[Case of Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm of the Papilla of Vater Metastasizing to the Lung after Resection].

A 79-year-old man visited a hospital for right upper abdominal pain and nausea. After conservative treatment for cholangitis and pancreatitis owing to a pancreatic head lesion, he was referred to our hospital for further evaluation and treatment of the lesion. He was diagnosed with pancreatic head cancer or carcinoma of papilla of Vater and underwent subtotal stomach- preserving pancreaticoduodenectomy. Postoperative histopathological examination revealed the coexistence of adenocarcinoma( 60%)and neuroendocrine carcinoma(40%)components, consistent with the diagnosis of mixed neuroendocrine- non-neuroendocrine neoplasm(MiNEN). In addition, regional lymph node metastasis of the adenocarcinoma component was found. Adjuvant chemotherapy was not administered because of a poor performance status. Lung metastasis occurred 13 months after surgery. Chemotherapy with S-1 was administered, and partial response was obtained 17 months after surgery. Herein, we report this rare case of MiNEN of the papilla of Vater with lung metastasis.

In Vivo Measurement of Ear Ossicle and Bony Wall Vibration by Sound Stimulation of Cartilage Conduction.

The cartilage-conduction pathway was recently proposed as a third auditory pathway; however, middle-ear vibrations have not yet been investigated in vivo. We aimed to measure the ossicles and bone vibration upon cartilage-conduction stimulation with a non-contact laser Doppler vibrometer. We recruited adult patients with normal ear structures who underwent cochlear implant surgery at our hospital between April 2020 and December 2022. For sound input, a cartilage-conduction transducer, custom-made by RION Corporation (Tokyo, Japan), was fixed to the surface of the tragus and connected to an audiometer to regulate the output. A posterior tympanotomy was performed and a laser beam was directed through the cavity to measure the vibration of the ossicles, cochlear promontory, and posterior wall of the external auditory canal. Five participants (three men, mean age: 56.4 years) were included. The mean hearing loss on the operative side was 96.3 dB HL in one patient, and that of the other patients was off-scale. The vibrations were measured at a sound input of 1 kHz and 60 dB. We observed vibrations of all three structures, demonstrating the existence of cartilage-conduction pathways in vivo. These results may help uncover the mechanisms of the cartilage-conduction pathway in the future.

A Pilot Study of Whole-Brain Low-Intensity Pulsed Ultrasound Therapy for Early Stage of Alzheimer's Disease (LIPUS-AD): A Randomized, Double-Blind, Placebo-Controlled Trial.

The prevalence of Alzheimer's disease (AD) has been rapidly increasing worldwide. We have developed a novel angiogenic therapy with low-intensity pulsed ultrasound (LIPUS), which is effective and safe in animal models of AD and vascular dementia. We performed two trials of LIPUS therapy for AD (mild cognitive impairment due to AD and mild AD); a roll-in open trial for safety, and a randomized, double-blind, placebo-controlled (RCT) trial for efficacy and safety. The LIPUS therapy was performed for whole brain through the bilateral temporal bones for one hour 3 times a week as one session under the special conditions (1.3 MPa, 32 cycles, 5% duty cycle) we identified. The LIPUS therapy was performed for one session in the roll-in trial, and 6 sessions in the RCT trial with 3-month intervals for 1.5 years. The primary endpoint was ADAS-J cog scores. The RCT trial was terminated prematurely due to the COVID-19 pandemic. In the roll-in trial (N = 5), no adverse effects were noted. In the RCT trial (N = 22), the worsening of ADAS-J cog scores tended to be suppressed in the LIPUS group compared with the placebo group at week 72 (P = 0.257). When responders were defined as those with no worsening of ADAS-J cog scores at week 72, the prevalence was 50% (5/10) and 0% (0/5) in the LIPUS and placebo groups, respectively (P = 0.053). No adverse effects were noted. These results suggest that the LIPUS therapy is safe and tends to suppress cognitive impairment although a next pivotal trial with a large number of subjects is warranted.

Hemostatic Control with Gelatin Sponge and Quantum Molecular Resonance Coagulation in a Case of Glomus Tympanicum.

