The measles virus hemagglutinin downregulates the cellular receptor SLAM (CD150).

Signaling lymphocyte activation molecule (SLAM), a cellular receptor for measles virus, was downregulated from the surface of cells infected with either the Edmonston or wild-type KA strain of measles virus. Transfection of the expression plasmid encoding the Edmonston or KA hemagglutinin, but not the fusion protein, induced downregulation of SLAM in not only cells expressing the envelope protein on the surface, but those not expressing it. After cocultivation with cells expressing the hemagglutinin, SLAM-expressing cells also exhibited downregulation of SLAM. Thus, the measles virus hemagglutinin can induce downregulation of SLAM in cells either expressing or coming in contact with it.

A case of spindle cell carcinoma of the breast--long survival achieved by multiple surgical treatment.

Spindle cell carcinoma of the breast was formerly called carcinosarcoma, and is relatively rare. We report a case of spindle cell carcinoma of the breast. The patient was treated with multiple surgeries and achieved long-term survival. The patient was a 52-year-old woman, in whom small induration developed at the areola of the nipple of the right breast. The lesion was resected, and benign tumor was diagnosed pathologically. Four years later, she had recurrence at the scar, and a typical mastectomy was performed. A tumor developed again 5 years later; the lesional focus was at the scar of the right chest wall and invasion of the ribs and the sternum was noted. The sternum and the right costal cartilage of ribs 3-9 were dissected together. The right chest wall was reconstructed and adjuvant radiation therapy performed. Four years after this operation, tumor recurred near the scar and chest wall resection including part of the pericardial cavity and the left lung was performed. However, 6 months later, invasion of the mediastinum, heart and lung were noted. The patient died 16 years after the first surgery. Dermatofibrosarcoma protuberance of the breast was diagnosed at the second operation. However, the diagnosis was changed to spindle cell carcinoma of the breast following immunohistochemical studies. Spindle cell carcinoma of the breast is rare, and definitive histopathological diagnosis is often difficult. When spindle cell carcinoma is suspected, comprehensive diagnostic studies including immunohistochemical examinations should be performed. Even in case with multiple recurrences correctly performed operations may contribute to prolongation of survival.

Position of immobilization after dislocation of the glenohumeral joint. A study with use of magnetic resonance imaging.

BACKGROUND: Glenohumeral dislocations often recur, probably because a Bankart lesion does not heal sufficiently during the period of immobilization. Using magnetic resonance imaging, we assessed the position of the Bankart lesion, with the arm in internal and external rotation, in shoulders that had had a dislocation. METHODS: Coaptation of a Bankart lesion was examined with use of magnetic resonance imaging, with the arm held at the side of the trunk and positioned first in internal rotation (mean, 29 degrees) and then in external rotation (mean, 35 degrees), in nineteen shoulders. Six shoulders (six patients) had had an initial anterior dislocation, and thirteen shoulders (twelve patients) had had recurrent anterior dislocation. Fast-spin-echo T2-weighted axial images were made when the dislocation had occurred less than two weeks earlier, and spin-echo T1-weighted axial images after intra-articular injection of gadolinium-diethylenetriamine pentaacetic acid were made when the dislocation had occurred more than two weeks earlier. Separation and displacement of the anteroinferior portion of the labrum from the glenoid rim were measured on the axial images, and coaptation of the anterior part of the capsule to the glenoid neck was assessed by measurement of the detached area, opening angle, and detached length. RESULTS: Separation and displacement of the labrum were both significantly less (p = 0.0047 and p = 0.0017, respectively) when the arm was in external rotation than when it was in internal rotation. The detached area and the opening angle of the anteroinferior portion of the capsule were both significantly smaller (p = 0.0003 and p < 0.0001, respectively), and the detached length was significantly shorter (p < 0.0001) with the arm in external rotation. CONCLUSION: Immobilization of the arm in external rotation better approximates the Bankart lesion to the glenoid neck than does the conventional position of internal rotation.

