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Biomedical subjects

J A Libnoch

Publications and source records attributed to J A Libnoch.

At least 37 records · Page 2Linked to original sources

Altered immunoregulation in Waldenström's macroglobulinemia. I. The absence of Con A-induced and spontaneous T suppressor cell activity in a patient and his kindred.

In vitro lymphocyte functions in a patient with Waldenström's macroglobulinemia and his kindred were examined. The percentage and number of total peripheral blood T cells and the absolute number of FC gamma bearing T cells were decreased in the patient and family members compared to controls but the B cells and monocytes were normal. In addition, PHA and PWM stimulated proliferation were decreased. Decreased responsiveness to PWM was abrogated by preculturing PBMC in media alone before PWM stimulation. Decreased responsiveness to PHA was not reversed by a similar period of preculture. To further define the above abnormalities in immunoregulation we examined mononuclear subpopulations. In controls, adding purified T cells or Con A activated lymphocytes to autologous cultures which had been stimulated with PHA and PWM significantly decreased proliferative activity. No such suppressive activity of T cells or Con A activated cells from the patient or family members was noted. These data demonstrate an absent or functionally inactive spontaneous and Con A activated T suppressor cells in the family of a patient with Waldenström's macroglobulinemia.

Adult↗

The role of thoracic and cranial irradiation for small cell carcinoma of the lung.

Since 1974, 120 previously untreated patients with small cell carcinoma of the lung seen in Therapeutic Radiology at The Medical College of Wisconsin have been entered into one of 4 successive studies. Study I used thoracic irradiation (TI) alone (4500-6000 rad in 3-6 weeks) with chemotherapy at progression. Study II randomized patients with limited disease to TI (3000 rad in 2 weeks) plus either cyclophosphamide, doxorubicin, vincristine (CAV) or total body irradiation (TBI); patients with extensive disease received TI + CAV. Study III employed prophylactic cranial irradiation (PCI) plus CAV and withheld TI unless there was incomplete response or recurrence. Of 93 evaluable patients from the first three studies, 55 had limited and 38 extensive disease. Study I (37 patients) showed a 62% complete response (CR) rate; 43% failed in the chest, 14% had brain metastases, and the median survival was only 22 weeks in spite of a preponderance of limited disease patients. Study II (27 patients) showed a CR of 59%; 30% had brain metastases and the median survival was 48 weeks. Study II patients (29) had a 69% rate; 72% failed in the chest, 4% with PCI developed brain metastases, and the median survival was 50 weeks. In March, 1979, Study IV was initiated; patients receive PCI (2500 rad in 2 weeks) plus high dose CAV, methotrexate and leucovorin. After 6 cycles, consolidation TI (3750 rad in 3 weeks) is given to patients with complete response. Preliminary results with 27 patients treated on this study show a 67% CR rate, a 41% chest failure rate (but only 11% for the patients who received thoracic irradiation) and no intracranial failures, but a 13% extracranial CNS failure rate. PCI, TI and spinal irradiation may be necessary to maximize the probability of long term disease free survival.

Antineoplastic Combined Chemotherapy Protocols↗

The role of consolidation irradiation in combined modality therapy of small cell carcinoma of the lung.

Forty-four patients with small cell carcinoma of the lung (SCCL) were treated with a program of combined chemotherapy and radiation therapy. Prophylactic cranial irradiation was given concurrent with the first of six planned cycles of chemotherapy consisting of Cyclophosphamide, Adriamycin, Vincristine and high dose Methotrexate (CAV-M). All patients judged as complete responders (CR) received consolidative thoracic irradiation (CTI) to the locoregional primary lung involvement. The CR rate to chemotherapy alone was 84% for patients with limited disease (LD) and 44% for extensive disease. In comparison to a prior trial, which used similar chemotherapy, but with irradiation withheld until primary site relapse, the actuarial primary site relapse rate at 2 years was reduced by CTI from 92% to 18% (P less than .01). The median primary site remission duration has not yet been reached in the CTI group and was 34 weeks without CTI (P less than .01). CTI increased the 2 year actuarial survival from 6% to 66% (P less than .01) in the chemotherapy CR patients. Median survival has not yet been reached in the CTI group, but was 48 weeks without CTI (P less than .01). Leptomeningeal spinal cord relapse in patients with no prior central nervous system (CNS) involvement occurred in 16% of patients relapsing.

Aged↗

Integration of chemotherapy and radiation therapy for small cell carcinoma of the lung.

