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Biomedical subjects

R Valenzuela

Publications and source records attributed to R Valenzuela.

At least 19 recordsLinked to original sources

Phosphorous metabolite and cell cycle kinetic response of two human squamous cell carcinomas to radiation.

Phosphorous metabolism and cell cycle phase kinetics in response to radiation of two perfused human squamous cell carcinoma cell lines, SQ20B (radioresistant) and SQ38 (relatively radiosensitive), embedded in both basement membrane (Matrigel) and agarose gel threads were studied. The findings for these human cancer cells in response to 2- and 50-Gy irradiation are as follows. (a) Well perfused pure cancer cells (both SQ20B and SQ38) in both proliferative (cells embedded in Matrigel) and static (cells embedded in agarose threads) states did not show significant alteration in either phosphorous bioenergetics or membrane metabolites at 24 and 48 h after irradiation, although a large fraction of the population was clonogenically impaired. Previously reported, sensitively detected, metabolite alterations in response to radiation in rodent and human tumors in situ were not seen in these homogeneous cancer cell populations. (b) The radiosensitive squamous cell carcinoma cell lines SQ38 exhibited G1 block (from 54.38 +/- 1.40% in control to 73.93 +/- 1.01% after irradiation; mean +/ SD) in response to low-dose 2-Gy irradiation and G2 block (from 12.98 +/- 2.15% in control to 25.6 +/- 3.15% after irradiation) in response to high-dose 50-Gy irradiation, while the radioresistant cell line SQ20B showed only conventional G2 block in response to both doses. The differential cell cycle phase response may indicate the difference in radioresistance. (c) The membrane metabolites (including phosphomonoesters and phosphodiesters) and phosphocreatine gradually increased from the early passages to late passages, suggesting that cell proliferation rates were increasing as the cells adapted to tissue culture. The results suggest that the radiation-induced metabolite changes observed in solid tumors in situ may not be a direct response to interim changes within the cancer cells but, rather, a consequence of radiation damage either to the vasculature or to other host-mediated factors.

Animals

Continuous dermoepidermal junction IgM detected by direct immunofluorescence: a report of nine cases.

BACKGROUND: Although a linear IgM dermatosis of pregnancy has been reported, other authors have not found evidence for a distinct linear IgM dermatosis. OBJECTIVE: We set out to determine whether or not continuous dermoepidermal junction IgM deposition detected by direct immunofluorescence was indicative of a specific disease. METHODS: We collected nine cases during a 9-year period in which biopsy specimens for direct immunofluorescence revealed continuous linear IgM at the dermoepidermal junction in the absence of other immunoglobulins. In all of these cases the medical record was available for review. RESULTS: Clinical correlation revealed that these patients had a heterogeneous group of diseases with urticaria and leukocytoclastic vasculitis being most common. No diagnostic specificity could be ascribed to the linear IgM pattern, although six of our nine cases could be considered manifestations of a hypersensitivity response (e.g., urticaria, leukocytoclastic vasculitis, pigmented purpuric dermatosis, or hypersensitivity dermatitis). CONCLUSION: Pathologists and dermatologists should be aware that linear IgM can be seen in a variety of clinical settings. The etiopathogenic significance of this finding, if any, remains to be determined. At present, the finding must be viewed as nonspecific.

Adult

Relapsing polychondritis: a case diagnosed by direct immunofluorescence and coexisting with pseudocyst of the auricle.

A case of relapsing polychondritis with perichondrial IgG and C3, dermoepidermal IgG, and a coexisting pseudocyst of the auricle is reported. The use of direct immunofluorescence testing in establishing a diagnosis of relapsing polychondritis and the expected findings are reviewed. In some cases direct immunofluorescence may allow a diagnosis of relapsing polychondritis before clinical criteria or a routine histologic evaluation suggests a definite diagnosis.

Aged

Paraneoplastic pemphigus: a report of three cases including one long-term survivor.