Virus entry is a major determinant of cell tropism of Edmonston and wild-type strains of measles virus as revealed by vesicular stomatitis virus pseudotypes bearing their envelope proteins.

The Edmonston strain of measles virus (MV) that utilizes the human CD46 as the cellular receptor produced cytopathic effects (CPE) in all of the primate cell lines examined. In contrast, the wild-type MV strains isolated in a marmoset B-cell line B95a (the KA and Ichinose strains) replicated and produced CPE in some but not all of the primate lymphoid cell lines. To determine the mechanism underlying this difference in cell tropism, we used a recently developed recombinant vesicular stomatitis virus (VSV) containing as a reporter the green fluorescent protein gene in lieu of the VSV G protein gene (VSVDeltaG*). MV glycoproteins were efficiently incorporated into VSVDeltaG*, producing the VSV pseudotypes. VSVDeltaG* complemented with VSV G protein efficiently infected all of the cell lines tested. The VSV pseudotype bearing the Edmonston hemagglutinin (H) and fusion (F) protein (VSVDeltaG*-EdHF) infected all cell lines in which the Edmonston strain caused CPE, including the rodent cell lines to which the human CD46 gene was stably transfected. The pseudotype bearing the wild-type KA H protein and Edmonston F protein (VSVDeltaG*-KAHF) infected all lymphoid cell lines in which the wild-type MV strains caused CPE as efficiently as VSVDeltaG*-EdHF, but it did not infect any of the cell lines resistant to infection with the KA strain. The results indicate that the difference in cell tropism between these MV strains was largely determined by virus entry, in which the H proteins of respective MV strains play a decisive role.

Amino acid substitutions at position 481 differently affect the ability of the measles virus hemagglutinin to induce cell fusion in monkey and marmoset cells co-expressing the fusion protein.

The hemagglutinin (H) protein of the measles virus (MV) Edmonston strain induced cell fusion in Cos (monkey) and B95a (marmoset) cells, when co-expressed with the fusion (F) protein, whereas the H protein of the wild-type KA strain induced fusion in B95a cells, but not in Cos cells. Asparagine residue at position 481 of the KA H protein was replaced by various amino acids through site-directed mutagenesis. Substitution with tyrosine, which was found at position 481 of the Edmonston H protein, enabled the mutant KA H protein (N481Y) to induce cell fusion in Cos cells co-expressing the F protein, which could be completely blocked by anti-CD46 antibody. This mutant, however, did not cause CD46 downregulation, unlike the Edmonston H protein. The other H protein mutants (N481S, N481T, N481D, N481H, N481F) did not produce syncytia in Cos cells. On the other hand, all of the mutants retained the ability to induce cell fusion in B95a cells. Thus, while tyrosine at position 481 was indispensable for the MV H protein's interaction with CD46, the residue at this position does not appear to be critically involved in the interaction with the receptor for wild-type strains present on B95a cells.

Enhanced IFN-gamma production in vitro by CD8+ T cells in hemophiliacs with AIDS as demonstrated on the single-cell level.

We examined T cells from HIV-infected hemophiliacs under antiviral therapy, on the single-cell level, for cytokine production in vitro in response to stimulation. The percentage of IL-2-producing cells was markedly decreased among both CD3+CD8- and CD3+CD8+ cells, while the proportion of IFN-gamma-producing cells was preserved among CD3+CD8- cells and increased among CD3+CD8+ cells in HIV+ subjects, compared with HIV-uninfected controls. The increase in IFN-gamma-producing CD8+ cells was accounted for by the expansion of CD8+CD28- cells among total CD8+ T cells and by the higher percentage of IFN-gamma-expressing cells among both CD8+CD28+ and CD8+CD28- cells in HIV+ individuals, compared with controls. The enhanced IFN-gamma production in CD8+ cells from individuals in the advanced phase of HIV infection might implicate the host's response to chronic viral infection or senescence of host CD8+ cells.