Surgical removal of tumor is the primary treatment of choice for glomus tympanicum (GT). However, because the tumor has abundant blood flow, bleeding control is crucial, and preoperative embolization may be performed. Here, we report the case of a 46-year-old female who visited our hospital with a complaint of right pulsatile tinnitus. A red pulsatile mass was found in the right tympanic cavity, and she was diagnosed with class B1 GT and subsequently underwent surgical treatment. We judged that bleeding could be controlled by intratympanic cavity manipulation alone and decided to perform transmeatal tumor resection without preoperative arterial embolization. After creating a tympanomeatal flap and performing an atticotomy, some pieces of Spongel® were inserted between the tumor and the tympanic wall. The Spongel® absorbed the blood and created a space between the tumor and tympanic wall, which allowed for the insertion of the tip of the Vesalius® handpiece to coagulate the tumor. The coagulation caused the tumor to shrink, thereby widening the space and allowing for further resection. Although the surgical manipulation caused bleeding, complete resection was achieved by the application of Spongel® and coagulation with Vesalius®. Since the tip of the Vesalius® was not burned, hemostasis was successfully achieved, and the operation proceeded while maintaining a clear field of view. There was little bleeding and no postoperative complications. The patient was discharged on the sixth postoperative day. One year after surgery, pure tone audiometry showed no change in the level of bone conduction. Spongel® and Vesalius® are useful tools that allow to safely perform surgeries even in narrow spaces such as the tympanic cavity.

Characteristics of repeated recidivism in surgical cases of cholesteatoma requiring canal wall reconstruction.

OBJECTIVE: Few reports discuss the characteristics of repeated recidivism of cholesteatoma. We describe the clinical characteristics of patients with cholesteatoma who experienced at least two recidivism episodes after initial surgery for cholesteatoma requiring canal wall reconstruction. METHODS: We reviewed the medical records of 11 patients who underwent surgery for cholesteatoma with canal wall reconstruction at our department between April 2008 and March 2018 and subsequently experienced two relapses that necessitated revision surgery involving tympanomastoidectomy with canal reconstruction. Patient age at the time of the first surgery ranged from 6 to 56 (mean, 25.7) years. Seven (63.6%) of the 11 patients were male. These 11 patients were classified according to the type of recidivism, and their characteristics (pathology, operation date, operation method, pattern of relapse, and position of recurrence) were investigated. RESULTS: Four cases involved secondary residual cholesteatoma, with the mean interval between the first revision surgery and the second revision surgery being 23.8 (range, 11-39) months. Secondary residual sites included the anterior tympanic cavity, tympanic sinus, and anterior end of the reconstructed cartilage of the canal wall. The other seven cases involved secondary recurrence, with the mean interval between the first and the second revision surgery being 26.1 (range, 12-57) months. The sites of recurrence were at the edges of the reconstructed cartilage. One notable case involved the cartilage junction, leading us to hypothesize that retraction of the temporal muscle flap and the patulous Eustachian tube was the underlying cause. CONCLUSION: For residual cholesteatoma, strict measures are necessary to maintain the operation under clear view, and more careful follow-up is necessary in patients who have had previous surgery at another hospital. For recurrent cholesteatoma, it was recognized that Eustachian tube function must be ascertained in advance, and careful observation of the reconstructed cartilage edge is necessary.

Low-intensity pulsed ultrasound therapy suppresses coronary adventitial inflammatory changes and hyperconstricting responses after coronary stent implantation in pigs in vivo.

BACKGROUNDS: We demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of drug-eluting stent (DES)-induced coronary hyperconstricting responses in pigs in vivo. However, no therapy is yet available to treat coronary adventitial inflammation. We thus developed the low-intensity pulsed ultrasound (LIPUS) therapy that ameliorates myocardial ischemia by enhancing angiogenesis. AIMS: We aimed to examine whether our LIPUS therapy suppresses DES-induced coronary hyperconstricting responses in pigs in vivo, and if so, what mechanisms are involved. METHODS: Sixteen normal male pigs were randomly assigned to the LIPUS or the sham therapy groups after DES implantation into the left anterior descending (LAD) coronary artery. In the LIPUS group, LIPUS (32 cycles, 193 mW/cm2) was applied to the heart at 3 different levels (segments proximal and distal to the stent edges and middle of the stent) for 20 min at each level for every other day for 2 weeks. The sham therapy group was treated in the same manner but without LIPUS. At 4 weeks after stent implantation, we performed coronary angiography, followed by immunohistological analysis. RESULTS: Coronary vasoconstricting responses to serotonin in LAD at DES edges were significantly suppressed in the LIPUS group compared with the sham group. Furthermore, lymph transport speed in vivo was significantly faster in the LIPUS group than in the sham group. Histological analysis at DES edges showed that inflammatory changes and Rho-kinase activity were significantly suppressed in the LIPUS group, associated with eNOS up-regulation and enhanced lymph-angiogenesis. CONCLUSIONS: These results suggest that our non-invasive LIPUS therapy is useful to treat coronary functional abnormalities caused by coronary adventitial inflammation, indicating its potential for the novel and safe therapeutic approach of coronary artery disease.