BACKGROUND: Paraneoplastic pemphigus is a newly described autoimmune disease characterized by painful mucosal ulcerations and polymorphous skin lesions in association with an underlying neoplasm. All reported patients with an associated malignant neoplasm have had a poor prognosis. OBJECTIVE: We present three new cases of paraneoplastic pemphigus associated with a malignant neoplasm and further characterize this disease. METHODS: We used clinical criteria, histologic and immunopathologic examinations, and immunophenotyping to characterize this disease. In addition, we performed immunoprecipitation studies with extracts of radiolabeled human keratinocytes to characterize the antigens to which patient serum binds. RESULTS: All three patients had clinical, histologic, and immunopathologic findings that were strongly suggestive of paraneoplastic pemphigus. Their sera immunoprecipitated a complex of four polypeptides from human keratinocyte extracts with molecular weights of 250, 230, 210, and 190 kd, confirming the diagnosis of paraneoplastic pemphigus. The 250, 230, and 210 kd antigens comigrated with desmoplakin I, the 230 kd bullous pemphigoid antigen, and desmoplakin II, respectively. Lymphocyte immunophenotyping revealed large populations of monoclonal CD19+, CD5+ B cells in two cases. Although two of the patients died, one patient is alive and well 2 years after the diagnosis of paraneoplastic pemphigus. CONCLUSION: We report three cases of paraneoplastic pemphigus. One patient is alive and well 2 years after diagnosis, which suggests that a subgroup of patients may have a more benign course.

Aged

Oral and cutaneous lichen planus pemphigoides.

Lichen planus pemphigoides is a rare bullous disorder characterized by tense bullae on lichen planus lesions and on clinically uninvolved skin. A diagnosis of lichen planus pemphigoides is made on the basis of clinical, histologic, and immunopathologic evaluation. We describe a patient who had lichen planus pemphigoides of the skin and oral mucosa and briefly review the literature on this uncommon entity.

Aged

Cell cycle analysis by flow cytometry of non-exposed, sun-exposed, and tretinoin-treated skin.

The percentage of keratinocytes in the proliferative phase of the cell cycle (S + G2 + M) was measured by DNA flow cytometry in sun-exposed, non-exposed, and tretinoin-treated skin. Before tretinoin treatment, the percentage of keratinocytes actively cycling was higher in sun-exposed than in non-sun-exposed skin (p = .002) and was correlated with clinically assessed photodamage (p = .007). Subsequently, tretinoin-treated sun-exposed skin was compared to the pre-treatment sun-exposed skin. Overall, there was no statistically significant change. However, there was a trend toward a decrease in the percentage of keratinocytes in the S + G2 + M phases immediately after four months of tretinoin use that was limited to the most severely damaged patients. This effect was no longer evident two months after discontinuing treatment. This is the first study, to our knowledge, utilizing flow cytometry to investigate the effects of tretinoin in patients with varying degrees of photodamage.

Adult

Delayed cyanide induced dystonia.

A 16 year old man ingested 1 g potassium cyanide in 1969. A few days after an apparently full recovery he developed a severe dystonia syndrome. He had a positive response to an apomorphine test and showed improvement with levodopa treatment. A 21 year follow up showed minimal neurological sequelae; CT showed bilateral putaminal lucencies. Visual and brain stem auditory evoked potentials were normal.

Adolescent

Immunoelectrophoretic and immunohistochemical characterizations of fibrinogen derivatives in atherosclerotic aortic intimas and vascular prosthesis pseudo-intimas.