Humeral attachment of the supraspinatus and infraspinatus tendons: an anatomic study.

We investigated the anatomic relationship of the supraspinatus (SSP) and infraspinatus (ISP) tendons to the three facets of the greater tuberosity. After removing the superficial layer of the cuff to expose the tendon fibers in 10 embalmed shoulders, the cuff tendon attachment to the facets was examined, and the location of attachment was measured in reference to (1) the anterior margin of the greater tuberosity and (2) the superior margin of the sulcus (anatomic neck without cartilage). The SSP tendon attached to the superior facet and the superior half of the middle facet. The ISP tendon attached to the entire middle facet, covering a portion of the SSP tendon. Thus, the anterior half of the superior cuff tendon (12.6 +/- 1.1 mm) was composed of only the SSP tendon, whereas the posterior half (9.8 +/- 3.2 mm) was composed of both the SSP and ISP tendons. The sulcus was located not at the SSP-ISP interval but slightly posterior to the posterior margin of the SSP tendon (4.3 +/- 2.4 mm). We conclude that (1) there is an overlap between the SSP and ISP tendons identifiable by the facets or the distance from the anterior greater tuberosity and (2) the sulcus is located slightly posterior to the posterior margin of the SSP tendon.

Isokinetic strength after tears of the supraspinatus tendon.

We measured the isokinetic strength of abduction, adduction, internal rotation, and external rotation in ten patients with full-thickness tears of the supraspinatus and ten with partial-thickness tears. The measurements were repeated after intra-articular or intrabursal injection of local anaesthetic. Pain blocks produced significant increases in strength in both full and partial-thickness tears. After the block, the strength in full-thickness tears compared with the opposite side was 67% to 81% in abduction and 67% to 78% in external rotation, both significantly smaller than those on the uninvolved side (p = 0.0064, p = 0.0170). In partial-thickness tears the strength after the block ranged from 82% to 111%, with no significant differences between the involved and uninvolved sides. The decreases in strength of 19% to 33% in abduction and 22% to 33% in external rotation after full-thickness tears appear to represent the contribution of supraspinatus to the strength of the shoulder.

Pathogenicity of glycoprotein C-deficient herpes simplex virus 1 strain TN-1 which encodes truncated glycoprotein C.

A clinical isolate of herpes simplex virus 1 (TN-1) from a stromal keratitis patient was found to be defective in the glycoprotein C (gC) gene (UL44), thus resulting in the production of truncated gC upon infection. To study the pathogenetic role of truncated gC, we prepared a recombinant LTN-8 derived from TN-1 with deletions of the 1.5 kilobase pairs of the gC gene including the initiation codon. A penetration assay revealed LTN-8 to be less efficient in its penetration ability than TN-1, the laboratory strain KOS and RTN-1-20-3, a recombinant derived from TN-1 with the KOS gC gene. The penetration of LTN-8 was facilitated by the addition of TN-1-infected culture medium. TN-1 virus preparations had no hemagglutinating activity. However, the animals infected with TN-1 did develop hemagglutination inhibition (HI) antibodies. The LTN-8-infected animals did not develop HI antibodies. The pathogenicity in BALB/c mice following either corneal, intraperitoneal or intracerebral inoculation did not significantly differ among TN-1, RTN-1-20-3 or LTN-8. Our results indicate that truncated gC was sufficient for the induction of HI antibodies and was also able to facilitate penetration in vitro. Although truncated gC might be a virulence factor acting as a decoy, both truncated gC and intact gC had little effect on the outcome following intracerebral, intraperitoneal or corneal inoculation.

Successful foscarnet therapy for mucocutaneous infection with herpes simplex virus in a recipient after unrelated bone marrow transplantation.