Two chemotherapy trials using cyclophosphamide, doxorubicin hydrochloride and high-dose vincristine sulfate with or without methotrexate have induced a 93% incidence of complete remission in limited disease presentation of small cell bronchogenic carcinoma of the lung and 39% incidence in extensive disease. The first trial without consolidation radiotherapy had a local failure rate of 65%, which dropped to 17% with consolidation radiotherapy to the primary and mediastinum. Prophylactic whole brain radiotherapy prevented local recurrence in 98% of evaluable patients. One carcinomatous meningitis and 5 intraspinal recurrences were noted among the 38 patients in the CAV-M trial. We conclude that high-dose vincristine sulfate is associated with an improved incidence of complete remission; that prophylactic whole brain radiotherapy has been highly successful; that prevention of intraspinal recurrence will necessitate the use of craniospinal axis radiation therapy and consolidation radiation therapy improves local control of primary and mediastinum.

Antineoplastic Agents↗

Local control of intrathoracic disease with chemotherapy and role of prophylactic cranial irradiation in small-cell carcinoma of the lung.

Between 1978 and 1979, 39 consecutive patients at the Medical College of Wisconsin were seen with small-cell carcinoma of the lung; of these, 31 were treated with chemotherapy and prophylactic CNS irradiation (2500 rad/10 fractions) and were evaluable after 22 month median follow-up. The intrathoracic primary was not irradiated unless there was no response to chemotherapy or subsequent recurrence. Of the 31 patients, 12 had limited disease (LD) and 19 had extensive disease (ED). Twenty, including all the patients with LD, had a complete response, eight had a partial response, and three were nonresponders. Of 24 patients with complete response at the primary site, 20 subsequently displayed local failure of the intrathoracic primary tumor, most developing disseminated extrathoracic disease simultaneously with or shortly after primary failure. The median survival time (MST) of the evaluable group was ten months with an actuarial one-year survival of 39%. Patients with LD had a median remission duration of 13 months and a MST of 16 months. Three patients are still alive with no evidence of disease at 14, 20, and 27 months. Of 26 patients receiving prophylactic cranial irradiation, all are free of CNS relapse. Chemotherapy alone appears insufficient to permanently control the bulky intrathoracic tumor, leading to the use of "consolidation" irradiation of moderate dose (3750 rad/15 fractions) to follow chemotherapy. Prophylactic CNS irradiation should be used routinely.

Antineoplastic Agents↗

Methemoglobin reduction in red cells: effect of a high oxygen affinity hemoglobin.

Erythrocytes from heterozygous carriers of the high oxygen affinity mutant hemoglobin, Hb Wood, demonstrate lower rates of methemoglobin reduction than normal human red cells when incubated in the in vitro system of Beutler and Baluda. The rate of methemoglobin reduction in red cells from an individual who is heterozygous for both NADH-methoglobin reductase deficiency and Hb Wood shows the combined effects of the two mutations.

Dihydrolipoamide Dehydrogenase↗

Comparison of hemoglobins Wood (alpha 2 beta 2 97 leu) and Malmö (alpha 2 beta 2 97 gln). Diagnostic value of citrate agar electrophoresis.

Diagnostic value of citrate agar electrophoresis. Am J Clin Pathol 71:668-671, 1979. Of approximately three dozen hemoglobin variants that have greater than usual oxygen affinity, nearly half are inseparable from hemoglobin A by electrophoresis at pH 8.6. A comparison of hemoglobins Wood (alpha2beta297leu) and Malmö (alpha2beta297gln) is of interest from several standpoints. They represent similar substitutions at the identical locus in the beta chain. They result in identical clinical and hematologic manifestations. Oxygen affinities of these variants are identical. Both are poorly resolved from hemoglobin A by electrophoresis at pH 8.6. The position of each is identical when studied by isoelectric focusing in polyacrylamide gel. Finally, they are easily distinguished by citrate agar electrophoresis at pH 6.2. The excellent resolution of hemoglobins Malmö and Wood from each other results neither from difference in charge, nor size, nor in quaternary structure. This technic provides a simple but effective means for identifying and differentiating these hemoglobin variants. Comparison with the results of citrate agar electrophoresis of other high oxygen-affinity hemoglobins indicates that the findings for hemoglobins Malmö and Wood are unique and unambiguous.

Adolescent↗

Interaction of thoracic irradiation and chemotherapy on local control and survival in small cell carcinoma of the lung.

