Human CD4⁺ T-cells recognize antigenic peptides in the context of human leukocyte antigen (HLA) class II molecules and produce various lymphokines to proliferate and activate other cells. It was once considered that the T-cell response is an all or nothing type event, but recent studies have clearly indicated that T-cells show many different types of activation in recognition of altered ligands for T-cell receptors (TCR). In this review, we summarize our recent findings on the human CD4⁺ T-cell response to altered peptide ligands (APL); peptides carrying single residue substitutions in antigenic peptides. We observed the following: 1) TCR antagonism for T-cell clones reactive to non-self or autoantigenic peptides, 2) partial activation (agonism) without cell proliferation, including production of lymphokines and increases in cell size, and in expression levels of several cell surface proteins or survival time in the absence of antigenic stimulus, 3) augmentation in cell proliferation and production of interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF), 4) augmentation of interleukin (IL)-12 production by antigen presenting cell (APC) and the subsequent augmented production of IFN-γ by T-cells. This information provides basic knowledge regarding the characteristics of T-cell recognition of antigens and the subsequent activation, and a novel method for modification of human T-cell responses by altered peptide ligands (APLs), as a possible candidate for antigen-specific immunopotentiating or immunosuppressive therapy against autoimmune diseases, allergies, infectious diseases and malignant tumors.
(Internal Medicine 37: 804-817, 1998)

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We investigated in humans the effects of adenosine triphosphate (ATP), administered by intracoronary bolus (4-16 μg) or intravenous infusion (25-200 μg/kg/min), on coronary and systemic hemodynamics and electrocardiogram (ECG) variables. All patients had normal epicardial coronary arteries. The maximal coronary blood flow velocity (CBFV) was determined with intracoronary bolus of papaverine. A 12 μg bolus of ATP (n=12) caused maximal coronary hyperemia similar to that caused by papaverine. Intracoronary boluses caused a small brief decrease in arterial pressure but no significant changes in HR or ECG variables. Intravenous infusion of ATP at 150 μg/kg/min (n=15) caused a decrease in the coronary resistance index similar to that caused by papaverine, but the rate of increase in CBFV by ATP was smaller than that caused by papaverine. No patients had a significant change in ECG variables, but some patients (40 %) had a serious decrease in arterial pressure. These studies suggest that maximal coronary vasodilation can be achieved safely with intracoronary ATP administration and that intravenous infusions at 150 μg/kg/min cause near-maximal coronary hyperemia in most patients.
(Internal Medicine 37: 818-825, 1998)

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We studied the influence of erythropoietin (EPO) treatment on hemoglobin A_1c (HbA_1c) levels under conditions which eliminate the effect of changes in the blood glucose concentration. HbA_1c levels, blood glucose, hematocrit (Hct) and reticulocyte counts were serially measured every two weeks after starting or stopping EPO administration in 15 non-diabetic hemodialysis patients. EPO treatment significantly influenced HbA_1c levels, and the more erythropoiesis fluctuated by changing the dose of EPO, the more HbA_1c levels changed, though there were no significant changes in blood glucose levels during the study period. The changes in HbA_1c during the 2-week period correlated inversely with both the changes in Hct during the same 2 weeks and the reticulocyte counts at that time. We concluded that the change in Hct should be kept in mind when the HbA_1c level is evaluated in EPO-treated patients and a formula should be proposed to correct HbA_1c levels based on the change in Hct or the reticulocyte count.
(Internal Medicine 37: 826-830, 1998)

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In-phase chest wall vibration (IPV) is known to decrease dyspnea in patients with chronic obstructive pulmonary disease (COPD) at rest and during leg exercise. In the present study, the effects of IPV (100 Hz) on dyspnea and arm fatigue during upper extremity activity were studied in 9 patients with COPD (mean FEV₁; 0.95 l). Dyspnea and arm fatigue (modified Borg scale) and ventilatory variables were measured during arm elevation (AE) with weights lifted straight above the head with and without IPV. Mean dyspnea during AE was 3.3 without IPV and 2.1 with IPV (p<0.05), but, arm fatigue, oxygen saturation and end-tidal Fco₂ were not affected by IPV. Minute ventilation during AE was significantly increased with IPV in 5 of 9 patients. The results suggest that IPV decreases dyspnea during AE.
(Internal Medicine 37: 831-835, 1998)

