Effect of aging on pancreatic exocrine function -Aging and fecal chymotrypsin activity-

膵外分泌機能に及ぼす加齢の影響を検討する目的で，健常人43名，非膵疾患患者41名，老人ホーム入居者39名を対象として比色法により糞便中キモトリプシン活性（FCA）を測定し，以下の結論を得た。1）FCAは逐齢的に低下し，60歳以上は60歳未満より有意の低値を示した。しかし，分布図のretrospectiveな検討からは，膵外分泌機能の低下は，実際には65～70歳あたりから明らかになることが示唆された。2）FCAの正常下限値を14.5U/gに定めたが，高齢者の診療にあたってはこの正常値のみを根拠にして疾病の有無を判定すべきではない。3）老人ホーム入居者のFCAは特に低値を取ったがその主要因は高齢者が多いためと考えられた。To examine the effect of aging on the pancreatic exocrine function, fecal chymotrypsin activity (FCA) was measured by the photometric method in 43 healthy controls, 39 controls in an old-age home and 41 patients with non-pancreatic diseases. Following conclusions were obtained. 1) Pancreatic exocrine function showed a significant decrease with aging as indicated by the present prospective study : ① a significantly lower FCA in the B group of 22 healthy controls (≧ 60 years of age) than the A group of 21 healthy controls (< 60 years of ago) ; ② significant correlationship between aging and FCA in the 43 healthy controls and also in the 41 patients with non-pancreatic diseases. 2) FCA in controls in an old-age home was especially low. Presumably it was due to their far-advanced aging. 3) The calculated lower limit of normal in FCA was 14.5U/g. However, the diagnosis of pancreatic diseases should not be coined solely on the basis of decreased FCA value

Histochemical studies on enzyme-digested protein plugs of patients with chronic pancreatitis: a preliminary report.

Sulfated acidic mucopolysaccharides have been found to be significant components of &#34;protein plugs&#34; in patients with chronic pancreatitis. The precise identification of the mucopolysaccharides and their distribution within the protein plugs may clarify the pathogenesis of the plugs. Pure pancreatic juice from five patients with chronic pancreatitis was obtained by endoscopic retrograde catheterization of the papilla of Vater. Enzymes for digestion of the plugs included hyaluronidase of the bovine testes and streptomyces hyalurolyticus, chondroitinase ABC and AC, and sialidase (neuraminidase). Our study indicated that: I) Sialic acid is distributed throughout the plugs and may be a major component, followed by a lesser amount of chondroitin sulfate B. 2) Chondroitin sulfate A, C, D and E and chondroitin may be minor components. 3) Hyaluronic acid is negligible in the plugs.</p

