Mechanism in progressive lacunar infarction: a case report with magnetic resonance imaging.

BACKGROUND: The mechanism of a progressive lacunar infarction is not well understood, and changes in ischemic tissue after onset have not yet been clarified clinically. OBJECTIVE: To investigate the pathophysiological characteristics of a case of progressive lacunar infarction using diffusion-weighted and conventional magnetic resonance imaging (MRI) scans. PATIENT: A 73-year-old woman was hospitalized 18 hours after stroke onset and was diagnosed as having a lacunar infarction in the perforating territory of the left middle cerebral artery. Despite treatment, the hemiparesis worsened, with the peak on the fourth day after onset. Diffusion-weighted and conventional MRI scans provided clues to the pathogenesis. FINDINGS AND CONCLUSIONS: In the acute stage, gradual enlargement of the hyperintense lesion, reflecting fresh ischemic tissue, and neurological deterioration were observed by serial examination of diffusion-weighted MRI scans. A conventional coronal MRI scan revealed a 2-layered ischemic lesion, suggesting the involvement of perforating arteries. These findings indicated that hemodynamic impairment of the microcirculation in the perforators was the major cause of the lacunar infarction.

[Diffusion MRI for evaluating TIA--a case of reversible ischemic injury in the territory of the deep perforators].

A 61-year-old man was admitted to our hospital because of left pure motor hemiparesis. Neuroradiological examination was performed after three hours of onset, but no apparent lesion responsible for the hemiparesis was detected by CT and MRI. Diffusion weighted MRI (DWI), however, demonstrated a high signal area with good contrast in the posterior limb of right internal capsule. This lesion was compatible with patient's clinical symptoms. Apparent diffusion coefficient (ADC) of the lesion was lower than that of normal control at the timing of admission. On the following day within 24 hours after the onset, it was revealed that both left hemiparesis and high signal area on DWI had disappeared, and the ADC on the ischemic lesion was restored to normal level. Changes in the intensity on DWI corresponded well with reversion of ischemic injury, which suggested that DWI was very useful for diagnosis of TIA.

[Exercise capacity and cardiovascular responses to exercise in hemiplegic patients].

We studied how the severity of hemiparesis was related to cardiovascular and metabolic responses to exercise. Eleven clinically stable patients who had had strokes were studied two to four weeks after they began walking as rehabilitation. After motor function of the lower limbs was assessed, the patients were divided into two groups according to Brunnstrom stage: one group comprised patients at stages III, IV, and V of lower limb function (n = 5), and the other comprised patients at stage VI (n = 6). A control group of 6 patients who had been hospitalized because of benign paroxysmal postural vertigo was also studied. Exercise consisted of 3-minute walks at speeds of 1.6, 3.2, and 4.8 km/hr. Blood pressure, heart rate, and the concentrations of catecholamines and of lactic acid in blood were measured before and after each stage of exercise. The double product (systolic blood pressure x heart rate) was also calculated. Changes in these variables were compared among the three groups. Increases in walking speed were associated with increases in systolic blood pressure and heart rate in hemiparetic patients, but no such changes occurred in the control group. In the patients at Brunnstrom stages III, IV, and V, the double product and the lactic acid level increased, and after the patients walked at the highest speed these were significantly higher than in the other two groups. Serum catecholamine levels did not differ among the three groups during exercise. Low intensity exercise can increase cardiovascular responses, and anaerobic metabolism can become dominant in patients with poor motor function.

[Bacterial cerebritis developed from purulent meningitis--serial CT and MRI study of a case].

A 54-year-old woman was admitted to our hospital because of purulent meningitis caused by Streptococcus pneumoniae during a long-term administration of prednisolone for the treatment of bronchial asthma. After admission, both antibiotics and steroids were given, which resulted in her good general and neurological condition, and the normal protein and glucose content in her cerebrospinal fluid three weeks later. However, post-contrast computerized tomography (CT) at this time showed various size of multiple irregular high-densities devoid of capsular component in the white matter of the bilateral cerebral hemisphere. MRI examination revealed that the lesions were of low intensity on the T1-weighted sequence whereas high on T2-weighted sequence. Gd-DTPA enhanced the T1-weighted images on these lesions. These findings may indicate that the lesions were at the pre-encapsulation stage of cerebritis, because the lesions were gradually reduced and disappeared after the subsequent antibiotic therapy. It is emphasized that patients with purulent meningitis under steroid therapy require careful observation for the risk of bacterial cerebritis.

Pulmonary alveolar proteinosis and disseminated atypical mycobacteriosis in a patient with busulfan lung.

A 32-year-old Japanese man with chronic granulocytic leukemia died of respiratory failure. Autopsy revealed alveolar proteinosis and pulmonary fibrosis, complicated by disseminated atypical mycobacteriosis. Epithelial hyperplasia caused by busulfan therapy was probably responsible for the induction of excessive surfactant production, resulting in alveolar proteinosis, and the immunosuppressive state due to chronic granulocytic leukemia was probably related to the induction of disseminated atypical mycobacteriosis.

