Biomedical subjects
Publications and source records attributed to M Korenaga.
A 52-year-old woman with Sjögren's syndrome presented with a dense lymphocytic infiltrate around the bronchial gland disclosed by a transbronchial lung biopsy specimen. Two and a half years after the initial evaluation, her pulmonary status had deteriorated and multiple bullae had developed at both lung bases.
Thoracic duct lymphocytes (TDL) collected 3 days after infection of rats with Trichinella spiralis (TS) and adoptively transferred into normal, uninfected recipients, increased the numbers of both mucosal mast cells (MMC) and eosinophils (EOS) in the intestine. The CD4+ T-helper cell population was separated into two subsets (OX22+ and OX22-) using OX22 monoclonal antibody (mAb) and panning techniques. After adoptive transfer of these T-helper subsets i.v., rats were challenged with TS 24 hr later. The intestine of recipient rats was examined histologically at intervals from Day 3 to Day 21. On Day 9 after transfer, OX22+ T helpers induced a substantial mastocytosis [94 +/- 3, mean +/- SE/villus crypt unit (VCU)], whereas the OX22- T-helper subset increased resident EOS numbers (60 +/- 2/VCU) compared to the challenge control (18 +/- 1 MMC, 27 +/- 1 EOS/VCU). The time of peak eosinophilia was advanced by 3-6 days for recipients of OX22- cells and that of mast cells by 9-12 days for recipients of OX22+ cells. The recipients of OX22-, but not OX22+, cells also showed a large increase in the numbers of B cells in the spleen and mesenteric lymph node (MLN) secreting antibody against adult TS. Recipients of OX22- cells displayed an even increase in EOS throughout the villi, lamina propria (LP) and muscularis, whereas in OX22+ cell recipients mast cells were only present in the lower villus and the epithelium just above the crypt as well as the muscularis layer. Only the CD4+ OX22- cell subset conferred protection against TS in the intestine. We conclude that the OX22+ and OX22- T-helper cells exert distinctive effects in the intestine on MMC and EOS. Because protection was established in the presence of an OX22- T-helper-induced eosinophilia but without a concurrent mastocytosis, the results suggest that MMC are probably not involved in expulsion of TS to terminate the primary infection.
To investigate the effects of intravenous verapamil (V) in coronary thrombolytic therapy, we serially observed the time course of perfusion of the myocardium by 201-thallium (Tl) SPECT in patients who were successfully reperfused within 6 hours from the onset. 201-Tl SPECT was attempted serially on the 1st-2nd day, the 7th-10th day and 28th-30th day. In addition to this, we calculated the count ratio of radioactivity of 99mTc-PYP (CR) in the infarcted myocardium to sternum to evaluate intracellular uptake of calcium during reperfusion. The infarct size, estimated by % Defect decreased significantly in the patients treated with V, while it remained unchanged in the patients without it. In the patients with V, the left ventricular ejection fraction was more favourable, and exercise-induced ischemia determined by redistribution of 201-Tl SPECT in the chronic phase was found more frequently. CR showed no difference between reperfused myocardium irrespective of the treatment. In conclusion, verapamil was considered to enhance myocardial salvage carried out by reperfusion, and not to affect the influx of intracellular calcium into the injured myocytes.
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The phenotype of T-helper cells conferring protection against Trichinella spiralis (Ts) was studied using adoptive transfer procedures and T-helper cell subsets isolated by monoclonal antibodies. With these techniques OX8- OX22+ and OX8- OX22- T-helper cell populations were isolated from thoracic duct lymph (TDL) of infected rats three-five-fold more concentrated than in unfractionated lymph. The OX8- OX22- cell subset alone transferred enhanced rejection of adult worms from the intestine. The origin of protective OX8- OX22- cells was examined in mesenteric lymphadenectomized (MX) rats. After MX, protective cells were found in the cell population draining directly from the intestine on Days 2-3 after infection. Protective cells first appeared in the mesenteric lymph node (MLN) and efferent lymph at Day 3. MX rats rejected T. spiralis at the same time as intact controls and showed enhanced rejection when immune TDL were transfused. No evidence was found for a direct role of the MLN in the generation or expression of parasite rejection. Depletion of migrating OX8- OX22- blast cells by 48-hr drainage of TDL did not influence the expression of an anamnestic response to challenge infection. This suggests that an intestinally resident cell population has a substantial role in mediating primary worm rejection and anamnestic immunity. Day 2 OX8- OX22- cells from MX rats proliferated in response to the presentation of adult and muscle larvae antigens in vitro. We conclude that protection resides in the OX8- OX22- T-helper cell subset that is produced and functions in the intestine.