A 36-year-old Japanese man who received an unrelated bone marrow transplant (BMT) developed severe mucocutaneous infection with herpes simplex virus (HSV) type 1 during oral acyclovir prophylaxis. The lesions progressed despite treatment with intravenous acyclovir and vidarabine. The HSV isolates were sensitive acyclovir, vidarabine and foscarnet in vitro, but peripheral CD3- or CD19-positive cells were barely detectable even 4 months after transplant. A 12-day course of treatment with foscarnet led to a rapid improvement. Foscarnet therapy should be considered for all severe HSV infections following BMT, regardless of whether or not the HSV isolates are sensitive to acyclovir.

Psychiatric morbidity in terminally ill cancer patients. A prospective study.

BACKGROUND: In the study by Derogatis et al., which included patients with all stages of cancer, 47% of the patients met the DSM-III criteria for a psychiatric disorder, with adjustment disorders being the most common. Although the cancer stage is one factor that influences the nature and incidence of psychiatric disorders, no study has demonstrated the extensive range of psychiatric disorders in terminally ill cancer patients. METHODS: Ninety-three terminally ill cancer patients were systematically assessed using the Mini-Mental State Examination (MMSE) and Structured Clinical Interview for DSM-III-R (SCID) within 1 week of admission. RESULTS: Of this sample population, 53.7% met the DSM-III-R criteria for a psychiatric disorder and 42% had a cognitive impairment. Delirium was observed in 26 patients (28%), dementia in 10 (10.7%), adjustment disorders in 7 (7.5%), amnestic disorder and major depression in 3 (3.2%), and a generalized anxiety disorder in 1 (1.1%). CONCLUSIONS: This preliminary investigation of the prevalence of psychiatric disorders in terminally ill cancer patients showed that more than half of the patients met the criteria for a DSM-III-R psychiatric disorder; delirium was the most common type of psychiatric disturbance. Further prospective trials are critically important to establishing treatment modalities that promote the psychiatric well-being of patients with terminal illnesses.

A survey of Japanese physicians' attitudes and practice in caring for terminally ill cancer patients.

To clarify the psychiatric liaison issues in cancer care, questionnaires were distributed to physicians at 31 teaching hospitals in Japan, including cancer centers and psychiatrists at 197 teaching hospitals. Data from 329 physicians and 156 psychiatrists showed that the majority of the physicians felt troubled by the psychiatric problems of terminally ill patients. However, actual psychiatric referrals were infrequent. An important factor that interferes with appropriate psychiatric referrals for cancer patients is that most physicians do not usually inform patients of a cancer diagnosis. This, it seems that close communication between physicians and psychiatrists is essential in caring for terminally ill cancer patients in the context of Japanese culture, when the psychiatric consultations are offered.

Detection of herpes simplex virus (HSV) in the saliva from 1,000 oral surgery outpatients by the polymerase chain reaction (PCR) and virus isolation.

Herpes simplex virus (HSV) was detected by a polymerase chain reaction (PCR) in 47 (4.7%) out of 1,000 saliva samples from the outpatients of an oral and maxillofacial surgery department compared with 27 (2.7%) by conventional virus isolation. There were 20 PCR-positive, culture-negative cases but no culture-positive, PCR-negative cases. Patients younger than 10 years or older than 60 years secreted HSV more frequently than the others. Those with inflammatory diseases showed higher positivity for HSV than those with malignancy, trauma or other complaints. All 27 virus isolates were typed as HSV type 1 and none were resistant to acyclovir, arabinofuranosyl-adenine, iododeoxyuridine or phosphonoacetic acid.

Necrotizing retinitis in severe combined immunodeficiency mice following intracameral inoculation of herpes simplex virus type 1.