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The glomerular changes of 188 consecutive autopsy cases with hepatitis C virus (HCV) infection were studied. The glomerular changes were classified as follows: Category I: membranoproliferative glomerulonephritis (MPGN; 21 cases, 11.2%), 2) Category II: membranous nephropathy (MN; 5 cases, 2.7%), 3) Category III: mesangial proliferative glomerulonephritis (MesGN; 33 cases, 17.6%), 4) Category IV: mesangial thickening type without proliferative mesangial cell (MT; 44 cases, 23.4%), and 5) Category V: almost normal glomeruli (85 cases, 45.2%). Glomerulonephritis was defined as glomeruli with an increase in mesangial matrix or a thickening of the capillary walls in the glomeruli; categories I-IV corresponded to glomerulonephritis in this study. Multivariate analysis, using a multiple logistic model, indicated that glomerulonephritis with HCV infection was the most strongly correlated to the existence of esophagogastric varices. Abnormal urinalysis, that is transient or continuous microhematuria or proteinuria, was observed in only 23 (12.2%) cases. These results showed that in HCV-RNA positive patients with esophagogastric varices the possibility of glomerulonephritis should be considered.
(Internal Medicine 37: 836-840, 1998)

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The effect of prostaglandin E₁ (PCE₁ on cerebral blood flow (CBF) was studied in 10 patients with chronic cerebral infarction. Regional cerebral blood flow (rCBF) was measured by single photon emission computed tomography before and after they received PGE₁ 120 μg daily for 2 weeks. The rCBF of the brainstem, cerebellum, and frontal, temporal, and parietal lobes increased significantly after PGE₁ administration. PGE₁ also significantly increased the rCBF of the non-infarcted area adjacent to infarction. The results indicate that PGE₁ increases the CBF of patients with chronic cerebral infarction without causing the intracerebral steal phenomenon.
(Internal Medicine 37: 841-846, 1998)

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An unusual autopsy case of systemic hemangiomatosis associated with honeycomb-like liver and splenic sarcomatoid changes is presented. The patient suffered from high-output ventricular heart failure secondary to hepatic arteriovenous shunting with hepatic failure, ending fatally due to disseminated intravascular coagulation and pulmonary bleeding. Postmortem examination revealed the characteristic distribution of vasoformative tumors presenting in the hematopoietic system including the liver, bone marrow, and spleen, with the liver appearing characteristically honeycomb-like. While these vasoformative tumors were mostly benign-appearing, partial shifts toward sarcomatoid change were observed in the splenic lesions.
(Internal Medicine 37: 847-852, 1998)

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A 17-year-old male diagnosed as having Cat Eye Syndrome (CES) with hypogonadotropic hypogonadism showed short stature and no development of secondary sex characteristics. Exogeneous gonadotropin replacement therapy combining human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) was started. As a result, the short stature and androgen deficiency were relieved. The critical region of CES was tetrasomy of 22 pter→q11. Abnormalities of other chromosomes which cause hypogonadotropic hypogonadism may exist, thus further investigation is needed.
(Internal Medicine 37: 853-856, 1998)

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A 14-year-old girl with anorexia nervosa was admitted to our hospital because of severe weight loss. She was 152 cm in height and weighed 27 kg. An echocardiogram demonstrated normal left ventricular contraction and a small left ventricular end-diastolic dimension. Pulsed Doppler transmitral flow demonstrated normal early filling velocities but a complete absence of late diastolic flow after the apparent electrocardiographic P wave, consistent with atrial electromechanical dissociation, so called atrial failure. Six months after admission, her body weight increased to 42 kg. Pulsed Doppler showed a normal transmitral flow pattern in both early and late diastole. We do speculate that atrial failure was related to malnutrition due to anorexia nervosa. Atrial failure can be one of the clinical features of patients with anorexia nervosa.
(Internal Medicine 37: 857-860, 1998)

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We report a 49-year-old woman with severe diabetic scleredema (DS). The patient had noninsulin-dependent diabetes mellitus (NIDDM) for 9 years and noticed thickened skin on her back 3 years previously. Her DS rapidly extended to her back and extremities with pain and immobility. Her symptoms of DS improved dramatically after establishing strict glycemic control and intravenous administration of prostaglandin E₁ (PGE₁). However, the histological findings of her skin biopsy did not change even after the treatment for 12 weeks, and her symptoms worsened again after discontinuation of glycemic control and PGE₁ treatment. The causes of DS have been considered to be metabolic abnormalities associated with hyperglycemia and hypoxia in the skin due to diabetic microangiopathy. PGE₁ was an effective treatment for DS in our patient. Strict control of hyperglycemia and PGE₁ treatment may be sufficient to manage DS, although a very long treatment period is necessary.
(Internal Medicine 37: 861-864, 1998)

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A 39-year-old man with chief complaints of aphasia, disorientation and acalculia was admitted to our hospital. He was diagnosed as a clinically probable case of multiple sclerosis (MS) and his symptoms improved while on steroid pulse therapy. The patient had been diagnosed as having diabetes mellitus 16 years before the onset of MS and his insulin secretion further decreased with time. Slight insulin resistance was observed during a euglycemic hyperinsulinemic clamp study. These results suggested that this patient developed diabetes mellitus mainly due to the decrease of insulin secretion.
(Internal Medicine 37: 865-869, 1998)

