Clinicopathological study of cases with Mycobacterium szulgai infection

Pulmonary mycobacteriosis is usually caused by Mycobacterium tuberculosis, Mycobacterium avium complex, or Mycobacterium kansasii. There are, however, other slow-growing mycobacteria which can cause pulmonary infection. Mycobacterium szulgai, first reported in 1972, is a scotochromogenic species which can affect human lungs, although human-to-human spread of infection is thought to be unlikely. We have recently treated three cases of middle-aged to elderly persons (45-87 year-old), two of them had underlying diseases (one with intrapulmonary and the other with extrapulmonary). All patients had constitutional symptoms (cough, sputum, dyspnea), and chest roentgenograms demonstrated either cavitation with scattered nodules or peripheral infiltrates predominantly in upper lobes, resembling pulmonary tuberculosis. In two cases, M. szulgai was identified by using DNA-DNA hybridization method. The in vitro susceptibility of M. szulgai to antimycobacterial drugs was better than that of M. avium complex, and it was resistant only to paraaminosalicylate, cycloserine, and partially to isoniazid. Pulmonary disease of three patients were successfully treated with a combination of multiple antimycobacterial agents including rifampin, ethambutol, isoniazid, or streptomycin.     

Glomerulonephritis in autopsy cases with hepatitis C virus infection

1. The inducible isoform of nitric oxide synthase (iNOS) is expressed in human and experimental cardiac allografts and is localized to infiltrating macrophages, cardiac myocytes, endothelial cells and smooth muscle cells. A recent clinical report proposes a causal link between myocardial expression of iNOS and ventricular contractile dysfunction, a potentially graft- and life-threatening post-transplant complication. 2. Coronary blood flow is elevated in human graft recipients with biopsy proven cellular rejection, indicating that vasodilation accompanies graft rejection. In Lewis-to-F-344 coronary resistance vessels, which show intimal expression of iNOS, pressure-induced myogenic tone is significantly inhibited. Selective iNOS inhibition partially reverses the inhibition of myogenic tone, confirming that iNOS produces vasoactive nitric oxide (NO) and may mediate the rejection-induced vasodilation seen clinically. 3. Endothelial dysfunction, identified as loss of endothelium-dependent dilation, has tremendous prognostic significance in vascular diseases of multiple aetiologies. In transplantation, endothelial dysfunction predicts early cardiac allograft vasculopathy and poor clinical outcome. Lewis-to-F-344 coronary vessels develop endothelial dysfunction at 1 week post-transplantation, but this is preceded by a transient state of endothelial cell hyperfunction, with enhanced endothelial production of NO. 4. The normal interaction between endothelial and smooth muscle cells in coronary resistance vessels is critical for the regulation of coronary blood flow and the maintenance of fluid homeostasis. With allospecific expression of iNOS, the inhibition of vascular tone predicts greatly enhanced intravascular pressure in precapillary arterioles and capillaries; this would be expected to cause a net movement of fluid from the intravascular compartment into the myocardial interstitium, resulting in ventricular oedema, non-compliance and poor contractile performance.     

Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens as a test for infection with the leprosy bacillus

BACKGROUND: Mycobacterium leprae (M. leprae) soluble antigen (MLSA) reagents have been developed with the aim of finding a reagent, comparable to tuberculin, which could identify individuals infected with the leprosy bacillus. They have yet to be evaluated fully in human populations. METHODS: More than 15000 individuals living in a leprosy endemic area of northern Malawi were skin tested with one of five batches of MLSA prepared using two different protocols. The main difference in preparation was the introduction of a high G centrifugation step in the preparation of the last three ('second-generation') batches. RESULTS: The prevalence of skin-test positivity (delayed-type hypersensitivity (DTH)) and association with the presence of a BCG scar were greater for first (batches A6, A22) than second (batches AB53, CD5, CD19) generation reagents. The association of positivity with M. leprae infection was investigated by comparing results among known (household) contacts of leprosy cases, and among newly diagnosed leprosy patients with those in the general population. While positivity to 'first-generation' antigens appeared to be associated with M. leprae infection, positivity to later antigens was unrelated either to exposure to leprosy cases or presence of leprosy disease. There were geographical differences in the prevalence of DTH to the various batches, probably reflecting exposure to various mycobacteria in the environment. CONCLUSIONS: Our results suggest that the 'second-generation' batches have lost antigens that can detect M. leprae infections, but that they retain one or more antigens which are shared between M. leprae and environmental mycobacteria. Natural exposure to these both sensitizes individuals and provides natural protection against M. leprae infection or disease. Identification of antigens present in these groups of skin test reagents may assist in production of improved skin test reagents.     