Necrotizing retinitis in severe combined immunodeficiency (SCID) mice following intracameral inoculation of herpes simplex virus type 1 provided an experimental model for acute retinal necrosis in AIDS and other immunocompromised patients. In order to assess the involvement of the immunological response in the pathogenesis, adoptive transfer experiments were conducted. Without transfer, SCID mice developed predominantly unilateral necrotizing retinitis and died within 10 days. Transfer of immune serum lengthened the survival time but resulted in bilateral necrotizing retinitis. Two of 5 mice transferred with CD4+ T cells and none of 7 transferred with CD8+ T cells developed bilateral necrotizing retinitis. Our results indicate that ipsilateral retinal necrosis occurs with or without a specific immunological response, and that antibodies and/or CD4+ T cells accelerate the contralateral retinal necrosis.

Induction of bilateral retinal necrosis in mice by unilateral intracameral inoculation of a glycoprotein-C deficient clinical isolate of herpes simplex virus type 1.

Herpes simplex virus can cause acute retinal necrosis, a blinding retinal disease in man. A unilateral intracameral inoculation of herpes simplex virus type 1 (HSV-1) in mice induces retinal necrosis primarily in the contralateral eye and provides an experimental model for the disease. Previous studies suggested that a major envelope glycoprotein of HSV-1, glycoprotein C (gC), is required for retinal necrosis. We studied HSV-1 strain TN-1, a gC-deficient clinical isolated from a lesion of herpetic keratitis, for its pathogenicity in mice with an intracameral inoculation of the virus and found that TN-1 could induce severe necrotizing retinitis in both inoculated and uninoculated eyes of BALB/c mice. Inoculation with a lower dose of TN-1 resulted in a unilateral necrotizing retinitis in the uninoculated eyes. Tissue virus titration of infected mice killed at various times after inoculation detected an infectious virus in various organs including the eyeballs, trigeminal ganglia, brain and adrenal glands. Anterior chamber-associated immune deviation (ACAID) was observed in TN-1-inoculated mice as well as in mice inoculated with gC-positive laboratory strain KOS 7 days postinoculation. Our findings suggested that gC of HSV-1 is not necessary for either the induction of retinal necrosis, neural spread of the virus, or ACAID.

Necrotizing chorioretinitis in mice inoculated with herpes simplex virus type 1 with or without glycoprotein C: anterior chamber-associated immune deviation does not persist.

BALB/c mice developed contralateral necrotizing retinitis following intracameral inoculation with herpes simplex virus type 1 (HSV-1). The animals showed a positive delayed-type hypersensitivity (DTH) response at 10 days postinoculation, indicating that the anterior chamber-associated immune deviation was transient after HSV-1 inoculation. Since glycoprotein C (gC) of HSV-1 is a major immunogen, we examined DTH and the antibody response induced by a gC-deficient strain TN-1 and compared them with those induced by the recombinant gC-positive mutants. We found that gC was not required for DTH reaction, and that gC was neither necessary for nor protective against the contralateral retinal necrosis. Serial lymphocyte subset analyses of the draining lymph nodes revealed an absolute increase of B cells, CD4-positive T cells, and CD8-positive T cells. CD4-positive T cells but not CD8-positive T cells increased in the contralateral eyes during the inflammation and necrosis. The coincident emergence of the positive DTH and contralateral retinal necrosis of HSV-1-inoculated mice, together with the presence of CD4-positive cells in the retina, indicated that CD4-positive T cells responsible for DTH induction may participate in the retinal necrosis.

Reactivation of cytomegalovirus in patients with cirrhosis: analysis of 122 cases.