Cadaveric aortic intimas with uncomplicated atherosclerosis were examined to determine the distribution and polypeptide chain composition of fibrinogen-related protein. Immunohistochemical staining showed deposits rich in fibrinopeptides A and B. The deposits were usually disseminated throughout intimas of moderate thickness < 0.7 mm, but were distributed focally in elongate patches bounded both lumenally and medially by deposit-free tissue in thick atheromas. Saline extracts generally showed undegraded monomers and dimers by electrophoresis. The residual protein contained A alpha and gamma-chains that were cross-linked predominantly (>80%) into unresolved high M(r) (>200 kd) derivatives, whereas B beta-chains were left non-cross-linked, as occurs in late stages of cross-linking by transglutaminases. The resolved components had electrophoretic mobilities corresponding to characteristic products of both factor XIIIa and tissue-transglutaminase. A greater incorporation of alpha- rather than gamma-chains into cross-linked products implicated tissue-transglutaminase as contributing heavily. By contrast, vascular graft pseudo-intimas and a cadaveric clot were rich in degraded fibrin devoid of fibrinopeptide A, and cross-linked in patterns typical of XIIIa with gamma 2 dimers constituting the principal product. The findings indicate that the fibrinogen in the aortic intima is comparatively well protected from thrombin and plasmin, and that much of it is deposited through direct cross-linking by tissue-transglutaminase without being converted to fibrin.

Antibodies, Monoclonal

Nitrogen mustard as induction therapy for rheumatoid arthritis: clinical and immunologic effects.

We treated 5 patients diagnosed with rheumatoid arthritis (RA) with nitrogen mustard (HN2) and monitored clinical and immunologic variables. HN2, 0.3 mg/kg ideal body weight was given over 7 days. Disease activity and immune function were monitored during and after treatment. Duration of morning stiffness (p = 0.0044), joint count (p = 0.0140), and assessment of pain (p = 0.0264) and function (p = 0.0057) improved by Day 6. T lymphocytes (p = 0.0060), especially T memory cells (CD4CD29; p = 0.0017) fell dramatically. HN2 is effective for rapidly gaining control of active RA. This effect is T cell specific.

Aged

Pseudo-gamma heavy chain (IgG4 lambda) deposition disease.

Two patients with Ig deposition disease presented with acute renal failure, moderate proteinuria, and hematuria. A plasmacytoid lymphocytic infiltrate was identified in bone marrow that produced IgG4 lambda and free lambda light chains. One patient developed an anaplastic plasmacytoma (secreting only lambda light chains) 1 yr after renal biopsy. Renal biopsy in both patients demonstrated a nodular intercapillary glomerulopathy and electron dense granular deposits, associated with a linear pattern of IgG4 heavy chain deposition in vascular, tubular, and glomerular basement membranes (VBM, TBM, and GBM). In one patient this entrapped IgG4 was unassociated with detectable kappa or lambda light chains. In the second patient, lambda light chains (1+) were detected only in the GBM, but IgG4 (4+) was identified in GBM/TBM. Neither circulating (peripheral blood and bone marrow serum) nor cellular free gamma chains were present. We propose the term "pseudo-gamma heavy chain deposition disease" for the process.

Aged

Pharmacological characterization of the inhibitory activity of beta h-endorphin (beta h-EP), [Arg9,19,24,28,29]-beta h-EP, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, in the neuroeffector junction of the mouse vas deferens.

The inhibitory opioid activities of beta h-endorphin (beta h-EP), its structurally related peptide analogues [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 (Gly-Gly-beta h-EP), [Arg9,19,24,28,29]-beta h-EP (Arg-beta h-EP) and methionine enkephalin have been examined in the electrically stimulated mouse vas deferens bioassay. All four peptides behaved as full agonists; methionine enkephalin was the most potent followed by Arg-beta h-EP, beta h-EP and Gly-Gly-beta h-EP. Neither Gly-Gly-beta h-EP nor Arg-beta h-EP antagonized the inhibitory action of beta h-EP or methionine enkephalin. An hour of tissue exposure to 30 nM beta-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of beta h-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for beta h-EP and Arg-beta h-EP, it was only about 3-fold for Gly-Gly-beta h-EP and methionine enkephalin. Naltrindole was the most potent antagonist of methionine enkephalin with an apparent pA2 of 9.4; its potency as an antagonist of beta h-EP and related analogues was approximately one-tenth of this with pA2 values approximately 8.5. Norbinaltorphimine also antagonized the action of the opioid peptides with pA2 values close to 7.8.

Animals

[Auditory evoked potentials in Fisher's syndrome. A clinical case].