Diagnosis of chronic pancreatitis

近年，各種膵疾患に対する検査法の発達には目を見張るものがあるが，実際の運用にあたっては各検査法の適応，限界，組合わせおよび実施する順序等に迷うことが少なくない。本研究では，最近我々が経験した慢性膵炎Ⅰ群116例の診断過程を振り返ることにより，慢性膵炎の診断における理想的な検査法の組合わせとそれぞれの役割を検討し，同時に診断名のみならず病態と病期が容易に理解できる表現方法を提案した。画像診断法，膵外分泌機能検査法（EX），膵内分泌機能検査法（EN）を比較検討し，以下の結果を得た。①画像診断法は必須である。②内視鏡的逆行性膵胆管造影（ERCP）を軸とした腹部超音波検査（US）あるいは腹部CTスキャン（CT）の組合わせは欠くことができない。③EXもまた必須の検査法である。④ENは慢性膵炎の診断に必要不可欠ではないが，治療方針を決めるうえで重要である。⑤純粋膵液（PPJ）の生化学的検査と組織化学的検査は膵炎の診断と病態生理の解明に重要である。⑥PPJ中の細胞診は慢性膵炎に合併した膵癌の検索に有用である。⑦以下に示すような診断の記載方法を提案した。"Calcified chronic pancreatitis, alcoholic, diffuse,　ERCP-3, US-2, CT-3, EX-2, EN-1, Lf(＋)"。Endoscopic retrograde cholangiopancreatography (ERCP), ultrasonography (US), computed tomography (CT), exocrine pancreatic function test (EX), endocrine pancreatic function test (EN), and analysis of pure pancreatic juice (PPJ) are currently available for the investigation of pancreatic diseases. The purpose of the present study is to evaluate the roles and preferable combinations of these tests in the diagnosis of chronic pancreatitis and then to propose a way to describe the results of the tests along with diagnosis for a better understanding of the disease process. Comparative studies of imaging, EX and EN led to the following conclusions. 1) imaging procedures (ERCP, US and CT) are mandatory, partly because they were frequently the test that showed diagnostic changes and partly because they often gave key information for operative treatment. Among the imaging procedures, ERCP combined with US and/or CT is mandatory because these combinations alone can reveal detailes of structural changes attendant on chronic pancreatitis. 2) EX is also mandatory, because it was occasionally the only test that showed diagnostic changes and partly because it often gave important information for medical treatment. 3) EN is also important, not because it was indispensable for detecting chronic pancreatitis, but because it often gave important information for medical treatment. For btter understanding of the disease process as well as diagnosis, we propose, as suggested by Seligson, that the test used for the establishment of the diagnosis and the degree as well as extent of abnormalities. An example is "Calcified chronic pancreatitis, alcoholic, diffuse, ERCP-3, US-2, CT-3, EX-2, EN-1, Lf(+)". This attitude will lead to a more rational approach to both diagnosis and treatment

Effect of spa-drink therapy on exocrine pancreatic function

膵外分泌機能におよぼす飲泉（三朝温泉水）の効果を飲泉群および非飲泉群を対象として検討した。膵外分泌機能検査法としては，糞便中キモトリプシン活性比色測定法（モノテストカイモトリプシン）を用いた。その結果，糞便中キモトリプシン活性は，飲泉開始2週後に40　％　の患者で上昇し，4週後は2週後と変わらなかった。以上より，2週間の飲泉は膵外分泌機能を改善させる効果があることがわかった。The effect of spa-drink therapy (Misasa hot spring) on exocrine pancreatic function was studied on 18 patients after their physical and psychological conditions were stabilized about two weeks following hospitalization. Patients were randomly divided into two groups : eight patients into a control group (continuance of spa-bathing) and 10 patients into a spa-drink therapy group (continuance of spa-bathing plus commencement of spa-drink therapy). Spa-drink therapy refers to drinking 200mℓ of warm spa-water (42℃) two times a day : between meals in the morning and in the afternoon. Exocrine pancreatic function was evaluated by fecal chymotrypsin activity, using a colorimetric method (Boehringer-Mannheim). Following results were obtained : 1) With 2-week's spa-drink therapy, fecal chymotrypsin activity was significantly enhanced in 40 % of the patients, while none of the controls showed an increase in fecal chymotrypsin activity. 2) Fecal chymotrypsin activity at the time of 4 weeks was similar to that obtained at the time of 2 weeks in both groups. In conclusion, spa-drink therapy for 2 weeks was effective for the enhancement of exocrine pancreatic function