Human cytomegalovirus causes severe and often fatal infections in immunocompromised patients. After organ transplantation cytomegalovirus in peripheral blood mononuclear cells is thought to be activated by alloreaction and to spread because of immunosuppression, and it may cause endogenous cytomegalovirus diseases. Patients with cirrhosis, one group of candidates for liver transplantation, often show various grades of immunosuppression before transplantation. To evaluate the status of cytomegalovirus infection in cirrhotic patients and its relevance to the degree of immunosuppression, we examined the presence of cytomegalovirus in mononuclear cells by polymerase chain reaction and immunocytochemical analysis. We studied 122 patients with definite cirrhosis and 43 normal volunteers. All cirrhotic patients (100%) and 40 (93%) of 43 normal controls were seropositive for cytomegalovirus. Cytomegalovirus DNA was detected by polymerase chain reaction in 77 (63.1%) of 122 seropositive cirrhotic patients, but in only 1 (2.5%) of 40 seropositive normal controls (p < 0.01). Cytomegalovirus antigen could not be detected in mononuclear cells by immunocytochemical staining with monoclonal antibodies. Cytomegalovirus DNA-positive patients have a greater impairment of liver function than do cytomegalovirus DNA-negative patients; this fact is manifested by delayed indocyanine green retention rates and elevated serum bilirubin levels (p < 0.05). Lymphocyte proliferative response induced by phytohemagglutinin and natural killer cell activity were also significantly lower in cytomegalovirus DNA-positive patients as compared with cytomegalovirus DNA-negative patients (p < 0.01). Our data suggest that the reactivation of cytomegalovirus may have already occurred in patients with cirrhosis before transplantation.

Neutralizing antibodies against HTLV-I in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and asymptomatic carriers.

We tested serum specimens from patients with HAM/TSP and asymptomatic HTLV-I carriers from endemic areas of Japan, Jamaica, Colombia, and Chile for neutralizing antibodies against HTLV-I. The data suggest a trend for neutralizing activity to be found more frequently in the sera from HAM/TSP patients than in sera from asymptomatic carriers. The result of this study emphasizes the importance of determining biologic properties of the envelope glycoprotein of HTLV-I.

Neutralizing antibody responses in patients with AIDS with neurologic complications.

Although the human immunodeficiency virus type 1 (HIV-1) is frequently isolated from the cerebrospinal fluid of infected patients, only a small percentage of patients are found to have clinical dementia or neuropathies (or both). The reasons for this remain unclear. In our study, serum neutralizing antibody titers against the human T cell leukemia virus-IIIB isolate of HIV-1 were tested in 10 patients with acquired immunodeficiency syndrome (AIDS) with neurologic complications and 20 patients with HIV infection without neurologic complications. Titers were significantly lower in the neuro-AIDS group, suggesting that impaired neutralizing antibody responses in this subpopulation of patients may be involved in the immunopathogenesis of AIDS encephalopathy.

Transmission of human T-cell leukemia virus type I from a patient with HTLV-I associated myelopathy/tropical spastic paraparesis and an asymptomatic carrier to rabbits.

Rabbits were infected successfully with two strains of human T-cell leukemia virus type I (HTLV-I), one isolated from a Colombian patient with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and the other from an asymptomatic carrier. HTLV-I was repeatedly demonstrated in peripheral blood mononuclear cells (PBMNC) of infected rabbits, and the rabbits had elevated antibodies against the various structural proteins of HTLV-I. Four rabbits inoculated with HTLV-I-infected autologous lymphoid cells intravenously (i.v.) and intracerebrally (i.c.) had virus present in their PBMNC for more than 40 weeks, while those that were inoculated either with HTLV-I-infected human lymphoid cells or with autologous rabbit lymphoid cells intraperitoneally (i.p.) had episodes during which virus was not recovered from their PBMNC. The one rabbit inoculated i.p. developed antibodies to viral envelope glycoproteins earlier than did those inoculated i.v. and i.c. Rabbit lymphoid cell lines persistently infected with HTLV-I were established by cocultivating the rabbit PBMNC with HTLV-I-infected human lymphoid cells that had been irradiated or by inoculation with cell-free supernatant fluids of HTLV-I infected non-irradiated lymphoid cell cultures. HTLV-I-infected rabbit cell lines were of T-cell origin and expressed HTLV-I antigens by immunofluorescence. Electron microscopy revealed type-C retrovirus particles.