The records of all patients with small cell carcinoma of the lung seen in the Division of Therapeutic Radiology at The Medical College of Wisconsin from 1971 through 1977 were reviewed. Of 69 patients (34 with limited disease and 35 with extensive disease), 35 received irradiation only, nine received local plus total-body irradiation, and 25 received irradiation plus chemotherapy. In spite of the prompt response of the tumor, 16 of 35 patients who were only irradiated failed locally. Two patients who received local plus total-body irradiation failed in the chest. Only four of 25 irradiation plus chemotherapy patients failed locally in spite of much lower doses of thoracic irradiation. Limited-disease patients who had local control by irradiation had a slight increase (29 vs 22 weeks) in median survival. Patients receiving irradiation plus chemotherapy (three with limited and 22 with extensive disease) survived for a median of 56 weeks if the local tumor was controlled and for a median of 28 weeks if there was local failure. Regardless of therapy, survival beyond the median is greatly influenced by local tumor control.

Adult↗

Remission of chronic lymphocytic leukemia after smallpox vaccination.

A 78-year-old man with untreated chronic lymphocytic leukemia (CLL) was revaccinated for smallpox. A severe local reaction and generalized rash followed that responded to treatment with vaccinia immune human globulin. After recovery, the leukocyte count fell to normal and all evidence of CLL disappeared. He remains in complete remission three years after smallpox vaccination.

Aged↗

Acute myelofibrosis and malignant hypercalcemia.

A 33 year old man presented with symptoms of one week's duration; he had a serum calcium of 22.5 mg/dl and a markedly hypercellular bone marrow. Despite therapy with saline diuresis, furosemide mithramycin, total parathyroidectomy and corticosteroids, symptomatic hypercalcemia was poorly controlled. Inappropriate serum parathyroid hormone (PTH) levels were found before and after parathyroidectomy whereas assays of the peripheral blood for osteoclast-activating factor and prostaglandin E (PGE2) were negative. An elevated leukocyte alkaline phosphate level, the inability to aspirate marrow, the marked generalized hyperplasia of all hematopoietic marrow elements, the focal accumulations of blastic cells and increasing reticulin fiber formation led to the diagnosis of acute myelofibrosis. A single course of cytosine arabinoside and thioguanine therapy was followed by profound hyperphosphatemia, hypocalcemia and death. The rarity of hypercalcemia with myeloproliferative disorders is documented by a review of the world literature, and the possible mechanism for hypercalcemia in this patient is discussed.

Acute Disease↗

Hemoglobin Wood beta97(FG4) His replaced by Leu. A new high-oxygen-affinity hemoglobin associated with familial erythrocytosis.

The characterization of hemoglobin Wood (beta97(FG4) His replaced by Leu), a high oxygen affinity hemoglobin with reduced Hill constant is described. The amino acid substitution occurs at the alpha1beta2 interface, in the same position as in hemoglobin Malmö (beta97(FG4) His replaced by Gln) and in an homologous position when compared with hemoglobins Chesapeake (alpha92(FG4) Arg replaced by Leu) and J. Capetown (alpha92(fg4) arg replaced by Gln).

Amino Acids↗

Nitrosylhemoglobin Wood: effects of inositol hexaphosphate on thiol reactivity and electron paramagnetic resonance spectrum.

Properties of Hb Wood (beta-97(FG4)His leads to Leu), a high oxygen affinity hemoglobin with reduced hemeheme interaction, were examined in its nitric oxide liganded form. The reactivity of the beta-93 thiol groups and the electron paramagnetic resonance (EPR) spectrum were examined to determine what effect the amino acid substitution, which occurs at the alpha1beta2 interface, would have on inositol hexaphosphate induced transition of this form of the tetramer. Binding of inositol hexaphosphate (IHP) in a 1:1 stoichiometry was demonstrated. In spite of apparently normal interaction with IHP, there was little or no change in the reactivity of the beta-93 thiol groups and in the electron paramagnetic resonance (EPR) spectrum as contrasted with the marked changes characteristic of normal hemoglobin (HbA). In contrast with NO-HbA, there was also no development of the EPR hyperfine structure in NO-Hb Wood with increased protonation of the protein at pH below 7.0. Taken together with the observations of Henry and Banerjee ((1973), J. Mol. Biol. 73, 469) on the development of NO-Hb EPR hyperfine structure and of Perutz et al. (1974a), Biochemistry 13, 2174) on changes in thiol reactivity with the R leads to T transition, the results suggest that IHP or H+ cannot switch NO-Hb Wood to the T conformation. Since the atomic structures of met- and deoxyhemoglobin offer no indication that His-97 plays any special part in the allosteric mechanism (M. E. Perutz, personal communication), it appears that the replacement of His-97 by Leu reduces the stability of the T structure relative to that of R.

Binding Sites↗