Chronic necrotising pulmonary aspergillosis caused by Aspergillus niger in a mildly immunocompromised host.
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Biomedical subjects
Publications and source records attributed to K Mano.
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Comprehensive genetic studies in which the genetic structure of a population is considered against the background of ecological factors, including environmental and social variables, often supply valuable information for the solution of a number of problems in human biology, including reproductive compensation and inbreeding depression. In the first section of this paper we consider the incidence of genetic diseases in Japan in reference to other populations. Some of the genetic disorders found elsewhere do not occur or are of lower frequencies in Japan. On the other hand, a number of genetic diseases occur at higher than usual frequencies, leading to an incidence of genetic disease of the order of about 1 per 100 in newborn Japanese. We next review the studies of consanguinity in Japan and report evidence of very high levels, ranging from 8.6% to 58.0%, for villages during the early part of the twentieth century. The rates are declining rapidly for the country but, because of traditional social values, inbreeding rates remain significant in many small villages. In the final section we consider the probable trends in the frequency of inbreeding on a worldwide basis and point out that frequencies of certain genetic diseases are likely to remain high and even increase in some societies because of various socially prescribed mating patterns.
This study was conducted on 39 patients whose severe attacks of bronchial asthma with disturbance of consciousness required admission to the ICU of our hospital between 1984 and 1989. Among the 39 patients, there were 16 deaths. Most patients collapsed suddenly at home and were taken to our hospital. Arterial blood gas analysis at the time of admission to the ICU revealed that the PaO2 levels were as high as 252.6 +/- 57.6 (mean +/- S.E.) Torr in non-survivors and 221.0 +/- 29.7 Torr in survivors, with no significant difference because of prior oxygen therapy in almost all cases. Systolic blood pressure was 14.8 +/- 10.8 (mean +/- S.E.) mmHg, with marked circulatory disturbance in the fatal cases. Most patients displayed marked disturbance of consciousness, but maintenance of blood pressure led to recovery without sequelae despite marked disturbance of consciousness in most patients.
A familial case with autosomal dominantly transmitted myoedema, muscular irritability, stiffness and hypertrophy was reported. The patient is 54 years old and his father, two sisters and niece had suffered from the similar symptoms. He had noticed a feeling of stiffness and pain in the femoral muscles after several minutes of erect position from the age of 5-6 years. He had observed that light tapping of muscles caused a bulge which persisted for several seconds in the whole body. These symptoms were not progressive. The patients had an athletic appearance, hypertrophy of gastrocnemius muscles, pes cavus and hammer toes. Mild muscular weakness and wasting were noted in the intrinsic hand muscles and the anterior tibial muscles. Myoedema was seen in the muscles of the whole body. His thyroid functions were normal. EMG studies showed no myotonic discharges. Light microscopy of biopsy specimens from the biceps brachii muscle showed unspecific myopathic changes. Electron microscopy showed many vacuoles between myofibrils. The symptoms and signs of this case are very like to those of the cases which Torbergsen described in 1975 and only four families were reported after that. The family presented here is the first report in Japan.
We describe the sural nerve pathology in 3 patients with HTLV-I-associated myelopathy (HAM). These patients showed remarkable symptoms of myelopathy and had high HTLV-I titers in the serum and CSF. The common pathologic findings in the sural nerves were as follows: slightly decreased density in myelinated fibers (6,567/mm2, 6,488/mm2, and 7,159/mm2; control 9,999 +/- 3,446/mm2), frequent occurrence of demyelinated and remyelinated fibers, and many degenerating fibers with globule-like myelin changes. Teased-fiber analysis indicated the globule-like changes (Dyck's G change) to be accompanied by the formation of adjacent demyelinated segments. The globules result from slowly repetitive degenerative changes of myelin and are considered to be a form of demyelination. However, they have seldom been found in other demyelinating neuropathies, indicating the demyelination process with globule formation in HAM to be rather specific for this disease.