Immunohistochemical study on human papillomavirus infection of the vulva

Two hundred and sixteen cases of human papillomavirus infection of the vulva from 1984 to 1991 in the Affiliated Hospital of Qingdao Medical College were reviewed, and were immunohistochemically studied by ABC method to detect HPV-Ag. The results showed that the demonstration of diagnostic koilocytes is very important in diagnosis of HPV infection in routine tissue slides examination. But in cases of atypical morphological changes; when diagnostic koilocytes were not formed in early stage, the demonstration of brown color granules in the nuclei of prickle cells is very diagnostic for positive HPV infection. In occasional cases, the diagnostic koilocytes do not demonstrate brown color granules in their nuclei. The explanation is that HPV-Ag was exhausted during metabolism. Besides, the cell membrane of basal cells are stained with brown color granules, while the morphological changes of upper layers of squamous epithelium have not appeared yet, therefore, there were no HPV-Ag positive reactive cells. It is probably showed that the HPV-Ag is primarily formed and appeared in the cell membrane of basal cells.     

Detection of IgA anti-PGL-I specific antigen to Mycobacterium leprae in mangabey monkeys inoculated with M. leprae

OBJECTIVE: This study examined the reliability of the three-cluster model for chronic low back pain patients found using the Integrated Psychosocial Assessment Model (IPAM). A replication study using a sample of patients from a different country was completed. PATIENTS: Seventy patients (average age = 47.05 years, SD = 16.11) with chronic low back pain of noncancer origin participated in the study. Sixty-two of these patients were attending The Auckland New Zealand Regional Pain Service, while a further eight were attending a private practice pain service in Auckland. OUTCOME MEASURES: Subjects were assessed on the IPAM, which measures pain intensity, disability, coping strategies, attitudes towards and beliefs about pain, depression and illness behaviour, the Medical Examination and Diagnostic Information Coding System, and the Multidimensional Pain Inventory. RESULTS: Cluster analyses using the kappa-means algorithm were performed on the IPAM data. The three-cluster solution was preferred according to both the Variance Ratio Criterion and cluster interpretability. Two of the three clusters correlated highly with clusters retrieved in the original study (r = 0.78, r = 0.71), while the third cluster showed partial resemblance (correlation of r = 0.31). Clusters were named "In Control," "Depressed and Disabled," and "High Deniers and Somatizisers." No differences were found on the physical pathology scores between clusters. Decision rules for cluster assignation resulted in 68% of the sample being correctly assigned. CONCLUSIONS: Support for this cluster model from two countries suggests its value in providing a multidimensional picture of patients with chronic low back pain. The possibility of using such cluster groups for determining treatment type is discussed.     

Activity of two doses of rifampin against Mycobacterium leprae

In the course of a clinical trial designed to re-examine the bactericidal efficiency of 600-mg doses of rifampin (RMP) against Mycobacterium leprae, two doses of RMP, either 600 mg or 1200 mg, were administered 28 days apart to 29 previously untreated patients with lepromatous or borderline leprosy. Seven, 28, and 35 days after the start of the trial, skin biopsies were performed and immunologically normal mice were inoculated with 5 x 10(3) or 10(4) M. leprae in each hind foot pad. The patients assigned to the two regimens did not differ significantly in terms of sex, age, disease classification, bacterial index, or the concentration of M. leprae in the skin lesion biopsied for the inoculation of mice. The concentrations of organisms in the skin-biopsy specimens did not change significantly over the course of the trial among the patients, whether they were being treated by the first or the second regimen. The M. leprae recovered from specimens obtained from 21 of the patients, before beginning treatment, multiplied in a majority of the mice inoculated. The results of mouse inoculation confirmed the rapid bactericidal effects of RMP against M. leprae: a single dose of RMP rendered the organisms obtained from all but two of the patients incapable of multiplying in mice. No significant difference was demonstrated between the two regimens, nor was an additional effect of the second dose of RMP observed.     