Augmented nonspecific resistance and simultaneous impairment of specific immunity to Listeria monocytogenes in tumor-bearing mice.

Meth A tumor-bearing mice were examined for changes in the host defense mechanism against infection with Listeria monocytogenes. The resistance of tumor-bearing mice to systemic, i.e., intravenous, infection in an early phase of the infection was suppressed for 1-3 days after tumor implantation (5 x 10(5) cells/mouse, subcutaneously), but was augmented thereafter even on the 35th day as compared with normal mice. Suppression and enhancement of the resistance of tumor-bearing mice to primary infection with L. monocytogenes was also observed in tumor-bearing athymic nude mice. Splenic macrophages from tumor-bearing mice on the 14th day after tumor implantation exerted potent bactericidal activity against L. monocytogenes in vitro as compared with those from normal mice. The function of macrophages as nonimmune scavenger cells seemed to be activated in mice bearing a progressing tumor. However, some of the tumor-bearing mice challenged with a sublethal dose of L. monocytogenes showed diminished resistance in the late phase of the infection; moreover listeria-immunized tumor-bearing mice showed less resistance to a secondary challenge with the bacteria than did normal immunized mice. This suppression of the specific immune response of tumor-bearing mice to L. monocytogenes was shown also in the assay of the delayed-type footpad reaction. The bacterial growth-inhibiting function of listeria-immune T lymphocytes, determined by the effect of adoptive transfer of the cells on the growth of Listeria, was also reduced in tumor-bearing mice as compared with normal mice.

Variability of haemolysin(s) produced by Vibrio vulnificus.

The peptide composition and antigenic cross-reactivity of partially purified and concentrated haemolysins of 16 strains of Vibrio vulnificus were examined by SDS-PAGE and immunoblotting analysis, using a monoclonal antibody (MAb), 6F8D, raised against the haemolysin. All strains produced a common peptide of 36 kDa and the MAb reacted with this peptide. In some strains, larger molecules, including a 56 kDa peptide, were produced, but the MAb did not react with this peptide. The haemolytic activity of the strains was effectively neutralized by the MAb, except in the case of strains producing the 56 kDa peptide. These findings indicate that the 36 kDa haemolysin is common to all 16 strains and that V. vulnificus can produce a second haemolysin which differs in molecular mass and antigenicity.

Monoclonal antibodies against the haemolysin of Vibrio vulnificus.

The extracellular haemolysin produced by Vibrio vulnificus strain FCC was partially purified from the culture supernate by sequential ammonium sulphate precipitation, gel filtration with Sepharose 4B, and DEAE-Sephacel ion-exchange column chromatography. Using this semi-purified haemolysin as the antigen, several monoclonal antibodies (MAbs) were established; they were all of the IgG2b class with lambda light chains. One representative MAb, 6F8D, completely neutralized the haemolytic activity and mouse lethal activity of extracellular toxin(s). In immunoblotting analysis of the peptides of the semi-purified haemolysin separated by SDS-PAGE, this MAb reacted, in particular, with a 36 kDa peptide. These findings suggest that the haemolysin is probably identical to the lethal toxin in the culture supernate of V. vulnificus strain FCC, which contained the 36 kDa peptide.

Effects of chitin and its soluble derivatives on survival of Vibrio cholerae O1 at low temperature.

Chitin concentrations greater than 0.04% (wt/wt) protected cholera vibrios against killing at low temperature. This protective effect was detected with both the soluble form of chitin, glycol chitin, and the insoluble particulate form of chitin. Some amino acids or peptides also showed the same protective effect.

Differing contribution of various effector cells in the elimination of syngeneic or allogeneic cells.

The growth of Meth A (MA) tumors was suppressed in tumor-antigen-specific manner in BALB/c mice immunized with mitomycin C-treated MA (MMC-MA) cells in saline or in Freund's complete adjuvant (FCA). The antitumor activity of their peritoneal exudate cells (PEC) was detected by in vivo neutralization test and in vitro cytostasis assay but not by in vitro cytolysis assay. Positive delayed footpad reaction was elicited by footpad injection of MMC-MA cells in such immunized mice, before or after the inoculation of viable MA cells. Expression of cytostatic activity in PEC required the interaction of non-adherent and adherent cells. Normal PEC could exert the cytostatic activity in the presence of a nonadherent population of immune PEC. These findings suggest that cytostatic macrophages are activated after the interaction between sensitized lymphocytes and tumor-specific antigens and that they play an important role in the principal effector mechanism in this syngeneic system. On the other hand, immunization with MMC-MA in FCA or viable MA cells also induced PEC the antitumor activity detected by in vivo neutralization test in allogeneic C57BL/6 hosts. Immunization with viable MA cells induced not only cytolytic but also cytostatic activity, whereas, immunization with MMC-MA in FCA induced cytostatic activity but not cytolytic activity. In contrast to a syngeneic system, cytolytic activity was effectively induced against allogeneic MA cells together with cytostatic activity. We conclude that there are various effector cells contributing to the elimination of syngeneic or allogeneic murine tumor cells.