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We describe a 70-year-old man who presented with a round opacity that disappeared after bronchoscopy. Chest computed tomograms (CT) showed a round opacity in the left lower posterior lung field. Brushings and washings of the left B¹⁰ through bronchoscope yielded neither malignant cells nor acid fast bacilli. The patient was diagnosed as having a benign tumor and was not medicated. Chest CT 1.5 months after bronchoscopy showed that the round opacity had disappeared. Although this course was unusual, this radiopacity was quite typical of round atelectasis on the basis of CT appearance.
(Internal Medicine 37: 870-871, 1998)

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We report a case of pulmonary Nocardia (N.) otitidiscaviarum infection in a 76-year-old man with chronic respiratory infection. The patient responded poorly to intravenous imipenem and oral minocycline, but later improved after treatment with trimethoprim-sulfamethoxazole. Pulmonary infection with N. otitidiscaviarum should be considered in the differential diagnosis of chronic respiratory infections. Further studies are needed to evaluate the correlation between species and drug susceptibility.
(Internal Medicine 37: 872-876, 1998)

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Spontaneous pneumomediastinum (SPM) is an uncommon disorder. The mechanism of spontaneous pneumomediastinum has been speculated as follows: when air pressure in the alveoli rapidly increases, free air leaks from ruptured alveoli and accumulates along the bronchovascular tissue sheath, and then free air moves toward the mediastinum. In this case report of a 19-year-old man of SPM, a chest computed tomography (CT) revealed air in a tubular shape along the pulmonary artery in the apico-posterior segment of the left lung field. This is the first case in which the process of SPM could be identified by chest CT.
(Internal Medicine 37: 877-879, 1998)

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We describe a case of left pneumothorax-induced left postpneumonectomy syndrome in the absence of anatomical anomalies developing at 10 years after the operation. We placed an endobronchial stent into the right truncus intermidius and the procedure resulted in recovery of the syndrome. We consider endobronchial stent placement as an effective treatment for postpneumonectomy syndrome, especially when surgical management is not feasible.
(Internal Medicine 37: 880-883, 1998)

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A 77-year-old female was admitted to our hospital because of pyrexia and a right retroperitoneal mass. Leukocytosis and other inflammatory findings were noted. Bone-marrow aspiration revealed hypercellularity with no malignant cells. An additional mass was detected sonographically in the pelvis. The serum concentration of granulocyte colony-stimulating factor (G-CSF) was highly elevated (299 pg/ml). The tumors were removed at laparotomy, and the pelvic mass was found to arise from the ileocecal mesentery. Postoperatively, white blood cell count and serum G-CSF concentrations decreased to normal levels. The mesenteric tumor showed weakly positive immunostaining for human G-CSF, and Northern and polymerase chain reaction (PCR) analyses detected CSF and its mRNA in the mesenteric tumor.
(Internal Medicine 37: 884-890, 1998)

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We present 2 cases of idiopathic CD4⁺ T-Iymphocytopenia (ICL) in elderly patients. Case 1, a 73-year-old man, with pneumonia had received several antibiotics with unsuccessful results at another hospital. On admission, his CD4⁺ T-lymphocyte count was 109/μl and Pneumocystis carinii was detected by bronchoalveolar lavage fluid staining. No evidence of human immunodeficiency virus (HIV) infection was found. Despite therapy, the patient died of respiratory failure. Case 2, a 72-year-old man, contracted severe pneumonia, and Hemophillus influenzae was believed to be the pathogen. On admission, his CD4⁺ T-lymphocyte count was 238/μl. No evidence of HIV infection was found. He received antibiotics and improved successfully. We suggest that ICL may currently be incubating in a number of elderly pneumonia patients.
(Internal Medicine 37: 891-895, 1998)

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A 50-year-old woman presented with progressive visual disturbance, ataxia, and dementia. The cerebral cortex became atrophic, as the disease progressed, and electroencephalography showed periodic synchronous discharges. The patient's prion gene revealed a point mutation (²³²Met to Arg), and a diagnosis of Creutzfeldt-Jakob disease was made. lomazenil single-photon emission computed tomography (SPECT) was performed to assess neuronal degeneration. Accumulation of the tracer in the late images was severely decreased diffusely spread throughout the cerebral cortex. Our experience with this case suggests that iomazenil SPECT is useful for detecting neuronal degeneration in Creutzfeldt-Jakob disease.
(Internal Medicine 37: 896-900, 1998)

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