AIDS complicated with disseminated toxoplasmosis: a pathological study of 9 autopsy cases

BACKGROUND: In addition to identifying and eradicating premalignant lesions, and detecting early cancer before the development of life-threatening consequences, new concepts and technological advances have stimulated a hightened interest in the secondary prevention of colorectal cancer. METHODS: People whose first degree relatives have had colorectal cancer are considered to run a higher risk of developing colorectal carcinoma. A screening program was carried out for 358 first degree relatives of colorectal cancer patients using colonoscopic screening. RESULTS: The mean age of these first degree relatives was 44 years, ranging from 13 to 78 years. Two hundred and eleven (58.9%) of them were asymptomatic. Totally 73 polyps were detected in 53 subjects (14.9%). Two cancer lesions were identified. Thirty polyps (41.1%) measured between 0.5 cm and 2.0 cm. The polyps were mostly located in the rectum and sigmoid colon (63%). One polyp was found in a subject below 30 years of age. Over the age of 30, the incidence of polyp increased dramatically. CONCLUSIONS: Our results confirmed that the screening program for the first degree relatives of patients with colorectal cancer is worthwhile. The program would have a more significant impact if the screening could start from subjects around the age of 30.     

3-D morphological study of the temporal bone

OBJECTIVE: To establish the 3-D(three-dimensional) morphological study of the temporal bone by means of computer graphic techniques. METHODS: The serial sections of the temporal bone were processed by the technique of computer-aided 3-D reconstruction. The 3-D images of the multi-structures in the temporal bone were displayed on the monitor. The 3-D parameters of these structures were measured by a special software. The stereo-images of the structures in the temporal bone were obtained by stereoscopy and stereo-pairs. RESULTS: Most structures of the temporal bone were reconstructed in 37 instances for the different purpose of study. Each set of the stereo-pair corresponding to the structures in the temporal bones and many 3-D parameters were obtained. The complex spatial relationship among the reconstructed structures such as the facial nerve, endolymphatic sac, posterior tympanum and posterior ampullary nerve was revealed and the mechanic model of the ossicular chain was set up. According to these results, the surgical approach of the posterior ampullary nerve transection was designed and simulated on the graphic computer. CONCLUSION: The technique of computer-aided 3-D reconstruction provides a new tool for the study of the temporal bone. It is also helpful for the designs and simulations of the surgical approaches. The results of this study contribute to developmout of a new branch of pathology of the temporal bone and a primary 3-D morphological study of the temporal bone.     

Molecular definition and identification of new proteins of Mycobacterium leprae

This report describes N-terminal group analysis of six new proteins isolated from in vivo-grown Mycobacterium leprae, three of which correspond to products of the cysA, ahpC, and rpIL genes, which were recently defined through the M. leprae genome project and which encode a putative sulfate sulfurtransferase, an antioxidant enzyme, and the L7/L12 ribosomal protein, respectively.     

Secondary tumor of the temporal bone with internal auditory meatus involvement--histopathological study

Nineteen cases of secondary tumor of the temporal bone with involvement of the internal auditory meatus (IAM) were studied. The cases were classified into 4 invasion modes; direct extension from head and neck tumors (12 cases), hematological dissemination (3 cases), diffuse leptomeningeal carcinomatosis (3 cases), and direct extension of tumors from the intracranium (1 case). There were some differences in the manner in which the tumor had spread among these 4 modes. In most cases involving "direct extension from head and neck tumors", the tumor had invaded the pyramis, and then the Eustachian tube and the middle ear. When the inner ear or the IAM was involved, it was directly invaded by massive tumor. In all cases of "hematological dissemination", metastatic tumor was found bilaterally, but there were some differences in the manner of invasion between the two sides. In "leptomeningeal carcinomatosis" and "intracranial tumor", the tumor had invaded the temporal bone bilaterally via the IAM. In the IAM, cochlear and inferior vestibular nerves were more vulnerable to tumor invasion than facial and superior vestibular nerves. It was suggested that there are some differences in vulnerability to tumor invasion between the superior and inferior vestibular nerves. The bottom of the IAM presented a barrier-like effect against the spread of tumor from the IAM to the labyrinth. In some cases, however, there was massive tumor invasion of the internal ear directly from the IAM. Whether denervation of the ganglionic neurons (spiral or vestibular) causes secondary degeneration of peripheral sensory endorgans remains controversial. In some cases in our series, degeneration of the auditory or vestibular peripheral organs might be attributed to denervation of neurons in the spiral or vestibular ganglia. In other cases, however, auditory and vestibular peripheral organs remained intact despite severe degeneration of ganglionic neurons.     

Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome

The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.     

Homologs of Mycobacterium leprae 18-kilodalton and Mycobacterium tuberculosis 19-kilodalton antigens in other mycobacteria

Most of the antigens of Mycobacterium leprae and M. tuberculosis that have been identified are members of stress protein families, which are highly conserved throughout many diverse species. Of the M. leprae and M. tuberculosis antigens identified by monoclonal antibodies, all except the 18-kDa M. leprae antigen and the 19-kDa M. tuberculosis antigen are strongly cross-reaction between these two species and are coded within very similar genes. Studies of T cell reactivity against mycobacterial antigens have indicated that M. tuberculosis bears epitopes that are cross-reactive with the M. leprae 18-kDa antigen, but attempts to identify an 18-kDa antigen-like protein or protein coding sequence in M. tuberculosis have been unsuccessful. We have used a combination of low-stringency DNA hybridization and polymerase chain reaction techniques to identify, isolate, and sequence genes from M. avium and M. intracellulare that are very similar to the 18-kDa antigen gene of M. leprae and others that are homologs of the 19-kDa antigen gene of M. tuberculosis. Unlike M. leprae, which contains a single 18-kDa antigen gene, M. avium and M. intracellulare each have two 18-kDa antigen coding sequences. Although the M. leprae, M. avium, and M. intracellulare 18-kDa antigen genes are all very similar to one another, as are the M. tuberculosis, M. avium, and M. intracellulare 19-kDa antigen genes, we have been unable to detect any 18-kDa antigen-like coding sequences in DNA from M. tuberculosis.     

A morphological study of human epipharyngeal mucosa: 10 autopsy cases

The epipharynx lies between the nasal cavity and the mesopharynx, which is behind the oral cavity. It is a conduit for respired air, contributes to the equalization of pressure within the middle ear space via the eustachian tube and is closed by the soft palate during swallowing of food and fluid. It acts as a drainage channel for the mucous secreted by the nose and the glands within the epipharynx area. Various exchanges of the epipharyngeal mucosa occur because of the function of the epipharynx. In this study, distribution of the 3 types of epithelium in the epipharynx, which are ciliated, transitional and squamous epithelium, was investigated. The specimens of the mucosa with the bony wall of the epipharynx were collected from 10 autopsy cadavers at, (6 males and 4 females, aged from 37 to 83 years). Distribution of the 3 types of epithelium differed with the type, but there was no marked difference between the right and left halves of the epipharynx. Therefore, the distribution pattern was investigated by drawing superimposed geographical schemata of the epithelia, which were confirmed histologically in all 10 cases. The results obtained were as follows. On the superior-posterior wall, the squamous epithelium was invaginated into an area of the ciliated epithelium just like islands or bands in the nasal side and the epithelia of all 3 types were mixed in the mesopharyngeal side. The lateral wall was covered with a mixture of ciliated and transitional epithelia on the nasal side from the posterior lip of the eustachian tube and with a mixture of transitional and squamous epithelia on its mesopharyngeal side. The inferior wall was covered mostly with ciliated epithelium on the nasal side and with squamous epithelium on the mesopharyngeal side from Passavant's ridge. The transitional epithelium was distributed like an island between the areas of the ciliated and squamous epithelia in the lateral wall. The clearly definite schema of the 3 types of epithelium in the epipharynx, reported by Ali, has been generally accepted. However, the 3 types appeared as a mosaic or an island in the epipharyngeal wall and their distribution pattern was different in each individual.     

Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae

alpha-Dystroglycan (alpha-DG) is a component of the dystroglycan complex, which is involved in early development and morphogenesis and in the pathogenesis of muscular dystrophies. Here, alpha-DG was shown to serve as a Schwann cell receptor for Mycobacterium leprae, the causative organism of leprosy. Mycobacterium leprae specifically bound to alpha-DG only in the presence of the G domain of the alpha2 chain of laminin-2. Native alpha-DG competitively inhibited the laminin-2-mediated M. leprae binding to primary Schwann cells. Thus, M. leprae may use linkage between the extracellular matrix and cytoskeleton through laminin-2 and alpha-DG for its interaction with Schwann cells.     

Molecular and immunological analyses of the Mycobacterium avium homolog of the immunodominant Mycobacterium leprae 35-kilodalton protein

The analysis of host immunity to mycobacteria and the development of discriminatory diagnostic reagents relies on the characterization of conserved and species-specific mycobacterial antigens. In this report, we have characterized the Mycobacterium avium homolog of the highly immunogenic M. leprae 35-kDa protein. The genes encoding these two proteins were well conserved, having 82% DNA identity and 90% identity at the amino acid level. Moreover both proteins, purified from the fast-growing host M. smegmatis, formed multimeric complexes of around 1000 kDa in size and were antigenically related as assessed through their recognition by antibodies and T cells from M. leprae-infected individuals. The 35-kDa protein exhibited significant sequence identity with proteins from Streptomyces griseus and the cyanobacterium Synechoccocus sp. strain PCC 7942 that are up-regulated under conditions of nutrient deprivation. The 67% amino acid identity between the M. avium 35-kDa protein and SrpI of Synechoccocus was spread across the sequences of both proteins, while the homologous regions of the 35-kDa protein and the P3 sporulation protein of S. griseus were interrupted in the P3 protein by a divergent central region. Assessment by PCR demonstrated that the gene encoding the M. avium 35-kDa protein was present in all 30 M. avium clinical isolates tested but absent from M. intracellulare, M. tuberculosis, or M. bovis BCG. Mice infected with M. avium, but not M. bovis BCG, developed specific immunoglobulin G antibodies to the 35-kDa protein, consistent with the observation that tuberculosis patients do not recognize the antigen. Strong delayed-type hypersensitivity was elicited by the protein in guinea pigs sensitized with M. avium.     

Implant/bone constructs in femoral neck osteotomy. An autopsy study

Previous studies have suggested that three rather than two screws may give better results in the treatment of femoral neck fractures. In the present study, the strength of various screw/bone constructs in femoral neck osteotomy was analyzed. Transverse osteotomies on 65 cadaver femora were fixed with two or three screws of two types: one with a shank diameter of 6 mm and thread diameter of 8 mm, and a prototype screw with equal shank and thread diameter of 7 mm. The femoral heads were subjected to static and cyclic loads in the one-legged stance position. Single-energy quantitative computed tomography measurements were correlated to load. The two experimental models resulted in different patterns of failure of the bone/implant constructs, otherwise the results were similar. Three of the prototype screws gave the strongest construct, while two of the other screw type were stronger than three. The explanations for the diverging properties of the different bone/implant constructs may be that large threads destroy too much of the bone trabeculae, and that screw threads larger than the shank may destroy the drill canal and produce an unstable situation compared with screws with equal shank and thread diameter.     

Nontuberculous Mycobacterium pulmonary infection with pleural effusion caused by Mycobacterium kansasii

A 28 year-old man was admitted to our hospital because of fever, cough and chest pain. A chest X-ray film taken on admission showed infiltrate in the left upper lung field with ipsilateral pleural effusion. Microscopical examinations of stained specimens of sputa and pleural effusions disclosed no acid-fast bacilli. The level of adenosine deaminase (ADA) in pleural effusion was 46.4 IU/l. A tuberculin skin test was moderately positive. The most probable diagnosis was pulmonary tuberculosis with pleural effusion. Isoniazid (INH) and rifampicin (RFP) were administered on the 5th hospital day and continued to lower the fever and reduce the pleural effusion. The cultured specimens of sputa and pleural effusions yielded Mycobacterium kansasii. After six months of treatment, chest X-ray film showed improvement and the administration of INH, RFP was discontinued without recurrence.