A 15 year old patient developed ataxia 2 weeks after an upper respiratory infection. Absent reflexes, external ophthalmoplegia, bilateral ptosis, isochoric mydriasis and week photomotor reflexes (Bell's phenomenon) were noted. A slight increase in protein but not cell content of the CSF was observed. Miller-Fisher syndrome was diagnosed on clinical grounds and visual and auditory evoked potentials were explored and found to be normal. This is in complete agreement to the literature and indicates indemnity of the central nervous system in Miller-Fisher's syndrome. Peripheral nervous system abnormalities that have been identified by pathologic and radiologic studies may explain all of the alterations observed in this syndrome.

Adolescent

Chronic glomerular microangiopathy and metastatic carcinoma.

Two patients with metastatic colonic adenocarcinoma developed deterioration of renal function six and nine months after the diagnosis of malignant disease. A renal biopsy specimen in one case and both postmortem specimens revealed thickening of glomerular capillary loops with focal reduplication of basement membrane-like material. Ultrastructural examination of all three specimens demonstrated a lucent subendothelial zone and no evidence of electron dense deposits. Antifibrinogen staining outlined most capillary loops in one case. It appears that chronic intravascular coagulation induced by the neoplasm was the major pathogenetic process involved in the production of the glomerular lesion in each case.

Adenocarcinoma

Chronic hereditary nephritis. A clinicopathologic study of 23 new kindreds and review of the literature.

Thirty-three patients with chronic hereditary nephritis, obtained from 23 unrelated families, were evaluated with respect to clinicopathologic features. Renal tissue was examined by light microscopy in 25 cases, immunofluorescence in 19 cases, and electron microscopy in 16 cases. The light microscopic findings varied, and foam cells were present in only four cases. Immunofluorescence was negative in all but four cases, and in these the immunomicroscopic pattern was compatible with the findings of end stage glomeruli and hyaline arteriolar sclerosis. Although electron microscopy uniformly showed marked thinning or splitting of the glomerular basement membrane, parallel splitting of the glomerular basement membrane with interposition of electron dense granular particles was seen in only eight cases. Association of glomerular basement membrane splitting with granular particles was observed in four of six patients with IgA nephropathy, in two patients with benign familial hematuria, and in a normal kidney donor. Eleven patients, seven men and four women, had chronic renal failure requiring dialysis. Of five patients who received renal allografts, three are alive, with post-transplant survival ranging from 24 to 70 months. The other two died of septicemia.

Adolescent

Reliability of immunofluorescence of renal tissue obtained at autopsy.

A retrospective study of kidney tissues accessioned in the Department of Immunopathology was undertaken to determine the reliability of the direct immunofluorescence technic applied to necropsy tissues. Of 72 accessioned specimens, 27 were positive and showed a spectrum of immunomicroscopic patterns corresponding to different renal diseases. Only two patients whose specimens were negative by immunofluorescence had shown any clinical or light microscopic evidence of active glomerular disease. Periods from death to autopsy ranged from one to 20 hours. Positive fluorescence was found in tissues obtained as long as 20 hours after death. These findings suggest that immunofluorescent studies of autopsy-derived renal tissue yield acceptable results.

Acute Kidney Injury

IgD myeloma. Report of a case with unusual clinical and immunologic features.

A case of IgD myeloma in a 48-year-old Caucasian man is reported. The unusual features of this case included the absence of osteolytic lesions by x-ray, absence of anemia, absence of monoclonal spike on serum electrophoresis, association of kappa light chains, absence of Bence Jones proteinemia and Bence Jones proteinuria, and a remarkable, temporary clinical response to therapy. Immunoelectrophoresis of whole serum yielded a pattern consistent with IgD kappa monoclonal gammopathy. Immunoelectrophoresis of a pure serum IgD preparation, previously separated by gel chromatography (Sephadex G-200), revealed definitive information about an IgD kappa monoclonal gammopathy. Immunomicroscopic examination of bonemarrow smears showed the presence of delta and kappa chains only in the cytoplasm of plasma cells.

Humans