A Case of Gorham-Stout Disease Treated with Fistula Closure by Transmeatal Approach.

Gorham-Stout disease, a rare and intractable disease of unknown etiology, causes systemic bone lysis and replacement with lymphoid tissue. Here, we report a case of Gorham-Stout disease with cerebrospinal fluid leakage in a 16-year-old boy. The patient complained of nasal discharge, right ear obstruction, fever, and headache. A computed tomography scan of the head showed osteolysis around the right internal carotid artery, vestibule, and cochlea and osteolytic changes in the left parietal bone. It was suggested that the patient had bacterial meningitis owing to the leakage of cerebrospinal fluid from the fistula caused by the temporal bone osteolysis. He was treated with meropenem, and a transmeatal fistula closure and a bone biopsy of the left parietal bone were performed. Intraoperatively, osteolysis was observed on the promontory and around the internal carotid artery. The fistula was closed by dense filling and compression around the fistula, in the middle ear cavity, and in the external auditory canal. The symptoms disappeared after the surgery. Bone biopsy showed the presence of a lymphangioma, and Gorham-Stout disease was diagnosed. Prophylactic bisphosphonate therapy was initiated. A 4-year follow-up revealed no progression of the disease.

A Case of Cochlear Implantation in a Patient with Superficial Siderosis.

Superficial siderosis is a disease in which iron from hemoglobin is deposited in the central nervous system, resulting in conditions such as progressive sensorineural hearing loss, cerebellar ataxia, dementia, and pyramidal signs. A 30-year-old man with superficial siderosis received a cochlear implant in the left ear, which had shown complete hearing loss. Good auditory responses were obtained at 14 days after implantation. The postoperative average hearing level with the cochlear implant was 56.7 dB at 3 months and 55.0 dB at 6 months. However, the patient showed gradual hearing loss, and the dynamic range changed each time the electrode parameters were adjusted. To assess residual hearing ability, single-photon emission computed tomography was performed together with an assessment of electrical auditory brainstem response, which showed a good response and increased blood flow in both the temporal lobes. Based on this result, we asked the patient to continue using the cochlear implant to see whether a perception of speech response would be obtained. However, the patient discontinued using the cochlear implant because he could not hear satisfactorily. Hearing outcomes after cochlear implant surgery for patients with superficial siderosis are not necessarily good. Therefore, the possibility of unsatisfactory results should be fully explained before recommending this surgery to patients.

Prognostic Links Between OCT-Delineated Coronary Morphologies and Coronary Functional Abnormalities in Patients With INOCA.

OBJECTIVES: Whether there are prognostic links between coronary morphologies and coronary functional abnormalities was examined in ischemia and nonobstructive coronary artery disease (INOCA) patients. BACKGROUND: Although INOCA has attracted much attention, little is known about the prognostic impact of coronary morphologies in this disorder. METHODS: A total of 329 consecutive INOCA patients were enrolled and underwent spasm provocation testing combined with lactate sampling for diagnosis of epicardial and microvascular spasm (MVS). On the basis of the functional tests, the patients were classified into 4 groups: a control group without epicardial spasm or MVS (n = 32), MVS alone (n = 51), diffuse spasm in ≥2 coronary segments (n = 204), and focal spasm in 1 segment (n = 42). In this population, optical coherence tomography imaging of the left anterior descending coronary artery was performed for evaluation of adventitial vasa vasorum (AVV) and intraplaque neovessels (IPN). Index of microcirculatory resistance was also measured. RESULTS: MVS frequently coexisted with diffuse (70%) and focal spasm (68%) with a good correlation between AVV and index of microcirculatory resistance (R = 0.353; p = 0.022). For a median follow-up of 1,043 days, focal spasm showed the worst prognosis (log rank p = 0.005), for which IPN was a significant prognostic factor. By contrast, diffuse spasm showed the greatest AVV with an intermediate prognosis. The prognostic value of INOCA was significantly enhanced by adding AVV and IPN to the physiological indices (area under the curve = 0.88 vs. 0.76; p = 0.048). CONCLUSIONS: These results provide the first evidence that there are important prognostic links between coronary morphologies (evaluated by optical coherence tomography) and coronary functional abnormalities in patients with INOCA, indicating the importance of both evaluations in this population.