The region of overlap of thallium-201 (Tl) and technetium-99m pyrophosphate (Tc) was evaluated as a scintigraphic prognosticator of future necrosis. Serial time courses of myocardial perfusion according to Tl and left ventricular wall motion evaluated by two-dimensional echocardiography (2D echo) were used in 22 patients. In all, dual energy emission computed tomography (dual-SPECT) showed the Tl/Tc overlap on identical slices on the third post-infarction day. According to the results of dual-SPECT, the patients were categorized in three groups: nine with large Tl/Tc overlap (group A); five with small Tc accumulation and small Tl/Tc overlap (group B); and eight with large Tl defect and Tc accumulation, which are concordant with each other (group C). Tl-201 SPECT and 2D echo were attempted serially on the 1st and 2nd days, the 7th-10th days and the 28th-30th days. To estimate infarct size with Tl-201 SPECT, we measured pixel counts of eight short-axis images with the 40% cut-off level and computed "% defect". To evaluate the viability of the myocardium, "% Tl uptake" was computed from the ROIs both in the centers of the infarct areas and their border zones. 2D echoes of the left ventricular short axis at the chordae tendineae level were recorded to identify the time course of percent fractional area change (% FAC) of the ischemic left ventricular wall. The scintigraphic results were compared with the serial changes of regional ejection fraction in the areas of infarcts and ischemic lesions. The % defect remained unchanged in group C (29.2 +/- 11.5----25.7 +/- 8.3%); whereas those of groups A and B decreased significantly (21.2 +/- 11.3----9.9 +/- 6.3%, 13.8 +/- 2.6----5.4 +/- 2.9%, respectively). In groups A and B, % FAC improved significantly in the centers of the infarct areas and the border zones, but not in group C. Exercise-induced ischemia determined by redistribution of Tl at the chronic phase was observed more frequently in groups A and B than in group C. These findings indicated that more myocardium can be saved from necrosis in group A than in group C. In conclusion, it is suggested that there is considerable viable myocardium in patients with large Tl/Tc overlap on dual-SPECT.
To assess the relationships among wall motion abnormality, myocardial ischemia and ST change in patients with myocardial infarction (MI), dobutamine stress thallium (Tl) myocardial scintigraphy, and two-dimensional echocardiography (2DE) and electrocardiography were simultaneously performed. Sixteen patients with anterior MI who underwent 2DE and ECG were studied at baseline and during dobutamine infusion with incremental doses of two to 40 micrograms/kg/min. The stress endpoints were chest pain, significant ST changes, tachycardia (greater than or equal to 110/min), and complicated arrhythmias. At the maximal tolerable dose of dobutamine, Tl scintigraphy was completed, and then repeated again four hours later. Left ventricular wall motion was evaluated using superimposed wall tracings of the configuration on 2DE, and was expressed as regional % area changes. Myocardial ischemia was quantified by SPECT and measured as regional % Tl uptake. Dobutamine stress testing was well tolerated by all patients, and no complications occurred. Hemodynamic changes included: heart rate increased from 61 +/- 9 to 113 +/- 11 beats/min, left ventricular end-diastolic volume (2DE) decreased from 93 +/- 27 to 59 +/- 33 ml, and mean blood pressure and ejection fraction were unchanged. In 11 of the 16 patients, redistributions on planar and SPECT images were observed. Although redistributions were observed in the areas adjacent to infarcts in patients with significant ST elevation in V3, additional wall motion abnormalities were not observed. The shape of the ST elevation had no relation to myocardial ischemia. In some cases, wall motion abnormality can be improved in spite of ischemia. Thus, this new combined method is useful for evaluating the relationship between ischemia and wall motion dynamics.
