, ParaRNA had tonic activity during tracheal tonic contraction. These findings suggested that rhythmic and tonic contractions of the trachea were mediated through the pararecurrent nerve but not through the recurrent laryngeal nerve.
A case of the diaphragmatic flutter with an electromyographic study of the respiratory muscles.
A 28-year-old female was complained with dyspnea and involuntary rhythmic movements in her chest and upper abdomen. Diagnosis of the diaphragmatic flutter was established since high frequency intermittent discharges of the respiratory muscles superimposed on her ordinary respiratory activities. The origin of these abnormal discharges may be in the central nervous system and the psychosomatic factor is participating in the development of the diaphragmatic flutter.
Effect of the respiratory-related bronchial rhythmic constriction on alveolar ventilation in the dog.
The middle-sized bronchus constricts during mid-inspiration through early-expiration. The purpose of this study was to elucidate the physiological role of this respiratory-related bronchial rhythmic constriction (RRBRC). The following parameters were measured in 12 decerebrated and paralyzed dogs: pressure from a balloon-tipped catheter in the fifth-generation bronchus (to reveal RRBRC), efferent neurogram from C(5) phrenic, and ventilatory flow and volume. We found a small but significant reduction of peak expiratory flow of mechanical ventilation during RRBRC. During bilateral vagal cold block, RRBRC was simulated by intermittent electric stimulation of vagal fibers distal to the cold block. This stimulus evoked a decrease in peak expiratory flow and in Pa(CO2) (approximately 1.5 mmHg). After vagal warming, mechanical ventilation was terminated, and blood gases were maintained normal by extracorporeal oxygenation. During each RRBRC ventilatory volume decreased by approximately 3 ml. The changes in gas volume and RRBRC disappeared after bilateral vagotomy. These findings support the concept that the physiological role of RRBRC is to facilitate alveolar gas exchange by reducing expiratory flow, anatomical dead space, or both.
Novel transdermal drug delivery system with polyhydroxyalkanoate and starburst polyamidoamine dendrimer.
In search of an efficient transdermal drug delivery system (TDDS), a polyhydroxyalkanoate (PHA)-based system with a polyamidoamine dendrimer was examined. Tamsulosin was used as the model drug. The dendrimer was found to act as the weak enhancer. By adding the dendrimer, the dendrimer-containing PHA matrix achieved the clinically required amount of tamsulosin permeating through the skin model. This is also the first report of the application of PHA and dendrimer to the TDDS.
Mechanism of enhancement effect of dendrimer on transdermal drug permeation through polyhydroxyalkanoate matrix.
The possible application of polyhydroxyalkanoate (PHA) in transdermal drug delivery systems (TDDSs) for tamsulosin was previously reported. PHAs containing the drugs, ketoprofen, clonidine and tamsulosin showed good adhesiveness to the skin model used, that is, shed snake skin, and dispersed well all model drugs tested. The model drugs hardly permeated through snake skin in solution form. However, these drugs permeated well through snake skin from the PHA matrix. It was previously reported that the addition of a dendrimer, a polymeric permeation enhancer, is effective for the TDDS for tamsulosin to establish an effective clinical TDDS. The effect of dendrimer addition was examined in TDDSs for ketoprofen and clonidine. The dendrimer added did not show an enhancement effect on the TDDSs for the two drugs. To investigate the mechanism of the enhancement effect of a dendrimer on the tamsulosin TDDS, X-ray analyses were performed. With dendrimer addition, drug crystallization in PHA was promoted. The crystal in PHA had highly ordered and changed its space group. These findings are very important for exploiting high-performance PHA-based TDDSs.
Effects of bronchial intermittent constrictions on explosive flow during coughing in the dogs.
This study tested the hypothesis that intrathoracic bronchi intermittently constrict during coughing and attempted to elucidate the effect on explosive flow. The subjects were 21 dogs having undergone tracheostomy. In the first group A (n = 7), the diameter of the fifth-generation bronchus was measured with a balloon-tipped catheter and the change during coughing was analyzed. In the other group (n = 14), the dogs were vagotomized and coughing was simulated by sequential application of positive and negative airway pressures (sham cough). The effects of the bronchial constriction, elicited by the stimulation of vagus efferent fibers, on explosive flow and airway pressure of sham cough were analyzed. The bronchus was constricted in explosive phase of spontaneous coughing in all the dogs of the first group. When cough bouts were repetitively developed, bronchial constriction and phrenic burst developed simultaneously. The intermittent bronchial constrictions fused and virtually acted as tonic constriction. In the second group of dogs the explosive flow of sham cough consisted of two phases; a short bout followed by a near-constant flow. When the bronchus was constricted, the explosive flow was still biphasic in 12 dogs and an exponential decay pattern formed in 2 of them. In these 12 dogs, the peak explosive flow slightly but significantly decreased (mean +/- SD, 1.39 +/- 0.23 vs. 1.34 +/- 0.23 l/s) and airway pressure in the segmental bronchus became smaller (-1.18 +/- 0.53 vs. -0.15 +/- 0.94 cmH(2)O). We concluded that intermittent bronchial constrictions act as tonic one during coughing. Bronchial constriction slightly decreased the peak explosive flow and moved the choke point to the proximal airway.
Continuous mattress suture for all hand-sewn anastomoses of the gastrointestinal tract.
BACKGROUND: The continuous vertical mattress technique for anastomoses in the gastrointestinal or colorectal surgery has not been well reported in literature. METHODS: We used the technique for all hand-sewn anastomoses with double-armed monofilament absorbable suture (Glycomer 631). RESULTS: In the 266 consecutive anastomoses in 242 cases, there were 4 anastomotic leakages (1.5%) and 1 anastomotic stenosis (0.4%). CONCLUSIONS: The technique was feasible, time-saving, economical and with satisfactory results.
[Clinical effect of high inhalation flow from a fluticasone diskhaler in chronic asthma].
The optimal inhalation flow of dry powder formula fluticasone dipropionate (DFP) is not known. This study investigated the clinical effects of inhaling a flow of DFP. A randomized cross-over trial was applied to 13 patients with chronic persistent asthma. After a 2-week run-in period using the current dose of beclomethasone from a metered dose inhaler (BDP-run), BDP was replaced with an equipotent amount of DFP. The patients entered either an 8-week run with high-flow (> 100 L/min) inhalation followed by a 4-week run with medium-flow (70 L/min) (HM group) or a medium-flow run followed by a high-flow run (MH group). The peak inhaling flow from DFP was measured daily. The mean of the inhalation flow in the high-flow run (111.4 +/- 3.6 (SE) L/min) was significantly higher than that (77.3 +/- 0.6 L/min) in the medium-flow run. In both groups, morning and evening peak expiratory flows (PEFs) increased in the first week of change from BDP to DFP, peaking in the first 8-week run, then maintained this level until the end of the following 4-week run. When PEFs in the last week of the 3 runs were compared, those during the DFP-run of either flow were significantly larger than those during the BDP-run, but the PEFs during the high-flow and medium-flow runs were not significantly different. The asthma symptoms also improved with a change from BDP to DFP, but the symptoms did not change with a change in the inhalation flow rate. An inhaled flow of up to 111 L/min is acceptable in terms of clinical efficacy for the use of DFP.