Factors Affecting Postoperative Hearing Results in Type IV Tympanoplasty: Preliminary Study of the Influence of External Auditory Canal Packing Material.

BACKGROUND: Postoperative hearing results of type IV tympanoplasty have been shown to have poorer results than other reconstruction techniques. There are numerous reports evaluating the factors for hearing improvement. This preliminary study aimed to analyze and determine the factors that affect hearing results. METHODS: A total of 80 patients who underwent type IV tympanoplasty were evaluated to participate in this study. The medical records of the candidate patients were collected retrospectively. Fifty out of the 80 recruited patients were excluded due to the following reasons: they could not be followed-up for more than a year after the final operation, their initial surgery was not performed in our department, or they needed a revision surgery. The pre-, intra-, and postoperative factors were evaluated and analyzed using EZR software. Cases were divided into two groups according to postoperative hearing results, and each factor was analyzed univariately. The explanatory variables included in the multivariate analysis were the variables that satisfied P < 0.1 in the univariate analysis. Furthermore, all cases were divided into two groups according to the qualitative variables that showed significant difference in the multivariate analysis, and the background factors were evaluated. RESULTS: The results of univariate analysis showed P < 0.1 for 'Age' and 'Material of external auditory canal (EAC) packing'. Multivariate analysis showed P < 0.05 for both. The comparison between the two packing material groups showed that the gauze group was more likely to have improved hearing than Spongel® group, and the ossicular chain condition of the gauze group was maintained better. CONCLUSION: 'Age' and 'Material of EAC packing' were considered to be significant factors affecting the postoperative hearing results. The selection and use of packing materials that provide stability should be considered to obtain better postoperative hearing results in type IV tympanoplasty.

A Case of Skull Base Chondrosarcoma with Intraoperative Trigemino-Cardiac Reflex.

A 75-year-old female patient presented with a suspected recurrence of a clival chordoma. The tumor was resected using the infratemporal fossa type B and anterior petrosal approach with the help of a neurosurgeon. During cauterization of the trigeminal nerve, the patient developed cardiac arrest for approximately 10 seconds because of the trigemino-cardiac reflex (TCR). After several sternal compressions, there was return of spontaneous circulation. The operation was resumed after the circulatory dynamics stabilized. Subsequently, the surgery was completed with partial resection of the tumor without the recurrence of cardiac arrest. The pathological diagnosis was chondrosarcoma, and postoperative treatment with radiotherapy was started. Stimulation of the sensory branches of the trigeminal nerve induces TCR. There are reports of TCR developing in approximately 10% of skull base surgery cases in the absence of atropine administration. We report a rare case of TCR during the surgical procedure for the treatment of a skull base chondrosarcoma.

Dietary protein restriction increases hepatic leptin receptor mRNA and plasma soluble leptin receptor in male rodents.

Leptin is an adipokine that regulates adipose tissue mass through membrane-anchored leptin receptor (Ob-R). Extracellular domain of Ob-R in plasma is called soluble leptin receptor (sOb-R), and is the main leptin-binding protein. Based on a previous DNA microarray analysis that showed induction of hepatic Ob-R mRNA in low-protein diet-fed mice, this study aimed to clarify the effect of dietary protein restriction on hepatic Ob-R mRNA and plasma sOb-R levels. First, the effect of protein restriction on hepatic Ob-R mRNA level was examined together with fasting and food restriction using male rats as common experimental model for nutritional research. Hepatic Ob-R mRNA level was increased by feeding low-protein diet for 7 d, although not significantly influenced by 12-h fasting and sixty percent restriction in food consumption. Then, effect of protein restriction on liver Ob-R and plasma sOb-R was investigated using male mice because specific sOb-R ELISA was more available for mice. Hepatic Ob-R mRNA level was also increased in protein restricted-mice although it did not increase in hypothalamus. Hepatic Ob-R protein was decreased, whereas plasma sOb-R was increased by protein restriction. Because the concentration of sOb-R increased without changing plasma leptin concentration, free leptin in plasma was significantly reduced. The direct effect of amino acid deprivation on Ob-R mRNA level was not observed in rat hepatoma cells H4IIE cultured in amino acid deprived medium. In conclusion, dietary protein restriction increased hepatic Ob-R mRNA, resulting in increased plasma sOb-R concentration, which in turn, reduces plasma free leptin level and may modulate leptin activity.