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To evaluate the hormonal effect of laparoscopic ovarian punch resection in polycystic ovary syndrome (PCO), seven PCO patients were examined for pulsatile gonadotropin secretions and pituitary sensitivity before and after operation. Marked reductions of luteinizing hormone (LH) pulse amplitudes, mean LH levels, pituitary LH responsiveness, and circulating androgen levels (P less than 0.05) were observed, 3 to 4 days and 6 weeks postoperatively. LH pulse frequency, follicle-stimulating hormone (FSH), and prolactin (PRL) did not change significantly. These results are consistent with the reported hormonal effects of wedge resection and suggest that the impairment of ovarian surface acts on the hypothalamo-pituitary axis to decrease pituitary hypersensitivity and the key factor behind the resultant hormonal change lies not deep inside the ovarian stroma but in the superficial ovarian capsule.
Eleven women with polycystic ovary syndrome (PCO) were treated with Laparoscopic Multiple Punch Resection (MPR) of the ovarian follicle and capsule and studied by hormone analysis before and after MPR. In 90.9% of the patients, ovulation appeared to occur within 9 weeks and 63.6% conceived within 26 weeks. No changes in serum LH and FSH levels were seen before and after MPR, but testosterone levels which were in the upper normal range or slightly elevated before treatment were reduced after MPR. Endocrine responses to MPR were similar to those described previously after wedge resection. Laparoscopic MPR is a simple and least invasive method and makes it unnecessary to worry about periovarian adhesion after operation. Furthermore, other causes of infertility can be examined by laparoscopy. MPR appeared to be a promising alternative treatment for patients with PCO.
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The cross-reactivity of the blood from onchocerciasis, loiasis, and dipetalonemiasis was tested by a micro-ELISA technique, utilizing adult Onchocerca volvulus antigen and blood samples taken on filter paper. The average ELISA values (OD at 500 nm) were as follows: 0.58 in persons with O. volvulus microfilariae (n = 81), 0.49 in microfilariae-negatives from the same endemic area (n = 39), 0.15 in dipetalonemiasis (n = 27), and 0.25 in loiasis (n = 12), while those of 65 Dipetalonema perstans-negative people were markedly low (average 0.14) and that of 22 Loa loa-negatives, 0.22, respectively. This ELISA could successfully differentiate onchocerciasis from dipetalonemiasis and loiasis.
In Trichinella spiralis-infected rats, a population of cells in thoracic duct lymph (TDL) that can adoptively transfer protection to naive rats was identified and characterized. During the course of T. spiralis infection, blast cells appeared in lymph from Day 3-4, and only Day 3-4 TDL cells had protective properties after transfer. Protection was evident in a 1-2-day increase in the slow rejection of adult worms beginning 8-9 days after the challenge infection. The minimum number of TDL cells capable of transferring protection was 1.8 X 10(8) cells. Transferred cells could protect against a challenge infection with adult worms alone. A double cross-over experiment demonstrated that major histocompatibility complex identity was essential for effective transfer of protection (MHC restriction). An experiment using the mitotic inhibitor vinblastine showed that the protective cells belonged to a dividing cell population. The phenotype of the protective TDL was confirmed by a two-step cell separation procedure. First, it was demonstrated that surface Ig- cells (T cells) separated by affinity chromatography could transfer protection. Second, these surface Ig- cells were divided into two subpopulations by panning using monoclonal antibodies OX-8 and W3/25. The results showed that W3/25+ or OX-8- cells (T-helper) were effective in transferring protection. Protection was only seen when rats adoptively transferred with cells were challenged 1 day after cell transfer.
Parasite-specific IgE antibody response was examined in Strongyloides ratti-infected rats. The results showed that the parasite-specific IgE antibody response was generated after a primary infection. However, repeated infections rather depressed the level of parasite-specific IgE antibody in the serum. Immunization limited to specific stages of the parasite revealed that stimulation of parasite-specific IgE antibody was related to the intestinal adult stage. On the other hand, depression of IgE titers was related to the tissue-migrating larval stage. The capacity of the each stage of the parasite to induce specific IgE response may be related to the variable results of the IgE responses in human strongyloidiasis.