A case of long-term survival of a female patient with complicated diffuse metastatic leptomeningeal carcinomatosis (DMLC) secondary to lung cancer is reported. A 36-year-old woman, hospitalized with a chief complaint of headache and unproductive cough, was diagnosed as having primary lung adenocarcinoma (T4N1M1 oss) and was given systemic chemotherapy. Although progressive deterioration of her headache continued, repeated neurological examination, cerebrospinal fluid (CSF) examination, and cranial CT scans failed to show evidence of metastasis to the central nervous system, and the only finding suggesting CNS involvement was an elevated CEA level in CSF. Later in the course of her treatment, the patient suddenly lost her vision and subsequently consciousness due to acute increased intracranial pressure, and emergency ventricular drainage was performed for therapeutic and diagnostic purposes. Malignant cells were found in CSF obtained from a ventricular drainage and she was treated successfully by systemic and intrathecal chemotherapeutic agents. She was discharged after a ventriculoperitoneal shunt operation for hydrocephalus; a double-dome reservoir was used for continuous intrathecal administration of the anticancer drugs, and a shunt filter was located in the tube to prevent the dissemination of cancer cells. In addition to methotrexate and cytosine arabinoside, ACNU and interleukin-2 were administered intrathecally without serious adverse effects, but no apparent therapeutic effects were noted either. She survived over 2 years after DMLC was first diagnosed. At autopsy DMLC secondary to lung adenocarcinoma was confirmed, but no evidence of leukoencephalopathy due to aggressive intrathecal chemotherapy was found. Current therapy for patients with DMLC and its clinical problems are discussed in relation to our experience in this case.
Deuterium oxide (D2O), which is known to stimulate microtubule aggregation, enhanced the IgE-mediated 45Ca2+ influx, (14C)-arachidonic acid and histamine release in rat basophilic leukemia cells (RBL-2H3) in the same dose-dependent manner (up to 90% (v/v]. We compared the interaction between D2O and a variety of groups of pharmacological agents. A microtubule depolymerizing agent, demecolcine, which inhibited the IgE-mediated (14C)-arachidonic acid and histamine release without affecting 45Ca2+ influx, was counteracted by 45% D2O. Taxol, a microtubule stabilizing agent, which had an inhibitory effect on the above three steps, was also reversed by 45% D2O. These results would support the previous data on the interaction between D2O and microtubules and would further suggest that the status of microtubule aggregation may be related to the secretory process. Calmodulin inhibitors (W-7, trifluoperazine) blocked the IgE-mediated 45Ca2+ influx, (14C)-arachidonic acid and histamine release in the same dose-dependent manner, but were counteracted by 45% D2O. In contrast, the effects of proteinase inhibitors (TPCK, TLCK), an adenylate cyclase inhibitor (ddAdo), a phosphodiesterase inhibitor (aminophylline), a phospholipid methylation inhibitor (DZA + Hcy) and microfilament blockers (cytochalasin B and D) were not counteracted by 45% D2O. These results would suggest that D2O may be associated with calmodulin directly or indirectly possibly through some relationship between calmodulin and microtubules.
An (125I) iodohydroxybenzyl pindolol (125IHYP) binding inhibition assay was performed. Various dilutions (1:5-1:500) of sera from asthmatics and controls were incubated with canine lung membranes for 60 minutes at 30 degrees C. 125IHYP was added to the membranes for 30 minutes at room temperature in the presence and absence of 10 microM 1-propranolol, and the samples were washed through a Gelman (Type A-E) glass fiber filter using a washing buffer. Radio activity was measured with Aloka gamma counter. In the presence of various serum dilutions from asthmatics, 125IHYP specific bindings of 0.16 fmol to 4.38 fmol were measured. 125IHYP binding was inhibited in a dose-related and nonspecific manner. Serum, albumin, L-histidine and L-cysteine also inhibited 125IHYP specific binding to beta-receptors. Percentages of inhibition of serum from asthmatics on 125IHYP specific finding to beta-receptors were -17.6% to +9.3%, which were compared with identical dilutions of control serum. There was no significant difference in 125IHYP binding inhibition assay between asthmatics and controls. From these results, development of autoantibody to beta-adrenergic receptors could not be detected in this study.
In order to clarify the relation between asthma and Chironomidae, we examined the cross-reactivity between Chironomidae and other common allergens. We noted significant correlations between positive skin tests with Chironomidae and with other allergens. The radioallergosorbent inhibition test, however, suggested that there may be no cross-reactivity or, if any, only very low cross-reactivity between midge allergens and mite, house dust (HD), silk, shrimp, or mosquito allergens.