Endoscopic diagosis of gastric malignant lymphoma

To delineate the pitfalls and counter-measures in the endoscopic diagnosis of gastric malignant lymphoma (GML), reviewed were 32 cases of primary GML and 16 cases of systemic ML with gastric involvement (secondary GML). 1) Accurate diagnosis of GML had been made in only 13 cases of primary GML ; 18 cases had been diagnosed of gastric cancer (GC); the remaining one of benign ulcer (BU). Review of the endoscopic films, however, revealed more than two of the three findings characteristic, but not pathognomomic, of GML in 84 percent. This result indicates that possibility of GML must be kept in mind in the differential diagnosis of malignant lesions despite its rarity, because endoscopists tend to be predisposed with an impression of GC. 2) Follow-up examinations made in nine cases of primary GML revealed marked changes in endoscopic findings in three cases : healing of an ulcer lesion in one case, healing of an ulcer lesion on an unchanged tumor in another and enlargement of a tumor in the remaining one. The first case had been followed up for two years with an impression of BU. This result indicates that improvement of ulcer does not necessarily rule out GML because it can show "malignant cycle" just as GC. 3) Endoscopic biopsy performed in 30 cases of primary GML had led to accurate diagnosis in only 16 cases and erroneous diagnosis of GC in five and no malignancy in nine. Review of the cases revealed the importance of having suspicion of GML at first from endoscopic findings, because it can lead to an increase of the number of biopsy specimens, careful selection of biopsy sites, careful use of biopsy instruments to obtain good specimens and closer contact with pathologists. 4) Prospective studies on systemic ML revealed gastric involvement in 17 percent. Examinations of the GI tract, especially of the stomach is one of the important steps for staging of systemic ML and deciding therapeutic modalities. 5) It is extremely difficult to diffierentate primary GML and secondary GML from endoscopic findings alone, although there are a few findings characteristic of the latter

Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes

Background: Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing on their short life spans and various age-related phenotypes, such as immune dysfunction, osteoporosis, and brain atrophy, the responsible gene mutations have not yet been fully elucidated. Results: To identify mutations specific to SAMP strains, we performed whole exome sequencing of 6 SAMP and 3 SAMR strains. This analysis revealed 32,019 to 38,925 single-nucleotide variants in the coding region of each SAM strain. We detected Ogg1 p.R304W and Mbd4 p.D129N deleterious mutations in all 6 of the SAMP strains but not in the SAMR or AKR/J strains. Moreover, we extracted 31 SAMP-specific novel deleterious mutations. In all SAMP strains except SAMP8, we detected a p.R473W missense mutation in the Ldb3 gene, which has been associated with myofibrillar myopathy. In 3 SAMP strains (SAMP3, SAMP10, and SAMP11), we identified a p.R167C missense mutation in the Prx gene, in which mutations causing hereditary motor and sensory neuropathy (Dejerine-Sottas syndrome) have been identified. In SAMP6 we detected a p.S540fs frame-shift mutation in the Il4ra gene, a mutation potentially causative of ulcerative colitis and osteoporosis. Conclusions: Our data indicate that different combinations of mutations in disease-causing genes may be responsible for the various phenotypes of SAMP strains.ArticleBMC GENOMICS. 14:248 (2013)journal articl

Studies on Hypoplastic Anemia (panmyelopathy); (Mainly depending on our departmental experiences)

In Japan, hypoplastic anemia has ever been presenting one of the most important problems among today's anemic diseases, it having proved as great frequency as that of pernicious anemia found both in Europe and America; besides, no fit therapeutic method been discovered as yet. Generally speaking, this disease shows a decrease of entire corpuscles, the bleeding tendency becoming prevalent in most cases; yet as to signs in concern to bone marrow, the number of nuclear cell is not fixed, as it has proved 16, 200 at the lowset, while, 263, 000 at the highest. Consequently, it has been classified into 5 types in our department, in view to obstructions of bone marrow. 1. Type of bloodcell-arrest. 2. Type of maturation-arrest. 3. Type of disturbanced regeneration. 4. Mixed type. 5. Panmyelophthisis. When we took record about 23 cases of hypoplastic patients, results were as follows; 1st type 7, 2nd type 2, 3rd type 3, 4th type 8, and 3 cases of 5th type. In all serum iron value proved an increase; in view to intravenous iron tolerance test, the degree of iron disappearance proved a marked delay, while hematopoetic function indicated an extreme decline. In tissue culture of bone marrow invented by our department. it has been recognized that there exists certain factor to inhibit any hyperplasia of parencyma of bone marrow in this anemic serum. As for method in therapy, several have been nominated through in vain, so that more or less effect have been achieved only by our inventions, i.e., imbedding of bone marrow as well as use of substances of polysaccharide extracted from bone marrow