Antigens in Onchocerca volvulus were characterized using anti-O. vovulus monoclonal antibodies (McAb). A total of 17 McAb which were not species-specific to O. volvulus was examined for the antigenic similarity of O. volvulus with 12 parasitic helminths using indirect immunofluorescence. The range of reactivity of these McAb was wider in nematodes in contrast to species of cestoda or trematoda. The antigenic similarity within helminths examined was generally in agreement with their taxonomic relationships but was not shown in the lower taxonomic hierarchy. The helminth which holds the antigens most in common to O. volvulus was not the filarial parasites but Ascaris suum, an intestinal nematoda. The least antigenic similarity to O. volvulus was found in Schistosoma mansoni and S. japonicum, trematoda, among helminths examined. On the other hand, the existence of a common antigen shared with all the 13 helminths examined was demonstrated by a IgM McAb.
Gestational variations in maternal beta-endorphin (beta-end) secretion were investigated by simultaneous measurements of plasma and urinary immunoreactive beta-endorphin (ir-beta-end). Urinary ir-beta-end was extracted by using a Sep-Pak C18 column and was found to be stable for at least 24 hours at room temperature. Plasma and urine (2 hour collection) samples were obtained from 41 pregnant women and 7 non-pregnant women. Almost parallel increases in plasma and urinary ir-beta-end were observed during the course of pregnancy and there was a good correlation between them. Compared with non-pregnant values, significant increases (p less than 0.001) were observed after 36 weeks of gestation. We also studied chromatographic patterns of urinary extracts of non-pregnant and pregnant women. Both of them consist of 4 peaks and resemble each other. They were essentially similar to those of plasma extracts except for the third peak which appeared between the elution position of beta-lipotropin (beta-LPH) and beta-end. In conclusion, maternal beta-end secretions increase in late gestation not only in plasma but also in urine.
In twenty two sterile women, endometriosis externa were diagnosed and classified laparoscopically. Classifying the severity of endometriosis by Beecham's and/or Sugimoto's classification, 17 cases were declared mild and only 5 cases severe (one was stage IV and the others were stage III by Beecham's classification, and 4 were grade III by Sugimoto's classification). All these patients were treated with Danazol (Bonzol) 400 mg/day or 300 mg/day for about 24 weeks. Four weeks after the termination of Danazol administration, the effects of Danazol therapy were examined according to the number of blueberry spots, adhesion severity and chocolate cyst size under re-laparoscopy, as well as dysmenorrhea and other complaints. The results were as follows: Dysmenorrhea was relieved in 60.0% of 15 cases, Blueberry spots were decreased or paled in 88.9% of 18 cases, Adhesion was weakened or partially separated spontaneously in 71.4% of 7 cases, Chocolate cyst size became smaller in 85.7% of 7 cases, The patient complained of mild side-effects, namely acne in 45.5% of cases, a weight gain of more than 2 kg in 54.5%, and hoarseness developed in one. The results of laboratory tests performed before and during the treatment remained slightly abnormal or within normal limits.
The susceptibility of congenitally anemic, and mast cell deficient W/Wv mice to infection with Strongyloides ratti was examined. After a primary infection, W/Wv mice showed greater and more persistent peak larval counts than did normal littermates. Worm expulsion was also slower in W/Wv mice than in +/+ mice. Furthermore, difference in susceptibility was expressed as early as 24 h after infection, suggesting not only that protective mechanisms of the gut but also of the connective tissue were defective in W/Wv mice. Reconstitution with bone marrow or spleen cells from +/+ mice was effective in restoring the protective response in W/Wv mice, whereas thymocytes or mesenteric lymph nodes had no effect. Both connective tissue and mucosal mast cells were repaired in W/Wv mice after marrow reconstitution and infection. Since relatively long incubation period was required for the expression of such reconstituting activities, bone marrow cells seem to contain precursor cells of the effector and/or regulator cells.