Rejection of syngeneic tumor cells by the interaction of Lyt-1+ T lymphocytes and macrophages.

A high degree of cytostatic activity was detected in peritoneal exudate cells (PEC) from BALB/c mice immunized with mitomycin C-treated Meth A cells (MMC-MA) given intraperitoneally (i.p.) While this cytostatic activity was not detected in a nonadherent fraction of immune PEC, the addition of starch-induced PEC to the nonadherent immune cells led to a cytostatic activity. Treatment of these nonadherent cells with anti-Thy-1 X 2 or anti-Lyt-1 X 2 antibody plus complement abolished the restored cytostatic activity. Normal PEC were also rendered cytostatic after addition of the culture supernate of a nonadherent fraction of immune PEC mixed with MMC-MA. These findings suggest that macrophages are rendered cytostatic by immunization with tumor antigen and that these cytostatic macrophages evolve after activation of sensitized Lyt-1 positive T lymphocytes.

Augmentation of host resistance to Listeria monocytogenes infection by Lactobacillus casei.

The effect of heat-killed Lactobacillus casei YIT 9018 (LC 9018), a potent antitumor agent as well as a potent macrophage-activating agent, on the resistance of mice to Listeria monocytogenes was studied. Mice pretreated intravenously (i.v.) with 0.5 mg of LC 9018 showed enhanced resistance to subsequent i.v. infection with L. monocytogenes. Antigenic cross-reaction between L. monocytogenes and LC 9018 was not seen in the delayed footpad reaction in mice, and LC 9018 inhibited the growth of L. monocytogenes in the liver and spleen of athymic nude mice. Therefore the antilisterial activity of LC 9018 was considered to be expressed nonspecifically and independently of the thymus. Carrageenan, a selective macrophage blocker, diminished the antilisterial effect of LC 9018. Peritoneal cells induced by intraperitoneal administration of LC 9018, which were composed mainly of macrophages and polymorphonuclear cells, showed enhanced phagocytosis and marked intracellular killing activity against L. monocytogenes in vitro as compared with those of the control. Kupffer cells of mice pretreated i.v. with LC 9018 produced a high oxygen radical level. The antilisterial effect of LC 9018 was maintained even at 21 days after its injection.

Protective effect of Lactobacillus casei on Pseudomonas aeruginosa infection in mice.

The protective effect of heat-killed Lactobacillus casei YIT9018 (LC 9018) against Pseudomonas aeruginosa infection in mice was compared with that of Corynebacterium parvum. Survival of mice after intraperitoneal (i.p.) infection with P. aeruginosa was augmented in mice that had been pretreated i.p. with LC 9018 5 days previously. Similar treatment of mice with C. parvum, however, was not effective at all. Moreover, mice became more susceptible to infection with P. aeruginosa after such treatment. Growth of P. aeruginosa in the peritoneal cavity and spleen was markedly inhibited in LC 9018-pretreated mice, whereas such inhibition of bacterial growth was not observed in C. parvum-treated mice. The protective effect of LC 9018 was observed in mice subjected to 800 rads of whole body irradiation but was abrogated when mice were treated with carrageenan. These results suggest that augmentation of the resistance of mice to P. aeruginosa was caused by the induction of activated macrophages. The number of macrophages detectable in the peritoneal cavity was almost the same in LC 9018- and C. parvum-treated mice. Growth of Listeria monocytogenes was inhibited by pretreatment with LC 9018. Inhibition of L. monocytogenes was also observed after the same pretreatment with C. parvum. It was suggested that macrophages activated with LC 9018 were involved in the protective immunity to P. aeruginosa.

Evidence for the presence of a capsule in Vibrio vulnificus.

Vibrio vulnificus strain FCC, isolated from a patient with a wound infection, and reference strain ATCC 27562, were examined by electron microscopy for the presence of capsules. Both strains had a layer heavily stained with ruthenium red. The number of stained cells was high in strain FCC and low in strain ATCC 27562. The proportion of stained cells correlated with virulence against mice and with susceptibility to the bactericidal activity of normal human serum. Rapid freezing and substitution fixation, a mild method, revealed on the cell surface a fibrous layer of relatively low electron density, which we considered to represent a capsule.

Existence of suppressor cells in the spleen of allogeneic and syngeneic primiparous pregnant mice.