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To evaluate coronary circulation in ischemic heart disease, digital image processing with cine coronary angiography was performed. Using time-density curves obtained from individual pixels, images showing the distribution of contrast density and transit time were obtained. To record angiograms, contrast medium was injected into the coronary artery in a steady manner during right atrial pacing. Frames in the end-diastolic phase immediately before the P wave were selected, and digitized into a 512 x 512 x 8 bit matrix using a system composed of a video camera, an analog-to-digital converter, and a computer. These digitized images were then stored in a disk memory. A mask image was prepared before the injection of contrast medium. Subtraction was performed using the mask image and a series of images following contrast injection. The subtracted images were of sufficient quality to permit clear observation of the individual coronary arterial branches. Time-density curves were then determined from these subtracted images. From these curves, time from the onset of contrast injection to its peak density (Tp), time from the peak density to the half peak density (T 1/2) and the attenuation factor of the curves (tau) were derived. Their distributions were expressed as color images. Examples of a normal control and a case of inferior infarction were demonstrated. Blood flow function images with good spatial resolution were thus obtained. This method is useful for evaluating coronary blood flow.
Isolated communities offer a unique opportunity for the study of biological and social consequences of consanguinity and migration. The studies of genetic polymorphisms have contributed greatly, not only to knowledge of the genetic constitution of a given individual and population, but also to clarify either relationship between structure and function of polymorphic traits or the susceptibility to multifactorial diseases, in which interaction between the gene and environment cannot be ignored. For over 25 years, we have investigated the effect of consanguinity and genetic polymorphisms in 9 isolated communities in Western Japan. We reported here different values of gene frequency for each polymorphic trait, compared with the neighboring communities and described how we applied these data to clarification of the genetic constitution of isolated communities as well as of genetic susceptibility to some diseases.
To improve the therapeutic result of patients with advanced carcinoma of the upper third of the stomach, it is necessary to extend further the range of resection and dissection especially in case of invading the lower esophagus with serosal involvement. The extended surgery consists of the following: abdominophrenicotomy or abdominothoractomy, lower esophagectomy and total gastrectomy, dissecting completely the second group of nodes combined with distal pancreatectomy and splenectomy, a block resection of adjacent organs in case of direct invasion, and even dissection of nodes in the lower mediastinum, within the hepatoduodenal ligament, behind the head of the pancreas and along the superior mesenteric vein. Operative procedures are, however, to be palliative in case of moderate or severe peritoneal or hepatic involvements or distant metastasis to the fourth group of nodes. Reduced procedures in case of no serosal invasion nor lymph node metastasis consist of 1/2 proximal gastrectomy and of dissection of the first group of nodes especially in superficial carcinoma. However, in cases free from serosal invasion but with metastasis to the first group of nodes or in cases with a slight serosal invasion, total gastrectomy with dissection up to the second group of nodes is recommended.
The effect of the thromboxane (TX) A2 synthetase inhibitor, OKY-046, on human leukocyte histamine release and bronchial hypersensitivity in asthmatic subjects was evaluated. It was found that OKY-046 inhibited IgE- and Ca2+ ionophore A23187-mediated leukocyte histamine release in a dose-dependent fashion (IC50: 1.0 and 3.0 X 10(-3) M, respectively) and that OKY-046 could diminish bronchial hypersensitivity, determined by leukotriene D4 inhalation, following a 2-week oral medication. These data suggest that the TXA2 synthetase inhibitor can produce favorable effects upon the course of immediate-type hypersensitivity reactions.
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Using rat heart perfusion, we found that an anabolic state can be induced with a medium which includes glucose, carnitine, branched-chain amino acids and arginine after arginine intubation at a dose of 250 mg/kg body weight. It showed diminished levels of glutamine, glutamate, branched-chain oxoacids and phenylalanine (a marker of heart protein metabolism) release, reflecting anabolic changes occurring in the myocardium. While ornithine intubation caused a catabolic state in which the release of alanine and glutamate was increased but phenylalanine release was unchanged. This anabolic state may be a useful model providing for myocardial protection.
In healthy humans after overnight fasting, an oral administration of ornithine induced a new steady state: an accumulation of serum alanine and proline, a decrease in serum valine concentration, transient reductions in serum urea and urinary urea contents, and then an increased urea excretion. On the other hand, an oral administration of arginine resulted in an anabolic state: decreases in serum leucine and isoleucine concentrations, reductions in serum glucose and free fatty acid contents and a rapid increase in serum insulin level. It was assumed that the effect of ornithine administration may be exerted through an activation of hepatic System A transport and that of arginine is an insulin-mediated action.
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