Effect of dietary vitamin E on oxidative stress-related gene-mediated differences in anxiety-like behavior in inbred strains of mice.

It has been reported that the degree of anxiety-like behavior differs between inbred strains of mice, and that this phenomenon was linked to the expression levels of the oxidative stress-related genes glyoxalase 1 (Glo1) and glutathione reductase 1 (Gsr) in the brain. Therefore, we investigated whether antioxidative activity in the brain affects the Glo1 and Gsr mRNA expressions and strain-dependent anxiety-like behavior using mice fed different amounts of vitamin E. First, we measured brain Glo1 and Gsr mRNA levels and evaluated the anxiety-like behaviors presented by C57BL/6J (B6) and DBA/2C (D2) mice. We demonstrated that D2 mice presented both significantly elevated Glo1 and Gsr mRNA levels as well as more prominent anxiety-like behavior in elevated plus-maze and open field tests. Next, we fed mice from these two strains either a control, vitamin E-free, or vitamin E-supplemented diet for four weeks. Plasma, liver, and brain α-tocopherol concentrations changed in a dose-dependent manner. However, neither brain Glo1 and Gsr mRNA levels nor anxiety-like behavior were affected by dietary vitamin E intake. These results demonstrated that while strain-dependent anxiety-like behavior in mice was related to oxidative stress-related gene expression, the regulatory mechanisms for these genes and anxiety-like behaviors were independent of antioxidative activity in the brain. Strain-dependent differences of the anxiety in mice are probably related to the anxiolytic effects of methylglyoxal, a substrate for Glo1 and Gsr.

Effect of Lansoprazole on the Control of the Intragastric pH in a Patient with Short Bowel Syndrome.

A 40-year-old man suffered from short bowel syndrome. Since a large amount of intestinal output and watery diarrhea hampered his quality of life, we tried to control the intestinal output by reducing the secretion of gastric acid with lansoprazole. Because the small intestine was only 10 cm in length and effective absorption of oral lansoprazole was doubtful, we monitored his intragastric pH for 24 hours and confirmed that the holding time above pH 3.0 was 14.5 hours (60.4%). He spent his home life eating porridge during the day, and receiving total parenteral nutrition of 1,100 mL/day at night while taking lansoprazole as an oral tablet (30 mg) once a day.

Effects of eicosapentaenoic acid and docosahexaenoic acid on anxiety-like behavior in socially isolated rats.

The effects of fish oil for improving mental health have been reported. The present study was undertaken to compare the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on anxiety-like behavior using a rat model. Experimental diets enriched in EPA or DHA as glycerides were prepared. Rats were exposed to social isolation stress and fed the experimental diet for 14 days. The results of behavioral tests revealed that rats fed the EPA-enriched diet exhibited less anxiety-like behavior than rats fed the control or DHA-enriched diets. Furthermore, EPA suppressed anxiety-like behavior only in socially isolated rats. The increase in EPA contents in the brain phospholipid fraction by feeding EPA-enriched diet was more significant than that of DHA by feeding DHA-enriched diet. These results suggest that dietary EPA is more anxiolytic than DHA in rats exposed to social isolation stress and is effective in increasing EPA content in brain membranes.

Sudden failure of ventricular pacing and recovery in a patient with cardiac sarcoidosis.

A 76-year-old woman with sarcoidosis who had an implantable pacemaker for complete atrioventricular block was admitted with syncope. Electrocardiogram revealed ventricular pacing failure, and a marked rise in the ventricular pacing threshold. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) indicated increased uptake of FDG in the ventricular septum. Three days after steroid therapy, the ventricular pacing threshold reverted to normal, and FDG-PET showed decreased FDG uptake in the ventricular septum. In this case report, we demonstrate that a sudden deterioration in the ventricular pacing threshold due to worsening cardiac sarcoidosis can be reversed with early steroid therapy.

Comparison of the measured pre-ejection periods and left ventricular ejection times between echocardiography and impedance cardiography for optimizing cardiac resynchronization therapy.