Mixed lymphocyte reaction (MLR) and in vitro induction of cytolytic cells against alloantigens were investigated using spleen cells from primiparous mice mated allogeneically or syngeneically. One-way MLR was reduced significantly in degree not only in allogeneic but also in syngeneic pregnant mice. MLR of virgin spleen cells was suppressed when mitomycin C-treated spleen cells taken from syngeneic or allogeneic pregnant mice were added as regulator cells. These suppressive effects disappeared when regulator cells were treated with anti-Thy 1 or anti-Lyt 2 serum plus complement. Generation of cytotoxic lymphocytes from syngeneic or allogeneic pregnancy spleen cells in MLR was depressed compared with that from virgin spleen cells. The addition of pregnancy spleen cells to MLR suppressed in vitro generation of cytotoxic lymphocytes from virgin spleen cells. These results indicated that reduction of in vitro cellular responses of pregnancy spleen cells was due to suppressor cells in the spleens. These cells suppressed non-specifically the reactions to alloantigens and could be detected both in allogeneic and syngeneic primiparous pregnancies.

Effects of antithyroid drugs on Con A-induced suppressor cell activity.

It is well established that Concanavalin A (Con A)-induced human peripheral blood lymphocytes exert suppressive effects on mitogen-induced proliferation of responder cells. Using peripheral blood lymphocytes from healthy individuals, effects of antithyroid drugs on Con A-induced suppressor function were studied. We found an enhancement of Con A-stimulated suppressor activity by MMI and PTU in all these subjects. In the light of these data, an enhancement in suppressor activity by antithyroid drugs may contribute, in part, to a remission of Graves' disease.

Effect of Bacillus Calmette-Guérin infection on delayed footpad reaction to Listeria monocytogenes.

The role of peritoneal macrophages induced by Bacillus Calmette-Guérin (BCG) in the induction of immune responses to Listeria monocytogenes was studied in mice. The peritoneal macrophages from mice treated with BCG 14 days previously contained a high proportion of Ia-bearing macrophages (approximately 56%) and the cells showed not only a high level of listericidal activity but also a strong ability for presentation of listerial antigen to Listeria-immune T cells. An intraperitoneal inoculation with a low dose of Listeria, which can induce the maximal level of delayed footpad reaction (DFR) and positive migration inhibitory activity of macrophages in untreated mice, did not induce a detectable level of such responses in BCG-treated mice. The bacterial growth at an early stage of infection was suppressed by scavenger macrophages in these mice. On the other hand, BCG-treated mice showed the early development of DFR and macrophage migration inhibitory activity after an inoculation with a high dose of Listeria. It is revealed in transfer experiments that Listeria-pulsed peritoneal exudate cells induced by BCG elicited the highest level of DFR and positive migration inhibition of macrophages in normal mice at the earlier period of injection compared with Listeria-pulsed resident peritoneal cells. These results suggested that the increased activities of macrophages acting as scavenger cells and as antigen-presenting cells play important roles in the modification of immune responses to Listeria in BCG-treated mice.

Relationship between bactericidal and phagocytic activities of peritoneal macrophages induced by irritants.

Cellular accumulation to the peritoneal cavity and modification of various functions of peritoneal macrophages were observed in mice injected intraperitoneally (ip) with thioglycollate medium (TG), liquid paraffin, proteose peptone and Corynebacterium parvum. The cellular composition of peritoneal exudates at 4 days after injection of irritants was almost the same in all the groups and the proportion of macrophages was increased approximately 4 times more than nontreated controls. The ability to kill Listeria monocytogenes and to generate chemiluminescence (CL) were augmented strongly in C. parvum-induced macrophages, while depressed in TG-induced macrophages. The activities of liquid paraffin- or proteose peptone-induced macrophages were almost the same as those in nontreated controls. However, the ability to phagocytose native sheep erythrocytes was greatly augmented both in C. parvum- and TG-induced macrophages. There is thus a discrepancy between bactericidal activity and phagocytic activity among macrophages induced with various irritants.

Peritoneal exudation of macrophages by irritants and its effect on immune responses against sheep erythrocytes and Listeria monocytogenes.

Relation between the degradation of antigenic substances by peritoneal exudate macrophages induced by different irritants and subsequent induction of immune responses against SRBC or Listeria monocytogenes were studied. Delayed footpad reaction and antibody production to SRBC were both suppressed by pretreatment with thioglycollate or with killed Corynebacterium parvum. In contrast, delayed footpad reaction and acquired cellular resistance to Listeria were augmented by pretreatment with thioglycollate. When pretreated with C. parvum, however, such augmentations in immune responses to Listeria were not observed but these responses were suppressed. It was suggested that the amount of antigenic stimuli was determined by the mutual relationship between the level of macrophage activity as scavenger cells and the susceptibilities of the antigenic substances to degradation by macrophages, and that induction of immune responses were affected by this mutual relationship.