BACKGROUND: The pre-ejection period (PEP) and left ventricular ejection time (LVET) are easily measured by impedance cardiography (ICG). We hypothesized that the PEP/LVET measured by ICG would correlate with that measured by echocardiography, and that PEP/LVET measured by ICG would be useful for cardiac resynchronization therapy (CRT) optimization. METHODS: Newly CRT implanted patients were optimized by echocardiography. The PEP/LVET was measured by echocardiography and ICG in two different settings: optimized setting and right ventricle (RV)-only pacing. RESULTS: The PEP/LVET was significantly decreased in the optimized setting compared with that in RV-only pacing (0.62±0.13 vs 0.75±0.16, p<0.05). The PEP/LVET values calculated by ICG and echocardiography were positively correlated (r=0.553, p=0.003). CONCLUSION: ICG was useful for the optimization of CRT.

Usefulness of Oblique Multiplanar Images on Multi-Detector Computed Tomography for Diagnosing Intersigmoid Hernia.

BACKGROUND: Intersigmoid hernia is a hernia of the small intestine into the intersigmoid fossa. Because the cavity of the intersigmoid fossa is so small, the preoperative detection of incarcerated intestine and/or mesenteric convergence is very difficult. We report a case of intersigmoid hernia in which the incarcerated bowel and mesenteric convergence could be visualized by oblique multiplanar reconstruction (MPR) images on multi-detector computed tomography (MDCT). CASE REPORT: An 82-year-old man with small bowel obstruction was treated conservatively with a long intestinal tube. Axial plane images of MDCT detected only a thickening of the small bowel wall and a narrowing of the lumen in the pelvis. Since a fourteen-day waiting period did not improve the condition at all, he underwent surgery. The small bowel was herniated into the intersigmoid fossa. After surgery, we studied the preoperative images of MDCT once again. However, neither converged mesentery nor hernia orifice had been depicted. We attempted to make oblique coronal/sagittal MPR images using SYNAPSE VINCENT® and succeeded in visualizing not only the incarcerated bowels but also the hernia orifice and mesenteric convergence. CONCLUSION: Creating oblique MPR images from the MDCT volume data would help in making a preoperative diagnosis of sigmoid mesocolon hernias such as intersigmoid hernia with increasing confidence.

Effects of muscle relaxation on sustained contraction of ipsilateral remote muscle.

The objective of this study was to clarify the temporal change of muscle activity during relaxation of ipsilateral remote muscles. While participants maintained a constant right wrist extensor isometric force, they dorsiflexed the ipsilateral ankle from resting position or relaxed from dorsiflexed position in response to an audio signal. The wrist extensor force magnitude increased in the 0-400 msec period after the onset of foot contraction compared to that of the resting condition (P < 0.05). On the other hand, wrist extensor force magnitude and electromyographic (EMG) activity decreased in the 0-400 msec period after the onset of ankle dorsiflexion compared to that of the resting condition (P < 0.05). Our findings suggest that foot muscle relaxation induces temporal reduction in hand muscle EMG activity and force magnitude.

A new type of lectin discovered in a fish, flathead (Platycephalus indicus), suggests an alternative functional role for mammalian plasma kallikrein.

A skin mucus lectin exhibiting a homodimeric structure and an S-S bond between subunits of ~40 kDa was purified from flathead Platycephalus indicus (Scorpaeniformes). This lectin, named FHL (FlatHead Lectin), exhibited mannose-specific activity in a Ca(2+)-dependent manner. Although FHL showed no homology to any previously reported lectins, it did exhibit ~20% identity to previously discovered plasma kallikreins and coagulation factor XIs of mammals and Xenopus laevis. These known proteins are serine proteases and play pivotal roles in the kinin-generating system or the blood coagulation pathway. However, alignment analysis revealed that while FHL lacked a serine protease domain, it was homologous to the heavy-chain domain of plasma kallikreins and coagulation factor XI therefore suggesting that FHL is not an enzyme but rather a novel animal lectin. On the basis of this finding, we investigated the lectin activity of human plasma kallikrein and revealed that it could indeed act as a lectin. Other genes homologous to FHL were also found in the genome databases of some fish species, but not in mammals. In contrast, plasma kallikreins and coagulation factor XI have yet to be identified in fish. The present findings suggest that these mammalian enzymes may have originally emerged as a lectin and may have evolved into molecules with protease activity after separation from common ancestors.